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Essentials of

INTERNAL MEDICINE
Essentials of
INTERNAL MEDICINE

Fourth Edition

Ardhendu Sinha Ray MD


Ex-Professor
Department of Medicine
Kolkata Medical College
RG Kar Medical College
Kolkata, West Bengal, India
Burdwan Medical College
Burdwan, West Bengal, India
Kalinga Institute of Medical Sciences
Bhubaneswar, Odisha, India

Abhisekh Sinha Ray MD (NY)


Staff Nephrologist
Department of Nephrology and Hypertension
Good Samaritan Medical Center
NE, USA
Formerly, Fellow
Kidney Institute, University of Kansas Medical Center
Kansas, USA

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Essentials of Internal Medicine
The first three editions have been published by other publisher
Fourth Edition: 2017
ISBN: 978-93-52700-72-1
Dedicated to
Memory of my parents
Late Sital Prasad Singha Roy
and
Late Namita Singha Roy
Preface

When we envisioned this book Essentials of Internal Medicine, our primary aim was to develop a compelling basic
textbook in internal medicine which would provide a solid understanding of the pathophysiology of diseases, help in
the development of strong clinical acumen in approach of common clinical syndromes and make one confident about
management of different diseases of various organ-systems. In this fourth edition, Essentials of Internal Medicine, we
have followed the same core principles that inspired us in our approach to the last three editions. We are grateful to
our students and colleagues, for their encouraging words and constructive criticisms. As per the feedback, suggestion
and comments we have received, cardiology, nephrology, neurology, and respiratory sections of the book have been
thoroughly updated in this edition. New chapters on general physical examination and examinations of different systems
like neurology, respiratory, gastrointestinal are added. Revised and improved fourth edition contains all essential points
of internal medicine in a student-friendly format.
  We believe, this book will continue to be a useful companion to the undergraduate students as well as postgraduate
trainees.
  Your feedback and suggestions are welcomed.

Ardhendu Sinha Ray


Abhisekh Sinha Ray
Contents

SECTION I  CARDIOVASCULAR SYSTEM SECTION IV  RESPIRATORY SYSTEM


1. Electrocardiogram  3 31. Approach to a Patient of Hemoptysis  201
2. Rheumatic Fever  29 32. Approach to a Patient of Dyspnea  203
3. Infective Endocarditis  32 33. Bronchial Asthma  205
4. Valvular Heart Disease  36 34. Chronic Obstructive Pulmonary Disease  209
5. Heart Failure  47 35. Pneumonia  213
6. Hypertension  55 36. Pleural Effusion  216
7. Congenital Heart Diseases  63 37. Respiratory Failure  221
8. Cardiomyopathy  71 38. Cor Pulmonale  223
9. Tachyarrhythmias  74 39. Acute Respiratory Distress Syndrome  225
10. Ischemic Heart Diseases  85 40. Bronchogenic Carcinoma  227
41. Pneumothorax  230
SECTION II  CENTRAL NERVOUS SYSTEM
SECTION V  GASTROINTESTINAL SYSTEM
11. Coma and Related Disorders  101
42. Viral Hepatitis  235
12. Meningitis  105
43. Chronic Hepatitis  242
13. Epilepsy  109
44. Alcoholic Liver Disease  247
14. Hemiplegia  114
45. Nonalcoholic Steatohepatitis  249
15. Cerebrovascular Accident  119
46. Cirrhosis and its Complications  251
16. Spinal Cord Disease (Paraparesis and
47. Approach to a Patient of Upper Gastrointestinal
Quadriparesis) 129
Bleeding   261
17. Guillain-Barré Syndrome  136
48. Budd-Chiari Syndrome  265
18. Peripheral Neuropathy  138
49. Acute Pancreatitis  267
19. Myasthenia Gravis  145
50. Approach to a Patient with Malabsorption  272
20. Myopathy and Myotonia  149
51. Inflammatory Bowel Diseases  275
21. Parkinsonism  152
22. Motor Neuron Diseases  155
23. Multiple Sclerosis  158 SECTION VI  RHEUMATOLOGY
24. Polymyositis, Dermatomyositis, Inclusion Body 52. Approach to a Patient of Monoarthritis  285
Myositis 163 53. Approach to a Patient of Polyarthritis  288
54. Approach to a Patient of Low Back Pain  292
55. Gout  295
SECTION III  NEPHROLOGY
56. Rheumatoid Arthritis  298
25. Acute Glomerulonephritis   169 57. Felty’s Syndrome  305
26. Nephrotic Syndrome  173 58. Still’s Disease  306
27. Acute Renal Failure/Acute Kidney Injury  179 59. Sjögren’s Syndrome  307
28. Chronic Renal Failure  185 60. Juvenile (Rheumatoid) Idiopathic Arthritis   309
29. Urinary Tract Infection  194 61. Systemic Lupus Erythematosus  310
30. Interstitial Nephritis  196 62. Antiphospholipid Antibody Syndrome  316
x Essentials of Internal Medicine

63. Seronegative Spondyloarthritis  319 SECTION XI  INFECTIVE DISEASES


64. Ankylosing Spondylitis  321
65. Reactive Arthritis  324 98. Dengue  453
66. Psoriatic Arthropathy  327 99. Rabies  455
67. Progressive Systemic Sclerosis  330 100. Tetanus  458
68. Mixed Connective Tissue Disorder  335 101. Diarrhea  460
69. Hemolytic Uremic Syndrome  336 102. Typhoid and Paratyphoid (Enteric) Fever  464
70. Thrombotic Thrombocytopenic Purpura  338 103. Leptospirosis (Weil’s Disease)  466
71. Vasculitis Syndrome (Vasculitides)  339 104. Malaria  468
72. Antineutrophil Cytoplasmic Antibody  345 105. Leishmaniasis (Kala-azar)  472
106. Approach to a Patient of Fever with Rash  475
SECTION VII  HEMATOLOGY 107. Management of Helicobacter pylori Infection  480
108. Human Immunodeficiency Virus, Acquired
73. Approach to a Patient of Anemia  349 Immunodeficiency Syndrome  481
74. Hemolytic Anemia and Its Investigations  352 109. Tuberculosis  488
75. Thalassemia  354
76. Hypoproliferative Anemia  358 SECTION XII  MISCELLANEOUS
77. Myelodysplastic Syndrome  361
78. Leukemias  364 110. Pyrexia of Unknown Origin  499
79. Lymphoid Cells Malignancy (Lymphoma)  371 111. Metabolic Syndrome X and Acanthosis
80. Approach to a Patient with Bleeding Disorder  384 Nigricans 502
81. Thrombocytopenic Purpura  386 112. Emergencies in Clinical Medicine and Its
82. Hemophilia  388 Management 503
83. von Willebrand Disease  390 113. Acid-Base and Electrolyte Disorder  515
84. Disseminated Intravascular Coagulation  391 114. Paraneoplastic Endocrine Syndrome  521
85. Thrombotic Disorder/Thrombophilia  392
86. Kikuchi-Fujimoto Disease  394
SECTION XIII  PSYCHIATRY
SECTION VIII  ENDOCRINE 115. Psychiatry  525
87. Thyroid Gland Disorders  397
88. Adrenal Gland Disorders  404
SECTION XIV  EXAMINATIONS
89. Acromegaly  412
90. Syndrome of Inappropriate Antidiuretic 116. Examination of Cardiovascular System  535
Hormone 415 117. Examination of Central Nervous System  543
118. Examination of Upper Gastrointestinal Tract  571
SECTION IX  DIABETES (ENDOCRINE) 119. Examination of Lower Gastrointestinal Tract  573
120. Approach to a patient of Lymphadenopathy  579
91. Diabetes Mellitus  419
121. Jaundice  582
122. Cyanosis  585
SECTION X  DERMATOLOGY
123. Clubbing  587
92. Scabies  435 124. Arterial Pulse  589
93. Fungal Infection of the Skin  437 125. Neck Vein  592
94. Psoriasis  439 126. General Examination/Survey  595
95. Vitiligo and Leukoderma  442 127. Examination of Respiratory System  602
96. Acne Vulgaris  446
97. Leprosy  448 Index  609
SECTION  I
CARDIOVASCULAR SYSTEM

• Electrocardiogram
• Rheumatic Fever
• Infective Endocarditis
• Valvular Heart Disease
• Heart Failure
• Hypertension
• Congenital Heart Diseases
• Cardiomyopathy
• Tachyarrhythmias
• Ischemic Heart Diseases
Chapter 1
Electrocardiogram

Introduction • V 8on posterior scapular line on the same plane of


V4V5V6V7.
An electrocardiogram is a graphical record of the change
In case of dextrocardia precordial leads are placed on
in membrane potential generated during cardiac muscle
the corresponding position on the right side of the chest
depolarization and repolarization.
and are called V2R to V6R respectively.
The ECG records the depolarization (stimulation) and
repolarization (recovery) potentials generated by atrial and
Esophageal Leads
ventricular myocardium and spread all over body.
This electric signals are detected by means of electrode Apart from these leads there is special lead called esoph-
(called lead) attached to the extremities and chest wall and ageal lead where the recording electrode is placed in
are amplified and recorded on a (millimeter) graph paper. esophagus 27 cm down from incisor teeth for recording of
The graph paper is divided into 1 mm2 grid-like boxes. the potential from the posterior aspect of heart.
Since the universal ECG paper speed is 25 mm/sec, the Standard ECG has the following wave and P, Q, R, S,
smallest 1 mm horizontal division corresponds to 0.04 T and U wave, and the following interval PR, QRS and QT
second with heavier line at interval of 5 small square which interval (Figs 1.1 and 1.2).
is equal to 0.2 second. Vertically the ECG graph measure the During examination of ECG we have to look for follow-
amplitude of a specific wave 1 mV = 10 mm with standard ing point. (1) Heart rate, (2) rhythm, (3) electrical axis of
calibration. QRS complex, (4) P-wave, (5) P-R interval, (6) Q-wave,
The conventional ECG is recorded by 12 lead of which (7) QRS complex, (8) ST-segment, (9) Q-T interval,
6 are extremity limb lead and 6 are precordial or chest lead. (10) T-wave and (11) U-wave.
Out of 6 limb leads. Three are bipolar lead [lead-I, lead-
II, lead-III] and three are unipolar (aVR, aVL, aVF). Heart rate
Bipolar leads are It can easily be calculated from an ECG by counting the
• Lead-I → Left arm potential – Right arm potential number of small square in between two consecutive
• Lead-II → Left leg potential – Right arm potential R-wave. And dividing 1500 by the number of small square
• Lead-III → Left leg potential – Left arm potential.
Unipolar limb leads are—aVR, aVL and aVF.
In these unipolar leads potential of right arm, left arm
and left leg are recorded against ‘zero’ potential which is
made within machine by joining the lead of all four limb
and passing it through in resistance.
Standard six precordial lead are V1 – V6. These are uni-
polar lead and one electrodes is placed on the following
position and the second electrode is zero potential.
• V1 on 4th intercostal space just right of sternum.
• V2 on 4th intercostal space just left of sternum.
• V3 on midway between V2–V4.
• V4 on midclavicular line on 5th space.
• V5 on anterior axillary line on the same plane of V4.
• V6 on midaxillary line on the same plane of V4 and V5.
• V7 on posterior axillary line on the same plane of V4V5V6. Fig. 1.1: Normal ECG
4 Essentials of Internal Medicine

Fig. 1.2 : Sinus bradycardia

in between two R-wave we get the heart rate. 1500 comes POSITIVITY OF THE LEADS
from the fact that the paper speed of all ECG machine is
As the depolarization wave runs from SA node and move
25 mm/sec. So in one minute 1500 small square (25 × 60 =
towards apex (downward and to the left) the left hand side
1500) comes out from the machine.
of lead-I is considered positive and the lower half of aVF is
considered positive and the upper half aVF is negative and
Rhythm right side of lead-I negative, then the simplified picture
If the R-R interval is equal in the rhythm strip (lead-II) and come out like Figure 1.8.
the QRS complexes are preceded by ‘P’—then it is called Degree of each lead and the extent of normal axis,
“regular sinus rhythm”. The R-R interval sometime may left axis and right axis deviation is determined by an
vary slightly which is called sinus arrhythmia (which is the international convention Figure 1.9.
respiratory variation of heart rate). • Left hand side of lead-I is 0°
• Right hand side of lead-I is ± 180°
• Lower half of aVF is + 90°
Axis of QRS complex
• Upper half of aVF is – 90°
The axis of an ECG means the direction of the mean electrical • Normal axis – 30° to + 110° (Fig. 1.10)
vector of QRS complex. It is determined from extremity lead. • Left axis – 30° to – 90° (Fig. 1.10)
In Enthovean concept the heart is located at the center of • Right axis + 110° to + 180° (Fig. 1.10)
a triangle formed by joining right arm, left arm and left leg • Indeterminate axis from – 90°–180° (Fig. 1.10).
(Fig. 1.3). Now in a given ECG for determination of mean axis of
In unipolar limb lead the heart is located at the center like QRS complex, we have to consider the mean deflection of
Figure 1.6. If we simplify Figure 1.4 like Figure 1.5 and if we QRS from the isoelectric line by summation of deflection of
superimpose Figure 1.6 over Figure 1.5 we get the hexaxial QRS complex in lead I and aVF.
picture (Fig. 1.7) which is very clumsy. Out of these six axis, For example (Fig. 1.11), suppose in lead-I the summation
we take only two mutually perpendicular leads one is lead-I of deflection of QRS complex in positive and is equal to 6
and the other is aVF (Fig. 1.8) for determination of QRS axis. small square and in lead aVF it is 5. Small square on the
Electrocardiogram 5

Fig. 1.3: Thin complex tachycardia

Fig. 1.4: Bipolar limb lead Fig. 1.6: Unipolar limb lead

Fig. 1.5: Simplified bipolar limb lead Fig. 1.7: Simplified bipolar limb lead superimposed
on unipolar limb lead
6 Essentials of Internal Medicine

Fig. 1.8: Simplified diagram from hexaxial system Fig. 1.11: Example of normal axis deviation

Fig. 1.9: Degree of each lead is allotted by international convention Fig. 1.12: Determination of left axis deviation with the help of lead II`

positive side then we have to give a mark 6 mm away from


the center on lead-I and 5 mm away from the center on
lead aVF on the positive side of the lead (Fig 1.11) and we
have to draw perpendicular at that point on lead-I and aVF
respectively. The meeting point of this two perpendiculars
is in the left lower quadrant joined with center with a line.
This line is the mean electrical axis of the QRS complex
(Fig. 1.11).
If in the second example (Fig. 1.12) suppose the
summation of deflection of QRS in aVF is negative we
have to give point on the negative side of aVF lead and the
summation deflection of QRS complex in lead-I is positive
then the meeting point of the perpendicular on lead-I and
aVF is in the left upper quadrant. Then the picture will be
like Figure 1.12. Now in such condition whether actual
left axis deviation have occured is to be determined by
examining lead-II. As perpendicular on lead II at the center
is –30°. If the summation of QRS in lead-II is positive then
Fig. 1.10: Hexaxial lead with allotted degree and axis deviation although the QRS axis has rotated upwards but it has not
Electrocardiogram 7

Fig. 1.13: Determination of right axis deviation Fig. 1.14: Example of indeterminate axis

crossed above –30°, i.e. although the QRS axis has rotated would be like Figure 1.14 in the right upper quadrant. This
leftward but it is within the limit of normal axis (–30°). If type of axis deviation is called, indeterminate axis or north-
the summation of QRS deflection is negative in lead-II. The west axis which is rarely seen in congenital heart disease
mean QRS vector has rotated upward and beyond –30° and where there is hypertrophy of the extreme superolateral
left axis deviation has taken place. wall of the both ventricle.
Suppose the summation of QRS deflection in aVF is
positive but in lead-I it is negative then the picture will be like P-wave
Figure 1.13. Then the meeting point of the perpendiculars
are in the lower right quadrant. In this condition whether It is due to depolarization of atria and in normal ECG P-wave
there is true right axis deviation is present to be determined is upright is lead-II negative in aVR and biphasic in V1.
by compairing the height of R-wave in aVF and lead-III. If Ascending limb of P is due to right atrial depolarization and
the complexes in aVF is taller than lead-III then the mean the descending limb of P is due to left atrial depolarization.
QRS axis is closer to +90° and it is within normal axis, but if • Abnormalities in P-wave
the complex in lead-III is taller than aVF then it is considered −− Absent P-wave—In atrial fibrillation, instead of
that the electrical axis is closer to 120° so right axis deviation P-wave there will be an uneven baseline with varying
is present. R-R interval (Fig. 1.15).
If in both lead-I and aVF the summation of QRS deflexion −− Tall peaked P-wave in lead-II—It is called
is negative then the meeting point of the perpendiculars “P-pulmonale”, where the height of P-wave is more

Fig.1.15: Atrial flutter with fibrillation


8 Essentials of Internal Medicine

Fig. 1.16: P-pulmonale

Fig. 1.17: P-mitrale

Fig. 1.18: High junctional rhythm

than 2 mm and is due to right atrial hypertrophy normally it ranges from 0.12–0.2 sec (3–5 small division of
(Fig. 1.16). the paper).
−− Broad with notched P-wave in lead-II— It is called Short P-R interval < 0.12 sec is seen in WPW and LGL
P-mitrale. P-wave is more than 2 mm broad seen in syndrome (Figs 1.19. and 1.20).
left atrial hypertrophy. The notch may or may not be It is due to the presence of aberrant conduction path-
present (seen in mitral stenosis) and usually there is way known as bundle of Kent which bypasses AV node. If
deep negative P-wave in V1 (Fig. 1.17). the bundle of Kent end in cardiac musculature it will pro-
−− Shaw tooth P-wave with fixed R-R interval —Seen duce WPW syndrome and if the bundle of Kent ends in His
in atrial flutter (Fig. 1.15). bundle it will produce LGL syndrome.
−− P-wave with different configuration seen in MAT In WPW syndrome, there will be short P-R interval
(multifocal atrial tachycardia) (Fig. 1.18). and QRS will start just after P-wave but as the initial part of
ventricular depolarization spread through musculature, it
P-R interval will produce a slow gradual upstroke in the initial part of
It is the time interval between beginning of atrial QRS but the later part of ventricular depolarization takes
depolarization to beginning of ventricular depolarization place through His bundle and the conducting tissue so the
Electrocardiogram 9

Fig. 1.19: WPW syndrome with short P-R interval with delta wave

Fig.1.20: WPW syndrome with short P-R interval with delta wave

later part of QRS will be sharp. This initial slow upstroke in 1st degree heart block—In this condition all the atrial
QRS is called delta wave (Figs 1.20 to 1.22). depolarization wave is conducted to ventricle but with
In LGL syndrome there will be also short P-R interval and some delay in AV node due to long refractory period. In
QRS will start just after P-wave as the bundle of Kent reenter this condition P-R interval is >0.2 second or greater than 5
His bundle after bypassing AV node (Figs 1.23A and B). small square (Fig. 1.40).
• The ventricular depolarization will start just after atrial 2nd degree heart block—In this condition not all atrial
depolarization. Creating a sharp upstroke of QRS. depolarization wave is conducted to ventricle. There is
Long P-R interval—Seen in 1st degree heart block. some drop of beat (impulse) in the AV node. Depending
10
Essentials of Internal Medicine

Fig. 1.21A: Dx: WPW syndrome


Clues: Short P-R interval and delta waves are obvious in the precordial leads. This tracing illustrates that not every lead will have a short P-R interval and a delta have in WPW
syndrome if the delta wave is isoelectric in that lead (see lead-I specially). RVH should accompany RAD and S-waves in the left precordial leads, which this tracing does not have
Electrocardiogram

Fig. 1.21B: Dx: WPW syndrome


Clues: At first glance, it appears to be posterolateral MI with pathologic Q-waves in lead-I and aVL. However, the P-R interval is short in the precordial leads and slurred upstroke
of typical delta wave is present. This delta wave is directed from the patient’s left to right, registering as a negative delta wave in lead-I and aVL, simulating lateral wall MI. In
lead-II, the P-R interval is normal and no delta wave is seen because the delta wave is isoelectric in that lead
11
12 Essentials of Internal Medicine

Fig. 1.22: WPW syndrome Fig. 1.23A: LGL syndrome

Fig. 1.23B: Schematic diagram of the conducting tissue of heart with aberrant path (bundle of Kent)

on the dropping fashion of ventricular depolarization it is ventricle is excited from a focus anywhere from the lower
subdivided into Mobitz type-I and type-II. part of the conducting system (AV node, His bundle, bundle
Mobitz type-I block (Wenckebach block)—In this branch, anterior or posterior, fascicle, Purkinje’s fiber) or
condition there is gradual prolongation of P-R interval in from ventricular musculature.
the successive beat followed by a drop of QRS complex
(ventricular depolarization) following a P-wave, called QRS interval
Mobitz type-I block Figure 1.24.
Mobitz type-II block—In this condition due to disease It is the time taken for ventricular depolarization. Normal
or ischemia AV node cannot conduct all depolarization wave interval is 0.1–0.12 second. If it is more than 0.12 second or 3
to ventricle. There is a fixed block in AV node and every 2nd small square then either LBBB or complete RBBB in present.
or 3rd or 4th atrial depolarization wave is blocked in the AV
node. Accordingly they are called 2 : 1, 3 : 1 or 4 : 1 heart block. Q-T interval
Complete heart block (Fig. 1.25)—In complete heart It is the total time of ventricular depolarization and
block none of the atrial impulse is conducted to ventricle. repolarization and is measured from onset of Q-wave to
All atrial depolarization wave in blocked at AV node and the end of T-wave.
Electrocardiogram

Fig. 1.24: In these three channel rhythm strips, P-waves occur regularly at a rate of about 85/min. Occasionally, the P-waves failed to result in a QRS. Prior to that, the P-R interval
progressively lengthens; a typical type-I 2nd degree AV block
Dx: Type-I 2nd degree AV block (AV Wenckebach phenomenon)
13
14 Essentials of Internal Medicine

Fig.1.25: Complete heart block with AV dissociation

Fig. 1.26A: Physiological Q-wave. In the septal wall electrical vector Fig. 1.26B: In postmyocardial infarction state, lead facing the infarcted
moves away from the lead-I, aVL V5, V6 creating physiological Q-wave wall (which is electrically neutral) actually looks towards the opposite
is the lead I, aVL, V5, V6. It is called physiological Q-wave wall where the electrical vector moves away from the corresponding
lead creating a broad and wide Q-wave

Q-T interval varies with heart rate and must be corrected creating Q-wave in the left-sided lead-I, aVL, V5, V6 (Fig.
(called QTC). The normal QTC is 0.42 second in men and 0.43 1.26A).
second in female. Person with prolong QT are susceptible Criteria for physiological Q-wave
to ventricular ectopic beat and arrhythmia. • Thin Q-wave less than one small square duration.
• Depth of Q-wave less than 1/3rd of the following R-
Q-wave wave.
Pathological Q-wave: In postmyocardial infarction
It is the first negative deflection in the QRS complex. state Q-wave is seen in the lead facing the wall of
Physiological Q-wave (Fig. 1.26A): In normal ECG it is infarction.
seen in the left-sided chest lead V5, V6, and aVL and lead-I The respective lead looks towards the opposite wall of
which is due to intraventricular septal depolarization. the ventricular cavity (through the infarcted zone which is
venticular septum is the first structure to depolarize during electrically neutral) where the electrical vector moves away
ventricular depolarization. As the septal depolarization from the corresponding lead creating Q-wave (Fig. 1.26B).
vector moves from left to right (moves away from the Criteria for pathological Q-wave—
lead) which originates from a twig from left bundle branch • Must be more than 1 small square width.
Electrocardiogram 15

• Depth of Q is more than 1/3rd of the following R wave. Criteria of LVH, —R taller than 25 mm in V5 /V6
In anteroseptal wall infarction Q-wave is seen in lead RV5 /RV6> 25 mm or RV6 + SV1 > 35 mm (Figs 1.27 and
V2–V4 (Figs 1.39, 1.42 and 1.43). 1.28).
In anterolateral wall infarction Q-wave is seen in lead Criteria of RVH is R > S in V1
V4–V6, aVL and lead-I.
In inferior wall infarction Q-wave is seen in lead-II, III QRS complex
and aVF (Figs 1.40 to 1.44).
From QRS complex we can conclude about bundle branch
block.
R-wave
In right bundle branch block (RBBB) (Figs 1.29 to
From the height of R-wave we can have an idea about 1.33) we see RSR’ pattern in V1 lead. The initial positive
ventricular hypertrophy.

Fig.1.27: LVH with left axis deviation

Fig.1.28: Narrow QRS tachycardia at a rate of 129/min. The P-waves are inverted in the inferior leads, suggesting either junctional rhythm or
low atrial rhythm. The P-R interval of 120 milliseconds favors junctional tachycardia. Voltage criteria and ST-T changes favor LVH is present
Dx: 1. Probable junctional tachycardia
2. LVH
16
Essentials of Internal Medicine

Fig.1.29: An example of typical RBBB


Electrocardiogram 17

Fig.1.30: Right bundle branch block (RSR’ pattern in V1)

Fig. 1.31: Right bundle branch block

R-wave in V1 is due to septal depolarization which occurs In left bundle branch block (LBBB) (Figs 1.34 to 1.36)
from left to right. Where the vector is running towards the In the left sided lead (V5, V6, aVL and lead-I). There will be
lead. Then left ventricle is activated and the S-wave is due no Q-wave at the beginning as the septal depolarization
to left ventricular depolarization which occurs from right in LBBB occurs from right to left (instead of normal left to
to left vector running away from the lead. After that right right). So it will produce a initial positive R-wave followed
ventricle is depolarized from left to right creating a R-wave.
by a notch or a short duration negative wave which is due
The late positive vector, i.e. R-wave is due to late right
to right ventricular depolarization vector (which moves
ventricular depolarization which produces right ward
vector. In this situation when the duration of QRS is less than towards right, away from in V5, V6) (Fig. 1.36) and in the late
12 second (< 3 small division), it is called incomplete RBBB part of QRS there is a positive deflection which is due to late
and when the duration of QRS is more than 0.12 second (> depolarization of left ventricle where vector moves towards
3 small division) it is called complete RBBB. left creating a late positive deflection in V5, V6.
18
Essentials of Internal Medicine

Fig. 1.32: An example of typical right bundle branch block


Electrocardiogram

Fig. 1.33: RBBB (RSR’ in V1 and slurring of S-wave in lead-I) and left axis deviation (negative QRS in aVF and II reflect BIFB. Acute anteroseptal STEMI is present (deep Q with ST
elevation and inverted T in V2 V3 V4)
19
20 Essentials of Internal Medicine

Fig. 1.34: Broad and notched QRS complex Fig. 1.35: LBBB broad or wide QRS complex
of right bundle branch block of right bundle branch block

Fig. 1.36: Irregularly irregular rhythm at a rate of 129/min with no definite P-waves indicating atrial fibrillation. The QRS is wide and has a typi-
cal LBBB pattern. If the rate is faster one could easily be mistaken the tracing for a run of VT.
Dx: 1. Atrial fibrillation with a ventricular response of 129/min
2. LBBB

ST-Segment • Deep and wide Q-wave gradually appear


• Height of R gradually comes down (Fig. 1.38).
ST-segment gives us information about ischemia and
All these four changes begins to appear simultaneously
infarction.
or sequentially within few hours after the onset of acute
In STEMI (ST-elevated myocardial infarction) there will
myocardial infarction (Figs 1.40 to 1.43).
be elevation of ST-segment with convexity upward which
Reciprocal change—In STEMI the lead facing the
incorporate T-wave within it and is seen in the early hours
opposite wall of infarction usually have ST-segment de-
of STEMI (Fig. 1.37) but as the times passes (Fig. 1.38)—The
pression which is called reciprocal changes. In case of
following changes in ECG gradually appear
inferior wall infarction. ST elevation is seen in II, III, aVF but
• The ST-segment gradually comes down
reciprocal changes (ST-depression) are seen in V2,V3 and V4.
• T-wave gradually become inverted
In true posterior wall infarction reciprocal changes are seen
Electrocardiogram 21

Fig. 1.37: Early stage of STEMI Fig. 1.38: Late stage of STEMI

Fig. 1.39: STEMI (involving anteroseptal wall)

Fig. 1.40: Sinus rhythm at 66/min with 1st degree AV block.


ST elevation in inferolateral leads with horizontal ST depression in V1–V3 is diagnostic of STEMI of inferoposterolateral wall. ST is reciprocally
depressed only in aVL, not in lead-I indicating RV is not involeved and the culprit lesion must be not in proximal RCA but either RCA not proximal
or circumflex coronary artery
Dx: 1. Sinus rhythm with 1st degree AV block; 2. STEMI of inferoposterolateral wall
22
Essentials of Internal Medicine

Fig. 1.41: The ‘sawtooth’ pattern of atrial flutter is obvious in the rhythm strip of lead-II. The flutter rate is somewhat slow at 240/min. Antiarrhythmics are well-known to slow the flutter
rate down to 200/min very easily. Complete RBBB is also present. Q-waves in lead-III aVF indicate inferior infaract as well
Dx: 1. Atrial flutter with 2:1 AV conduction
2. RBBB
3. Inferior wall myocardial infarction (MI), probably old
Electrocardiogram

Fig. 1.42: Irregularly irregular rhythm with no visible P-waves indicates atrial fibrillation. Significant, coved ST elevation in the precordial leads as well as in lead-I and aVL indicate acute
extensive anterior myocardial infarction (MI). Lead-I and aVL represents high lateral wall which often is perfused by diagonal branch which takes off very proximaly in LAD. Therefore
infarction pattern involving precordial lead-I and aVL means the culprit lesion is in the proximal LAD. If lead-I and aVL are not involved, the lesion is in the LAD not proximal. If only lead-I
and aVL are involved without precordial leads, the lesion is in the diagonal branch. The ST depression in the inferior leads is the reciprocal change of the ST elevation in aVL
Dx: 1. Atrial fibrillation with a ventricular response of 85 min
2. Acute, extensive anterior infarct
23
24
Essentials of Internal Medicine

Fig. 1.43: Normal sinus rhythm at a rate of 74/min. QS pattern in the right precordial leads with a slight elevation of the ST-segment and a terminal T-wave inversion reflect recent AMI
Dx: 1. Normal sinus rhythm
2. Recent anteroseptal infarct of some duration
Electrocardiogram 25

Fig. 1.44: Inferior wall STEMI with reciprocal changes in the anterior wall

in V2,V3 and V4. In anteroseptal wall infarction reciprocal • Horizontal depression of ST-segment > 2 mm and longer
changes are seen in lead-II, III aVF. >2 small division (Fig. 1.47). Sensitivity (80–85%).
In non-ST elevated myocardial infarction (NSTEMI)— • J point is the junction of end ventricular depolarization
Three changes are seen— and beginning of ventricular repolarization.
• Depression of ST-segment (<1 mm). • Upslopping ST-segment (Fig. 1.48) is also seen in
• Transient elevation of ST-segment (<20 minutes ischemia but sensitivity is (60–65%).
duration). Rarely there may be elevation of ST-segment with
• Deep isometric inversion of T-wave (Figs 1.45 and 1.52). convexity downward and present in the adjacent leads seen
In myocardial ischemia, three classic changes are seen in pericardial diseases (Figs 1.49A and B). Also called early
in ST-segment not associated with chest pain. repolarization.
The ischemic changes in ST-T segment are—
T-wave
• Down slopping of ST-segment with inversion of T-wave
(Fig. 1.46). With unequal length of the ascending and Tall peaked T-wave commonly seen in two conditions—
descending limb of T-wave (sensitivity 95%). (a) hyperkalemia and (b) early stage of acute myocardial
26 Essentials of Internal Medicine

Fig. 1.45: Deep isometric inversion of T-wave is V4, V5, V6 suggestive of NSTEMI

Fig. 1.46: Down slopping ST with inversion of T-wave seen in ischemia Fig. 1.47: Horizontal depression of ST-segment seen in ischemia
with unequal length of the ascending and descending limb of T-wave

Fig. 1.48: Upslopping ST-segment seen in ischemia Fig. 1.49A: Elevated ST with convexity downward known as early re-
polarization seen in pericardial disease and may be seen as a normal
varient
Electrocardiogram

Fig. 1.49B: Normal sinus rhythm at a rate of 80/min. QRS voltage for LVH is present. There is about 4 mm ST elevation in V3–V4, and to a lesser degree in other precordial leads. The
notching in the junction in V4 and upward concavity of the ST-segment are all diagnostic of early repolarization pattern as a normal variant. The PR-segment is slightly depressed which
is also part of this condition. Sometimes these findings may be mistaken for an acute MI or pericarditis
Dx: 1. NSR
2. LVH by voltage
3. Early repolarization pattern as a normal variant
27
28 Essentials of Internal Medicine

Fig. 1.50: Tall peaked T-wave with J point below isoelectric line seen Fig. 1.52: Isometric inversion of T-wave seen in NSTEMI and UA
in hyperkalemia (P-R interval is considered isoelectric line) ascending and descending limb of T-wave are of equal length

Fig. 1.51: Tall peaked T-wave with ‘J’ point above isoelectric line (P-R Fig. 1.53: Flattening or depression of T-wave without chest pain seen
interval) seen in very early stage of acute myocardial infarction in chronic ischemia

infarction STEMI. The differentiating point between these Isolated inversion of T-wave may be seen in (a) NSTEMI
two conditions are— (non-ST elevated myocardial infarction and (b) old
a. In case of hyperkalemia the J point is much below the infarction or ischemia (Figs 1.45 and 1.52).
isoelectric line (Fig. 1.50).
b. In case of early stage acute myocardial infarction the U-wave
‘J’ point in much above the isoelectric line (Fig. 1.51) It is rare and is due to repolarization of conducting tissue of
followed by tall peaked T wave. heart. It is prominent in hypocalcemia (Fig. 1.53).
Chapter 2
Rheumatic Fever

• Acute rheumatic fever (ARF) is an acute immunologically –– Migratory polyarthritis (75%)


mediated multisystem inflammatory disease that –– Sydenham’s chorea (<10%)
follows an episode of GrA streptococcal pha-ryngitis –– Subcutaneous nodule (<10%)
after an interval of few weeks. –– Erythema marginatum (<10%).
−− Minor jones criterias
• Anticident pharyngitis may be asymptomatic at times –– Clinical
• Any strain of GrA streptococcal appears to be particularly »» Fever (39.5°C)—95%
associated with risk of rheumatic fever, perhaps due to a well- »» Polyarthralgia.
developed highly antigenic capsule
–– Laboratory criteria
• Rheumatic fever rarely develops following an infection by
streptococci at other sites like skin »» Elevated acute phase reactant—ESR
• It only occurs in 3% case of Gr-A streptococcal pharyngitis »» Elevated leukocyte count.
• It is postulated that a series of repeated streptococcal –– ECG
infection is necessary to prime the immune system prior to »» Prolonged PR interval >0.2 second.
final infection that have caused the disease 
Plus
Pathogenesis • Supportive evidence of previous Gr-A streptococcal
• It is strongly suspected that acute rheumatic fever is a infection within 45 days—
hypersensitivity reaction induced by Gr-A streptococci −− Positive throat culture (present in 25–40% of patient)
• It is proposed that antibody directed against M protein of −− Rapid antigen detection test for Gr-A streptococcus
Gr-A streptococci cross reacts with normal connective tissue −− Rising or elevated ASO titer or other streptococcal
protein present in heart, joint, brain, skin and other tissue due
antibody.
to molecular mimicry
• Hypersenstivity phenomenon is supported by the fact that— −− Recent scarlet fever.
1. Streptococci cannot be demonstrated from the site of –– To fulfil Jones criteria
inflammatory lesion »» 2 major criteria.
2. Symptom typically developes 3–4 weeks after infection »» 1 major + 2 minor criteria with evidences
of anticident streptococcal infection are
Diagnosis required. If the 3 antibody tests are negative
the diagnosis should be seriously reconsidered.
• No specific diagnostic test is available for diagnosis of
ARF. Carditis
• The diagnosis is therefore a clinical one but requires
supportive evidence from microbiology and immuno- Younger the patient more in the chance of carditis. Overall
logy. 40–60% of ARF patients have evidence of carditis.
• Jones criteria was proposed in 1944, later on updated When acute rheumatic fever affects child at 3 years
Jones criteria was published in 1992 and now WHO of age 90% of then develop carditis whereas when acute
criteria is followed for clinical diagnosis of acute rheumatic fever develops in patient at 15 years of age 30%
rheumatic fever. of them have carditis.
• 5 major criteria and minor criteria • Mitral valve is usually involved and second one is the
−− Major jones criterias aortic valve. Isolated aortic valve involvement is very
–– Pancarditis (40–60%) rare.
30 Essentials of Internal Medicine

• Usually over years as a result of recurrent episode of rheumatic SYDENHAM’S CHOREA (ST VITUS DANCE)
endocarditis leaflet thickening, scarring and calcification lead (Present in10% CASES)
to either stenotic or regurgitant lesion or both of mitral or
aortic valve Commonly occurs in the absence of other manifestation of
ARF it may be restricted to one side (hemichorea).
• It is 3–4 times more common in female.
• Rheumatic pericarditis may lead to fibrin deposit, serous
• It is a late manifestation.
effusion leading to pericardial calcification but does not
• Involves head, tongue and upper extremity.
lead to constrictive pericarditis.
• Usually have the longest latent period of onset may be
several months (~ 6 month) in most of the cases.
Features of Carditis
• Many patients who appear to have only chorea may
• Breathlessness is the most common symptoms is due present several decades later with evidence of typical
to heart failure or pericardial effusion. RHD.
• Palpitation or chest pain is due to pancarditis or • It has a selflimiting course of 4–6 weeks.
pericarditis. • There is no definitive diagnostic test for Sydenham’s
• Tachycardia is due to atrial fibrillation or sinus chorea and the diagnosis is by way of exclusion. That is
tachycardia. why all patients with Sydenham’s chorea should receive
• Cardiomegaly is due to pericardial effusion or heart secondary prophylaxis for prevention of recurrent attack
failure. of rheumatic fever even if they do not appear to have
• Features of congestive cardiac failure—Pulsatile rheumatic heart disease.
neck vein, pedal edema and hepatomegaly as of
manifestations chronic heart failure. SUBCUTANEOUS NODULE
• S1 is soft. (Present in 10% CASES)
• S3 gallop may be present over apex.
• Murmur of MR—95% of the patients of acute rheumatic Seen as small (0.5–2 cm) nontender and mobile lump.
carditis have MR murmur. • It is mostly a late manifestation—Appears around
−− Murmur of AR is present in a quater of them who 2–3 weeks after the onset of rheumatic fever and lasts
have murmur of MR. for 2–3 weeks.
−− 5% of patients have murmur of isolated pure AR. • Subcutaneous nodule present over extensor aspect
Mitral stenosis murmur in a patient with acute of joint in forearm (elbow) and behind ear (occiput)
rheumatic carditis is due to inflamed valve cusps and usually with long standing RHD and usually rare in
is known as Carey-Coombs murmur. patient with initial attack.
• Pericardial friction rub and small effusion are due Patients with subcutaneous nodule are usually
to pericarditis. associated with carditis.
• Increased PR interval greater than 0.2 second (1°st
degree heart block) may be present. ERYTHEMA MARGINATUM
• Second degree of AV block (Mobitz—type II) seen (Present in 10% CASES)
rarely.
• It is an early manifestation predominantly seen over
MIGRATORY POLYARTHRITIS the trunk rare on limb and never on face.
• Considered to be more specific than other variety
It is seen as typical migratory polyarthritis. of skin manifestation known to be extremely rare in
• Polyarthritis affects 70% of cases in Western countries. Indian.
In India it affects only 30–50% patients. • The rash is faintly reddish, evanescent not raised
• Younger the patient more is the chance of developing above the skin, nonitchy, starts as a red spot with a
the arthritis. pale center, rapidly increasing in size to qualace with
• Affects knee, ankle, wrist, elbow and hip joint over adjacent spot to form a serpiginious outline and fades
a period of hours to days in asymmetric manners. away within 2–3 hours.
Rheumatic polyarthritis usually do not involve small
joint of hands and feet and spinal joint.
• Joints are painfull swollen and tender, appear quickly
Differential Diagnosis of Rheumatic Fever
last for few hours to days disappear spontaneously • Juvenile arthritis.
to reappear in other joints leaving no residual joint • Collagen vascular disorder—SLE and RA.
deformity. • Acute arthritis due to virus—Rubella, pervovirus, HBV
• Aseptic monoarthritis may be a presenting feature. and herpes.
Rheumatic Fever 31

• Hematological disorder—Sickle cell disease and Antistreptococcal antibiotics


leukemia.
Primary and secondary prevention
• Poststreptococcal reactive arthritis.
Primary prevention
Treatment • Penicillin is the drug of choice.
But 10-day course of oral cephadroxil/ cephalexin is
Supportive and symptomatic treatment superior to 10 day course of oral penicillin.
Supportive treatment 5 day oral cephalosporins is comparable to 10 days oral
a. Rest—Specially for carditis patient. penicillin in eradication of Gr A streptococcus from
b. Salt poor, high calorie, high protein, diet supple- pharynx.
mented with vitamins and minerals. Phenoxymethyl penicillin—500 mg BD for 10 days.
Salt restriction is not necessary in patient without CCF. Amoxicillin—500 mg TDS for 10 days.
c. In management of chorea—Assurance and protection Benzathin penicillin—1.2 MU IM single dose.
from self-injury. • Appropriate antibiotic therapy started up to 9 days after
In severe forms carbamazepine, sodium valproate for the onset of acute streptococcus pharyngitis is effective
1–2 weeks. in primary prevention.
Use of IVIG is controversial. • Erythromycin is used when patient is allergic to
penicillin.
Symptomatic treatment—In selecting a suppressive
drug (salicylate/steroid) for an individual patient, the Secondary prevention
guidelines are • Benzathine penicillin G 1.2 MU 4 weekly recommended
• Patient without carditis—Aspirin is preferred. in USA, but in endemic area with high-risk cases
• Carditis without CCF—Steroid or aspirin may be used and in special circumstances 3 weekly regimen is
(steroid is preferred). recommended.
• Carditis with CCF—Steroid is mandatory. • Oral prophylaxis is discouraged due to non-adherence
−− Aspirin—80–100 mg/kg/day in 4 divided doses in and failure of therapy even with optimal adherence.
children. In adult 4–8 g/day in 4–5 divided doses. • Sulfar-containing drugs is contraindicated in pregnancy.
−− Full dose is given for 2 weeks and then reduced to • Prophylaxis should continue even after valve surgery or
60–70 mg/day for further 4 weeks. prosthetic valve implantation for life-long.
−− Blood salicylate level should be 20–25 mg/dL. • Patient with history of rheumatic carditis or Sydenham’s
−− Naproxen 10–20 mg/kg/day has a good symptomatic chorea are at high-risk patient for recurrence.
response. • Duration of secondary prophylaxis
−− Steroid—Use of steroid is controversial. In pediatric 1. Patient without 5 years after last attack
age group proved carditis or up to 21 years of age
–– Patient >20 kg body weight 1–2 mg/kg/day. Maxi- which ever is longer
mum 80 mg/day for 3 weeks followed by 50 mg/ 2. Patient with mild 10 years after last attack
day for 1 week followed by 40 mg/ day for 1 week MR or healed or 21 years of age
then reduction is 5 mg/week till it is finished. carditis whichever is longer
–– Patient <20 kg body weight. Initial dose is 30 mg 3. More severe Lifelong/for 10 years/
divided 6 hourly for 4–6 weeks reduced in similar valvular disease up to 40 years of age
fashion. 4. Valve surgery Lifelong

Primary prevention
1. Benzathene penicillin G 6 lac <27 kg IM Single dose
12 lac >27 kg
2. Penicillin V Child—250 mg bd/tds Oral For 10 days
Adolescent—500 mg bd/tds
3. Erythromycin (patient allergic to penicillin) 40 mg/kg/day in 2–4 divided doses or 250 mg bid Oral For 10 days

Secondary prevention
1. Benzathene penicillin 1.2 MU at 3 weeks interval IM
2. Penicillin V 250 mg bid daily PO
3. Sulfadiazine 0.5 G <27 kg daily PO
(not used in primary prevention) 1 G >27 kg daily
4. Erythromycin (patient allergic to penicillin) 250 mg bid daily PO
Chapter 3
Infective Endocarditis

Definition Common causative agents


−− Streptococcus viridans
Infection and proliferation of microorganism with
−− Enterococci
formation of vegetation on the heart valve (native
−− HACEK group of organism
or prosthetic) or on mural endocardium (on the low
−− Coagulase negative staphylococci.
pressure side of VSD where it is damaged by aberrent jet or
an intracardiac devices) is called infective endocarditis.
Etiology
An analogous process involving arteriovenous shunt,
arterioarterial shunt (PDA) or coarctation of aorta is called
infective endarteritis.
1. Native valve is usually affected by—
Vegetation • Streptococcus viridans—50–60% (involve damaged valve),
source—oral
Vegetation is a mass composed of platelet—fibrin and
• Staphylococcus aureus—10–20% (source—skin) involve
microcolony of microorganism with scant inflammatory cell. both, normal and damaged valve
• HACEK group of organism—Source—URTI (involve
Site of Formation damaged valve)
• Streptococcus bovis—GI polyp or colonic tumor
• Damaged or normal heart valve (native). • Enterococci—Source—Genitourinary tract
• Prosthetic heart valve. • Nosocomial—Route of entry is either intravascular catheter
• Low pressure side of IVS at the site of VSD where the and wound, UTI [25% cause of valvulitis] Diagnosed by
mural endocardium damaged by aberrent jets. transesophageal echocardiography
• Foreign bodies like intracardiac devices (leads of 2. Prosthetic valve—
pacemaker/defibrillator). • When develops vegetation within 2 months of operation
• Arterioarterial/arteriovenous shunt or coarctation of either by intraoperative contamination or postoperative
bacteremia by the causative agent like
aorta leading to endarteritis.
1. Coagulase negative Staphylococcus
2. Staphylococcus aureus
Types of Endocarditis
3. Facultative gram-negative bacilli
It is classified according to temporal evolution of the disease 4. Diphtheroids
into two types: 5. Fungi
1. Acute infective endocarditis—It is a hectically • When prosthetic valve develops vegetation within 2–12
months of implantation causative agents are same but
febrile illness rapidly damages cardiac structure with
with delayed onset
hematogenous seedlings at extracardiac site and if • But when it is delayed >12 months—It is community
untreated leads to death within few weeks. acquired and infectious agents are similar to native valve
Common causative agents endocarditis
−− β-hemolytic streptococci 3. Transvenous-prosthetic pacemaker lead/defibrillator lead
−− Staphylococci (coagulase positive) when develop vegetation within 7 days—It is usually by no-
−− Pneumococci. socomial infection—same as prosthetic valve.
2. Subacute infective endocarditis—Causes structural Most common agent—Staphylococcus aureus and coagulase
damage very slowly (if at all), rarely causes metastatic negative staphylococcus
4. IV drug abusers—Staphylococcus aureus. Affects right side of
infection, gradually progressive, unless complicated by
heart
major embolic event or ruptured mycotic aneurysm.
Infective Endocarditis 33

Other Bacteria in IV Drug Users Systemic manifestation


• Pseudomonas Cardiovascular manifestation (directly due to micro-
• Bacillus organism)
• Candida • Incompetence murmur (80–85%)—Mostly MR
• Lactobacillus murmur. Others are VSD, AR, AS murmur.
• Diphtheroids
• Polymicrobials
• CCF (30–50%) It is due to
−− Myocarditis
−− Valvular dysfunction
−− Intracardiac fistula.
Pathogenesis • Varying degree of AV block—It is due to extension
of perivalvular abscess arising from mitral valve or
• Endothelial injury by low velocity jets or low pressure site noncoronary cusp of aortic valve to nearby AV node or
of cardiac structural lesion allows either direct infection by bundle of His.
virulent organism (Staphylococcus aureus) or formation of
• Acute myocardial infarction—It is due to embolization
NBTE (nonbacterial thrombotic endocarditis)
• NBTE subsequently serves as site of bacterial attach- of coronary artery by vegetation.
ment during transient bacteremia, except Staphylococcus • Perivalvular abscess causing intracardiac fistula.
aureus which can directly attach to intact endocardium
or subendocardial exposed tissue. NBTE occurs in AS, Immunological manifestation seen in (2–15% cases
MR, AR, VSD and complex congenital heart disease or in and are nonembolic)
hypercoagulable state as in marantic endocarditis seen in They are as follows
dying patient of endocarditis • Osler’s node
• Libman-Sacks endocardities seen in SLE and in APLA
syndrome where hypercoagulability is a feature
• Rheumatoid factor
• Organism resistant to microbicidal activity of serum and • Glomerulonephritis
platelet, proliferate and stimulate the surrounding tissue • Roth’s spot.
to release or itself release procoagulant which leads to Risk of embolization is high in three conditions
further deposition of platelet-fibrin causing propagation of • Endocarditits caused by Staphylococcus aureas
vegetation
• Vegetation > 10 mm diameter
• Receptors of the bacteria that help in attachment with the
injured endocardium or thrombi are— • Vegetation involving mitral valve.
1. Fibronectin receptor of gram-positive bacteria
2. Clumping factor of Staphylococcus
Suppurative peripheral embolic manifestation can
3. Dextran of Streptococcus involve many organs but mainly
• Organism enmeshed in platelet-fibrin vegetation prolif- • Skin (microabscess)
erate to form dense microcolonies in which > 90% of • Spleen (splenomegaly)
microorganisms are metabolically inactive, thus resis- tant • Kidney (flank pain, hematuria)
to antibiotic
• Skeletal muscle
• Meninges (purulent or aseptic meningitis)
• Stroke due to cerebrovascular emboli
• Intracranial hemorrhage due to hemorrhagic infarct or
rupture mycotic aneurysm.
Clinical Manifestation
Nonsuppurative peripheral manifestation are
Mechanism a. Subungual hemorrhage
• Cytokine production from damaged intracardiac b. Osler node
structure. c. Janeway lesion
• Embolization of the vegetation fragment leading to d. Conjunctival hemorrhage
infection and infarction. e. Seizure, embolic stroke, intracranial hemorrhage (due
• Tissue damage due to circulatory immune complex. to hemorrhagic infarct or ruptured myotic aneurysm).

Clinical Feature Manifestation Related to Predisposing Factor


General manifestation (due to cytokines) • IV drug users have involvement of tricuspid valve which
• Fever (80–90%), chills and sweating (40–70%) is manifested by
• Anorexia, malaise, weight loss (25–50%) −− Faint murmur
• Myalgia, arthralgia (15–30%), back pain (7–15%) −− Cough
• Clubbing. −− Pleuritic chest pain
34 Essentials of Internal Medicine

−− Pyopneumothorax Major criteria


−− Nodular pulmonary infiltrates.
• Positive blood culture
• Transvenous pacemaker/defibrillator lead asso-
• Evidence of endocardial involvement
ciated SABE may have overt or cryptic symptoms and
−− By transesophageal echocardiography
signs and are marked by comorbid illness results in
−− Clinical—New valvular regurgitation murmur.
fever, minimal murmur, pulmonary symptoms due
to septic emboli. Minor criteria
• Prosthetic valve endocarditis—Those who have
early onset (within 60 days)—they lack in peripheral • Predisposing factor
manifestation. Typical symptoms are marked by −− Previous heart disease (congenital or MR)
comorbidity associated with surgery. Late onset −− IV drug abusers.
features are paravalvular infection causing valvular • Fever >100.4°F
dehiscence, regurgitant murmur, heart block and CCF. • Vascular phenomenon
−− Major arterial embolization
−− Septic pulmonary infarction
INVESTIGATION OF INFECTIVE
−− Mycotic aneurysm
ENDOCARDITIS −− Intracerebral hemorrhage
• Blood culture—Reveals typical microorganism for −− Conjunctival hemorrhage
infective endocarditis from −− Janeway lesion.
−− Two separate blood cultures drawn 12 hours apart. • Immunological phenomenon
−− All of the three blood cultures. −− Osler’s node
−− Majority of four. −− Roth’s spot
−− More positive blood cultures with the first and the −− Glomerulonephritis
last drawn at least 1 hour apart. −− Positive rheumatoid factor.
Causes of Negative Blood Culture • Microbiological evidence of positive blood culture not
−− Prior antibiotic exposure. meeting major criteria.
−− Pyridoxal requiring streptococci (abiotropic −− Presence of 2 major or 1 major and 3 minor or 5
streptococci). minor criteria allows a clinical diagnosis of definitive
−− HACEK group of organism or when endocarditis endocarditis.
is caused by Bartonella quintana or henselae or −− Presence of 1 major and 1 minor or 3 minor criteria
Tropheryma whipplei—Cause indolent culture indicates possible endocardits.
negative afebrile endocarditis.
• Echocardiography— Treatment
−− TEE (transesophageal echo)—If negative almost Definitive treatment
exclude endocarditis but may have to be repeated
within 7–10 days with optimal multiplanner • Streptococci
technique. −− Penicillin susceptible (any one of the followings)—
−− TTE (transthoracic echo)—Less informative. –– Penicillin G 2–3 MU IV 4 hourly for 4 weeks.
• Cardiac catheter and coronary angio—In older –– Penicillin G 2–3 MU IV 4 hourly for 2 weeks and
individuals who are to undergo surgery. gentamicin 3 mg/kg IV od for 2 weeks.
• Laboratory investigations— –– Ceftriaxone 2 g IV od for 4 weeks.
−− Complete blood count for anemia (present in 90%), −− Relatively penicillin resistant streptococci
leukocytosis (present in 30%). –– Penicillin G 4 MU IV 4 hourly for 4 weeks and
−− ESR—Elevated in more than 90% cases. gentamicin 1 mg/kg IV tds for 2 weeks.
−− Rheumatoid factor present in 50% patient. –– Vancomycin 15 mg/kg IV bd for 4 weeks.
−− Circulating immune complex detected in (65–100%) −− Total penicillin-resistant streptococci or Abiotropic
patients. species
−− Complement—Decreased (in 5–40%) patients. –– Penicillin G 4 MU IV 4 hourly and gentamicin 1
−− C-reactive protein (CRP)—Increased. mg/kg IV tds → Both for 6 weeks.
−− Urine RE—Microscopic hematuria present in –– Vancomycin → 15 mg/kg IV bd over 1 hour for 4
(30–50%). weeks.
• Enterococci
Diagnosis −− Penicillin 4 MU IV 4 hourly and gentamicin 1 mg/kg
IV tds → Both for 4–6 weeks.
Duke’s criteria (for diagnosis of infective endocarditis). Or
Infective Endocarditis 35

−− Ampicillin 2 g IV 4 hourly and gentamicin 1 mg/kg –– Clindamycin (600 mg PO 1 hour before the pro-
IV tds) → Both for 6 weeks. cedure)/clindamycin 600 mg IM/IV 1 hour before
Or the procedure.
−− Vancomycin 15 mg/kg IV bd and gentamicin 1 mg/ * Patient unable to take oral medication—
kg IV tds → Both for 4–6 weeks. Cephazolin (1 g IV ½ hour before the procedure).
• Staphylococcus— • Genitourinary and GI tract procedures—
−− Methicillin susceptible (native valve) (any one)— −− High-risk patients—To be given ½ hour before the
Nafcillin/oxacillin—2 g IV 4 hourly for 4–6 weeks. procedure.
Or –– Patient nonallergic to penicillin— Ampicillin
−− Cefazolin 2 g IV tds for 4–6 weeks. (2 g IV) and gentamicin (1.5 mg/kg IV).
Or –– Patient allergic to penicillin— Vancomycin
−− Vancomycin 15 mg/kg IV bd for 4–6 weeks. (1 g IV) and gentamicin (1.5 mg/kg IV).
−− Methicillin resistant staph. (native valve) −− Moderate risk patients—
−− Vancomycin 15 mg/kg IV bd for 4–6 weeks. –– Patient nonallergic to penicillin— Ampicillin
−− Methicillin susceptible Staph. (prosthetic valve)— (2 g IV ½ hour before the procedure).
−− Nafcillin/oxacillin 2 g IV 4 hourly for 6–8 weeks. and Or
gentamicin 1 mg/kg IV 8 hourly for 2 weeks and –– Amoxycillin (2 g PO 1 hour before the procedure).
rifampin 300 mg tds po for 6–8 weeks. –– Patient allergic to penicillin— Vancomycin
−− Methicillin-resistant Staph. (prosthetic valve)— (1 g IV—infused over 1–2 hour and completed
Vancomycin 15 mg/kg IV bd for 6–8 weeks and within ½ hour of the procedure).
gentamicin 1 mg/kg IV 8 hourly for 2 weeks and
rifampicin 300 mg tds po for 6–8 weeks. INDICATIONS FOR SURGERY
• HACEK Group (any one)
−− Caftrioxone 2 g IV od for 4 weeks. Relative Indication
Or • Moderate to severe CCF due to valvular dysfunction.
−− Ampicillin 2 gm IV 6 hourly and salbactum 1 G IV 6 • Unstable/obstructed orifice of prosthetic valve.
hourly → Both for 4 weeks. • Uncontrolled infection despite optimal antibiotic
therapy.
Preventive treatment • Endocarditis caused by brucella, fungus, pseudomonas.
• Oral cavity, esophagus and respiratory tract • Prosthetic valve endocarditis (PVE) caused by Staph.
procedure— aureus.
−− Patient nonallergic to penicillin (any one of the • Relapse of PVE after optimal therapy.
following)— • Fistula formation to the pericardial sac.
–– Amoxycillin—3 g PO 1 hour before the procedure.
Or Absolute Indication
–– Ampicillin—2 g IV 1 hour before the procedure. • Perivalvular extension of infection.
−− Patient allergic to penicillin (any one of the • Myocardial abscess.
following)— • Intracardiac fistula.
–– Clarithromycin (500 mg PO 1 hour before the • Poorly responsive Staphylococcus aureus in native valve
procedure). endocarditis (NVE) (mitral/aortic).
Or • Relapse of NVE after optimal antibiotic therapy.
–– Cephalexin/cephadroxyl (2 g PO 1 hour before • Large (>10 mm) hypermobile vegetation.
the procedure). • Endocarditis caused by resistant enterococci or gram-
Or negative bacilli.
Chapter 4
Valvular Heart Disease

MITRAL STENOSIS • Rest are combined.


−− Commissural—Valve cusp fuse at their edges.
Mitral stenosis (MS) is the most common complication of −− Cuspal—Fibrous obliteration, revascularization,
acute rheumatic fever. Female : Male ratio 2:1. thickening and rigidity of cusp.
• Mitral valve apparatus is composed of −− Chordal—Fusion, thickening and shortening of the
−− Valve leaflets. structures.
−− Valve annulus. All these changes lead to typical funnel-shaped
−− Chordae tendinae. appearance. Shaped like fish mouth with calcium deposition
−− Papillary muscles. over the leaflets and ring.
−− Myocardium to which the papillary muscles are Progressive thickening, fibrosis, and calcification may
attached. be due to—
All components of mitral valve may be involved in • Smouldering rheumatic activity or
rheumatic process. • Constant trauma by turbulant flow initiated by deformed
valve leads to progressive thickening fibrosis and
Etiology of Mitral stenosis calcification of valve apparatus.
Major Causes
PATHOPHYSIOLOGIC COURSE of Mitral
• Rheumatic fever (predominant cause 98%)
40% of all RHD have pure MS stenosis
40% of all RHD have MS with MR Latent period is at least a decade or more from acute
Rest are associated with other valvular abnormalities. rheumatic fever to develop severe MS. Symptoms commonly
• Congenital (mitral valve stenosis and cor triatriatum). commence at 3rd and 4th decade.
• Rare causes In tropics and underdeveloped area, disease progresses
−− Senile calcification of valve annulus. very rapidly and present in early adolescent.
−− SLE. Once a patient of MS become symptomatic seriously the
−− Rheumatoid arthritis. disease progresses continuously to death within 2–5 years.
−− Infective endocarditis—Ball-valve thrombus.
−− Associated with ASD in Lutembacher syndrome.
GRADING OF Mitral stenosis
−− Malignant carcinoid.
−− Mucopolysaccharidosis of Hunter-Hurler pheno- Normal cross-sectional area of valve orifice 4–6 cm2
type. • Mild MS have valve orifice = <2 cm2
−− Amyloid, Fabry disease and Whipple’s disease. • Moderately severe MS have valve orifice ≅ 1.0–1.5 cm2
−− Methyserzide therapy. • Critical MS valve orifice – <1 cm2.
−− Congenital diaphargm.
−− Cor triatriatum.
−− Left atrial myxoma. PATHOPHYSIOLOGY of Mitral stenosis
• In case of mild MS, the blood can flow from LA to LV only
PATHOLOGY of Mitral stenosis if propelled by abnormally elevated LA to LV pressure
Fibrosis resulting from acute rheumatic fever causes fusion gradient (hemodynamic hallmark of MS).
of mitral valve apparatus over 2–12 years time: • In critical MS, the LA pressure is approximately 25
• Commissural fusion (30%) mmHg to maintain normal COP (cardiac output).
• Cuspal fusion (15%) • Elevated LA pressure leads to increased pulmonary
• Chordal fusion (10%) venous pressure resulting in increased pulmonary
Valvular Heart Disease 37

capillary wedge pressure which ultimately results −− Pulmonary infarction from pulmonary embolism is
in decreased compliance of lung and exertional a late complication of MS associated with leg veins
dyspnea. thrombosis.
Combination of mitral valve disease and atrial −− Anticoagulation overdose.
inflammation secondary to RHD leads to: • Chest pain—
• LA dilation. −− 15% of MS patients have chest pain indistin-
• Fibrosis of LA wall. guishable from angina.
• Disorganization of LA muscle bundle. −− Causes of chest pain—
• Entry of atrial muscle sleeve into the opening of –– Right ventricular hypertension
pulmonary vein. –– Coincidental coronary atherosclerosis
All these factors lead to: –– Coronary arterial embolization.
• Disparity in conduction velocity. • Thromboembolism—Thrombus formation occurs in
• In homogenous refractory period which ultimately leads left atrial appendage
to atrial fibrillation resulting either from ectopic focus −− 10–20% of MS patients suffer from systemic
or from reentry. thromboembolism with atrial fibrillation.
−− 10–15% of thromboembolism patients die and
CAUSES OF PULMONARY HYPERTENSION IN responsible for 25% of all fatalities in MS.
Mitral stenosis Precipitating factor of thromboembolisms
−− Atrial fibrillation
• Passive backward transmisston of LA pressure.
−− Decrease COP
• Reflex pulmonary arterial constriction (reactive
−− Increase age
pulmonary hypertension).
−− Underlying infective endocarditis.
• Interstitial edema surrounding pulmonary vascular bed.
• Organic obliterative changes in pulmonary vasculature. Site of embolism—
Severe pulmonary hypertension results in pulmonic −− Cerebral.
regurgitation, RV enlargement secondary TR and right −− Coronary.
heart failure. −− Sudden death may be caused by obstruction of mitral
orifice outlet by large pedunculated thrombus.
CLINICAL FEATURES of Mitral stenosis • Infective endocarditis—Rare in isolated MS.
−− More common in milder form of MS and MR than
History in severe MS.
• Other symptoms
Most patients remain asymptomatic when valvular obs-
−− Compression of recurrent laryngeal nerve causing
truction remains mild or in case of moderate obstruction
hoarseness of voice by dialated LA, pulmonary
with slight increase of LA–LV pressure gradient.
artery and tracheobroncheal lymph node known as
Ortner’s syndrome.
Principal Symptoms
−− Features of RVF—
• Dyspnea— –– Pulsatile neck veins
−− It is due to reduced lung compliance. –– Hepatomegaly
−− Patients with critical obstruction to left atrial –– Edema
emptying are NYHA class-III dyspneic and generally –– Ascites
have orthopnea and at risk of developing Frank –– Hydrothorax (in extreme case).
pulmonary edema precipitated by any condition
which will increase the flow across the AV valve Signs
(exercise, emotional stress, respiratory infection,
• Mitral facies
atrial fibrillation, tachyarrhythmia, pregnancy).
−− Pinkish pimple patches on the cheeks.
• Cough and wheeze —It accompanies dyspnea.
−− Differential diagnosis—Cushing, thyrotoxicosis, SLE
• Hemoptysis—It is due to
and alcoholism.
−− Rupture of pulmonary bronchial venous connection
• Arterial pulse
secondary to pulmonary venous hypertension.
−− Low/normal volume (low volume pulse indicates
−− Blood-stained sputum complicating chronic bron-
severe MS) may be irregular due to associated atrial
chitis, bronchopneumonia, and lobar pneumonia.
fibrillation.
−− Pinkish frothy sputum characteristic of pulmonary
• JVP
edema due to rupture of alveolar capillary when left
−− Prominent a-wave in patient with sinus rhythm.
atrial failure develop.
38 Essentials of Internal Medicine

−− In atrial fibrilation → a wave disappears only one –– Most readily audible at expiration at or medial to
crest, i.e. prominent V or CV pattern when associated cardiac apex following A2 with the diaphragm of
with TR. the stethoscope.
• Apex— −− OS is indicative of
−− Inconspicuous LV. –– MS is organic
−− Tapping S1 suggestive of still pliable anterior leaflets. –– Significant MS.
−− Apex may be of RV type in severe RVH. −− Loud OS signifies
−− Diastolic thrill at the apex (better palpable with the –– High LA–LV pressure gradient.
patient in left lateral recumbant posture). –– Valve cusp are still pliable and not calcified.
• Palpable P2/diastolic shock over left 2nd ICS. –– Severe AR, MR, SABE, AF and atrial failure are
• RV lift on left parasternal region also suggestive of absent.
RVH/left atrial enlargement. –– MS is readily amenable to surgery.
• Auscultation— −− Differential diagnosis of middiastolic murmur of
−− S 1—Generally short, sharp, accentuated due to MS
fibrosis of cusp and incomplete filling of LV. –– Carey Coombs murmur of acute rheumatic fever.
−− Loud P2 — Loud P2 with closely split S2 due to reduced –– Austin Flint murmur of AR.
compliance of pulmonary vascular bed which –– Flow murmur of severe MR, VSD and PDA.
shortens the hangout time interval of pulmonary –– Left atrial myxema.
valve. –– Diastolic flow murmur through tricuspid valve
Finally S2 becomes single and accentuated. in ASD.
−− Other signs of pulmonary hypertension—
–– Nonvalvular pulmonary ejection sound (click) Severity of MS is indicated by
–– Systolic murmur of TR a. Short A2–OS gap
–– Graham Steell murmur of PR b. Long duration of delayed diastolic murmur
–– S4 originating from RV.
−− Diastolic murmur—
–– It is a low pitch middiastolic rumbling murmur −− Dynamic auscultation—Sudden standing and
with a presystolic accentuation, commensing resultant reduction of venous return lower LA pres-
immediately after OS. Best heard at the apex sure and widen the A2–OS interval. This is useful in
with the bell of stethoscope, patient in left lat- distinguishing an A2–OS combination from a split S2
eral position and the breath held at the end which narrows on standing.
of expiration provided the patient is in sinus Investigations
rhythm. If atrial fibrillation is present with MS, the
auscultatory finding of MS is middiastolic rum- • ECG—Changes in MS are
bling murmur with variable intensity 1st heart −− Evidence of LA enlargement in lead-II, as wide
sound. Presystolic accentuation of the murmur notched P-wave (P. mitrale).
will be absent. −− In lead-V1 → Biphasic P-wave with >1 small square
–– Murmur is accentuated by mild exercise or in any duration and deapth.
condition which increases the transmitral valve −− Features of RVH in V1.
pressure gradient. • X-ray—Evidence of MS.
–– The duration, and not the intensity of the mur- −− LA enlargement as a double contour at the right
mur is a guide to the severity of MS. border of heart (specially if associated with MR) and
–– In mild MS middiastolic and late diastolic/ presys- prominent LA appandages at the left border.
tolic component of murmur are not continuous. −− Enlargement of pulmonary artery appears as
There may be a gap in between mid and late di- fullness of plumonary bay at the left border in PA
astolic murmur. view.
–– In severe MS, the murmur is hollow diastolic. −− LA enlargement is also evident by C-shaped
−− Opening snap (OS) indentation over barium swallow esophagus in left
–– Mechanism of production of OS—It is due to sud- lateral view.
den tensing of mitral valve leaflets after the valve −− RVH is demonstrated by
cusp has completes its opening excursion. During –– Apex is much above the diaphragm.
downward depression of mitral cusp from upward –– Diminution of retrosternal space in left lateral
position to downward position at the beginning of view with slight increase in transverse diameter
ventricular diastole. of heart which is boot-shaped due to upturn apex.
Valvular Heart Disease 39

Peasant’s wooden boot with upturn toes—Coer- 5. Warfarin for 1 year in patient with systemic/pulmonary
en-saboot appearance of cardiac silhouette. embolization.
−− Karley’s B-line 6. Medical/electrical cardioversion of AF should be
–– Dense short horizontal line commensing from pe- attempted if AF is of recent origin and LA is not husely
riphery at the costophrenic angle due to thickened dialated.
intralobular septa.
−− Karley’s A line—Straight dense line about 4 cm in Surgical management
length running towards the hilum from periphery (in Indications of surgery in MS
severe long-standing mitral stenosis). 1. Symptomatic patient with moderate to severe MS
−− Evidence of pulmonary hemosiderosis. (valve size < 1.0 cm2/m2 body surface or 1.5 cm2).
−− Evidence of pulmonary edema (rarely). 2. Mild MS but symptomatic with ordinary activity.
−− Bat’s wing-shaped opacity spreading from hilum. 3. Complication—Development of embolism.
−− Evidence of parenchymal calcification. 4. Patient’s symptom cannot be controlled only by
−− Evidence of mitral valve calcification (retrosternal medical therapy.
location at the level of 4th ICS). 5. Pregnancy with MS whose previous pregnancy was
−− Deviation of left main and upper lobe bronchus. symptomatic.
−− Prominent upper lobe pulmonary vein. 6. PHTN—Pulmonary arterial SBP >60 mm after exercise
−− Hilar arterial prominence. and >50 mm at rest.
−− Peripheral prooning of blood vessel. Mean pulmonary capillary wedge presure >25 mm.
• Echocardiography Valvotomy is not recommended for entirely asymp-
−− M-Mode echo shows tomatic patient or when mitral valve orifice is >1.5
–– Thickened, calcified and stenotic mitral valve cm2.
–– LA enlargement
–– Restricted valve casp movement. Operative procedure
−− 2D echo shows
• Mitral valvotomy—Unless contraindicated should be
–– LA thrombus.
done in all symptomatic patients with isolated MS of
–– Restricted motion and doming of valve leaflets.
orifice size is <1.5 cm2.
–– Valve orifice size measurement.
Two techniques
–– Detection of valve—calcification and thickening
−− Percutaneous mitral balloon valvotomy (PMBV)—
of subvalvular apparatus with fusion and retrac-
Short and long-term results are similar to those of
tion of chordae.
surgical valvotomy.
–– LV contractility.
−− Surgical valvotomy—Opening of valve commissure,
−− TEE gives superior image of mitral valve and LA
loosening of any subvalvular fusion of papillary
thrombus.
muscles and chordae with removal of deposition of
−− Doppler study shows—Functional status of LA, LV,
calcium and left atrial thrombus.
RV can be assessed and quantification of the severity
Mortality is about 2%.
of MS.
About half of the patients after surgical mitrals
−− Estimate pulmonary artery wedge pressure.
valvotomy require reoperation by 10 years.
−− Assessment of any other valve anomaly.
• Mitral valve replacement (MVR)—Is required
−− In MS (orifice <1 cm2).
Cardiac Catheter −− NYHA class-III symptomatic despite optimal medical
To rule out CAD in patient with chest pain. therapy.
−− When MS is associated with significant MR or
Management whose valve in severly disorganized by PMBV or
prior operative manipulation should have valve
Medical therapy replacement.
1. Penicillin prophylaxis for acute rheumatic fever and Operative mortality is 6% and 10 years survival is
infective endocarditis. about 70%.
2. Restriction of fluid and Na+ intake.
3. Oral loop diuretics (frusemide with potassium- AORTIC REGURGITATION
sparing diuretic).
AORTIC REGURGITATION CAUSED BY
4. Digitalis in patient with AF—To slow the ventricular
rate and also in patient with right ventricular failure. 1. Primary aortic valve disease
β-blockers or non-DHP CCB can also be used. 2. Aortic root dilation.
40 Essentials of Internal Medicine

Causes of Aortic Valve Disease • LV function—Due to decompensation of LV function


and reduction of LV compliance, LV end diastolic
• Rheumatic heart disease.
pressure rises which leads to rising LA, PCWP, RV and
−− Puckering of valve cusp due to infiltration of cusp by
RA pressure which at first occurs during exercise later at
fibrous tissue.
rest. It leads to fall in EF causing pulmonary congestion.
−− Commissural fusion prevent proper apposition.
• Myocardial ischemia is due to
• Calcific AS in elderly is the most common cause of AS
−− Increase in LV wall tension.
with AR.
−− Increase in LV mass.
• Infective endocarditis
−− Decrease in coronary blood flow in diastole as DBP
−− Destruction or perforation of valve leaflet.
is less than normal.
−− Vegetation interfering with proper apposition of
cusp.
Clinical Features
• Iatrogenic
−− Catheterization. History
−− Percutaneous aortic balloon valvotomy.
Patients remain asymptomatic when patients are in com-
−− Radiofrequency catheter ablation.
pensated state but LV gradually enlarges.
• Bicuspid aortic valve.
Most patients develop symptoms in 4th or 5th decade
• Large VSD.
only after considerable cardiomegaly and myocardial dys-
• Membraneous subaortic stenosis.
function have developed.
• Myxomatous degeneration of aortic valve.
• Structural deterioration of bioprosthetic valve. Principal symptoms
• Dyspnea—On exertion.
Causes of Aortic Root Disease • Orthopnea.
• Degenerative aortic dilation (age-related) • PND.
• Ankylosing spondylitis, RA, SLE, Crohn’s disease • Palpitation—Usually during exertion and lying down
• Psoriatic and other seronegative spondyloarthritis posture.
• Systemic HTN • Pain chest—Due to pounding of heart against chest wall.
• Dissecting aortic aneurysm Out of these symptoms, dyspnea develops early and rest
• Cystic medial necrosis (Marfan) are the late features which are more prominent with stress,
• Aortic dilation secondary to bicuspid valve exertion and tachycardia.
• Osteogenesis imperfecta These complaints are present for many years before the
• Syphilitic aortitis symptoms of overt LVF develops.
• Appetite-suppressant drug.
Past history
Pathophysiology of Chronic • Past history of rheumatic fever, SABE may be there.
• Features of RA, SLE, ankylosing spondylitis may be
Aortic Regurgitation
present.
• In chronic AR, blood is ejected into comparatively
high pressure aorta which results in left ventricular Peripheral signs of AS
hypertrophy along with dilation due to increase EDV. The following peripheral signs are seen in chronic AR due
• In compensated AR there is sufficient wall thickening to increased pulse pressure—
so that the ratio of wall thickness : cavity radius remains • Lighthouse sign—Alternate blanching and flushing of
normal. forehead.
• In long-standing chronic AR with increasing severity • Ladolfi sign—Change in pupil size with cardiac
over time wall thickening fails to keep peace with the pulsation.
hemodynamic load and the end systolic wall stress rises. • Müller sign—Pulsation of uvula.
At this point after load mismatches results in declining • De Musset’s sign—Head nodding with carotid pulsation.
of systolic function and EF falls. • Corrigan’s sign—Dancing carotid in neck.
• Left ventricular mass is greatly increased often greater • Suprasternal pulsation—Visible.
than 1 kg. Severe chronic AR has the largest EDV of all • Locomotor brachialis—Visible brachial artery
heart diseases. pulsation.
• Regurgitant flow may exceed 20 L/min in severe cases, • Bisferiens pulse—More commonly palpable in brachial
so that LV output reaches about 25 L/min. and femoral artery than carotid artery. In this condition
Valvular Heart Disease 41

percussion wave and dicotic wave are separately • The murmur may be holodiastolic and may have a rough
palpable also known as “double kicking pulse”. quality in severe AR.
• Wide pulse pressure—Korotkoff ’s sound often per- • When murmur have musical quality (cooing dove
sists up to zero even though intraarterial pressure rarely murmur) it indicates eversion or perforation of aortic
falls below 30 mmHg. cusp.
• Water hammer pulse (high volume collapsing • The severity of regurgitation correlates better with
pulse)—Pulse pressure greater than 60 mm Hg. the duration rather than intensity of the murmur.
Diastolic blood pressure usually less than 60 mm Hg. The greater the severity of the AR, shorter the length
• Prominent digital arterial pulsation. of the murmur. In long-standing severe AR the late
• Quincke’s sign—Visible capillary pulsation at finger diastolic component is abolished due to equilibration
nail and lip. of LV pressure and aortic pressure.
• Rosenbach sign—Pulsation of liver. • An enjection systolic flow murmur radiating to
• Gerhardt sign—Pulsation of spleen. carotid (but more high pitched and less rasping than
• Traube’s sign—Also known as pistol shot sound— murmur of organic AS) may be heard associated with
A booming systolic and diastolic sound heard over a systolic thrill due to increased flow through aortic
femoral artery. valve in systole.
• Duroziez’s sign—Systolic murmur heard over the • A functional mid and late diastolic apical rumble
femoral artery when it is compressed proximally and a known ‘Austin Flint murmur’ may be heard in severe
diastolic murmur when it is compressed distally. AR in presence of normal mitral valve due to impinging
• Hill sign—Popliteal SBP 60 mm or more higher than of aortic reflux jet on the aortic leaflet of mitral valve
brachial SBP. (absence of OS and loudness differentiate it from
organic MS).
Palpation • Dynamic auscultation—Murmur of AR may be
• Apex heaving LV type (forceful and ill-sustained) accentuated by increasing the afterload as in equating
appear with features of LV enlargement. posture, with leaning forward and isometric exercise.
• Systolic retraction over left parasternal region.
• Systolic thrill at the base of the heart (aortic area) which Laboratory Investigations
is also palpable at suprasternal notch or over carotid • ECG
artery called ‘carotid shudder’ (due to increased flow −− Left axis deviation.
through carotid artery in systole). −− LVH.
−− LV strain pattern—ST depression with upright T or
Auscultation more commonly inverted T with down-slopping ST
• Soft S1. segment.
• S2 may be absent or single or exhibit narrow para- −− Q wave in I, AVL, V3–V6 with small R-wave (precordial)
doxical splitting. leads due to LV diastolic overload.
• A2 is soft or absent in valvular AR but A2 may be normal −− ECG is not a accurate predictor of cardiac weight.
or rarely may be accentuated in aortic root disease. • Chest X-ray
• P2 may be obscured by early diastolic murmur. −− In acute AR—Minimum cardiac enlargement.
• Systolic ejection sound (click) may be present due to −− In chronic AR—Marked cardiac enlargement with
abrupt distension of aorta by augmented stroke volume. downward and outward shifting of apex.
• S3 gallop reflects increased EDV of left ventricle or may Apex may be displaced below diaphragm.
be a feature of LV dysfunction who are candidate for Left lateral view shows encroachment in the posterior
surgical treatment. mediastinum by LV.
• S4 may be audible in late stage of AR with severe LV −− Calcification of aortic valve—Specially in com- bined
dysfunction. AS with AR.
• A high pitch decrescendo, blowing early diastolic −− Linear calcification in the wall of aorta — Specially
murmur starting immediately after A2, best heard in syphilitic aortitis and degenerative aortic diseases.
at left 3rd ICS parasternal region (neoaortic area) −− Dilation of ascending aorta (unfolding of aortic
with radiation towards apex with the diaphragm of arch)—Specially in aortic root disease.
stethoscope and the patient in sitting posture leaning
forward with the breath held at the end of expiration Echocardiography
(when the AR is due to primary valve defect). • M-Mode echo identify
• When the AR is due to aortic root dilation the same −− Cause of AR
murmur radiates along the right sternal border. −− Thickening of valve cusp
42 Essentials of Internal Medicine

−− Presence of congenital abnormality like bicuspid −− Patients with severe AR having limitation of cardiac
valve reserve and evidence of decreased LV function
−− Presence of prolapse of the valve cusp should not engage in vigorous exercise.
−− Presence of vegetation and dilation of aortic root. −− Systemic arterial diastolic hypertension, if present,
• 2-D echo quantify should be treated (because it increases the regurgitant
−− LV–EDV flow) with nifedipine and ACEI. (β-blocker should be
−− LV–ESV used with great caution).
−− Ejection fraction −− Atrial fibrillation and bradyarrhythmia are poorly
−− Venticular mass. tolerated and should be treated if possible.
• TEE (transesophageal echocardiography) gives more −− Vasodilator therapy—Chronic AR with significant
detailed information about volume overload and increased EDV should be
−− LV size considered for vasodilator therapy with hydralazine,
−− Regurgitant blood volume nifedipine or ACE.
−− Presence of vegetation. Chronic medical therapy may be necessary for the
• High frequency fluttering of anterior leaflet of mitral patient who refuses surgery or considered inoperable
valve due to impingement of regurgitant blood even due to serious comorbid condition. Chronic medical
in mild AR is an important echo sign but is not seen therapy consists of agressive management of heart
in rheumatic involvement of mitral valve as the valve failure and vasodilator therapy with
is rigid. –– Diuretic
• Doppler—Most sensitive and accurate noninvasive –– Salt restriction
technique for detecting mild AR, regurgitant flow, –– ACEI or nifedipine (vasodilator).
orifice size, progression of regurgitation and its effect –– Digoxin.
on ventricle, ejection fraction and timing of surgical • Surgical therapy—Since severe symptoms (NYHA
intervention. class III or IV) and left ventricular dysfunction with an
ejection fraction less than 50% are independent risk
Radionucleotide imaging is necessary for factor for poor postoperative survival, surgery should
Accurate noninvasive assessment of severity of AR by be carried out in NYHA class-II patient before severe
allowing determination of regurgitant fraction and of left ventricular dysfunction has developed.
the LV/RV stroke volume ratio. Usually radionucleotide −− Indications for surgery
imaging is only done when— –– Symptomatic chronic severe AR
• Echo resolution is suboptimal –– Poor exercise tolerance
• Discrepancy between clinical and echo finding. –– EF less than 50%
–– LV EDD more than 70 mm
MRI –– LV ESD more than 50 mm.
−− Operative procedure
• Accurate measurement of the regurgitant volume and –– Annuloplasty for primary aortic root disease.
regurgitant orifice size. Two procedures
• Most accurate noninvasive technique for detecting LV »» Encircling suture of the aorta
mass and LV end diastolic volume. »» Subcommissural annuloplasty.
–– Excision of a part of aorta with replacement by
Management a graft or prosthetic valve in case of aneurysmal
• Medical therapy dilation of aorta.
−− All patients with AR of any severity should receive –– AVR (aortic valve replacement) in severe AR, if it
prophylaxis for infective endocarditis. is due to primary valve disease.
−− Asymptomatic patients with mild to moderate
AR and normal or minimal increase in cardiac AORTIC STENOSIS
size require no therapy but should be followed up
Types of Aortic Stenosis
clinically and by echo every 12–24 months.
−− Patients with mild to moderate AR and patients There are three types of aortic stenosis present depending
with severe AR but normal EF and mild ventricular on to anatomical site
dialation may engage in aerobic exercise. • Valvular
−− Asymptomatic patients with chronic severe AR −− Congenital
and normal LV function should be examined 6 −− Rheumatic
monthly. −− Degenerative.
Valvular Heart Disease 43

• Supravalvular • Moderate stenosis : Valve orifice size—1–1.5 cm2.


−− Hourglass constriction of aorta • Severe stenosis : Valve orifice size—less than 1 cm2.
−− Membranous—Diaphragm in the aorta. • Critical stenosis : Valve orifice size—less than 0.8 cm2.
• Subvalvular. Cardiac output is often within normal limit in most of
the patients of severe AS in resting condition but often fails
Valvular to rise during exercises.
• Congenital
−− Unicuspid—Aortic valve produces severe obstruc- Clinical Features of Aortic Stenosis
tion in infancy.
History
−− Bicuspid aortic valve have abnormal architecture
causes turbulent flow which traumatises the valve There is a long latent period for onset of symptoms.
cusp resulting in fibrosis and calcification. Manifestations most commonly commence at the 5th
It may be stenotic due to commissural fusion. decade in congenital and rheumatic AS whereas 7th–9th
−− Tricuspid valve cusps are unequal in size with decade in degenerative AS.
commissural fusion. Cardinal manifestations are—
• Acquired • Angina (seen in 66% of critical AS) is due to—
−− Rheumatic valvular AS usually with mitral valve −− Decreased oxygen supply—
involvement –– Due to decreased BP
–– It is mostly associated with AR or mitral valve –– Due to increased LVEDP.
disease. −− Increased demand of O2 due to increased LV mass.
−− Degenerative—Leading cause of AS in developed • Syncope is due to—
countries. −− Decreased cerebral perfusion, specially during
–– Two types exercise.
»» Atherosclerotic −− Malfunction of baroreceptor mechanism.
»» Calcific −− Vasopressor response due to greatly increased LV
»» Rare causes are systolic pressure during exercise.
NJNJ Rheumatoid involvement of cusp −− Ventricular fibrillation causing graying out spell or
NJNJ Ochronosis with alcaptonuria. dizziness.
−− Transient AV block.
Supravalvular • Exertional dyspnea.
• Hourglass constriction (most common)—It is associated • Heart failure.
with marked thickening and disorganization of tunica Dyspnea may be associated with PND and orthopnea,
media of aorta produce a constricting annular ridge at pulmonary edema reflecting varying degree of pulmonary
the superior margin of the sinus of Valsalva. HTN.
• Membranous type—Result of fibrous or fibromuscular Marked fatiguability, debilitation, peripheral cyanosis
semicircular diaphragm with a small central opening are not prominent until late stage of the disease.
stretched across the lumen of the aorta. Survival curve shows that interval from the onset of the
Subvalvular symptom to the time of death is approximately—
• 2 years with heart failure
• Static obstruction—due to fibromuscular band.
• 3 years with syncope
• Dynamic obstruction—HOCM (hypertrophic obstruc-
• 5 years with angina.
tive cardiomyopathy).
Infective endocarditis is more common in younger with
mild valvular disease but less common with old people with
Pathophysiology of Aortic Stenosis
rock-like calcific aortic stenosis.
In adult obstruction usually develops and progresses
gradually. Physical Examination
This form of chronic progressive AS is well-compensated • Palpation—Outside precordium
by LVH maintaining stroke volume for many years. −− Pulsus parvus et tardus—Slow and low rise pulse.
Late in the course of AS, left ventricular aortic pressure −− Systolic thrill felt most prominent over carotid
gradient, stroke volume, COP all decline resulting in PHTN producing carotid shudder.
and RVH. −− Simultaneous palpation of apex and carotid reveals
LVEDV remains normal until late but LV mass increases a lag in the later.
due to concentric hypertrophy of left ventricle. −− Pulsus alternans—Suggests left ventricular
• Mild stenosis : Valve orifice size—1.5–2 cm2. dysfunction.
44 Essentials of Internal Medicine

−− Jugular venous pulse—Prominent a-wave reflecting Investigations ofAortic Stenosis


diminished RV compliance consequent to pulmonary
• Doppler echocardiography for diagnosis and as-
hypertension and hypertrophy of septum.
sessment of aortic stenosis and LV function every yearly
Due to pulmonary hypertension secondary RVF and
in symptomatic patients and at 2–5 years interval in
TR develop for which ‘C V’ or ‘V’ wave may seen in neck
asymptomatic patients with a mild to moderate AS.
venous pulse.
• Cardiac catheterization—When AS is associated with
• Palpation of precordium
coronary artery disease and when there is discrepancy
−− Apex
between the clinical picture and echocardiographic
–– Usually normal in position but may be shifted
finding.
down and out which forceful and well-sustained.
–– Systolic thrill best appreciated when patient in up-
Management of Aortic Stenosis
right position leans forward during full expiration.
Palpated most readily in 2nd ICS on right side of • Medical management—In patient with severe AS (<1
sternum or suprasternal notch and is frequently cm2).
transmitted to carotids (carotid shudder). −− Avoid strenuous physical activity even in asymp-
−− Features of RVH and RVF tomatic stages.
–– Right parasternal heave −− Avoid dehydration, low COP and hypovolemia.
–– Engorged pulsatile neck veins (earliest) −− β-blocker and ACEI are safe in asymptomatic patient
–– Pedal edema used for CAD or HTN.
–– Hepatomegaly −− Nitroglycerine may be used for angina.
–– Ascites.
} Late feature −− Statin (atorvastatin or rosuvastatin) is beneficial for
degenerative calcific AS.
Auscultation of Aortic Stenosis • Surgical treatment of AS—(mortality <1%)
Indications
• S1—Normal or soft. −− When orifice size is less than 1 cm2.
• S4—Prominent due to vigorous atrial contraction and −− Symptomatic AS.
partially closed mitral valve during presystole. −− Aneurysmal dilation of aortic root in moderate AS.
• S2— −− When hypotensive response to exercise develops in
−− S2 may be single due to inaudibility of A2. AS with left ventricular dysfunction.
−− A2 may be inaudible due to immobility caused by Valvoplasty can be done in small number of selected
calcification of valve cusps. patients.
−− P2 is burried in prolonged ejection systolic murmur. • In children—In noncalcified congenital AS who
−− Prolongation of LV systole causes overlapping of A2 commonly have bicuspid valve—two types of procedure.
with P2 or there may be reverse splitting. −− Commissural incision under direct vision (mortality
• Aortic ejection click—Due to sudden halting of upward less than 1%).
movement of aortic valve—heard 0.06 second after S1. −− Balloon aortic valvoplasty when valve orifice area
• Ejection systolic murmur of AS is low pitch, rough >0.8 cm2. The development of regurgitation and
and grasping in character—Best heard at the base of restenosis after 10–20 years requires reoperation or
the heart on right 2nd ICS close to sternum and breath valve replacement.
held at the end of expiration, with the diaphragm of the • In adult—Aortic valve replacement (AVR) is recom-
stethoscope and well-transmitted to the carotids. The mended.
high-pitched component may be transmitted to the
apex (Gallavardin’s phenomenon) comes in differential MITRAL REGURGITATION
diagnosis of murmur of MR.
In patient with severe aortic stenosis but with pre Abnormality of any one of the five components of mitral
serve COP, the murmur is of grade III/IV whereas in valve apparatus may cause MR. But the major causes of
severe aortic stenosis with heart failure and low COP MR are
the murmur is relatively soft and brief. 1. Rheumatic endocarditis
• More severe is the stenosis. 2. Mitral valve prolapse
−− More prolonged is the murmur of AS 3. Infective endocarditis
−− Peaks later in systole. 4. Cardiomyopathy
• Dynamic auscultation—Murmur of valvular AS is 5. Ischemic heart disease.
augmented by squatting and reduces in intensity during • Other rare causes are
starting of Valsalva maneuver and on standing. −− Endocardial cushion defect
Valvular Heart Disease 45

−− Calcification of mitral annulus complain of severe fatigue and exhaustion secondary


−− Carcinoid to low COP. AF is invariably present.
−− Collage vascular disorder
−− Trauma. CLINICAL FEATURES of Mitral regurgitation
• Acute MR—
Symptoms
−− Papillary muscle rupture (post-MI)
−− Endocarditis 1. In chronic severe MR
−− Trauma −− Fatigue.
−− Rupture chordal/flail leaflet (MVP). −− Exertional dyspnea.
• Chronic MR— −− Orthopnea.
−− Myxomatous MVP −− Right-sided heart failure or its other presentation
−− Rheumatic (33%) may be found where MR is associated with pulmo-
−− Endocarditis nary vascular disease or marked PHTN.
−− Annular calcification 2. In acute severe MR
−− Congenital −− LV failure with acute pulmonary edema is the
−− HOCM common presenting feature.
−− DCM. 3. Physical finding—
Irrespective of cause, severe mitral regurgitation (MR) a. General examination
is most often pro- gressive, since enlargement of LA places –– BP—Normal.
tension on the posterior mitral leaflet pulling it away from –– JVP—Prominent a-wave in patient with sinus
the mitral orifice, thereby aggravating valvular dysfunction. rhythm and marked PHTN.
Similarly LV dilatation (LVEDD >6 cm) increases the re- –– Prominent v-wave in patient with MR with TR.
gurgitation which in turn enlarges LA and LV further caus- b. Systemic examination—
ing chordal rupture resulting in a vicious cycle hence it is –– Laterally displaced apex.
said that, mitral regurgitation begets mitral regurgitation. –– Palpable systolic thrill at the apex in 25% patients.
–– Hyperdynamic apex with brisk systolic impulse.
–– Left parasternal thrust and diastolic knock over
PATHOPHYSIOLOGY of Mitral pulmonary area due to pulmonary hypertension.
regurgitation c. Auscultation—
In MR the volume of the regurgitant blood varies directly –– Soft S1 buried (in murmur).
with LV systolic pressure and size of the regurgitant –– Wide splitting of S2.
orifice. But later it is profoundly influenced by extent of LV –– Low-pitched S3 due to sudden tensing of papillary
dilatation. muscle, cordae tendinae and valve leaflet.
• Normally ejection fraction rises in severe MR and –– Pansystolic blowing murmur of grade 3 or 4
in presence of normal LV function. Even a modest intensity found at the apex radiating to axilla,
reduction in ejection fraction (EF) reflects significant best heard during expiration with the bell of the
dysfunction. stethoscope in case of dysfunction of anterior
• V-wave in the LA pressure pulse in usually prominent cusp of mitral valve.
with rapid Y descent. –– In case of primary involvement of posterior mitral
• In chronic MR there is often increase in LV compliance leaflet, or ruptured chordae the regur- gitant jet
so that LV volume rises with little elevation of diastolic strikes LA wall adjacent to aortic root; hence the
pressure. The cardiac output is usually not affected but murmur is transmitted to base of the heart and in
reduced in seriously symptomatic patient. these cases it may be confused with murmur of AS.
• In severe cases as much as 50% of total LV stroke volume –– In MVP the murmur usually commences at late
regurgitates with each beat. Qualitative and clinically systole after a midsystolic click.
useful estimate of the severity of MR is made by the –– A middiastolic rumble over mitral area due to in-
degree of LA opacification after injection of contrast crease in flow across the mitral valve during first
material in LV or by color Doppler. rapid filling phase of diastole may be heard. S4 is
• Patient with acute MR usually have normal or reduced audible in patient with acute severe MR who are
LA compliance with marked pulmonary congestion in sinus rhythm.
and edema. –– In case of ruptured cordae the murmur has cooing
• Patient with long-standing chronic severe MR usually dove quality called Seagull murmur.
have marked increase in LA compliance and are at the –– In case of flail leaflet the murmur may have musi-
opposite end of the spectrum. These patients usually cal quality.
46 Essentials of Internal Medicine

Investigations of Mitral regurgitation IV GTN or nitroprusside reduces afterload thereby reduces


the volume of regurgitant flow in acute severe MR with AMI.
1. Chest X-ray—Enlargement of LA and LV but later LA • ACE inhibitors in ischemic MR.
enlarges massively and forms double contour on the • Anticoagulant and tight elastic stocking to reduce
right border of cardiac silhouette in chest X-ray (PA). venous thrombi and pulmonary embolism.
2. ECG—Shows features of • Prophylaxis for endocarditis should be given.
−− LA enlargement
−− RA enlargement Indications of Surgery
−− Atrial fibrillation
−− LV hypertrophy. 1. In severe MR whose limitations do not allow full time
3. Echocardiography employment or the performance of normal household
−− Color flow Doppler is most accurate for diagnosis activities despite optimal medical management.
of MR. 2. In asymptomatic MR with progressive LV dysfunction
−− 2D echo can identify the etiology. with LVEF <60% and end systolic cavity dimension on
−− LA is usually enlarged and exhibits increased echo >45 mm.
pulsation. 3. In asymptomatic patient when PHTN or atrial fibril-
−− LV may be hyperdynamic. lation are present.
−− Mitral valve calcification and LV dyskinesia in Procedure
ischemic MR.
−− Ruptured chordae, flail leaflet in post-AMI mitral 1. Mitral valve replacement with prosthesis is indicated
regurgitation can easily be detected in echo. where the valves are markedly deformed, shrunken,
−− Coarse erratic motion of involved leaflet in infective with calcified leaflet secondary to rheumatic fever.
endocarditis can be seen. 2. Mitral valvoplasty or annuloplasty is indicated in
TEE (transesophageal echocardiography)—Provides patient with—
greater detailing. a. Severe annular dilation.
b. Flail leaflet.
c. MVP (mitral valve prolapse).
Management of Mitral regurgitation d. Ruptured chordae.
e. Infective endocarditis.
Medical Therapy (Table 4.1)
–– MVR (mitral valve replacement) carries operative
• Rest. risk ~ 6%.
• Reduced NaCl intake. –– Valvoplasty or annuloplasty caries operative risk
• Enhanced NaCl excretion by diuretic. ~ 3%.
• Vasodilator (nitrates) increase cardiac output by –– Thromboembolic or hemorrhagic complications
lowering BP and reducing regurgitant flow. occur with mechanical prosthesis requires re-
• Digitalis to slow ventricular rate. placement by bioprosthesis.

Table 4.1: Concise conservative medical therapy for valvular heart disease
Symptoms control Long-term therapy
A. Mitral stenosis 1. β-blocker 1. Penicillin prophylaxis for RF
2. Non-DHP CCB For rate 2. Warfarin for AF or thromboembolism
3. Digoxin Control in AF
4. Cardioversion for new
onset AF may be tried
5. Diuretic for HF
B. Mitral regurgitation 1. Diuretic for HF 1. Warfarin for AF or thromboembolism
2. Vasodilator therapy for acute MR with nitrate, ACEI 2. Vasodilator for HTN
3. Counterpulsating aortic balloon for acute MR (in AMI)
C. Aortic stenosis 1. Diuretic for HF 1. Nil
D. Aortic regurgitation 1. Diuretic and vasodilator, 1. Vasodilator for HTN
for HF ACEI and nitrate
Chapter 5
Heart Failure

Definition STAGEs OF HEART FAILURE


Heart failure (HF) is a pathophysiological condition in •• Stage A—Patients are at high-risk for developing HF but
which heart is unable to pump adequate amount of blood have no structural disorder or signs and symptoms of the
required by the metabolizing tissue of the body or can do so heart failure. Patients with HTN, CAD, DM, cardiotoxins,
with elevated ventricular filling pressure. dyslipidemia are in this group.
•• Stage B—Patients have a structural disorder of heart
CAUSES OF HEART FAILURE but have never developed signs and symptoms of HF.
(patients with previous MI, LV diastolic dysfunction,
A. Primary factor— asymptomatic valvular or congenital heart diseases).
a. Ischemic heart diseases (responsible for 75% cases) •• Stage C—Patients with past/current symptoms of HF,
b. Hypertensive heart diseases associated with underlying structural heart diseases.
c. Cardiomyopathy (patients with known structural heart diseases with
d. Congenital shortness of breath, fatigue, reduced exercise tolerance).
e. Valvular. •• Stage D—Patients have end-stage heart diseases
B. Precipitating factor and require specialized treatments strategy such as
mechanical circulatory support, continuous inotropic
infusions, cardiac transplantation or hospice care.
Precipitating factor places an additional load on a myocardium NYHA (New York Heart Association) functional
which is chronically overburdened. Such a patient usually have a classification of dyspnea primarily gauges the severity
compensated heart failure in normal condition with little cardiac of symptoms in patients who are in stage C and D heart
reserve. The additional load imposed by the precipitating factor failure.
results in further deterioration of cardiac function and the
−− NYHA class-I—Patients with cardiac disease but
patient develops overt sign and symptom of heart failure
ordinary physical activity do not cause undue fatigue
or dyspnea, palpitation or angina (without limitation
of physical activity).
−− NYHA class-II—Patients with cardiac disease
Factors that precipitate acute heart failure in a case of
resulting in slight limitation of physical activity. They
compensated chronic heart failure
1. Arrhythmia are comfortable at rest but ordinary physical activity
2. Dietary excess causes fatigue, dyspnea, palpitation and angina.
3. Silent myocardial infarction −− NYHA class-III—Patients with cardiac disease have
4. Accelerated hypertension marked limitation of physical activity and less than
5. Discontinuation of heart failure therapy ordinary, physical activity cause fatigue, dyspnea,
6. Systemic or pulmonary infections
7. Anemia
palpitation and angina.
8. Medication that worsen heart failure −− NYHA class-IV—Patients with cardiac disease who
a. CCB—Verapamil, diltiazem are unable to carry out any physical activity without
b. β-blocker discomfort. Symptoms of heart failure may be
c. NSAID present even at rest.
d. Antiarrhythmic agent (class-I agent and sotalol)
e. Anti-TNF antibody
9. Alcohol FORMS OF HEART FAILURE
10. Pregnancy
Heart failure is classified in various ways:
11. Acute valvular insufficiency (MR)
•• Systolic failure/diastolic failure
48 Essentials of Internal Medicine

•• Forward failure/backward failure Low Output Failure


•• High output failure/low output failure
•• Acute failure/chronic failure Causes
•• Right-sided failure/left-sided failure. •• Ischemic heart disase, DCM, hypertension and VSD
•• Normal COP → 2.5–3.5 L/min/m2
Systolic Failure Same as Forward Failure •• At rest—Within normal limit
At exercise—Fail to increase adequately.
Inability of the ventricle to contract normally and expel
sufficient amount of blood.
Acute Heart Failure
Causes Sudden fall in cardiac output.
IHD, MI and cardiomyopathy. [Sudden fall in systolic blood pressure and sudden
decrease in COP lead to systemic hypotenstion without
Clinical features of left ventricular systolic failure pedal edema].
Inadequate COP resulting in weakness, fatigue, exercise in
Causes
tolerance and other symptoms of hypoperfusion.
•• Sudden development of large MI.
Diastolic Failure Same as Backward Failure •• Rupture of chordae tendineae.
•• Accelerated hypertension (acute left heart failure).
The ventricle is unable to relax and/or fill normally and •• Massive pulmonary embolism (acute right heart failure).
adequately (increase resistance to ventricular filling).

Causes Chronic Heart Failure


•• Constrictive pericarditis Gradual fall in cardiac output.
•• Restrictive cardiomyopathy
•• Hypertrophic cardiomyopathy Causes
•• Cardiac tamponade. •• DCM.
•• Multivalvular heart disease that affects slowly due to
Clinical features of salt, H2O retention.
•• Left ventricular diastolic failure [Arterial pressure well-maintained with accumulation
−− Orthopnea of water in extravascular space leading to edema].
−− PND.
•• Right ventricular diastolic failure Right Heart Failure
−− Increase jugular venous pressure Causes
−− Pedal edema
−− Congestive hepatomegaly. •• Cor pulmonale.
•• Congenital valvular pulmonary stenosis.
High Output Failure •• Pulmonary hypertension, secondary to pulmonary
emboli.
Causes
Clinical features
•• Hyperthyroidism
•• Arteriovenous fistula •• Edema, elevated venous pressure and hepatomegaly.
•• Anemia
•• Pregnancy Left Heart Failure
•• Beriberi
•• Paget’s disease. Causes
[Arteriovenous O2 concentration difference will be below •• MI, cardiomyopathy, hypertension and AS.
normal (35–50 mL/L)].
•• Cardiac output may not recede below the lower limit Clinical features
in normal condition but it will be below the lower limit •• Dyspnea
during exercise. •• Orthopnea
Heart Failure 49

•• Pinkish frothy sputum •• Cough.


•• Cyanosis •• Paroxysmal nocturnal dyspnea—Severe shortness of
•• Basal rales due to pulmonary congestion breath and cough that generally occurs at night during
•• S3 gallop. sleep although when metabolic demand is minimum.
It is caused by
Causes of right heart failure secondary to left heart failure −− Depression of respiratory center during sleep.
•• Pulmonary hypertension. −− Due to reduced pulmonary compliance from
•• Salt-water retention. interstitial pulmonary edema.
•• Muscle bundle composing both the ventricles are −− Due to redistribution of blood from leg and abdomen
continuous. to cardiopulmonary circuit in recumbent posture.
•• Both ventricles share a common wall. •• Cheyne-Stokes respiration is due to—
•• Biochemical changes that occur in left heart failure −− Decreased sensitivity of respiratory center to PaCO2.
involve and impair the function of right ventricle and −− Increased circulation time from lungs to brain in
cause right heart failure. atherosclerotic and hypertensive patient.
•• Fatigue and weakness is due to low COP.
Backward Failure Same as Diastolic Failure •• Abdominal symptoms—Due to congested liver and
When the ventricle fails to fill normally. portal hypertension.
−− Anorexia
Causes −− Nausea
−− Abdominal pain and fullness.
•• HOCM
•• Cerebral symptoms
•• Constrictive pericarditis
−− Confusion.
•• Restrictive cardiomyopathy
−− Difficulty in concentration and impairment of
•• Cardiac tamponade.
memory, headache, insomnia and anxiety.
Forward Failure Same as Systolic Failure Signs
When the ventricle cannot discharge normally. •• General—
−− Hypotension—Acute heart failure results in systolic
Causes
hypotension (reflecting reduced stroke volume). But
•• Myocardial infarction DBP will rise due to peripheral vasoconstriction.
•• AS −− Edema—Pitting bipedal edema—due to increased
•• Cardiomyopathy. venous pressure. Presacral edema seen in bedridden
In backward failure pressure in atria rises, resulting in patient.
increase release of ANP which causes retention of Na+ −− Cyanosis—Sequelae of acute LVF.
and water, leading to transudation of fluid in interstitial −− Sinus tachycardia due to compensatory sympathetic
space of lung. In forward failure salt-water retention is drive.
due to decrease in renal perfusion causing excessive −− Pulsus alternans due to LVF.
proximal and distal tubular Na+ and water absorption −− Pulsus pervus feeble pulse due to low stroke volume.
through activation of RAAS system.
(Other causes of pulsus alternans—Cardiomyopathy, hyperten-
CLINICAL FEATUREs of heart failure sion, IHD and following extrasystole)

Symptoms −− Increase systemic venous pressure (normal <8 cm


•• Dyspnea and orthopnea of H2O) and positive abdominojugular reflux. Neek
−− Dyspnea—Severity of dyspnea correlates with the venous pressure may be normal at rest but may
functional NYHA classification. It is due to interstitial become abnormally elevated for 15 second with
pulmonary edema which causes activation of receptor sustained (<10 sec) pressure over abdomen.
in the lung result in rapid shallow breathing, and * Giant cv-waves indicate the presence of tricuspid
increase fatigue of respiratory muscle due to imbalance regurgitation.
of O2 demand and supply to respiratory muscle. −− Extremity may be cold, pale and diaphoretic.
−− Orthopnea—Dyspnea in recumbent position. It is −− Jaundice—Increase in conjugated and uncon-
a late manifestation of HF than exertional dyspnea jugated bilirubin due to impairment of hepatic
due to redistribution of fluid from leg and abdomen function secondary to hepatic congestion and
to thorax causing increase in pulmonary capillary hepatocellular hypoxia associated with centri-
pressure combined with elevation of diaphragm. lobular atrophy of liver.
50 Essentials of Internal Medicine

−− Cardiac cachexia is due to Contd...


–– Increased TNF. 6. Basal rales 6. Vital capacity is reduced
–– Increased BMR. to two-third of normal
–– Anorexia, nausea, vomiting (due to central cause, 7. Acute pulmonary edema 7. Tachycardia > 120/min
chronic digitalis intoxication and congestive
8. S3 gallop
hepatomegaly).
–– Diminished absorption from intestine due to
intestinal congestion. Common Criteria
–– Protein losing enteropathy (usually in right heart Weight loss >4.5 kg over 5 days of treatment.
failure). •• To establish the heart failure → 1 major + 2 minor
•• Systemic signs criteria are required.
CVS— −− Investigations (in a patient of heart failure)
−− Apex is usually shifted downward and outward –– Complete hemogram
and palpable over 6th or 7th intercostal spaces and –– Urine analysis
well-sustained. –– Serum electrolytes including Ca2+ and Mg2+
−− S3 (protodiastolic gallop) is audible and some time –– BUN (blood urea nitrogen) and creatinine
palpable over apex in patient with volume overload –– Blood sugar (fasting and postprandial)
and tachycardia. –– LFT (liver function test)
−− S4 is usually present with diastolic dysfunction and –– TSH and free T4.
is not a specific indicator of heart failure. –– Both BNP and N-terminal pro-BNP are sensitive
Lungs marker for heart failure, false-positive elevation
−− Dull percussion note over base of both lung is due are associated with—
to hydrothorax. Pleural effusion most commonly »» Right heart failure
seen in biventricular failure. Pleural effusion in HF is »» CRF
usually bilateral but when unilateral, it is frequently »» Elderly person
on right side. »» Women.
−− Pulmonary rales or crepitations is due to transuda- •• 12 lead ECG for MI, arrhythmia and LVH.
tion of fluid from pulmonary capillary into alveoli. It •• Chest X-ray (PA view) for heart size, pulmonary
is frequently absent in chronic heart failure due to vasculature and PHTN.
increased lymphatic drainage of alveolar fluid. •• 2D echo with Doppler study or EF, RWMA and structural
−− Expiratory wheeze is usually found in acute heart disease.
failure. •• Cardiac catheterization with angiography (in patient
Abdomen with IHD and heart failure).
−− Hepatomegaly is an important sign. Usually liver is
tender and may pulsate in systole if TR is present. MANAGEMENT OF CHRONIC HEART FAILURE
Ascites usually a late sign and is due to impairment
TREATMENT OF STAGE A (Patient at high-risk
of venous drainage.
−− Jaundice is due to hepatic dysfunction is also a late of developing heart failure)
sign. •• Control of systolic and diastolic hypertension.
•• Treatment of hyperlipidemia.
DIAGNOSIS OF HEART FAILURE •• Avoidence of patient behavior that may increase the risk
of heart failure (smoking, alcohol and illicit drug use).
Table 5.1: Framingham’s criteria •• ACEI in patient with a history of atherosclerotic vascular
Major criteria Minor criteria diseases, DM, HTN and associated cardiovascular risk
factor.
1. PND 1. Extremity edema
•• Control of ventricular rate in patient with supra-
2. Neck vein distension 2. Night cough ventricular tachyarrhythmias.
3. Increased venus pressure (>16 3. Dyspnea on exertion •• Treatment of thyroid disorders.
cm of H2O). Normal ≤8 cm •• Periodic evaluation for signs and symptoms of heart
4. Positive abdominojugular reflux 4. Hepatomegaly failure.
5. Cardiomegaly 5. Pleural effusion ACC/AHA guideline does not force for lifestyle
interventions to prevent HF including exercise, salt
Contd... restriction or routine use of nutritional supplement.
Heart Failure 51

TREATMENT OF STAGE B (Patients with TREATMENT OF DIASTOLIC


left ventricular dysfunction who (DYSFUNCTION) FAILURE
have not developed symptoms) The major management strategies are
The goal of therapy is to reduced risk and also to minimize •• Control of hypertension.
the rate of progression of heart failure. •• Control of ventricular rate in patient with ventricular
•• ACE inhibitors. fibrillation.
•• β-blockers. •• Use of diuretic to control pulmonary congestion.
•• Valve replacement or repair for patients with hemody-
namically significant valvular stenosis or regurgitation. THERAPEUTIC MEASURES of heart failure
•• Regular evaluation for signs and symptoms of heart •• Activity—Heavy exercise is contraindicated. Routine
failure. moderate exercise is recommended.
•• Diet—Restriction of Na 2–3 g/day, fluid <2 L/day.
PLUS •• Diuretics—Diuretics is the cornerstone in the
•• Measures taken in stage A heart failure. management of HF.
−− Acute heart failure is treated by loop diuretics like
TREATMENT OF STAGE C (Patients with LV furosemide, torsemide, bumetanide. Chronic heart
dysfunction with current/prior symptoms) failure is treated by thiazide.
−− Treat diuretic resistance by
•• Diuretic. –– IV administration of diuretics.
•• ACE inhibitors. –– Use of >2 diuretics in combination (furosemide +
•• β-blockers (unless contraindicated). metolazone).
•• Aldosterone antagonist—Spironolactone/eplerenone –– Use of short-term dobutamine/dopamine to
when EF < 35% who are symptomatic despite standard increase the renal blood flow.
antifailure therapy (diuretic, β-blocker and ACEI). −− Weigh the patient daily to select and adjust the dose
•• Combination of hydralazine with isosorbide dinitrate. of diuretics.
•• Digitalis. •• ACE inhibitor— Indicated in all patients with left heart
•• Withdrawal of drugs known to adversely effect the dysfunction or left heart failure and it increases life
clinical status of patients (NSAIDs, antiarrhythmic drugs expectancy.
and CCB).
•• Immunization with influenza and pneumococcal Contraindications of ACEI—
vaccine may be encouraged. • Angioneurotic edema
• Anuric renal failure
PLUS • Creatinine >3 mg/dL
• K+ >5.5 mmol/L
•• Measures taken for patients in stage A and stage B • Bilateral renal artery stenosis
heart failure. • Pregnancy
In contrast with the recommendation for stage B • Hypotension
patients the guidelines support the use of moderate sodium Enalapril—5–40 mg/day, ramipril—1.25–20 mg/day.
• Use ARB who develops angioedema or cough with ACE inhibi-
restriction as well as daily measurement of weight.
tor [losartan/valsartan/irbesartan/candesartan/telmisartan/
The patient should not engage himself in heavy labor olmesartan]
or exhaustive sports.

TREATMENT OF STAGE D (Patients with  ombination of ACEI with ARB is probably better
C
than ACEI Alone.
refractory end-stage heart failure)
•• β-blockers—It is the only drug that reduces the
•• Meticulous identification and control of fluid retention. morbidity and mortality associated with heart failure
•• Continuous intravenous inotropic support. and increases life expectancy.
•• Aortic counterpulsating balloon therapy specially in
acute VSD and MR. • Used in all NYHA Class-II and III patients with systolic heart
failure
•• Hospice care.
• Use together with ACE inhibitor and diuretic
•• Cardiac transplantation/assisted mechanical device. • Metoprolol—To start with 12.5 mg/day slow release form
gradually increase the dose over 4 weeks to reach a target
PLUS dose of 200 mg/day
•• Measures taken for the patient of stage A, stage B and • Bisoprolol : 1.25–10 mg/day
stage C heart failure. • Carvedelol : 3.125–50 mg/bid
52 Essentials of Internal Medicine

•• Digitalis—In patient with left ventricular systolic heart 5. Phosphodiasterase inhibitor—


failure along with diuretic, ACE inhibitor and β-blocker, −− Levosimendan—12 μg/kg loading dose followed by
digitalis can be added. Specially useful in patient with 0.1–0.2 mg/kg/min continuous infusion.
acute heart failure with AF. −− Milrinone—50 mg/kg loading dose followed by
0.25–0.75 mg/kg/min continuous infusion.
Contraindications of β-blocker These two agents stimulate myocardial contrac-
• Bronchospasm
• Bradycardia (<60 bits/min)
tility with systemic and pulmonary vasodilation. They
• Advance heart block and PR interval >0.2 S reverse the major hemodynamic abnormality associated
• Basal rales >10 cm above diaphragm with HF.
•• Device therapy—Patient of symptomatic HF (NYHA
Dose—0.25 mg/day (0.125 mg/day in old patient). class III and IV stage) despite optimal therapy with
•• Sympathomimetics QRS duration >120 mg require biventricular pacing
−− Dobutamine for cardiac resynchronization to stimulate both the
–– 2.5–10 μg/kg/min ventricle simultaneously and improve the ejection
−− Dopamine fraction.
–– 1–2 μg/kg/min causes renal and mesenteric
vasodilation. ACUTE DECOMPENSATED HEART FAILURE
–– 2–10 μg/kg/min causes β1 receptor stimulation but WITH PULMONARY EDEMA
little tachycardia.
Acute decompensated left heart failure with pulmonary
–– >10 μg/kg/min causes α1 receptor stimulation with
edema are medical emergency. LV dysfunction leads to
elevation of DBP. Peripheral vasoconstriction.
pulmonary congestion and systemic hypoperfusion.
Constant infusion leads to receptor downregulation
Cardiogenic shock is characterized by systemic hy-
so intermittent sympathomimetics therapy is
poperfusion due to severe depression of cardiac index
advised.
[<2.2 (L/min) m2] and sustained systolic arterial hypoten-
sion <90 mmHg inspite of raised PCWP >18 mm Hg.
SPECIAL MEASURES FOR CHRONIC Leading causes of acute decompensated HF and
HEART FAILURE pulmonary edema are the following—
•• Hydralazine and Isosorbide dinitrate combina- •• Silent myocardial infarction (most common) with
tion in patient who are intolerant to ACE inhibitor. or without VSD, chordal rupture, ventricular free wall
[Hydralazine—37.50 / ISDN—10 one tab tid. rupture.
•• Spironolactone (25–50 mg/day). •• Accelerated hypertension
Eplerenone 25–50 mg/day specially in NYHA class-IV •• Cardiomyopathy
heart failure patient. •• Endocarditis
•• Cardiac tamponade
•• Tachyarrhythmia
• Do not use CCB for treatment of hypertension or angina as it
has a negative ionotropic effect
At this stage, three basic hemodynamic determinants should be
searched for—
•• Antiarrhythmic therapy—Is not recommended for • Elevated LV filling pressure
patient with asymptomatic/nonsustained ventricular • Depressed cardiac output
arrhythmia. • Increase systemic vascular resistance.
−− Class-I antiarrhythmic—Should be avoided except Depending on these factors patients are divided into four
in life-threatening condition. categories—
• Profile A (warm and dry) (normal LV filling pressure with
−− Class-III antiarrhythmic—Specially amiodarone,
normal perfusion)—They are not congested, have normal
have no negative inotropic and proarrhythmic effect tissue porfusion, their symptoms are due to hepatic or
and may be used not for prevention of sudden death pulmonary disease or myocardial ischemia and should be
but for treatment of supraventricular arrhythmia. It treated accordingly.
also improves the success of electrical cardioversion. • Profile B (warm and wet) (elevated LV filling pressure wih
•• Implantable cardiac defibrillator (ICD) are highly normal perfusion)—These patients present with acute
pulmonary edema. Treatment of elevated filling pressure with
effective in treatment of sustained VT or VF. They have diuretics and vasodilators are required to reduce LV filling
also shown to reduce the incidence of sudden death, pressure. 
when they are implanted prophylactically in mild to
moderate HF (NYHA-II and III). Contd...
Heart Failure 53

Contd... Treatment
• Profile C (cold and wet) (elevated LV filling pressure with Management of acute decompensated heart failure with
decreased perfusion)—They have pulmonary congestion,
reduced cardiac output and elevated systemic vascular
pulmonary edema.
resistance. They are treated by intravenous ionotropic
agent with vasodilator property, e.g. dobutamine, low dose 1st line of management
dopamine, milrinone. These drugs increase the myocardial •• Oxygen by nasal catheter or by intratracheal intubation
contractility and decrease the peripheral resistance thereby as needed.
increase the cardiac output.
• Profile L (cold and dry) (normal or low LV filling pressure •• Nitroglycerin—0.4 mg × 3 dose by S/L route.
with decrease tissue perfusion)—They should be carefully •• Injection furosemide—0.5–1.0 mg/kg IV.
evaluated by right heart catheterization for elevated LV filling •• Injection morphine—2–4 mg/IV.
pressure. If LV filling pressure <12 mm Hg a cautious trial of Every effort should be made to identify the preci-
blood volume expansion by normal saline should be tried. pitating factor that leads to the development of acute
Therapy may not be successful if profound RV dysfunction or
decompensated heart failure to guide further therapy.
cardiorenal syndrome develops which is the usual cause of
death in hospital (approx 25%).
2nd line of management (guided by blood pressure)
•• If SBP >100 mm Hg injection nitroglycerine—10–29 μg/
•• Acute AR or MR min IV infusion.
•• Severe AS or MS •• If SBP = 70–100 mm Hg with sign and symptoms of shock,
•• Aortic dissection injection dopamine—5–15 μg/kg/ min IV infusion.
•• Pulmonary embolism •• If SBP = 70–100 mm Hg without sign and symptoms of
•• β-blocker or CCB overdose shock, injection dobutamine—2–20 μg/kg/min infusion.
•• Hyperglycemia and ketoacidosis •• If SBP <70 mm Hg with sing and symptoms of shock,
•• Pregnancy injection norepinephrine 0.5–30 μg/min IV infusion.
•• Dietary excess It should be started with very low dose then gradually
•• Infection. titrated upward to maximum dose up to 15 μg/min to
maintain systolic BP >90 mm Hg.
Management
3rd line of management (guided by etiology)
•• Clinical features
−− Aggravation or rapid onset dyspnea at rest •• Identify and treat reversible cause like
−− Tachypnea −− Severe HTN—By nitroprusside/nitroglycerine—IV
−− Tachycardia infusion.
−− Pulsus alternans −− AMI—By coronary angiography followed by
−− Cyanosis angioplasty or CABG.
−− Hypotension −− AMI with MR/VSD—Intraaortic balloon pump
−− Wheeze/ronchi followed by surgical repair.
−− Rales −− AMI with LBBB—Three chamber pacemaker
−− S3, S4 gallop. implantation. One lead in atrium, second lead in
•• Laboratory investigation right ventricle and the third one for simultaneous
−− Hypoxia in arterial blood gas. depolarization of left and right ventricle to be placed
−− Chest X-ray—Kerley’s B line and loss of distinct in coronary sinus. In this way resynchronization of
vascular margin. both ventricle is done to maximize the cardiac output.
−− Echo and color Doppler for determination of ejec- −− Avoidence of the offending agent.
tion fraction and structural heart disease. −− Appropiate management of tachyarrhythmia AFSVT,
−− Increase N–terminal pro-BNP—Diagnostic of heart VT, VF.
failure.
−− Measurement of PCWP (pulmonary capillary wedge
Drugs Used for Acute Decompensated Heart Failure
pressure) to differentiate high pressure from normal •• Diuretics
pressure pulmonary edema. −− Furosemide—40 mg Bid
−− Measurement of systemic vascular resistance. −− Torsemide—20 mg Bid
54 Essentials of Internal Medicine

−− Hydrochlorthiazide—25 mg OD −− Levosimendan—Bolus 12 μg/kg → 0.1–0.2 μg/kg/


−− Metolazone—5 mg OD/BD. min.
•• Intravenous vasodilators •• Intravenous vasoconstrictor
−− Nitroglycerin—20–200 mg/min −− Dopamine—5–15 μg/kg/min
−− Nitroprusside—10–350 mg/min −− Epinephrine—0.5–50 μg/kg/min
−− Nesiritide—2 mg/kg → 0.03 mg/kg min. −− Phenylephrine—0.3– μg/kg/min
•• Intravenous isotropic agent −− Vasopressin—0.05–0.4 U/min.
−− Dobutamine—1–2 μg/kg/min → 10 μg/kg/min. •• Mechanical and surgical intervension
Chronic infusion over 72 hour develops tachyphy- −− Intraaortic balloon counterpulsation.
laxis require higher dose. −− Percutaneous and surgically implanted LV-assisted
−− Milrinone—50 μg/kg/min bolus followed by 0.1– 0.75 devices.
μg/kg/min. −− Cardiac transplantation.
Chapter 6
Hypertension

Definition •• Malignant hypertension—When hypertension causes


papilledema, deteriorating renal function and encepha-
Elevation of systolic or diastolic blood pressure above the
lopathy—it is called malignant hypertension. The DBP
normal range is called hypertension. In 92–94% patients
is usually in stage–II (DBP >130 mm Hg) with retinal
no cause could be found out after extensive investigation
hemorrhage and exudate.
and is called essential hypertension and in the remaining
•• Accelerated hypertension—Defined as significant
6–8% patients hypertension is secondary to diseases of the
recent increase over previous level of hypertension
kidney or other endocrine organ and is called secondary
associated with vascular damage on fundoscopic
hypertension.
examination but without papilledema.
•• Orthostatic hypotension—It is defined by a fall of
systolic pressure >20 mm Hg or diastolic pressure >10 mm
Classification (according to JNC-7) Hg is response to assumption of upright posture from a
SBP DBP supine posture within 3 minutes. There should also be
Normal <120 <80 lack of compensatory tachycardiac seen in autonomic
Prehypertension 120–139 80–89 insufficiency in patient with diabetes and Parkinson’s
disease.
Stage–I 140–159 90–99
•• Isolated systolic hypertension—It is defined as SBP
Stage–II >160 >100 >140 mm Hg and DBP <90 mm Hg and staged appro-
priately. Systolic blood pressure increases steadily with
age by contrast diastolic blood pressure tends to decline
Classification of BP based on current European guideline
from about the age of 50–60 years. As a consequence
most person older than 60 years (75–80% in this age
SBP mmHg DBP mmHg
group) have isolated systolic hypertension.
Optimal <120 <80
Normal 120–129 80–84 TYPES OF HYPERTENSION
High normal 130–139 85–89
1. Primary (essential)—90–94%
Grade–1 HTN (mild) 140–159 90–99 2. Secondary—6–10%.
Grade–2 (moderate) 160–179 100–109 −− Etiology of secondary hypertension
Grade–3 (severe) ≥180 ≥110 a. Renal hypertension—
Isolated systolic HTN ≥140 <90
−− Renoparenchyma (2–3%)
−− Renovascular (1–2%).
b. Endocrine hypertension—
−− Primary hypereldosteronism (0.3%)
•• Labile hypertension—Those persons whose BP −− Cushing (0.1%)
sometimes but not always is in the hypertensive range −− Pheochromocytoma (0.1%)
are called labile hypertensive. −− OCP induced (0.5–1%).
56 Essentials of Internal Medicine

Table 6.1: Blood pressure measurement techniques Symptoms related to underlying disease
•• Polyuria

}
Method Notes Secondary to
•• Polydypsia
1. In-office–Length and Two readings, 5 minutes •• Muscle weakness hypokalemia in primary
width of the cuff should apart, sitting on chair •• Cramps/tetany hyperaldosteronism
be 80% and 40% of arm after 10 minutes
•• Weight gain Cushing’s disease
circumference respectively relaxation.
Confirm elevated reading
••
••
Emotional lability
Episodic headache
}

}
in contralateral arm.
Systolic leg pressure is •• Palpitation
usually 20 mm higher •• Diaphoresis
than systolic arm pressure •• Postural dizziness Suggest
•• Tremor, pallor/flash, pheochromocytoma
2. Ambulatory BP 1. Indicated for
monitoring evaluation of white nausea, vomiting.
coat hypertension
Signs
3. Patient self-check 2. Absence of 10–20%
•• Moon facies
decrease in BP during
sleep may indicate •• Truncal obesity } Suggest Cushing’s
increase CVD risk •• Muscular development in upper limb out of propor- tion
than that of lower limb—coarctation of aorta.
3. Provides
•• Rise in DBP when the patient goes from supine to erect
information on
response to therapy
posture—essential hypertension.
•• Fall (in absence of antihypertensive drug) of DBP on
4. May help to improve sudden standing from supine posture → secondary
adherence to
hypertension.
therapy and is useful
•• Height and weight—ideal BMI 18.5–24.9 kg/m2 (every
for evaluating white
coat hypertension
10 kg fall in weight cause fall in SBP by 5–20 mmHg.)
•• Pulse—
5. To assess patient
−− Whether palpable in all peripheral sites or not.
with resistant
−− When any radioradial/radiofemoral delay is present
hypertension
→ Suggest Takayasu disease/coarctation of aorta.
6. To assess adequacy • Neck vein—Engorgement or pulsation of neck vein is a
of 24 hour BP-control indicator of right ventricular functional status.
• Edema.
Signs and Symptoms •• Fundoscopic examination—
−− Detailed fundoscopic examination for hemorrhage
Symptoms related to exudate and papilledema.
1. Elevated BP •• Detail examination of CVS including auscultation of
2. Hypertensive vascular disease heart, palpation and auscultation of carotid artery.
3. Underlying disease in secondary hypertension. Evidence of LVH, LVF should be searched for. Search
for murmur over midline of trunk, palpable collateral
Symptoms (related to increased BP) vessel (from coarctation of aorta) should be done.
•• Patient may be asymptomatic. •• Palpation of abdomen for polycystic kidney.
•• Occipital headache (early morning)—most common •• Auscultation of abdomen and flanks for any murmur of
presentation. renal artery stenosis/coarctation of aorta. [Important for
•• Dizziness, palpitation and easy fatiguability. patient with hypertension below 30 years of age].
•• Impotence. •• Femoral arterial pressure should be recorded.
Symptoms due to hypertensive vascular disease
•• Epistaxis.
Investigations
•• Hematuria. •• Blood sugar, urea, creatinine, Hb, PCV and cholesterol.
•• Blurring of vision due to retinal changes. •• Urine—RE and ME for pus cell, RBC, epithelial cell, cast
•• Weakness/dizziness due to transient cerebral ischemia. and protein, glucose and blood.
•• Angina pectoris. •• Serum electrolyte—K+ and Na+.
•• Dyspnea—Due to CCF/ischemic heart diseases. •• ECG and USG of KUB.
Flowchart 6.1: Management of essential hypertension Hypertension
57
58 Essentials of Internal Medicine
Hypertension 59

Additional • Drugs used for treatment of hypertension


•• TC and DC • Drugs (ABCD)
•• Electrolyte—Ca+2 and PO4–3 A. ACEI → Enalapril → 2.5–40 mg/day
•• Total lipid profile Ramipril → 1.25–20 mg/day
Quineapril → 5–80 mg/day
•• TSH
ARB → Losartan 25–50 mg OD/BD
•• Chest X-ray Telmisartan 40–80 mg
•• Echocardiography. Olmesartan 20–40 mg
B. β-blocker → Metoprolol 25–200 mg/day
Special screening for secondary hypertension Atenolol → 25–100 mg/day
1. Renovascular disease Bisoprolol → 5–10 mg/day
a. ACEI radionuclide renal scan (isotope renal scan). Nebibolol → 5–10 mg/day
b. Renal duplex Doppler flow study. C. CCB → Diltiazem—30–90 mg QID nifidipine 20 mg TDS
c. MRI and angiography. Amlodipine—2.5–10 mg/day; verapamil 40–240 mg/day
D. Diuretic—Frusemidc 40–80 mg
d. Renal vein renin study.
Thiazide → 12.5–25 mg/day
2. Pheochromocytoma Indapamide → 2.5 mg/day
−− 24 hour urinary assay for creatinine, metanephrine Metolazone → 2 mg/day
and catecholamines.
3. Cushing’s—Serum cortisol assay.
−− Overnight dexomethasone suppression test for
MALIGNANT HYPERTENSION
serum cortisol (normal <5 mg/dL).
−− 24 hour urine cortisol (normal <100 mg) and It is a syndrome associated with an abrupt increase in
creatinine. blood pressure. Clinically associated with progressive
4. Primary aldosteronism retinopathy (arteriolar spasm, hemorrhages, exudate and
−− Plasma aldosterone—Renin activity ratio—High. papilledema), deteriorating renal function (proteinuria,
microangiopathic hemolytic anemia) and encephalopathy.
TREATMENT OF HYPERTENSION The absolute level of BP is not as important as its rate
of rise.
Hypertension is the most common condition seen in Pathologically it is associated with—(a) diffuse
primary care and leads to myocardial infarction, stroke, necrotizing vasculitis, (b) arteriolar thrombi and (c) fibrin
renal failure and death if not detected early and treated deposition in arteriolar wall.
appropriately. Patients want to be assured that blood •• Less than 1% of all hypertensive patients (both essential
pressure (BP) treatment will reduce their disease burden. and secondary) developed malignant hypertension.
There is strong evidence to support treating hypertensive •• Average age of diagnosis is 40.
persons aged 60 years or older to a BP goal of less than •• Male predominate over female.
150/90 mmHg and hypertensive persons 30 through 59 •• With effective antihypertensive therapy life expec- tancy
years of age to a diastolic goal of less than 90 mmHg; greater than 5 years is not uncommon.
however, there is insufficient evidence in hypertensive
persons younger than 60 years for a systolic goal, or in
CLINICAL FEATURES of Malignant HP
those younger than 30 years for a diastolic goal, so JNC-8
recommends a BP of less than 140/90 mmHg for those 1. Manifestations of hypertensive encephalopathy are,
groups based on expert opinion. The same thresholds e.g. headache, vomiting, visual disturbances including
and goals are recommended for hypertensive adults with transient blindness, paralysis, convulsion, stupor and
diabetes or nondiabetic chronic kidney disease (CKD) coma.
as for the general hypertensive population younger than These manifestations are due to spasm of cerebral
60 years. There is evidence to support initiating drug vessel and cerebral edema.
treatment with an (1) angiotensin-converting enzyme 2. Cardiac decompensation resulting in heart failure.
inhibitor, (2) angiotensin receptor blocker, (3) calcium 3. Rapidly declining renal function.
channel blocker, or (4) thiazide-type diuretic in the Exact pathogenesis of malignant hypertension is not
nonblack hypertensive population, including those with known.
diabetes. In the black hypertensive population, including Two separate pathology are observed
those with diabetes, (a) a calcium channel blocker or −− Diffuse necrotizing vasculitis.
(b) thiazide-type diuretic is recommended as initial therapy. −− Generalized arteriolar fibrinoid necrosis of the walls
There is moderate evidence to support initial or add-on of small arteriole (which can be reversed by timely
receptor blocker in persons with CKD ACEI or ARB as to antihypertensive therapy) contribute to the other
improve kidney outcomes. associated signs and symptoms.
60 Essentials of Internal Medicine

Pathophysiology of Malignant HTN •• Preeclampsia—Hydralazine—10–50 mg IV at 30


minutes interval.
•• Cerebral vasodilation due to marked elevation of blood Methyl dopa
pressure causes loss of autoregulation of cerebral blood Labetolol—100 mg bd
flow and produces cerebral encephalopathy. •• Adrenergic crisis—Phentolamine and nitroprusside.
•• Elevated level of plasma renin and aldosterone are •• Aortic dissection—Nitroprusside, esmolol and
responsible for vascular damage. labetolol.
•• Microangiopathic hemolytic anemia is the cause of
deterioration of renal function. INAPPROPRIATE HYPERTENSION/
(SECONDARY HYPERTENSION)
Table 6.2: Drugs used in treatment of hypertension with indication DIAGNOSTIC FEATURES THAT FAVOR
and contraindication
Inappropriate HTN
Class of Compelling Compelling
drugs indication contraindication •• Age of onset of HTN <20 years or >50 years.
Diuretic HF, ISH and elderly person Gout •• BP >180/110.
•• Poor response to therapy despite good compliance.
β-blocker Angina, AMI and Asthma, COPD and heart
tachyarrhythmia block •• Evidence of target organ damage at diagnosis—
−− Fundoscopy—Showing retinopathy of grade II or
ACEI HF, LV dysfunction, AMI Pregnancy, hyperkalemia,
and diabetic nephropathy bilateral renal artery
higher grade.
stenosis, serum creatinine −− Serum creatinine >1.5 mg%.
>3 mg% −− Cardiomegaly.
Calcium Angina, elderly person Heart block, heart failure −− LVF.
antagonist and ISH
ARB Same as ACEI and ACEI- Same as ACEI Features Indicative of Secondary HTN
induced cough and
•• Unprovoked hypokalemia.
angioneurotic edema
•• Abdominal bruit.
•• Variable blood pressure at different limb with
Drugs for Treatment of Hypertensive Emergencies tachycardia, sweating and tremor.
Although blood pressure should be lowered rapidly but •• Family history of renal disease.
overaggressive lowering of BP may precipitate cerebral
ischemia or infarction. CAUSES OF SECONDARY HYPERTENSION
The initial goal of therapy is to lower the BP by 25%
•• Renal—
within minutes to 2 hour or the BP in the range of 160/100–
−− Renoparenchymal diseases—
110 mmHg. This can be done by—(a) nitroprusside,
–– AGN (acute glomerulonephritis)
(b) labetolol and (c) nicardipine (d) nitroglycerin.
–– Chronic nephritis
In malignant hypertension without encephalopathy the
–– PCKD (polycystic kidney disease)
goal BP can effectively be achieved with frequent dosing
–– Diabetic nephropathy
of short-acting oral agent like captopril, clonidine and
–– Hydronephrosis.
labetolol.
−− Renovascular diseases—
Parenteral Drug for Hypertensive Emergencies –– Renal artery stenosis (arteriosclerosis and fibro-
mascular dysplasia).
•• Hypertensive encephalopathy— Nitroprusside—2–10 –– Internal vasculitis.
μg/kg/minutes IV for 10 minutes. Nicardipine—5–15 mg −− Renoprival.
IV titrated by 2.5 mg/hour. Labetolol—20 mg IV over −− Renin-producing tumor.
2 minutes then 40–80 mg at 10 minutes interval up to •• Endocrine—
maximum 300 mg total. −− Acromegaly
•• Malignant HTN—Labetolol, nicardipine, nitroprusside, −− Hypothyroid
enalaprilat—0.625–1.25 mg IV over 5 minutes 6–8 −− Hyperthyroid
hourly. −− Hyperparathyroid.
•• Stroke—Nicardipine, labetolol and nitroprusside. −− Adrenal—
•• AMI/UA—Nitroglycerine—5–200 μg/min, nicardipine, –– Cortical—Cushing’s syndrome, Conn’s syndrome,
labetolol and esmolol. CAH (congenital adrenal hyperplasia).
•• LVF—Nitroglycerine, enalaprilat and loop diuretic. –– Medullary—Pheochromocytoma.
Hypertension 61

−− Extraadrenal—Chromaffin tumor. −− β-blocker for 10 days


−− Carcinoid tumor. −− ACE inhibitor for 1 day
−− Exogenous hormone—OCP (oral contraceptive pill), −− Restriction of sodium intake for 4 days.
glucocorticoid, mineralocorticoid, erythropoietin,
tyramin-containing food, sympathomimetic (nasal Features of renoparenchymal hypertension
decongestant, NSAID, MAO inhibitor, cocaine). Clinical features—Enlarged kidney (bimanually palpable
•• Coarctation of aorta and ballotable kidney seen in PCKD and hydronephrosis).
•• Pregnancy-induced hypertension
•• Stress Investigations
•• Obstructive sleep apnea •• Urine analysis—RBC, WBC, cast, proteinuria, increase
•• Increased intravascular volume. in specific gravity.
•• Serum creatinine >1.5 mg%.
History •• USG (Diagnostic of PCKD, hydronephrosis and granular
contracted kidney)—Contracted kidney with increase
•• Age— <20 year >50 year. cortical echogenicity with loss of corticomedullary
•• Onset—Abrupt onset. differentiation—suggestive of renoparenchymal
•• Family history—Positive. disease.
•• History of therapeutic failure. •• Isotope renogram.
•• History of headache, palpitation, nausea, vomiting, •• Renal biopsy.
chest pain, nervousness, tremor coming in episodic
manner—Pheochromocytoma. Features of pheochromocytoma-associated hypertension
•• History of atherosclerotic disease—Smoker, worsening
of renal function with history suggestive of recurrent
Clinical features
•• Sweating, palpitation, pallor, weight loss, tremor,
flush pulmonary edema—renovascular HTN.
arrhythmia, headache, anxiety, nausea and vomiting.
•• History of OCP and other drugs.
•• May be associated with MEN2B and neuro- fibromatosis.
•• History of diabetes.
•• Orthostatic hypotension.
•• History of chronic renal disease (e.g. oliguria, polyuria
•• Sudden paroxysmal hypertension.
and hematuria).
•• Palpable adrenal mass (rarely).
Examination and Investigation Investigations
•• Estimation of free catecholamine in blood and urine.
Features of renovascular hypertension •• Metanephrine concentration in plasma and urine (most
•• Abdominal bruit sensitive).
•• Advanced fundal change •• VMA in urine.
•• Deterioration of renal function with ACEI. •• CT/MRI, PET scan—For detection of adrenal tumor.
•• MIBG (metaiodobenzyl guanidine) scan for deter-
Basic investigations
mination of source of catecholamine/for ectopic source.
•• Captopril-enhanced renal scan.
•• Catecholamine estimation in adrenal venous sampling.
•• Duplex-Doppler renal artery flow study.
•• MR-angio of renal arteries and kidney with gadolinium
enhancement. Features of Coarctation of Aorta
•• Suzman sign—Pulsation over the inferior angle of
Special investigation features are as follows
scapula.
•• Low sodium and low potassium with high renin.
•• Differential cyanosis (upper half of body is red while
•• Secondary hyperaldosteronism.
leg and toe are cyanosed) with PDA.
•• Moderate proteinuria.
•• SBP difference in arm and leg >20 mm Hg.
•• Serum creatinine >1.5 mg%.
•• Bruit over aorta.
•• >1.5 cm difference in kidney size on USG.
•• MR-angio/CT-angio for evaluation of renal blood flow.
•• Ratio of renal vein renin with IVC renin >1.5. or If the Investigations
ischemic kidney liberates 1.5 times higher renin as •• X-ray chest—‘3’ sign—Notching of ribs due to coarctation.
evidence by renal vein renin study then benefit will be •• Aortogram—Diagnostic.
obtained from surgical intervention on the ischemic kidney. •• Echo/CT.
Care to be taken to prepare the patient properly •• Doppler.
before renal vein blood sampling by discontinuing renin •• CT angio/MR angio is diagnostic (by noninvasive
suppressing drugs. method).
62 Essentials of Internal Medicine

Features of Cushing’s Syndrome •• Adrenal carcinoma


•• Ectopic malignancy (ovarian arrhenoblastoma).
•• Typical clinical features—Moon facies, acne and truncal
obesity.
Clinical Features
−− Investigations
–– 24 hours urine cortisol below 100 mg rules out •• Headache.
Cushing’s. •• Muscle weakness, tetany, muscle cramp, fatigue, polyu-
–– Overnight dexamethasone suppression test— ria and polydipsia.
Measurement of plasma cortisol at 8 AM. After •• Diastolic hypertension.
administration of 1 mg dexamethasone at bed •• Glucose intolerance.
time—plasma cortisol below 5 mg/dL, rule out
Cushing’s. Investigations to Establish Conn’s Syndrome
•• High dose dexamethasone suppression of plasma •• Increase sodium, decrease potassium, decrease rennin
cortisol. and increase aldosterone in serum.
•• Late night salivary cortisol is also a sensitive and •• Serum aldosterone >555 p mol/L.
convenient screening test. •• Aldosterone : Renin ratio remains high (>30 : 1).
•• CT/MRI of abdomen and pituitary. •• ECG—Cardiomegaly, LVH, U-wave (in ECG), arrhythmia
•• Petrosal venous sampling—For ACTH. and ventricular ectopic.
•• Adrenal venous sampling—For cortisol.
Investigation to Determine the Side of Tumor
Features of Conn’s Syndrome (primary •• High resolution CT/MRI to determine the side of
hyperaldosteronism) adrenal tumor because surgical removal of unilateral
tumor reduces arterial blood pressure.
Causes
•• Bilateral adrenal venous sampling for measurement of
•• Adrenal adenoma (60–70%) plasma aldosterone for differentiating unilateral from
•• Bilateral adrenal hyperplasia bilateral primary aldosterone.
Chapter 7
Congenital Heart Diseases

ATRIAL SEPTAL DEFECT (ASD) HEMODYNAMIC ALTERATION


•• Anatomically ASD are of four types •• Left to right shunt through ASD occurs at very minor
−− Osteum primum type (AV septal defect/ endocardial pressure difference; hence silent on auscultation.
cushion defect) the defect located adjacent to •• RA receives additional amount of blood (apart from SVC
atrioventricular valve either of which may be or IVC) from LA. So, there is enlargement of RA in size.
deformed and regurgitant. Common in Down’s •• This increased amount of blood when passes through
syndrome associated with VSD. normal-sized tricuspid valve produce a delayed di-
−− Osteum secundum type—Osteum secundum type astolic murmur (DDM) which is audible at left lower
of defect is 10 times more common than osteum sternal border.
primum type. • RV also enlarges in size and due to passage of large
This is the most common type of ASD located at volume of blood through normal size pulmonary orifice,
fossa ovalis (associated with fetal alcohol syndrome) a pulmonary ejection systolic murmur is produced.
midseptal in location and should not be confused The P2 component of second sound is delayed due to
with patent foramen ovale. excess blood flow through pulmonary valve both during
This type of defect is due to— inspiration and expiration causing wide fixed splitting
–– Either due to excessive resorption of septum of S2 without any change in the gap between A2 and P2
primum. during inspiration and expiration.
–– From deficient growth of septum secundum.
–– May be associated with total anomalous pulmo- Clinical Features
nary venous connection (TAPVC).
•• The degree of symptoms and the age of its appearance
−− Sinus venosus type—Located high in atrial septum
is related to the size of ASD.
near the entry of superior vena cava associated with
•• Large ASD (pulmonary flow/systemic flow >2) may
anomalous pulmonary venous connection from right
cause CCF and failure to thrive in an infant.
lung to superior vena cava or right atrium.
•• Undetected ASD without significant shunt pulmonary
−− Coronary sinus defect.
flow/systemic flow >1.5 probably causes symptom in
adulthood.
PATHOPHYSIOLOGY of ASD
In any type of ASD the degree of left to right shunt depends Symptoms
on
•• Size of the defect. •• Patients are generally asymptomatic except physical
•• Relative diastolic feeling property (diastolic compliance) under development.
of both ventricle. •• Mild effort intolerance is present.
•• Any condition causing decreased left ventricular •• Frequent chest infection usually develop with large
compliance, e.g. systemic HTN, cardiomyopathy and size asd.
MI. •• CCF is rare.
•• Any condition causing increased LA pressure— MS •• Beyond 4th decade
and MR. −− Atrial arrhythmias may develop
64 Essentials of Internal Medicine

−− PAH usually seen •• Sinus venosus ASD


−− Bidirectional or right to left shunt may be present. −− Atrial ectopic with 1st degree heart block.
Patient of high altitude due to hypoxemia develop PHTN
at younger age. Echocardiography
In older age group left to right shunt increases due to Shows the size of the chamber and the defect can be
reduced compliance of left ventricle. measured.

Other Examination Complications


•• Parasternal impulse (due to RVH). Development of pulmonary arterial HTN, rare below the age of
•• Palpable systolic thrill in left 2nd space due to increased 20 years, recognized by disappearance of systolic and diastolic
flow through pulmonary artery. murmur and appearance of a constant loud pulmonary
•• Mild to moderate cardiac enlargement. Apex—RV type. ejection click and loud P2. Second heart sound remains
•• S 1 is normal or accentuated due to loud tricuspid to be wide and fixed split (without respiratory variation).
component.
•• S 2 is widely split and the split is fixed without Treatment
respiratory variation. P2 is accentuated and widely
transmitted along left sternal boarder upto apex. •• Medical management
•• Ejection systolic murmur of grade III or less, over −− Treatment of chest infection
the left 2nd and 3rd interspace (flow murmur through −− Treatment of infective endocarditis
pulmonary artery), may be transmitted all over the −− Treatment of SVT
chest. −− Treatment of CCF.
•• DDM at the left lower sternal boarder (tricuspid flow •• Surgical management—Risk of operation is very low
murmur due to excess flow). and even patients are operated above 40 years of age.
•• Presence of pansystolic murmur at apex in a patient Ideal age for operation is between 2–5 years.
with ASD suggest— The defect is closed by a—
−− Osteum primum type defect (other features are left −− Decron patch/patch of pericardium
axis deviation in ECG > –30° associated with MR, TR −− Direct suturing.
and VSD). Using heart lung bypass, the operation may be done
−− Floppy mitral valve (along with ASD). below 2 years of age by application of hypothermia causing
−− Rheumatic MR (right axis deviation in ECG). CAC (complete arrest of circulation).
−− ASD with a cleft in the mitral valve.
VENTRICULAR SEPTAL DEFECT (VSD)
X-ray features are as follows MORPHOLOGY of VSD
•• Mild to moderate cardiomegaly.
VSD constitute about 27% of all CHD either singly or in
•• RAH.
combination with other anomalies.
•• RVH.
•• Ventricular septum can be divided in four parts
•• Fullness of pulmonary bay due to prominent main
−− Inlet.
pulmonary artery.
−− Onlet.
•• Relatively small aortic kunckle (hypoplastic aortic
−− Trabecular.
kunckle).
−− Small membranous part lying just below the aortic
•• Plethoric lung field (pulmonary plethora is due to
valve.
increased flow through pulmonary circuit). Vascularity
•• VSD can be classified into 3 main categories.
diminishes if PHTN develops.
−− Muscular VSD—Bordered entirely by myo- cardium,
ECG features are can be trabecular, inlet or outlet in position/location.
−− Membraneous VSD (90%)—Most common type
•• Ostium secundum type of VSD.
−− Right axis deviation. It often have inlet, outlet or trabecular extension
−− RVH. and bordered in part by fibrous continuity between
−− RSR´ in V1. rSr´ is right preordial lead suggest leaflets of AV valve and aortic valve.
RV outflow tract enlargement. −− Doubly committed subarterial VSD—Situated
•• Osteum primum type in outlet septum. Common in Asian patient.
−− Left axis deviation in ECG. Counter clockwise Bordered by fibrous continuity between aortic and
rotation of heart and RV conduction defect. pulmonary valve.
Congenital Heart Diseases 65

PATHOPHYSIOLOGY of VSD Complications and Prognosis of VSD


•• Restricted VSD—Produce significant pressure gradient •• Restrictive VSD—Spontaneous closer, no hemo-
between LV and RV. dynamic burden.
Pulmonary/aortic/systolic pressure ratio is <0.3. Small −− High-risk of endocarditis.
shunt (pulmonary/systemic flow <1.4). •• Perimembranous defect and doubly committed
•• Moderately restricted VSD Pulmonary/aortic systolic VSD—
pressure ratio is <0.66. −− Progressive AR.
Moderate shunt (pulmonary : systemic flow = 1.4– −− Later development of subaortic and subpulmonary
2.2 : 1) stenosis.
•• Large (nonrestricted) VSD •• Moderately restrictive VSD
Pulmonary/aortic systolic pressure ratio is >0.66. Large −− LA, LV, dilation and dysfunction.
shunt (pulmonary systemic flow >2.2). −− Increase pulmonary vascular resistance.
•• Eisenmenger VSD—Right to left shunt. •• Nonrestricted VSD
Aortic/pulmonary/systolic pressure ratio is 1 : 1. −− Progressive rise in pulmonary vascular resistance
Pulmonary/systemic flow is <1 : 1. starting early in life.
−− Eisenmenger’s syndrome develop at later stage.
Natural History and Hemodynamics
Clinical Features in Pediatrics
Restrictive VSD cause very little hemodynamic alteration
and may close spontaneously in late childhood and •• Restrictive VSD—Present with murmur in the neonatal
sometimes in early adult life. age group only when pulmonary vascular resistance
Moderately restrictive/nonrestrictive VSD cause shuting falls.
of blood from LV to RV across ventricular septum. •• Large nonrestrictive VSD—Present at a later age due to
The flow of blood from LV to RV starts very early in equalization of pressure of both ventricle obviates the
systole even before closure of AV valve (S1) and continue generation of pansystolic murmur.
throughout the systole—even after closer of aortic valve (S2) −− Presents with breathlessness, congestive heart failure
as LV pressure is still higher than RV pressure. and failure to thribe at 2nd and 3rd month of life.
So a pansystolic murmur starting before S1 ends beyond −− Pulmonary ejection murmur due to increased flow
A2 completely masking it (A2). through pulmonary artery.
The shunted blood from LV almost directly enter the −− Middiastolic mitral rumble due to increased flow
pulmonary artery because both ventricle is contracting through mitral orifice.
simultaneously.
An ejection systolic murmur is heard over pulmonary Clinical Features in Adults
region due to increased flow of blood through the •• Small restrictive VSD are asymptomatic.
pulmonary artery. On examination—A harsh, high frequency pansystolic
In the background of pansystolic murmur at VSD murmur usually grade 3/6–4/6 with maximal intensity
site, pulmonary ejection systolic murmur cannot be at the left sternal boarder on left 3rd or 4th ICS.
well-recognized. But it can be recognized as selective •• Moderately restrictive VSD—Presents with dyspnea
transmission of ejection systolic murmur to the left 2nd usually triggered by atrial fibrillation.
space where its ejection character can be recognized. Apex—Displaced down and outward.
Increased pulmonary flow causes delayed loud P2 with Pansystolic murmur of grade 3/6–4/6 with a apical
wide variable split of S2. diastolic rumble and S3 due to increased flow through
Increased blood flow through the pulmonary circuit mitral valve.
produces pulmonary plethora on X-ray. •• Large nonrestrictive VSD with Eisenmenger—
Increased pulmonary flow produces left heart volume Central cyanosis, clubbing with pedal edema due to RVF.
overload. Sign of pulmonary hypertension—Right ventricular
Left atrial enlargement produces parasternal thrust. heave—
Accentnated S1 usually not appreciated at the bed side. −− Palpable and loud P2.
Early A2 is due to decrease LVET (left ventricular ejection −− Right-sided S4.
time). −− Pulmonary ejection click.
Increased flow across mitral valve produces a functional −− Soft ejection systolic murmur.
delayed diastolic murmur (differential diagnosis of murmur −− High pitch early diastolic murmur of pulmonary
of MS). regurgitation (Graham steell murmur).
66 Essentials of Internal Medicine

Investigations −− Obstructive—Thrill absent. S 2 is closely split. No


mitral DDM. N
o thrill or parasternal impulse.
ECG
•• The congenital right ventricular hypertrophy disappears Complications and Fate
slower than normal. •• CCF—Develops around 30–40 years of age.
Small restrictive VSD have normal ECG tracing. •• Infective endocarditis—It is the most common
Moderately restrictive/Nonrestrictive VSD— congenital lesion producting SABE.
•• Evidence of LA, LV volume overload and distension. •• Subvalvular pulmonary stenosis.
•• Deep Q, Tall R, Tall T, LV enlargement. •• PHTN.
•• Wide bifid/notched LA enlargement. •• AR due to prolapse of right coronary/noncoronary cusp.
•• Following repair there may be features of RBBB. •• Spontaneous closure—90% by 3 years.
Chest X-ray Treatment
•• Reflects the magnitude of the shunt and degree of
pulmonary vascular resistance. Medical management
•• Heart size is enlarged with LV type enlargement. •• Control of CCF—by diuretic and ACEI in child to
•• Pulmonary plethora. buy time prior to surgery for diminution of size or
•• Hypoplastic aorta. spontaneous closer.
•• LA - enlargement. •• Treatment of repeated chest infection.
•• In small/restrictive VSD pulmonary vasculature is •• Prevention and treatment of anemia.
normal. •• Prevention and treatment of infective endocarditis.
•• A moderate size shunt causes signs of left ventricular
dilation with some pulmonary plethora. Surgical management
Indications
Echocardiography •• CCF in early childhood and not responding to treatment.
Identify •• Large (left to right) shunt (Qp/Qs >1.4).
•• The location, size and hemodynamic consequence of •• Associated pulmonary stenosis.
VSD. •• Associated pulmonary HTN (>50 mm Hg).
•• Presence of associated AR and/ or LVOT obstruction. •• Increased LA/LV size.
•• Mitral valve motion.
•• Presence of pulmonary stenosis/RVOT obstruction. Relative Indications
•• Presence of pulmonary hypertension. •• Associated AR.
Cardiac catheterization is to be done for •• History of recurrent endocarditis.
•• Early surgical intervention is done at 3–9 months of age.
•• Measurement of pulmonary arterial pressure. •• In presence of evidence of PHTN (>50 mm Hg) surgery
•• Therapeutic percutaneous closure of VSD specially in is done at 2 years of age.
muscular VSD. •• In presence of evidence of CCF which is refractory to
medical treatment surgery is done at 1 year of age.
Assessment of Severity
Interventional Options and Outcomes
•• Small restrictive VSD—Pansystolic murmur with
normal S 2 (P 2-normal intensity, normally split S 2). •• Direct suturing.
Absence of DDM over apex. •• Patch (Dacron) repair is preferred. It has the following
•• Very small VSD—Ejection systolic murmur (small VSD advantages like—
acts as stenosing valve). −− High closure rate.
Functional systolic murmur that disappear when the −− Low perioperative mortality.
patient grows up. −− Patch leak is uncommon and seldom needs reop-
•• Short ejection systolic murmur eration.
−− RVOT obstruction. Soft P2 but delayed. Widely split •• Right atrial approach is preferred to right ventri-
variable S2. culotomy (complication RBBB).
−− Large nonrestrictive shunt. Loud and delayed P2 with •• Device closure by cardiac catheter, is useful in muscular
wide variable split. VSD and perimembranous VSD.
•• PHTN (P2 loud / accentuated) •• Eisenmenger syndrome is contraindication of surgery.
−− Hyperkynetic—Pansystolic murmur with thrill •• Yearly check up is necessary after surgery of with VSD
widely split—variable S2 and mitral DDM. with other complications.
Congenital Heart Diseases 67

Complications of Surgery •• As the systolic pressure difference between two ventricle


is very low, VSD remains silent (no murmur at the site
Risk of complication is <2% in surgery
of VSD).
•• Complete heart blocks
•• Right to left shunt is also silent as there is insignificant
•• Bifascicular blocks
pressure difference between RV and aorta.
•• RBBB
•• As RV is effectively decompressed by VSD, CCF never
•• Residual VSD or incomplete closer.
occur unless the patient is associated with other
abnormality like—anemia, infective endocarditis, HTN,
FALLOT’S TETRALOGY (TOF) unrelated myocarditis, AR and PR.
The four components of the defect in TOF:
•• Obstruction of right ventricular outflow tract. CLINICAL FEATURES of TOF
•• Outlet VSD. •• Patient may become symptomatic anytime after birth.
•• RVH. Neonates as well as infants may face anoxic spell.
•• Overriding of aorta (<50%). Cyanosis may be present from birth or may appear later.
The fundamental abnormalities are abnormal anterior
and cephaloid deviation of outlet septum in respect to Symptoms of TOF
trabecular septum.
1. Dyspnea on exertion (DOE)—The most common
The dominant site of obstruction of right ventricular
symptoms is DOE (dyspnea on exersion) and exercise
outflow tract is usually at the subvalval level of pulmonary
intolerance.
valve but sometime the whole right ventricular outflow tract
2. Squatting—It is the most common congenital lesion
may be atretic.
where squatting is noted. During exercise the systemic
•• Associated abnormality
resistance fall so more amount of blood from right
−− Right sideed aortic arch (25%).
ventricle is shunted to aorta and thereby flow through
−− The origin of anterior descending (anterior
pulmonary artery fall further and this cause increase in
interventricular) artery is from right coronary artery.
cyanosis and increase in dyspnea. Squatting increases
−− Absence of pulmonary valve.
the systemic resistance which diverts blood from aorta
to pulmonary artery and results in improvement of
PATHOPHYSIOLOGY of TOF cyanosis.
In the absence of alternative source of pulmonary blood 3. Anoxic spell—Mostly occurs after wakeing up from
flow the degree of cyanosis is directly proportional with— sleep or after exersion—child starts crying and
•• Severity of right ventricular outflow tract obstruction become dyspneic, bluer than before and may become
•• Level of systemic vascular resistance. unconscious or convulsion may develop. Frequency of
anoxic spell may vary from once in a few day to multiple
EPIDEMIOLOGY of TOF attacks in a day.

•• TOF accounts for 75% of all congenital cyanotic heart Signs of TOF
disease >2 years of age.
•• Cyanosis
•• Clubbing
NATURAL HISTORY of TOF
•• Neck vein with prominent a-wave.
Progressive hypoxemia is the most prominent feature
in the first few years of life. Survival into adult life with CVS
palliation or correction is possible.
•• Normal-sized heart.
•• Mild parasternal impulse.
HEMODYNAMIC ABNORMALITY of TOF
•• Systolic thrill over pulmonary artery present in less than
•• Physiologically pulmonary stenosis causes concentric 30% patient.
RVH. •• Normal S1.
•• Then the right ventricular pressure is greater than aortic •• Single S2, the audible sound is A2.
pressure then right to left shunt appear to decompress Delay in P2 due to RVOT obstruction.
RV. P 2 is reduced in intensity and is due to decrease
•• With increase in severity of PS greater will be the shunt, pulmonary pressure.
but the intensity of systolic murmur (which is due to PS) Late and soft P2 is generally inaudible in TOF since aorta
will decrease. is somehow anteriorly displaced.
68 Essentials of Internal Medicine

•• Ejection systolic murmur in left 2nd ICS which usually Symptomatic treatment
ends before S2 and is due to pulmonary stenosis.
•• Correction of anemia and other complicating factor that
•• Constant aortic ejection click due to dilated aorta.
may precipitate CCF.
•• In constant pulmonary ejection click due to valvular
•• Management of anoxic spell
PS.
−− Squatting.
−− Humidified 100% O2 by mask.
X-ray −− Morphine – 0.1–0.2 mg/kg IV.
•• Normal-sized heart with features of RVH (upturn apex, −− Correct acidosis by IV infusion NaHCO3.
absence of main pulmonary artery segment gives the −− Propranolol 0.1 mg/kg IV during cyanotic spell and
heart boot shape (Coeur-en-sabot). 0.5 –1 mg/kg every 4–6 hourly as maintenance dose.
•• Aorta is enlarged and in 30% cases right-sided which −− Vasopressor—Methoxamine may be used IM or IV.
is diagnosed by concave impression on right side of •• Management of arrhythmia—
trachea. −− Medical or catheter ablation.
•• Pulmonary fields are oligemic.
Palliation
ECG 3 types of operative treatment usually done.
•• Blalock- Taussig shunt (preferred method)
•• Right axis deviation Anastomosis of subclavian artery with pulmonary artery.
•• Feature of RVH Anastomosis is made with a goretex graft, usually done
•• T-wave is inverted in right precordial lead on the opposite side of aortic arch.
•• P-pulmonale may be present. •• Potts shunt—Descending aorta is anastomosed with
pulmonary artery.
ECHO •• Waterston’s shunt—Ascending aorta is anastomosed
with right pulmonary artery.
Can identify the followings: These 3 operations are usually done to prolong the
•• Overriding of aorta life and to increase the exercise tolerance.
•• RVH
•• RVOT obstruction Indications of Surgical Intervention
•• VSD. •• Children—
−− Symptomatic infants are now repaired at any age.
Complications of TOF −− Asymptomatic infants are repaired in the first 6
•• Anoxic spell which are potentially fatal. months of age.
•• Anemia may complicate the disease and may predispose –– This is done by transannular patch for en-
CCF. largement of RVOT.
•• Very prone to develop infective endocarditis. –– Balloon valvuloplasty of RVOT and pulmonary
•• Neurological complication are frequent and is due to artery is preferred in prematurity and marked
paradoxical embolism. hypoplasia of pulmonary artery.
−− Venous thrombosis develop in leg vein due to •• Adult (unoperated)—Surgical repair is still
sluggish circulation and polycythemia which may recommended as the results are gratifying.
dislodge and pass via VSD from right side to left •• Adult (palliative)—Seldom intended as a perma-
side and ultimately embolize in cerebral vessel nent strategy as palliated patients are at increased risk
causing cerebral abscess is called paradoxical of cyanosis and erythrocytosis (from gradual shunt
embolism. stenosis or development of pulmonary hypertension).
Brain abscess presents with headache, convulsion, •• Adult (repaired)—The following situation may warrant
vomiting with or without fever and neurological reoperation.
deficit. −− Residual VSD (with shunt >1.5 : 1)
−− Residual pulmonary stenosis
−− Severe pulmonary regurgitation
Management
−− Rapid enlargement of RVOT aneurysm
Treatment actually consist of: −− Significant AR—aortic root diameter >55 mm
•• Symptomatic treatment −− Progressive left ventricular dilatation.
•• Palliation Curative surgery—Consist of closing the VSD and
•• Curative surgery. resecting the RVOT obstruction.
Congenital Heart Diseases 69

PATENT DUCTUS ARTERIOSUS (PDA) −− Hepatomegaly


−− On auscultation–left-sided infraclavicular and
Introduction of PDA sometime interscapular systolic murmur over
back (occasionally continuous in nature).
Patent ductus arteriosus, derives from the left 6th primitive •• Full-term infant, children and adult
arch and connects the proximal left pulmonary artery to −− S mall PDA usually cause no symptom but may
descending aorta just (5–10 mm) distal to left subclavian present as endarteritis.
artery. −− On exam—Grade - 1/2 continuous murmur peaking
It is present in fetal life but functional closure of in late systole, best hard in left 2nd and 3rd ICS.
the duct occurs shortly after a term birth due to vaso- •• Moderate size PDA
constriction whereas anatomical closure from intimal −− Dyspnea and palpitation due to atrial arrhythmia.
proliferation and fibrosis takes several weeks afterbirth −− Louder continuous/mechinary murmur on 1st and
to complete. 2nd left ICS with LV type of apex and left-sided thrill.
PDA are present in 5–10% of term infants. Females −− When pulmonary HTN develops the diastolic
predominate over males as M : F = 1 : 3. component of murmur disappear.
•• Large PDA—Presents with short ejection—systolic
TYPEs of PDA murmur with cyanosis more over abdomen than in
PDA are categorized according to the degree of left to right hands (differential cyanosis due to reversal of shunt
shunt which is determined both by the size and length of in PDA).
the duct and the difference between systemic and vas- cular
resistance as follows— INVESTIGATIONs of PDA
•• Silent—Tiny PDA detected only by nonclinical measure
ECG
(e.g. Echo).
•• Small—Continuous murmur common, Qp/Qs <1.5 : 1 •• In infant—May be normal/demonstrate LVH/RVH or
(pulmonary flow : systemic flow). both.
•• Moderate—Continuous murmur uncommon Qp/Qs •• In full-term child and adult—
= (1.5–2.2): 1. −− Small PDA may present with normal ECG
•• Large—Qp/Qs >2.2 : 1. −− Moderate size PDA

}
•• Eisenmenger’s—Continuous murmur absent, subs- –– Notched P-wave
tantial pulmonary hypertension, differential cyanosis –– Deep Q
In V5,V6
and hypoxemia is present. –– Tall R
–– Peaked T
NATURAL HISTORY of PDA −− Large size PDA—produce RVH
PDA is common in preterm infants and delayed sponta- Chest X-ray
neous closure of PDA may be anticipated if the infant does
not succumb to other problem. •• In infant—Cardiomegaly with increased pulmonary
Full-term infant—Sometime full-term newborn have vascular marking. (differential diagnosis—hyaline
PDA because of relative hypoxia which contribute to membrane disease of lung).
vasodilatation of the duct. These include •• In full-term child and adult
1. Infant born at high altitude. −− Small duct—Normal chest X-ray.
2. Congenital malformation causing hypoxia. −− Moderate duct—Cardiomegaly with LVH
3. Malformation in which the PDA supply systemic –– With prominent aortic knuckle
circulation such as hypoplastic left heart syndrome. –– Increased pulmonary markings
Interrupted aortic arch and aortic coarctation. –– Sometimes calcification may be seen.
−− Large duct—Present with prominent aortic knuckle
characteristic of Eisenmenger syndrome.
CLINICAL FEATURES of PDA
•• Most preterm infant (birth weight <1.5 kg) have a PDA ECHO
of which 1/3rd is large enough to cause significant •• In infants—PDA can be imaged entirely from high
cardiopulmonary deterioration. parasternal and suprasternal notch view.
−− On examination •• In child and adult—Determine the size, pressure,
−− Bounding peripheral pulse degree of shunting with its physiological consequence.
−− Precordial pulsation It can measure LA and LV size to provide indirect
−− Multiple episode of apnea and tachycardia. evidence of the magnitude of left to right shunt.
70 Essentials of Internal Medicine

Treatment
1. Transcatheter device closer is the procedure of choice for duct smaller than 8 mm. Complete closer in achieved in >85% within 1 year.
Mortality is <1%
2. Surgical treatment : Surgical closer by ligation or division is the method of choice with difficult ductal morphology (calcified or
aneurysmal). Complete closer is achieved in 95%. Mortality >25%.
Differential diagnosis of continuous murmur
It includes all the condition capable of producing a contineous murmur over the precordium and also the conditions capable of producing
a combination of pansystolic murmur along with a early diastolic murmur
a. Coronary A-V fistula
b. Ruptured sinus Valsalva
c. Aortopulmonary window
d. Pulmonary AV fistula
e. Systemic A-V fistula over the precordium
f. Bronchial collateral
g. Peripheral pulmonary stenosis
h. Small ASD in combination with MS
i. Venous hump arising from TAPVC
Differential diagnosis of combined pansystolic and early diastolic murmur—
a. MR/TR with AR
b. VSD with AR
c. AS and AR—Not as continuous murmur because there is little gap in between the two murmurs
Chapter 8
Cardiomyopathy

Definition CLINICAL FEATURES of DCM


The cardiomyopathies are group of diseases that affect the Symptoms
heart muscles primarily and the changes in myocardium
are not secondary to ischemic, hypertension or congenital or •• Symptoms of left or right-sided heart failure develop
acquired valvular, coronary or pericardial diseases. gradually in most patient.
The diffuse myocardial fibrosis that accompanies multi- •• Vague chest pain may be present but typical angina
ple myocardial scar produced by extensive coronary artery does not occure.
disease can impair LV function and is frequently termed as •• Syncope due to arrhythmia or cerebral embolism from
‘ischemic cardiomyopathies’. heart is a rare finding.
This irrational use of the term should be avoided; the
term cardiomyopathy should be restricted to a condition Signs
primarily involving the myocardium. •• Systolic pressure is low. Diastolic pressure is more or
less normal.
Clinical Classification of •• Pulse pressure is narrow (decapitation of blood
Cardiomyopathies pressure).
•• JVP elevated.
•• Dilated—Left ventricular or right ventricular or •• Apex shifted down and out.
biventricular enlargement, impaired systolic function, •• S1 and S2 are soft. S3 and S4 are commonly present.
characterized by CCF along with arrhythmias and •• Murmur of MR or TR may be present.
embolization may be present.
•• Restrictive—Endomyocardial scarring or infiltration Investigation
resulting in restriction to ventricular filling.
•• Hypertrophic—Disproportionate LV hypertrophy, •• Chest X-ray—Shows enlargement of cardiac silhouette.
involving IVS more frequently than free wall, with or Lung field shows evidence of pulmonary venous hyper-
without intraventricular pressure gradient. tension and interstitial or alveolar edema.
•• ECG—Shows sinus tachycardia, atrial fibrillation,
ventricular arrhythmias, diffuse nonspecific ST-T
DILATED CARDIOMYOPATHY
changes or intraventricular conduction block and low
About 33% of all cases of CHF is due to dilated cardio- voltage complexes.
myopathy. Systolic pump function is impaired leading to •• Echo is the best method for diagnosis. It shows LV
progressive cardiac enlargement with hypertrophy which dilatation (LVEDD >7 cm) with thinned wall and
is known as ‘remodeling’. reduced ejection fraction with hypokinesia of both
Although no cause is apparent in many cases, dilated ventricles.
cardiomyopathy is usually produced by toxic, metabolic or •• Cardiac catheterization and coronary angio is done to
infectious agent (viral). exclude IHD.
A reversible form of DCM may be found in alcoholic, •• Brain natriuretic peptide (BNP) is elevated due to heart
peripartum, thyroid disease, cocaine abuse. 20–40% failure.
have familial form of disease. The disease is genetically
heterogenous and most commonly autosomal dominant, Prognosis
but autosomal recessive and mitochondrial or X-linked Majority of patients show rapid down hill course specially
inheritance is also found. over 55 years of ages and die within 3 years.
72 Essentials of Internal Medicine

Spontaneous improvement and stabilization seen in •• Sudden death can occur during or after physical
25% of patients. Death in dilated cardiomyopathy is due to— exercise, probably due to arrhythmia.
•• Congestive heart failure (CHF)
•• Ventricular arrhythmias Signs
•• Embolism. •• Double or tripple apical impulse.
•• Rapidly rising carotid arterial pulse.
Treatment •• S4 is usually present.
•• Standard therapy of heart failure with diuretic, digitalis, •• Diamond-shaped ejection systolic murmur begins well
ACEI, β-adrenergic blocker and spironolactone. after S1 best heard at lower left sternal border, due to
•• Alcohol—To be avoided. dynamic LV outflow tract obstruction and a holosystolic
•• About 33% of patients who have conduction defect blowing murmur at apex due to MR may be present.
(RBBB/LBBB) biventricular pacing improves symptoms.
•• Immune suppressive therapy—not beneficial. Investigations
•• Antiarrhythmic agent is best avoided for fear of its •• ECG findings are the followings:
proarrhythmic effect. CCB and NSAID are best to be −− LVH.
avoided. −− Widespread deep and broad Q simulating old MI but
•• Cardiac transplantation should be considered who are is due to septal hypertrophy.
refractory to medical therapy.

}
−− SVT, atrial fibrillation.      Can be demon-
−− VT. strated by holte
HYPERTROPHIC CARDIOMYOPATHY monitoring
It is characterized by left venticular hypertrophy (LVH) •• Chest X-ray—
(typically with nondilated chamber) and not secondary to −− May be normal.
obvious cause like HTN or aortic stenosis. −− Mild to moderate cardiomegaly is common.
Two characteristic features are— •• Echocardiography is the best method for diagnosis
•• Asymmetric LVH with striking regional variation shows the followings:
in the extent of hypertrophy in different portions of −− LVH.
LV often with preferential hypertrophy of IVS called −− IVS is 1.3 times or more thicker than posterior wall
asymmetric septal hypertrophy (ASH). Other group and has ground glass appearance due to myocardial
shows disproportionate hypertrophy. fibrosis.
•• Dynamic LV outflow tract obstruction as evidenced −− SAM (systolic anterior motion of mitral valve) is seen
by pressure gradient due to midsystolic apposition of with MR and pressure gradient.
anterior mitral leaflet against the hypertrophied septum −− LV cavity size is small with vigorous posterior wall
[due to systolic anterior motion (SAM) of mitral valve]. motion and reduced septal excursion.
Only 33% of patients of HCM demonstrate outflow
tract pressure gradient at rest and 66% after provocative
Cardiac catheter
test. It is not essential for diagnosis but two typical features are
•• Elevated LV diastolic pressure.
Genetic Consideration of HCM •• Systolic pressure gradient between body and sub-
aortic region of LV.
Half of the patients have autosomal dominant transmission.
Treatment
Clinical Features •• β-blocker is used for angina and syncope but does not
give protection form sudden cardiac death.
Symptoms
•• Amiodarone for arrhythmia like SVT and VT.
•• Many patients are asymptomatic. •• Verapamil or diltiazem may reduce the stiffness of the
•• Most common symptoms are ventricle and reduce the diastolic pressure and improve
−− Dyspnea—Due to increased stiffness of LV wall disastollic filling.
which impairs LV filling leading to elevated LV •• Atrial fibrillation must be treated either by β-blocker
diastolic and left atrial pressure. or ablation of AV node and insertion of a pacemaker
−− Angina. when sinus rhythm cannot be sustained.
−− Fatigue. •• Surgical myotomy or myectomy of the hypertro-phied
−− Syncope: Symptoms are not closely related to septum—results in long-lasting improvement in 75%
outflow pressure gradient and are probably related of severely symptomatic patient with large pressure
to diminished ejection fraction and arrhythmia. gradient.
Cardiomyopathy 73

•• Infarction of the IVS by intraarterial ethanol injection Investigation


reduces obstruction and improves symptoms.
•• ECG—Low voltage, nonspecific ST-T changes and
•• Digitalis, diuretic, nitrates, vasodilator, β-adrenergic
various arrhythmias.
agonist and alcohol are avoided particularly in those
•• Echo—Symmetrically thicked LV wall with slightly
with outflow tract pressure gradient.
reduced ventricular volume and systolic function.
•• Implantable cardioverter defibrillator (ICD) should
•• Catheter—Decreased cardiac output with elevated
be considered in patients with high-risk profile to
RV and LV end-diastolic pressure and a dip-and-
prevent sudden cardiac death due to arrhythmia.
plateau configuration of the diastolic portion of the
RESTRICTIVE CARDIOMYOPATHY ventricular pressure pulse (resembling constrictive
pericarditis).
The hallmark of restrictive cardiomyopathies is diastolic
dysfunction. The rigid ventricular wall impede ventricular Differential Diagnosis
filling. Myocardial fibrosis, hypertrophy and infiltration
are the causes of restrictive cardiomyopathy. •• Constrictive pericarditis
Infiltrative disease like amyloid, hemochromatosis, −− RV transvenous endomyocardial biopsy—reveals
glycogen deposition, endomyocardial fibrosis, sar- myocardial infiltration or fibrosis.
coidosis, Fabry’s disease, eosinophilia and scleroderma, −− CT/MRI —Shows thickened pericardium in
radiation, malignant infiltration are the common causes constrictive pericarditis.
of secondary restrictive cardiomyopathy.
Treatment (Usually Disappointing Except)
CLINICAL FEATURES of RC •• Hemochromatosis by deferoxamine (iron-chelating
Symptoms agent) continuous SC infusion.
•• Fabry’s disease—Infusion of galactose. Stimulate the
Most prominent symptoms are activity of deficient enzyme with attendant improvement
1. Exercise intolerance in cardiac function.
2. Dyspnea. •• Chronic anticoagulation—To reduce the risk of
embolization.
Signs •• Endomyocardial fibrosis—Surgical excision of fibrotic
•• Raised JVP does not fall normally or it may actually rise endocardium and replacement of A-V valve.
during inspiration (Kussmaul’s sign). •• Eosinophilic endomyocardial disease
•• Pedal edema. −− Diuretic.
•• Enlarged tender liver. −− Afterload reducing agent.
•• Ascites. −− Anticoagulation.
•• Apex is easily palpable. −− Glucocorticoid and cytotoxic drug like hydroxy- urea
•• Heart sounds are diminished in intensity. improves survival.
•• MR usually present. −− Surgical treatment like endomyocardial fibrosis.
Chapter 9
Tachyarrhythmias

Three basic mechanisms responsible for tachyarrhythmia SITE OF ORIGiN of APC


are—
APC usually arises from orifice of superior vena cava,
•• Increase automaticity—It is due to—
pulmonary vein, coronary sinus, crista terminalis, mitral
−− An increased slope of phase ‘4’ of the action potential.
and tricuspid valve annuli, left and right atrial appendages.
−− Decrease in the threshold for phase ‘O’ of the action
Configuration of P-wave in APC differs from that arising
potential.
from SA node but APC arising from right atrial appendages,
•• Triggered activity (Fig. 9.1)—It is due to—
SVC and superior aspect of crista terminalis region may
−− Early after depolarization (EAD) during phase ‘3’ of
mimic P-wave of sinus origin.
action potential and is due to alteration of plateau
Usually APC has long PR interval as the impulse is
current, responsible for VPC that triggers TDP.
conducted through muscle bundle but when the areas
−− Delayed after depolarization (DAD) during phase ‘4’
of APC is near AV-node it is conducted rapidly through
of action potential due to intracellular accumulation
AV node and the partially recovered His-Purkinje system
of calcium responsible for atrial, junctional and
producing RBBB or LBBB pattern. The wide ORS with
fascicular tachyarrhythmias due to digoxin toxicity.
P-wave overlap looks like VPC.
•• Reentry—The basic requirement for reentry is the
As APC resets the sinus node the pre and post APC-RR
presence of two pathways that have heterogenous
interval is less than twice sinus PP interval.
electrophysiologic properties which allow conduction
to block in one pathway and to propagate the impulse
slowly in the other (due to varied refractory period) Treatment of APC
allowing sufficient time so that the blocked site a. APC usually requires no treatment.
gets time to recover and to allow reentry. Reentry is b. For extremely symptomatic patient β-blocker or
responsible for VF in AMI, and polymorphic VT in when no structural heart disease is present class IC
genetically determined channel abnormality in Brugada antiarrhythmic agent may eliminate APC.
syndrome, LQTS, catecholaminergic polymorphic VT, c. Catheter ablation may be done in extreme cases.
AVNRT, accessory pathway mediated VT.
JUNCTIONAL PREMATURE COMPLEXES
ATRIAL PREMATURE COMPLEXES (APC)
These are extremely rare arrhythmias. It arises from AV
It is the most common arrhythmia and incidence increases node and His bundle region and may cause retrograde atrial
with age and presence of structural heart disease and is conduction. In that condition P-wave distorts the initial or
usually asymptomatic. Patient may complain of palpitation terminal portion of QRS complex producing pseudo Q or
or irregular pulse. S-wave in II, III and AVF.

Fig. 9.1: Mechanism of production of ectopic


Tachyarrhythmias 75

Junctional ectopic arising from His bundle sometime ETIOLOGY of AFib


may not be conducted to ventricle as the lower pathway
•• Incidence of AF increases with age and seen in > 5% of
is in refractory period and also block the oncoming sinus
adult population over 70 years of age.
beat producing an unexplained long PR interval that
•• IHD and hypertension.
does not follow typical wenckebach periodicity (gradual
•• Acute thyrotoxicosis.
prolongation of P-R interval with a drop of beat).
•• Acute vagotonic episode.
•• Acute alcohol intoxication.
Treatment •• Rheumatic mitral stenosis.
Symptomatic patient with junctional premature complexes •• Acute or recovery phase of abdominal vascular or
are treated by β-blocker or if there is no structural heart thoracic surgery.
disease it can be treated with class IC antiarrhythmic •• May be triggered by AVNRT such as paroxysmal SVT in
agent. WPW syndrome.

SINUS TACHYCARDIA (ST) CLINICAL IMPORTANCE OF AFib


It is recognized by the configuration of P-wave. P-wave is •• Loss of atrial contractility aggravates heart failure.
upright in II, III, aVF, negative in aVR and biphasic (positive- •• Fast ventricular rate reduces the diastolic period which
negative) in V1. interferes with ventricular filling and aggravates heart
Physiological condition producing sinus tachycardia failure.
are—exercise, anxiety and fever. •• Loss of contractility of atrial appendages enhances
Pathological condition producing sinus tachycardia the chance of clot formation within it and subsequent
are—hypotension, thyrotoxicosis and anemia. thromboembolic manifestation.
Onset of sinus tachycardia is gradual and moderate
slowing occurs in response to carotid sinus pressure but CLINICAL FEATURES of AFib
there is no abrupt termination.
Inappropriate sinus tachycardia—This form of sinus •• Occasionally the patient may be asymptomatic or only
tachycardia occurs due to dysautonomia after viral fever in minor palpitation may be present.
which heart rate increases either spontaneously or out of •• Occasionally severe dizziness or syncope are associated
proportion to the degree of physiologic stress or exercise with long ventricular pause.
and persist over 3–12 months. •• Exercise intolerance and easy fatigability are present
when ventricular rate is poorly controlled.
Treatment of ST •• Hypotension, pulmonary congestion and angina may
be present.
Treatment of sinus tachycardia is directed toward the •• Symptoms may be more severe with fast ventricular rate
underlying condition, e.g. anemia, thyrotoxicosis and due to diastolic dysfunction associated with HTN, aortic
correction of hypotension. stenosis and hypertrophic cardiomyopathy.
Inappropriate tachycardia usually resolves spontane-
ously. Rarely β-blocker may be needed in the background MANAGEMENT OF AFib
of IHD and angina.
Those who are intolerant to β-blocker catheter ablation •• The following facts are to be considered before starting
and atrial pacing may be considered as a second line of treatment of atrial fibrillation—
therapy. −− Etiology of AF
−− Chronicity of AF
−− Hemodynamic status of the patient and symptom
ATRIAL FIBRILLATION (AFib)
−− Ventricular rate
It is the most common sustained arrhythmia. −− Level of anticoagulation
Initiation of the arrhythmia occurs from atrialized −− Presence of risk factor for stroke.
musculature that enters the pulmonary vein or other •• Correction of etiological factor like anemia,
vein of the atria either by focal abnormal automaticity or thyrotoxicosis and structural heart disease (like MS) is
triggered firing. the first step of management of AF.
The maintenance of arrhythmia is done by disorganized •• Anticoagulation to be started in patient whose AF is
atrial musculature with microreentry. more than 48 hours duration [or TEE (transesophageal
The ventricular rate is usually 120–160/min but may echocardiography) shows presence of thrombus in left
be > 200/min or in patient with heightened vagal tone or atria] and to be continued for 1 month after restoration
intrinsic AV block the rate may be <100/min. of sinus rhythm.
76 Essentials of Internal Medicine

•• Another alternative option of chronic anticoagulation •• Rate control—


is gradually coming up is in the form of surgical −− Pharmacotherapy—This is usually done in
elimination or isolation of left atrial appendages asymptomatic patient or symptomatic patient with
with endovascular insertion of left atrial appendage tachycardia who have persistent form of AF.
occluding device. Rate control is done either by β-blocker, CCB
(diltiazem and verapamil) or digoxin. Combination
therapy may be done to avoid the side effect of high
• Chronic anticoagulation with warfarin targetting INR between dose monotherapy.
2–3 is recommended in patient with chronic or frequent long
−− Ablative therapy—If rate control could not be
paroxysmal AF with risk factors like—(i) TIA, (ii) P/H of stroke,
(iii) systemic embolism, (iv) MS, (v) diabetes, (vi) HTN, (vii) achieved by pharmacotherapy; then His bundle/
LV dysfunction with LA >5 .0 cm, (viii ) age >65 year and (ix) AV junction ablation coupled with implantation of
history of CCF pacemaker to be done.
Biventricular pacing should be used to minimize
the degree of dyssynchronization that occurs with
•• Termination of AFib—If hemodynamic compromise is RV apical pacing.
present [as suggested by (i) SBP <90 mm, (ii) presence of Rate control treatment (both pharmacologic or
angina, (iii) sign of cerebral anoxia, and (iv) dyspnea], ablative) should be coupled with chronic anticoagu-
emergency termination of AF to be done by— lation.
−− DC transthoracic cardioversion under cover of short-
acting anesthesia with 200 J biphasic shock delivered
Class I agent—Blocks inward sodium current
synchronously with QRS complex. It is the most
Class II agent—β-blocker
reliable way of termination of AF; success rate > 90%. Class III agent—Prolongs action potential
−− IV administration of ibutilide facilitates termina- Class IV agent—Calcium channel blocker
tion of AF with DC cardioversion or can be used
singly for pharmacologic termination of AF.
−− Pharmacological termination of AF is less reliable
•• Surgical or catheter ablative therapy for prevention
but can be tried with oral or IV amiodarone or
of AFib—Two types of procedure are available. In this
procainamide with moderate success.
new approach isolation of atrial muscle sleeves entering
•• Rhythm control—If hemodynamic compromise is
the pulmonary vein are done as these muscle sleeves
not present (as suggested by SBP >90 mm, absence
are thought to be the major trigger for AF. Elimination
of angina, no sign of cerebral anoxia and dyspnea),
of AF upto 50–80% can be done with catheter ablation
maintenance of sinus rhythm can be tried by:
procedure. It can be considered as an alternative to
−− It can be better achieved by class IC agent like
His bundle ablation with pacemaker implantation.
flecainide or propafenone which have no
Complications are— (i) pulmonary vein stenosis,
proarrhythmic risk in absence of HTN and LVH.
(ii) atrioesophageal fistula, (iii) systemic embolisms and
−− In presence of structural heart disease, like CAD,
(iv) perforation of atria with cardiac tamponade.
depressed LV function, HTN, LVH with rapid heart
−− Surgical ablation of AF is usually done at the time of
rate and significant symptoms, sinus rhythm can be
valve surgery or coronary artery surgery. Previously
achieved by sotalol, amiodarone, dofetilide. Due to
cox surgical maze procedure was designed to
risk of QT prolongation and polymorphic VT, sotalol
interrupt all macroreentrant circuit that might
and dofetilide to be initiated in hospital.
potentially develop in atria by giving multiple
incision on the atrial wall.
−− Now it is done by linear lines of ablation and
pulmonary vein isolation using a variety of energy
• Over 50% of patients have recurrence of AF within 1 year source.
who are receiving pharmacologic maintenance therapy
• Pharmacologic maintenance of sinus rhythm is not superior to ATRIAL FLUTTER (AFL) (Table 9.1)
chronic rate control and anticoagulation
• To reduce the risk of tachycardia related cardiomyopathy, Atrial flutter (AFL) and macroreentrant atrial tachycardia
heart rate to be kept <80/min during rest or <100/min during are synonymous both denoting a nonfocal source of an
moderate exercise atrial arrhythmia.
Tachyarrhythmias 77

Table 9.1: Summary of indication of antiarrhythmic in AF


Indication of antiarrhythmic in AF First line Second line
Normal heart without CAD Class IC antiarrhythmic agent Sotalol/amiodarone
Adrenergic-induced AF without structural heart disease Standard β-blocker Sotalol
HF Amiodarone, defetilide
CAD with preserved LV function Sotalol Amiodarone
HTN with LV wall thickness <1.4 cm Classic IC antiarrhythmic agent (flecanide, Sotalol/amiodarone
propafenon)
HTN with LV wall thickness >1.4 cm Amiodarone

The typical circuit for AFL rotates clockwise or coun- MULTIFOCAL ATRIAL TACHYCARDIA (MAT)
terclockwise direction around tricuspid valve annulus. The
It is commonly associated with pulmonary disease like
posterior boundary of the right atrial—AFL circuit are crista
chronic obstructive or restrictive lung disease. There should
terminalis, eustachian ridge, the inferior and superior vena
be at least three distinct type of P-wave morphology and
cava. 80% AFL circuit in right atrium rotates in an anticlock-
three different P-R interval. Ventricular rate is in between
wise direction with sawtooth-like P-wave in II, III, aVF lead.
100–150 beats/min. The presence of isoelectric baseline
When the same right atrial circuit rotates in clockwise direc-
helps to differentiate MAT from AF.
tion produces upright P-wave in lead II, III, aVF.
The AFL circuit in left atrium is rare but may develop
Treatment of MAT
after valve surgery or congenital heart disease or catheter
ablation and rotates around mitral valve. •• Initial therapy to be directed towards COPD and
In typical right atrial AFL atrial rate is 250–300/min with restrictive lung disease.
2 : 1 ventricular response. •• Judicious use of CCB, flecainide or propafenone can
Sometime coarse AF may look like AFL in V1 or sometime resut in decrease in arrhythmia.
one atria may show AF and the other may show AFL or may •• Low dose amiodarone can also control the arrhythmia
alternate between AF and AFL overtime. with minimum pulmonary toxicity.

FOCAL ATRIAL TACHYCARDIA


TREATMENT of AFL
Focal atrial tachycardia are of two types—
•• Rate control—Pharmacological ventricular rate •• Focal automatic AT—Start with a warmup period of
control can be tried out but not very effective with CCB 3–10 complexes and a slow in rate for 3–10 complex
(diltiazem, verapamil) β-blocker, and/or digoxin. prior to termination. The first P-wave has the same
•• Rhythm control— morphology as the remaining P-waves. This AT can be
−− Pharmacological—Rhythm control can be tried initiated by isoproterenol infusion and terminated by
with procainamide, amiodarone or ibutilide. adenosine with evidence of AV block and slowing of
Antiarrhythmic drug also enhance the efficacy of DC atrial rhythm.
cardioversion and maintenance of sinus rhythm after •• Focal microreentrant AT—This can be initiated by
cardioversion to the range of >80% by 1 year. programed atrial stimulation or spontaneous premature
−− DC cardioversion—Atrial flutter can be termi- nated beat. The initiating P-waves have different morphology
by low energy external cardioversion using 50–100 J than the P-wave of sustained AT. They usually do not
but the risk of thromboembolism to be managed in terminate in response to adenosine or carotid massage.
the line of atrial fibrillation. The focal AT arises by repetitive firing from anatomic
−− Catheter ablation—An isthmus ablation line from location like crista terminalis, valve annulus, limbus
tricuspid annulus to the opening of inferior vena cava of fossa ovalis, atrial muscular sleeves entering SVC,
can permanently eliminate recurrent atrial flutter. coronary sinus and pulmonary vein.
The anticipated success rate is more than 90%. P-wave morphology is distinct from P and P-R
Patient who have both flutter in right atrium and interval is shorter than sinus (R-P) interval when there
fibrillation in left atrium hybrid therapy with is 1:1 conduction.
antiarrhythmic agent coupled with right atrial •• Focal macroreentrant tachycardia incorporating
isthmus ablation can control both AF and AFL. AV node—The primary difference from focal AT is the
78 Essentials of Internal Medicine

persistence of AT in presence of AV block that may be


due to carotid massage or administration of adenosine.
The ECG distinction between focal automatic AT,
microreentrant AT, macroreentrant AT or atypical AFL
is not always possible.
−− Sustained focal AT tends to be slower but the
ventricular rate may frequently overlap with
reentrant tachycardia.
−− Focal AT is common in absence of structural heart
disease.
−− Focal AT tends to demonstrate isoelectric baseline
between P-wave.
−− Macroreentrant AT represents atrial activation that
is continuous.
−− In macroreentrant tachycardia, isoelectric base- line
is absent.
−− History of prior atrial surgery is present in macro-
reentrant AT. Fig. 9.2: Mechanism of nodal reentry

Treatment of Focal Atrial Tachycardia When an APC occurs after a short pause, it is blocked
in the fast pathway due to long refractory period while it is
Pharmacological therapy is the first line treatment of choice. conducted down through the slow pathway due to short
•• Nodal blocking agent is used for control of rapid refractory period. The blocked fast pathway can recover
ventricular rate. excitability by this time and the impulse can be conducted
•• Acute IV administration of procainamide or retrogradely upwards to activate atria.
amiodarone may terminate tachycardia. The APC initiating AVNRT has a long PR interval as
•• If tachycardia is not responding to pharmacologic the impulse is conducted via slow pathway. The P-wave in
therapy electrical cardioversion will terminate the AVNRT is typically buried in the QRS complex either not
tachycardia. visible or will distort the QRS complex.
•• Anticoagulation prior to cardioversion is usually As the atrial activation originates in the region of AV-
not needed unless there is severe left atrial dilatation node a negative P-wave is formed due to retrograde atrial
>5.0 cm with high-risk AF. depolarization.
•• Catheter ablative therapy is highly successful (>90%) in Occasionally AVNRT can occur due to conduction down
focal AT and should be tried in patients who are resistant the fast pathway and returning up via the slow pathway.
to medical therapy and who are reluctant to take chronic This type of AVNRT occurs less commonly and produces
drug therapy except when the focal AT arises from para- prolonged RP interval during tachycardia with a negative.
Hisian location or from left atrium. P-wave in lead II, III and AVF.

AV NODAL REENTRANT TREATMENT of AVNRT


TACHYCARDIA (AVNRT) (Fig. 9.2)
Treatment is directed towards slowing of conduction
•• It is the most common regular SVT. through AV node. This can be done by
•• It is more frequently seen in women and typically •• Physical measure like Valsalva maneuver or carotid
manifest in the second to fourth decade of life. sinus massage.
•• It is usually well-tolerated except in patient with IHD •• Adenosine 6–12 mg IV bolus is the drug of choice.
or HTN. •• β-blocker or Ca++ channel blockers are 2nd line agent.
•• AVNRT develops due to the presence of two distinct •• If hemodynamic compromise is present R-wave
electrophysiologic pathway within the AV node. synchronous DC cardioversion using 100–200 J can
The fast pathway located superiorly with a long terminate the tachycardia.
refractory period.
The slow pathway located below with a short refractory PREVENTION of AVNRT
period.
As a result of inhomogeneous conduction and •• It is done by digitalis, β-blocker or calcium channel
refractoriness a reentrant circuit can develop within AV blocker that slows the antegrade conduction through
node in response to premature stimulation of atria. slow pathway. If this drugs fails then class IA or IC agent
Tachyarrhythmias 79

directed at alternating conduction through fast pathway The evidence of AP and ventricular preexcitation
can be considered. includes (a) short P-R interval with (b) slurred delta wave.
•• Catheter ablation therapy using cryoablation tech- In some patient instead of atrioventricular accessory
nique can almost cure AVNRT (> 95%) specially in those pathway there may be atriofascicular accessory pathway.
who are reluctant to chronic drug therapy. Permanent These atriofascicular accessory pathways have decremental
pacemaker is needed in 1% patient. antegrade conduction.
Other accessory pathways connecting AV node with
AV JUNCTIONAL TACHYCARDIA fascicle may exist which are called ‘Mahaim fiber’.
a. Most common macroreentrant tachycardia associated
This type of arrhythmia can occur in the setting of with WPW syndrome is ‘orthodromic AV conduction’
•• Enhanced normal automaticity where ventricular activation occurs through AV node
•• Abnormal automaticity and His-Purkinje system and returns to atria via
•• Triggered activity. retrograde conduction through accessory pathway (AP)
This arrhythmias may develop as a manifestation of called ‘orthodromic AV reentry’.
•• Increased adrenergic tone b. Rarely the impulse activates the ventricle via accessory
•• Drug effect in patient with sinus node dysfunction pathway and returns to atria via AV node His-Purkinje
•• Following surgical or catheter ablation system is called ‘antidromic AV reentry or preexcitated
•• Digoxin toxicity. macroreentry’.
Sinus activity is usually dissociated or there may be c. Another most common serious arrhythmia associated
intermittent capture with prolonged P-R interval. If the rate with WPW syndrome is rapidly conducting AF (atrial
is 50–100 beats/min it is termed as accelerated junctional fibrillation).
rhythm.
Some AVNRT fails to depolarize the atria when it
CONCEALED ACCESSORY PATHWAY (AP)
may mimic AV junctional tachycardia and then the two
conditions are differentiated by the presence of triggering In half of the AP there is no antegrade conduction over
premature atrial beat that initiates AVNRT. AP but retrograde conduction is preserved and AP is not
Absence of atrial premature beat at the initiation of overt in sinus rhythm and only manifest during sustain
this type of tachycardia with gradual acceleration suggests tachycardia.
automatic AT. In this situation of retrograde conduction, P-wave will
follow ventricular activation with a short R-P interval. As
TREATMENT of AV junctional tachycardia this AP connects left ventricle with left atrium, the atrial
activation during the tachycardia frequently produces
•• Junctional tachycardia due to abnormal automaticity negative P-wave in lead I and aVL.
can be treated by β-blocker. Occasionally the AP conducts extremely slowly in a
•• A trial of class IA or IC agent may also be given. retrograde fashion resulting in ‘long R-P tachycardia’.
•• If digoxin toxicity is suspected digoxin therapy to be
stopped. Digoxin-specific antibody can be used.
TREATMENT OF ACCESSORY PATHWAY-
•• For incessant automatic junctional tachycardia focal
catheter ablation can be done with implantation of MEDIATED TACHYCARDIA
pacemaker. •• Acute treatment
−− Vagal stimulation
ACCESSORY AV PATHWAY (AP)- –– Valsalva maneuver
MEDIATED TACHYCARDIA –– Carotid sinus pressure.
−− Pharmacologic therapy
Tachycardia is often encountered in person who have –– Adenosine 6–12 mg IV bolus.
accessory AV pathway bypassing AV node. –– Calcium channel blocker—Verapamil and
Accessory pathway (AP) is typically able to conduct diltiazem IV.
impulse both in antigrade and retrograde direction. –– β-blocker IV.
In case of antigrade conduction the sinus impulse In patient with preexcitation (WPW) and AF.
quickly activates the ventricle bypassing AV node resulting −− In life-threatening situation—DC cardioversion
in ventricular preexcitation. The P-R interval is shorter and should be used to terminate AF.
the initial portion of QRS is slurred creating characteristic −− In nonlife-threatening situation
‘delta wave’. The remaining portion of the QRS complex is –– Procainamide at a dose of 15 mg/kg IV over
created by the fusion of faster impulse conducted via AV 20–30 min will slow the ventricular rate or can
node His-Purkinje system. terminate AF.
80 Essentials of Internal Medicine

–– Ibutilide can also be used to terminate AF. Treatment


Digoxin or verapamil should not be used in
VPC of sufficient frequency can cause reversible cardio-
AP-associated AF, as these two drugs shorten
myopathy but drug therapy that slows myocardial
the refractory period of AP thereby can lead to
conduction with increase in refractoriness can actually
development of VF.
increase the risk of life-threatening arrhythmia (drug-
In patient with AP associated with AF and rapid
induced, QT prolongation and TDP). For that reason drug
ventricular rate or in patient with recurrent SVT on AV
therapy is not universally recommended for VPC.
nodal blocking agent, class IA or IC antiarrhythmic drug
such as quinidine flecainide or propafenone should be
considered. ACCELERATED IDIOVENTRICULAR
Patient with recurrent symptomatic SVT or incessant RHYTHM (AIVR)
SVT or SVT with heart rate > 200 beat/min catheter ablation Three or more consecutive VPC at a rate of 40–120/min are
should be considered and is successful in >95% of patients. called AIVR. There is an overlap between AIVR and slow VT
Complications of catheter ablation that manifests between 90–120 beats/min.
•• ParaHisian AP ablation is associated with complete AIVR is a
heart block. •• Brief self-limiting arrhythmia with a gradual onset and
•• Ablation of left atrial path is associated with thrombo- offset.
embolic manifestation. •• AIVR has variable cycle length without any structural
heart disease.
•• It is usually associated with AMI, acute myocarditis,
VENTRICULAR TACHYARRHYTHMIAS cocaine intoxication, digoxin and after heart surgery.
•• Hemodynamic compromise can occur in AIVR
VENTRICULAR PREMATURE COMPLEXES (VPC) especially in RV infarction due to proximal RCA block.
Impulse that arises remote from Purkinje network with These patients are treated either by atropine (IV) or
a QRS duration >140 ms is called VPC. atrial pacing.
It increases with age and structural disease of heart.
•• Bigeminy—In which every sinus beat is followed by a VENTICULAR TACHYCARDIA (VT)
VPC. It originates below His bundle at a rate >100 beats/min
•• Trigeminy—In which two sinus beats is followed by a but usually >120 beats/min. VT at a rate of 100–120/min
VPC. is confused with AIVR and is usually due to concomitant
•• Cuplet/Pairs—Two successive VPC are called cuplets/ antiarrhythmic drug. VT usually occurs in chronic infarction
Pairs. or cardiomyopathy and is less likely to be associated with
•• Multiformed VPC—VPC that have different morphology AMI or myocarditis and has a fixed QRS cycle length.
in ECG are termed as multiformed VPC. Duration of QRS in VT may be uniform (monomorphic VT)
•• Ventricular tachycardia (VT)—Three or more or may vary from beat to beat (polymorphic).
consecutive VPC with a rate >100 beats/min is called VT.
•• Nonsustained VT—If the VT terminates spontaneously Polymorphic VT usually seen in a patient who has long QT
and is more than three beats in duration is called interval in basic rhythm and is called ‘Torsades de pointes’ (TDP).
nonsustained VT. Polymorphic VT associated with QT prolongation oscillates
•• Compensatory pause—Usually VPC are followed by around the baseline in the ECG mimicking the turning of the
fully ‘compensatory pause’, i.e. the gap between the last points stiching pattern
QRS and the next QRS complex is equal to twice that of
sinus rate. The VPC are usually not conducted to the •• Monomorphic VT usually arises from stable tachycardia
atrium. Occasionally the VPC can occur early and may focus without any structural heart disease or froms a
conduct retrogradely to atrium to reset the sinus node fixed area which forms stable reentrant VT circuit.
and then pause will be less than compensatory. •• Polymorphic VT is due to dynamic or unstable process
•• Interpolated VPC—When VPC fails to influence like ischemia, myocarditis which causes changes
outcoming sinus complexes is called interpolated in QT interval (enhanced dispersion of ventricular
VPC. refractoriness).
•• Parasystolic focus—VPC which fires repeatedly from −− VT persisting less than 30S is called nonsustained VT.
a fixed ventricular site at a fixed interval and coupled −− VT persisting for more than 30S or hemodynamically
variably with sinus complex that ventricular site is called unstable VT that requires termination within 30S is
parasystolic focus. called sustained VT.
Tachyarrhythmias 81

−− Ventricular flutter—looks like sine wave on ECG with •• For sustained polymorphic VT, ventricular flutter and
a rate >250 beat/min. ventricular fibrillation (all leads to hemodynamic
−− Polymorphic VT, ventricular flutter, or VF produce collapse)—
hemodynamic collapse if allowed to continue. −− Asynchronous defibrillation with 200 J monophasic
•• The presence of aberrant QRS pattern that matches or 100 J biphasic shock is the treatment of choice.
exactly with wide complex rhythm suggest SVT. Asynchronous shock is delivered to avoid delay
VT usually occurs in the setting of coronary artery related to sensing of QRS complex.
disease but there may be other causes like— −− If arrhythmia still persists IV lidocaine or
•• Idiopathic outflow tract VT. amiodarone should be administered followed by
•• Idiopathic LV septal/fascicular VT. repeated shock with maximum energy output.
•• Bundle branch reentrant VT. •• Focal outflow tract tachycardia who demonstrate
•• VT associated with LV-DCM. triggered or automatic VT may respond to intravenous
•• VT associated with hypertropic cardiomyopathy. β-blocker.
•• VT associated with infiltrative and neuromascular •• Idiopathic LV septal VT—responds to IV verapamil.
cardiomyopathy. •• VT in a patient with structural heart disease is treated
•• Arrhythmogenic RV cardiomyopathy. with ICD to manage anticipated VT.
•• VT after repair of TOF. •• Prevention of VT is an important task.
•• Fascicular tachycardia caused by digoxin.
•• Genetically determined VT (LQTS—long QT syndrome). Prophylactic Pharmacologic Management of VT
•• Acquired LQTS.
•• Short QT syndrome. More than 50% of patients with ICD require adjunctive
•• Brugada syndrome. antiarrhythmic drug like sotalol, amiodarone to suppress
•• Catecholaminergic polymorphic VT. recurrent VT or atrial arrhythmia. This therapy is specially
required in patient with structural heart disease and life-
threatening monomorphic or polymorphic VT not due to
ECG Criteria for VT
long QT syndrome. Of these two drugs amiodarone is better
•• AV dissociation (atrial capture or fusion beat). tolerated by patient with compromised LV function and low
•• QRS >140 ms for RBBB type V1 morphology. SBP but have high chance of end organ toxicity.
•• QRS >160 ms for LBBB type V1 morphology. Other antiarrhythmics like quinidine, procainamide
•• Frontal plane axis—90°–180°. or propafenone are not normally used in patient with
•• Delayed activation during initial phase of QRS complex— structural heart disease but may be considered in patient
−− LBBB pattern—R-wave in V1, V2 >40 ms. of recurrent VT with ICD.
−− RBBB pattern—Onset of R-wave to nadir of S >100
ms.
Catheter Ablation Therapy for Prevention of VT
•• Bizarre QRS pattern that does mimic typical RBBB and
LBBB concordance of QRS complex in all precordial Cure rate of catheter ablation therapy for VT without
lead. structural heart disease is > 90%.
RS or dominant S is V6 for RBBB pattern. Q-wave in Catheter ablation therapy with epicardial and endo-
V6 with LBBB pattern. cardial mapping in VT patient with structural heart disease
Monophasic R or biphasic QR or R/S in V1 with RBBB can reduce or eliminate the use of adjunctive toxic anti-
pattern. arrhythmic drug therapy.
Catheter ablation therapy is now actively considered
Treatment of VT even in patient with ICD to reduce the incidence of ICD
shock.
•• For wide complex tachycardia without hemodynamic
compromise—
Management of VT storms
−− Pharmacologic therapy with procainamide,
lidocaine or amiodarone can be tried but with a More than two episodes of VT/24 hour is known as VT
limited success rate <30%. storm. Practically repeated episodes of VT requiring
−− If unsuccessful R-wave synchronous DC—cardio- external difibrillation or ICD defibrillation is termed as VT
version under cover of sedation is appropriate. storm.
•• For monomorphic wide complex VT with hemodynamic •• Recurrent polymorphic VT storm in absence of long QT
compromise—A prompt R-wave synchronous DC is due to IHD or myocarditis and is initially managed
shock is delivered under cover of sedation. by intravenous lidocaine or amiodarone followed by
82 Essentials of Internal Medicine

search for etiology by coronary angio and endocardial Treatment


biopsy.
•• The amiodarone or procainamide slows the conduction •• No treatment is required as the VT is usually not
and facilitate recurrent VT. So early catheter ablation sustained and hemodynamically tolerable.
of the VT focus is the treatment of choice that could •• IV β-blocker can terminate the tachycardia.
eliminate the necessity of defibrillation. •• Oral β-blocker or CCB can suppress the recurrence.
•• Patients who have long QT with recurrent pause- •• Catheter ablation therapy to eliminate the tachycardia
dependent polymorphic VT (TDP) is due to drug or is successful >90% patient.
electrolyte disturbance. Steps of general management
are— IDIOPATHIC LV SEPTAL/FASCICULAR VT
−− Removal of the offending drug that prolongs the
Q-T interval. It is the secondmost common idiopathic VT.
−− Correction of potassium and magnesium It is due to macroreentry involving calcium-dependent
deficiency. slow response fiber of the Purkinje system in LV. In 12
−− Emergency pacing to prevent pause should be lead ECG there is RBBB with left or right axis deviation,
considered. Depending on whether the VT originates from posterior or
−− Intravenous β-blocker should be considered for anterior fascicle.
polymorphic VT storm.
Targeted treatment can be done if the etiology of Treatment
polymorphic VT is established— This VT can be effectively suppressed by verapamil
•• For Brugada syndrome—Quinidine or isoproterenol β-blocker but catheter ablation is the method of choice
can be used. which can eliminate the VT >90% patient.
•• For coronary ischemia—Intraaortic balloon counter
pulsation a nd emergency coronary angioplasty. BUNDLE BRANCH REENTRANT VT
•• For repeated VPC trigger for polymorphic VT storm the
VPC focus to be targeted for by catheter ablation. Monomorphic VT with idiopathic nonischemic cardio-
myopathy or valvular cardiomyopathy due to large macro-
UNIQUE VT SYNDROME entry circuit involving His-Purkinje network.
The VT impulse pass down the right bundle and
VT usually occur in the setting of coronary artery disease retrograde up via left posterior or anterior fascicle and left
with prior myocardial infarction. But a significant number of bundle branch producing LBBB and left axis deviation in
patients develop VT in other setting. These are as follows— the ECG during VT.
Rarely the circuit rotates in opposits direction, i.e.
IDIOPATHIC OUTFLOW TRACT VT antegrade through left bundle and retrograde through right
VT in absence of structural heart disease is called idiopathic bundle producing RBBB during VT.
VT.
Approximately 80% of outflow tract VT originates from Treatment
RV and rest 20% from LV outflow tract.
It appears to rise from an area beginning above the 1. Catheter ablation of the right bundle to block the VT
tricuspid valve and extending along the root of the out- flow circuit.
tract region to include the free wall and septal aspect of right 2. Implantation of ICD is required as LV function is severly
ventricle, just beneath the pulmonic valve, the aortic valve depressed and high-risk of SCD.
region and the anterior and superior margin of the mitral
valve annulus. VT ASSOCIATED WITH DCM
This arrhythmia is common in female and manifested Monomorphic or polymorphic VT can occur in non-
as palpitation with exercise, stress and caffeine ingestion. ischemic DCM patient.
This VPC and VT can lead to tachycardia-induced Sustained VT can arise from fibrosis around mitral and
cardiomyopathy. aortic valve region of DCM patient.
Mechanism of production of these types of VT is
probably calcium-dependent triggered activity due to Treatment
somatic mutation of inhibitory G protein.
Outflow tract VT produce large monomorphic R-wave •• Implantation of prophylactic ICD is the best way of
in II, III aVF. As most VT originates from the RV outflow treatment. Drug therapy (sotalol and amiodarone)
tract LBBB pattern is seen in V1 and when originates from can be tried to reduce the frequency of VT after ICD
LV outflow region it is RBBB in V1. implantation.
Tachyarrhythmias 83

•• Catheter ablation via endocardial route is not very much •• ICD may be implanted in patients who have recurrent
effective, as VT originates from epicardium. Catheter VT after drug therapy.
ablation through epicardial route via percutaneous •• Catheter ablation of endocardial and epicardial scar
pericardial puncture improves the outcome of ablative provides significant amelioration of recurrent VT
therapy. episodes.

VT ASSOCIATED WITH HYPERTROPIC VT AFTER TOF REPAIR


CARDIOMYOPATHY It is due to development of macroreentant circuit around RV
VT/VF, unexplained syncope and SCD all are associated scar to valve annuli long after operation. Catheter ablation
with HCM. from pulmonary or tricuspid annuli to the ventriculotomy
HCM with septal wall thickness >30 mm are associated scar can prevent VT recurrence.
with frequent nonsustained spontaneous VT and SCD. ICD may be required to them who have rapid VT or
These patients with HCM are associated with PRKAG 2 persistent VT after catheter ablation or with LV dysfunction.
mutation and WPW syndrome.
•• Sustained VT are at high-risk of SCD and ICD FASCICULAR TACHYCARDIA CAUSED BY
implantation is indicated. DIGOXIN TOXICITY
•• Amiodarone, sotalol and β-blocker are used to control
recurrent VT. Digoxin can cause ventricular ectopic with bradycardia
•• Catheter ablation of the areas of low voltage consistent which can predispose to sustained polymorphic VT or VF.
with fibrosis are promising. This VT is bidirectional and is due to triggered activity
as a result of calcium overload from inhibition of Na+/K+
ATPase pump by digoxin.
VT WITH INFILTRATIVE CARDIOMYOPATHIES
This VT arises either from left anterior or posterior
Sarcoidosis, amyloidosis, hemochromatosis, myotonic fascicle producing incomplete (narrow) RBBB with rapid
muscular dystrophy, Duchenne’s and Becker’s muscular alteration from left to right axis from beat to beat in ECG.
dystrotrophy and Friedreich’s ataxia all infiltrative type of
diseases are at increased risk of arrhythmia. Treatment
They usually have conduction block and require
pacemaker implantation. 1. Correction of electrolyte disturbances
When syncope and depressed LV function (EF < 35%) 2. Infusion of digoxin-specific Fab antibody.
with class 2 or 3 heart failure symptoms are present. ICD
implantation is indicated. These conditions may be treated GENETICALLY DETERMINED LQTS
with antiarrhythmic like amiodarone or sotalol before
(LONG QT SYNDROME)
implantation of ICD but not with other antiarrhythmic
drugs. In LTS the corrected QT interval (by Bazettis formula) lies
between 4–460 ms in men and 4–480 ms in women.
ARRHYTHMOGENIC RV CARDIOMYOPATHY/ •• OT interval >500 ms is associated with high-risk of
DYSPLASIA (ARVCM/D) arrhythmia.
•• Risk of arrhythmia is also high in those whose QT fails
It is either a genetically determined process or developed as
to shorten appropriately with exercise.
a sequele of viral myocarditis and associated with VT/VF.
•• In some individual the syndrome manifests only when
The arrhythmogenic focus is traced to perivalvular
they are exposed to drug like sotalol which alter channel
fibrosis around tricuspid and pulmonary valve involving
function.
mostly free wall.
Genotype associated with LQTS is very important. The
In sinus rhythm the ECG in V1 – V3 lead shows terminal
first three genotypes (LQTS1, LQTS2 and LQTS3) account for
notching of QRS complex (epsilon wave) with inverted T.
clinically important LQTS.
The epsilon wave indicates marked delay in activation of RV
•• LQTS1 is the most common genotype in whom the QT
free wall near pulmonary and tricuspid valve due to fibrosis.
fails to shorten with exercise or exercise may actually
MRI shows fatty infiltration with thinning of RV free wall
prolong it. The ECG shows broad T Exercise and
and apical aneurysm formation.
emotional stress are the most common trigger for
arrhythmia for LQTS.
Treatment Patients respond to β-blocker therapy.
•• Medical therapy consist of β-blocker like sotatol along •• LQTS2 is the 2nd most common genotype and associated
with other antiarrhythmic drug. with notched or bifid T-wave.
84 Essentials of Internal Medicine

Emotional stress, auditory stimulus and sleep Patients with this syndrome are vulnerable to AF
are the most common trigger for arrhythmia. Patients and VF. Mutation of HERG, KVLQT1 and KCNJ2 gene are
respond to β-blocker therapy. noticed.
3. LQTS3 is due to defect in cardiac sodium channel. It
has either late onset peaked biphasic T or asymmetric Treatment
peaked T-wave.
The arrhythmia is more life-threatening, and prog- •• ICD implantation is recommended.
nosis is poorest of all the LQTS. Most arrhythmia occur •• Quinidine which prolongs QT and reduces the
during sleep and β-blocker is not recommended and amplitude of T is currently evaluated for long-term
exercise is not restricted in LQTS3. medical therapy for this type of arrhythmia.

Treatment BRUGADA SYNDROME

•• ICD implantation is strongly recommended to all LQTS The disease is more common in Asian male. Mutation of
patients with arrhythmia. inward Na+ current channel in the region of RV outflow
•• Patients with syncope and unequivocal ECG change or tract epicardium appears to be responsible for Brugada
positive genetic testing should be strongly considered syndrome.
for ICD. Due to lack of inward Na+ current and the unopposed
•• Prophylactic ICD implantation is considered in all male outward K+ current results in dramatic shortening of the
with LQTS3 or in all LQTS with QT >500 ms particularly duration of action potential. This results in a large potential
when associated with family history of SCD. difference between normal endocardiun and a rapidly
•• Drug that prolongs QT must be avoided in all depolarizing epicardium. This dynamic potential difference
documented or suspected LQTS. predisposes to local reentry and life-threatening VT in
absence of any structural heart disease.
ACQUIRED LQTS
Treatment
Patients with genetic predisposition can develop marked
QT prolongation in response to drug, that alters repola- History of syncope, spontaneous ST elevation in V 1,
rization current. V 2 provocative drug testing with procainamide and
QT prolongation and associated polymorphic ventricu- flecainamide (Na+ channel blocker) may be used to identify
lar tachycardia (TDP) frequently exaggerated in acquired the presence of this abnormality in family members.
LQTS patient with hypokalemia and bradycardia. •• Acute arrhythmia responds to isoproterenol or
Altered drug metabolism and failure of excretion due quinidine.
to hepatic or renal dysfunction can lead to development of •• ICD treatment is recommended to manage the
arrhythmia in acquired LQTS. recurrence.

Treatment CATECHOLAMINERGIC POLYMORPHIC VT

•• Elimination of the offending drug. Mutation of the myocardial ryanodine release channel
•• Correction of K+ and Mg++. which creates a leak of Ca+ from sarcoplasmic reticulum
•• Temporary pacing in pause-dependent arrhythmia, or that causes accumulation of intracellular Ca + which
cautious infusion of isoproterenol. ultimately results in delayed after depolarization and
•• Lidocaine (class IB antiarrhythmic agent) which do not triggered activity.
cause QT prolongation can be tried but with limited ECG manifestations are bidirectional VT, nonsustained
success. polymorphic VT, or reentrant VF. Both autosomal, recessive,
•• For anxiety relief by benzodiazepine (SQTS). dominant and sporadic forms have been identified.
•• DC shock therapy for sustained arrhythmia. Arrhythmia is precipitated by exercise and emotional
stress.
SHORT QT SYNDROME
Treatment
QT interval <320 ms is essential to establish the diagnosis
of short LQTS. Managed by β-blockers and ICD implantation.
Chapter 10
Ischemic Heart Diseases

Definition UNSTABLE ANGINA (UA)


It is a condition that arises due to imbalance between myo- It is defined as angina pectoris or anginal equivalent (dysp-
cardial oxygen demand and supply. The inadequate supply nea, nausea, fatigue, faintness) ischemic discomfort with at
of oxygen and blood is due to atherosclerotic disease of least one of the three following features:
epicardial coronary artery causing regional reduction in •• It occurs at rest or with minimal exertion usually lasting
myocardial perfusion. more than 10 minutes.
It is composed of two groups of diseases— •• It is severe and/or new onset.
•• Stable angina •• It occurs with crescendo pattern (more severe, more
•• Acute coronary syndrome. prolonged, more frequent than previously).

STABLE ANGINA NSTEMI


It is characterized by chest or arm discomfort (rarely If a patient with clinical and ECG features similar to unstable
described as pain) but it is reproducibly associated with angina develops the evidence of myocardial necrosis as
physical exertion or stress and is relieved by rest or sublingual reflected by the elevated cardiac biomarker (CKMB and
nitroglycerine within 5–10 minutes. cardiac troponin); then the patient is stamped as suffering
It is a symptom complex caused by transient myocar- from NSTEMI.
dial ischemia and constitutes clinical syndrome rather than
a disease, occurs whenever there is imbalance be- tween PATHOPHYSIOLOGY OF UA/NSTEMI
myocardial oxygen demand and supply. Reduction of oxygen supply can be due to
The cause is impaired coronary perfusion and is due to— •• Rupture or erosion of atheromatous plaque with
•• Fixed block of coronary artery by stable atheroma. superimposed nonocclusive platelet-rich thrombus
•• HOCM (hypertrophic obstructive cardiomyopathy). (most common cause).
•• Aortic valve disease (aortic stenosis or regurgitation). •• Coronary spasm as in Prinzmetal’s variant angina.
•• Rapidly advancing coronary atherosclerosis or
ACUTE CORONARY SYNDROME (ACS) restenosis following PCI.

It is characterized by prolong precordial ischemic dis- ECG FINDING IN UA/NSTEMI


comfort (more than 20 minutes duration usually lasting •• ST depression
for several hours) at rest and not relieved by sublingual— •• Transient ST elevation
nitroglycerine. •• T-wave inversion occur in 30–50% patients.
It comprises of three entities: In patient with clinical features of UA/NSTEMI:
•• Unstable angina (UA 30–45%). •• New ST segment depression even of (0.05 mV) have
•• Non-ST-elevated myocardial infarction (NSTMI adverse prognosis.
—25–30%). •• Transient ST segment elevation for less than 20 minutes
•• ST-elevated myocardial infarction (STEMI—20–25%). seen in greater than 10% patients.
86 Essentials of Internal Medicine

Flowchart 10.1: Diagnosis of ischemic heart disease

•• T-wave changes are sensitive for ischemia but are less Apart from these two above-mentioned markers, newer cardiac
specific unless it is—(a) of new onset, (b) deep T-wave biomarkers are—
inversion greater than 0.3 mV. 1. C-reactive protein
2. B-type natriuretic peptide
3. CD-40 ligand
CARDIAC BIOMARKER These biomarker correlates independently with increased mor-
tality and recurrent cardiac event in patient presenting with clini-
Elevated level of (Fig. 10.1): cal features of NSTEMI and STEMI. These multimarkers are now
•• CKMB rises within 4–8 hours and returns to normal gaining favor to stratify patient’s risk
within 2–3 days.
•• Troponin (more specific for myocardial necrosis). It is
found raised in NSTEMI (for 7–10 days) but normal in
MANAGEMENT OF ISCHEMIC
UA (unstable angina). However, without a clear history
suggestive of angina minor elevation of troponin can
HEART DISEASES
occur in CCF, myocarditis, pulmonary embolism, Treatment (Flowchart 10.2)
cardiac surgery and DC shock. When a patient with precordial or retrosternal chest pain
So, without a clear history of angina small elevation or discomfort comes to emergency unit, our first task is to
of troponin can be considered false-positive. differentiate pain of cardiac origin from pain of noncardiac
origin. This is done by—
•• History
•• Physical examination
•• ACC/AHA guideline for IHD.

ACC/AHA guidelines for factors associated with high likelihood


of ACS (acute coronary syndrome)—
1. History of typical ischemic discomfort
2. History of established CAD by previous angiography
3. Prior myocardial infarction
4. Sign of congestive heart failure
5. New ECG changes
6. Elevated cardiac biomarker
Factors associated with intermediate likelihood disease—
1. Age >70 years
2. Male patient
3. Diabetes mellitus
4 . Known peripheral arterial or cerebrovascular disease
5. Old ECG abnormality

Those patients who are diagnosed as pain of non-


Fig. 10.1: Level of cardiac biomarker after AMI cardiac origin (pulmonary, vascular, gastrointestinal,
Ischemic Heart Diseases 87

Flowchart 10.2: Evaluation and management of ACS

musculoskeletal or infectious diseases) or due to stable The differentiation between these two groups of patients
angina (relieved by rest and nitroglycerine) are treated is done by the presence of elevated cardiac biomarker
accordingly and discussed in the subsequent chapter. (troponin, CKMB). Patient with elevated level of troponin
But those patients in whom a noncardiac cause could and CKMB are stamped as suffering from NSTEMI and those
not be established, they are supposed to be suffering from who have normal level of cardiac biomarker are stamped as
ACS. In these group of patients next step of management is— unstable angina (50% of UA/NSTEMI are female).
•• ECG monitoring (continuous) which differentiates However, both these two groups of patients (UA/
STEMI from UA/NSTEMI. NSTEMI) are initially managed by same protocol.
•• Estimation of cardiac biomarker (repeated).
If the ECG shows—typical ST elevation or evolving IMMEDIATE MANAGEMENT OF
Q-wave in the precordial or inferior wall lead then the UA/NSTEMI (Flowchart 10.3)
patient is stamped as STEMI and management of these
group of patients is discussed in subsequent chapter (75% •• General management
of STEMI are male). −− Continuous ECG monitoring.
If instead of typical ST elevation in the ECG we see: −− Bed rest (ambulation is permitted in patient showing
•• ST-segment depression >0.05 mV no recurrence of ischemic pain or not developing any
•• Transient ST segment elevation (less than 20 minutes biomarker for MI within 12–24 hours).
duration). •• Antiischemic management
•• New T-wave inversion >0.3 mV. −− Nitrates—Sublingual or buccal spray 0.3–0.6 mg
Then the patient is supposed to be suffering from either × 3 dose each at 5 minutes apart—if pain is not
unstable angina or non-ST-elevated MI (UA or NSTEMI). controlled by oral agent.
88 Essentials of Internal Medicine

Flowchart 10.3: Management of UA/NSTEMI


Ischemic Heart Diseases 89

Injection NTG—IV infusion 10 μg/min using a »» During chronic therapy 5–8% develop
non-absorbing tubing—the rate of infusion to be aspirin- resistance—they have higher risk of
increased by 10 μg/min every 3–5 min until the CAD-related death.
symptoms are relieved or SBP falls below 100 mm –– Clopidogrel/ticlopidine
Hg or a ceiling dose of 200 μg/min is reached. »» It blocks platelet adenosine receptors (P2Y12
↓ AD preceptor).
Patient to be transferred to topical/oral NTG when »» It causes 20% reduction of CAD-related death,
the patient is free from pain 12–24 hours later. MI, stroke compared to ASA alone in both high
Absolute contraindication of nitroglycerine: and low-risk patients with UA/NSTEMI.
1. Hypophosphatemia »» Moderate (or 1%) increase in bleeding
2. Prior sildenafil use wihin 24 hours. tendency specially in patient undergoing
−− β-blocker—In absence of any absolute contra- CABG.
indication the β-blocker is to be given in the same »» Continued benefit can be achieved of long-
does as STEMI. term combination of ASA + clopidogrel for
at least 9–12 months in patients treated
Metoprolol—50 mg 6 hourly.
conservatively/PCI and is recommended for
Targeted heart rate—50–60/min
all UA/NSTEMI patient.
If pain persists despite IV nitroglycerine and
»» Loading dose—300 mg initially followed by
β-blocker.
75 mg/day.
−− Morphin sulfate 4–5 mg IV every 5–30 minutes
−− Intravenous antiplatelet therapy—Used for
(maximum 15 mg) as needed to control pain. Side
upstream management of high-risk patient especially
effect of morphine vomiting, shock or respiratory
in whom invasive management is intended.
depression may appear which are treated accord-
–– Abciximab is beneficial for patient undergoing
ingly.
PCI but epitifibatide and tirofiban are used for
−− CCB—Non-DHP CCB are used in patients who have
patient treated conservatively and bleeding is an
persistent/recurrent pain after full dose of β-blocker/
important adverse effect.
nitrate or in a patient with contraindication for
–– Abciximab—0.25 mg/kg bolus followed by 0.125
β-blocker is present.

}
μg/kg/min (maximum—10 μg/min) for 12–24
−− ACEI / ARB.        These two agents mostly
hours.
−− HMG-CoA reductase   used in long-term manage-
–– Eptifibatide—180 μg/kg bolus followed 2.0 μg/kg/
inhibitor. ment or secondary pro-
minutes for 72–96 hours.
phylaxis rather than in –– Tirofiban—0.4 μg/kg/min for 30 minutes followed
emergency management by 0.1 μg/kg/min for 48–96 hours.
of UA/NSTEMI.
TIMI risk scores
•• Antithrombin therapy— a. Age >65 years
−− ACC/AHA guidelines for UA/NSTEMI prefer b. Three or more risk factors for CAD
LMWH to UFH specially for its, (a) anti Xa-IIa c. Documented coronary block greater than 50% by prior
angiography
activity, (b) SC applicability, (c) twice daily dosing,
d. Development of UA/NSTEMI while on aspirin for last 7 days
(d) nonrequirement of APTT monitoring. e. More than two episodes or angina in last 24 hours
−− LMWH—Enoxaparin—30 mg IV bolus followed by f. Elevated cardiac biomarker
1 mg/kg BD. g. New ST deviation greater than 0.05 mV
−− Fondaparinux is equivalent to enoxaparin but have
less chance of bleeding. During initial emergency management risk stratifica-
−− Bivalirudin (thrombin inhibitor) may be used tion is done by TIMI risk score and the patients are divided
alternatively. into three groups
•• Antiplatelet therapy •• High-risk group
−− Oral antiplatelet therapy •• Intermediate-risk group
–– Aspirin •• Low-risk group.
»» It has beneficial effect—at least 21% reduction −− TIMI high-or intermediate-risk groups are those
of mortality from MI in patient presenting with who have the following risk factor
UA/NSTEMI. –– Recurrent ischemic discomfort
»» Dose—325 mg initial chewable tablet followed –– Trop T-positive
by 75–162 mg/day (enteric coated). –– New ST depression.
90 Essentials of Internal Medicine

And they are subjected to coronary angiography. The •• Vascular cause


decision for subsequent management (CABG/PCI) depends −− Aortic dissection
on angiography finding. −− Pulmonary embolism
−− Pulmonary hypertension.
Invasive strategy for UA/NSTEMI (ACC/AHA guideline) •• Pulmonary cause
If in the angiography we find—
−− Pleurisy and/or pneumonia
1. LMCA block—CABG
2. 3 vessel disease with EF <50%—CABG −− Spontaneous pneumothorax
3. Multivessel disorder with proximal LAD involvement and EF < −− Tracheobronchitis.
50% or diabetic patient —CABG •• Gastrointestinal cause
4. 2–3 vessel disease with EF >50% with suitable coronary anatomy
or without diabetes—PCI
−− Esophageal reflux
5. One or two vessel disease without proximal LAD involvement −− Peptic ulcer
but large area of myocardial ischemia high-risk patient on −− Gallbladder disease
noninvasive tasting—CABG/ PCI −− Pancreatitis.
•• Musculoskeletal cause
Class I recommendation for use of early invasive strategy—
−− Costochondritis
1. Recurrent angina at rest or at low level of activity despite −− Cervical disk disease
treatment −− Radiculopathy due to collapse of vertebral body
2. Elevated cTnT or CTnI (T2–T4/T5).
3. New ST segment depression
4. Recurrent angina or ischemia with heart failure symptoms •• Infectious cause
and rales or MR −− Herpes zoster.
5. Positive stress test •• Psychological cause
6. Decrease BP −− Panic disorder.
7. Sustain VT
8. PCI <6 months or prior CABG.
Any one of the high-risk factors is indicator for invasive CARDIAC causes for central chest pain
strategy.
B. TIMI low-risk group are those who have— •• Stable angina—Clinical features—Retrosternal chest
a. No history of myocardial infarction pain, burning or heaviness, radiating occasionally to
b. Rapid resolution of symptoms neck, jaw, epigastrium and shoulders or left arm.
c. Minor or no ECG changes Precipitated by exercise, cold weather or emotional
d. cTnT less than 0.1 mg/L
They are subjected to stress testing within 6–72 hours of onset of stress, duration <2–10 minutes. Diagnosed by positive
chest pain by any one of the following tests— stress testing defined as flat depression of ST segment
1. Trade mill test (TMT) >0.1 mV below isoelectric line (i.e. PR segment) and
2. Dobutamine stress thallium perfusion (DST)
3. Dobutamine stress echo (DSE). Among those patients who lasting for longer than 0.08 second (2 small square).
have— •• Unstable angina—Clinical features—Same as stable
a. More than 3 mm depression of J point in the stress testing angina but may be more severe usually >20 minutes,
(TMT/DST/DSE) are subjected to coronary angiography and duration, lower tolerance for exersion. Marker of MI absent.
are managed) according to TIMI high-risk group
b. Those who have less than 3 mm J point depression in the •• AMI—Clinical features—Same as angina but usually
stress testing (TMT/DST/DSE) are managed in the outpatient more severe sudden onset, usually lasting more than
department with aspirin, clopidogrel, β-blocker, statin and 30 minutes, often associated with shortness of breath,
ACEI/ARB weakness, nausea, vomiting. Diagnosed by ECG and
c. The residual group who have no ST depression in the stress
testing, are actually have noncardiac chest pain and managed cardiac biomarker.
accordingly •• Pericarditis—Clinical features—Sharp pleuritic like
pain aggravated by changes in position, highly variable
in duration, associated with pericardial friction rub on
ACUTE RETROSTERNAL CHEST PAIN/ auscultation.
CENTRAL CHEST PAIN ECG—Elevated ST segment with convexity down-
ward but cardiac biomarker are absent.
DIFFERENTIAL DIAGNOSIS OF CENTRAL CHEST
PAIN VASCULAR causes of central chest pain
•• Cardiac cause •• Aortic dissection—Clinical features—Excruciating
−− Stable angina. ripping unrelenting pain of sudden onset on anterior
−− Unstable angina. chest often radiating to back. Usually associated with
−− Acute myocardial infarction (both STEMI and HTN and artherosclerosis or connective tissue disorder
NSTEMI). like Marfan syndrome, ankylosing spondylitis.
−− Pericarditis. Diagnosed by CT or MRI.
Ischemic Heart Diseases 91

•• Pulmonary embolism—Sudden onset dyspnea, be reproduced by movement of neck or spine. X-ray


pleuritic chest pain, tachypnea, tachycardia and cervical spine, CT/MRI of cervical or dorsal spine is
signs of right heart failure—diagnosed by pulmonary diagnostic.
angiography and confirmed by contrast CT/MRI. •• Infectious
Ventilation Perfusion scan V/Q scan. −− Herpes zoster— Clinical features—Prolonged
•• Pulmonary hypertension—Clinical features— burning pain over dermatomal distribution with
Substernal chest discomfort, accelerated by exercise. vesicular rash, never cross the midline—Diagnosed
Pain associated with dyspnea and sign of pulmonary by viral serology.
hypertension like wide split S2 loud P2. PCWP (pulmonary •• Psychological
capillary wedge pressure) >20 mm Hg. −− Panic disorder—Clinical features—Chest tightness
or aching often accompained by dyspnea lasting > 30
PULMONARY causes of central chest pain minutes, unrelated to exertion or movement. With a
•• Pleurisy/Pneumonia—Clinical featureslo—Pleuritic background of emotional disorder.
chest pain, usually brief over involved area, lateral to
midline associated with dyspnea-fever and cough—
Chest X-ray is diagnostic. CLINICAL FEATURES OF STEMI
•• Spontaneous pneumothorax—Clinical features—
Symptoms
Sudden onset unilateral pleuritic pain with dyspnea.
With past history of tuberculosis or pneumonia or lung •• Chest pain—Retrosternal or precordial in location
abscess–chest X-ray is diagnostic. frequently radiates to neck, jaw, left shoulder (but not
•• Tracheobronchitis—Clinical features—Burning trapizius), left arm, back, abdomen (epigastric) region
discomfort in midline upper retrosternal location (never below umbilicus).
associated with cough and fever. Nature of pain is usually described as heaviness,
squeezing, crushing, stabbing or burning in nature.
GASTROINTEsTINAL causes of •• Angina equivalent—Dyspnea, fatigue, faintness,
central chest pain nausea and epigastric discomfort may occur.
•• But painless infarct can occur in diabetes and elderly.
•• Esophageal reflux—Clinical features—Burning •• It is often associated with weakness, sweating, nausea,
discomfort substernal and retrosternal in location vomiting and anxiety.
usually of 10–60 minutes duration after heavy meal or •• Rarely sudden loss of consciousness, confusional
during recumbency—Endoscopy is diagnostic. state, profound weakness, unexplained arrhythmia,
•• Peptic ulcer—Clinical features—Prolong epigastric or hypotension or peripheral embolism are the unusual
substernal pain releived by food, antacid, H2 blocker presenting symptoms.
and PPI—Endoscopy is diagnostic.
•• Gallbladder disease—Clinical features—Prolongs
epigastric or right upper quadrant pain, unprovoked or Signs
following fatty meal in middle-aged fatty lady radiating
•• About one-fourth of patients with anterior wall in-
to tip of right shoulder or inferior angle of scapula—USG
farction have features of sympathetic overactivity as
of abdomen is diagnostic.
evidenced by tachycardia and hypertension whereas up
•• Pancreatitis—Clinical features—Prolonged intense
to one-half with inferior wall infarction have evidence
epigastric and substernal pain with the history of
of parasympathetic overactivity as manifested by
alcohol, hypertriglyceridemia diabetes or gallbladder
bradycardia and hypotension.
disease. Diagnosed by high serum amylase, lipase and
•• Apical impulse may be difficult to palpate.
USG/CT of abdomen also help diagnosis.
•• Rarely abnormal systolic pulsation may develop in the
periapical area within 1st day of infarction.
MUSCULOSKELETAL causes of •• Intensity of S 1 and S 2 decreased with paradoxical
central chest pain splitting of S2.
•• Costochondritis—Clinical features—Sudden onset •• S3 and S4 may be audible.
intense fleeting pain reproduced by pressure over •• A transient mid or late systolic apical murmur due to
affected joint, occasional patient have swelling and dysfunction of mitral valve apparatus may be audible.
inflammation over costochondral joint—chest X-ray is •• A pericardial friction rub may be heard in transmural
usually negative. Diagnosed by exclusion. infarct.
•• Vertebral disk disease—Clinical features—Sudden •• Basal body temperature may be elevated to 38°C in the
onset of radiating pain may have radiation to back may 1st week.
92 Essentials of Internal Medicine

Investigations Details of Emergency Management


• Aspirin
Apart from positive cardiac enzyme, e.g. troponin and • Block TxA2—Receptor of platelet and decrease platelet
CKMB the following investigations can be done in AMI. aggregation
•• TLC—12000–15000/cmm appear with 1st few hours and • Reduce mortality by 21%
persist for 3–7 days. • Useful in primary prevention and also in the whole spectrum
•• ESR—Raised. of AMI treatment strategy
• To increase the blood level of aspirin rapidly, patient
•• Cardiac imaging. should chew nonenteric coated ASA tablet (162–
−− Echocardiography with Doppler flow study is done 325 mg) for better absorption through oral mucosa
to see the following— Combination treatment strategy for control of chest pain
–– Regional wall motion abnormality • Nitrate, morphin, O2 inhalation and β-blocker is used in
–– Ejection fraction combination to reduce the chest pain
–– Presence of RV infarct • Not to underdose the patient, because pain increases
–– Ventricular aneurysm sympathetic response that causes tachycardia which
ultimately increases the cardiac demand
–– LV thrombus
–– Pericardial effusion Morphin
• It is the analgesic of choice in STEMI patient except in patient
–– VSD and MR associated with AMI. with well-documented morphin hypersensitivity
−− High resolution cardiac MRI by late enhancement • 4–8 mg IV followed by 2–4 mg repeated at interval of 5–15
with gadolinium—Images are obtained 10 minutes minutes until the pain is relieved or evidence of toxicity
after gadolinium injection which shows bright signal (hypotension, depression of respiration, vomiting) preclude
from area of infarction which appears as a sharp its use
• Also useful in relieving pulmonary edema associated with CCF
contract to the dark area of normal myocardium.
in MI
• Hypotension can be managed maintaining the patient in
MANAGEMENT OF STEMI supine posture with leg elevated if SBP <100 mm Hg. If not
effective normal saline 500 mL infusion can be given.
Treatment of STEMI starts from the time of onset of pain • Respiratory depression can be managed by naloxone 0.1–0.2
and can be divided into—(a) prehospital care, (b) initial mg IV repeated every 15 minutes if necessary
recognition, (c) emergency management, (d) reperfusion, • Vomiting can be managed by injection metoclopramide 10
and (e) late hospital management (management of mg IM
complication and secondary prophylaxis). • Can cause bradycardia and heart block which is managed by
injection atropin 0.5 mg IV
Nitrate
Management in Emergency (Outline)
1. It enhance coronary blood flow
(According to ACC/AHA class-I recommendation) 2. It decrease preload
1. ECG monitoring (continuous). Sublingual nitrate should be given in patient with ACS
except—
2. Aspirin—300 mg chewable tablet. a. Inferior wall MI
3. O2 administration (when hypoxia is present) 2–4 L/ b. Right venticular infarction
min by nasal prong or facemask. c. Marked hypotension SBP <90 mm Hg
4. Nitroglycerine—0.4 mg (sublingual) × 3 dose at 5 d. Bradycardia
minutes interval. 3. In patient with prolonged period of waxing or weaning chest
pain IV. NTG is beneficial for controlling pain and ischemia
5. Morphin—2–4 mg IV at 5 minutes interval till the
• Blood pressure should be regularly checked during nitrate
total dose of 15 mg in reached or desired level of infusion and SBP should be >100 mm Hg
analgesia is reached or side effects like hypotension,
β-blocker
vomiting or respiratory depression appear. 1. Relieve pain
6. β-blocker—Metoprolol 5 mg IV × 3 dose at 5 minutes 2. Reduce analgesic dose
interval, wait for 15 minutes after the last dose for 3. Reduce infarct size
appearance of side effect like—(a) heart rate <60 4. It is the only drug that can prolong life expectancy—so should
BPM, (b) SBP <100 mm Hg, (c) P-R interval >0.24 be given in every cases excepting in strongly contraindicated
sec, (d) Rales >10 cm from the diaphragm. If they patient
are absent, metoprolol—50 mg IV every 6 hourly × Relative contraindication of β-blocker
48 hour followed by 100 mg bid. 1. Heart rate <60 BPM
2. SBP <100 mm Hg
7. Reperfusion strategy—(a) Thrombolysis and (b)
3. P-R interval >0.24 S
primary PCI. 4. 2nd or 3rd degree heart block
Ischemic Heart Diseases 93

5. Bilateral rales >10 cm from lung base and if hemodynamic stability persist 15 minutes after last IV
6. Signs of peripheral hypoperfusion dose, oral metoprolol is continued in a dose. 50 mg 6 hourly
7. Severe COPD for 1st 48 hours, then 100 mg BD/day
8. History of severe asthma • In patient with relative contraindication to β-blocker.
9. Type–I diabetes Esmolol 50–250 mg/kg/min given as infusion or non-
10. Severe peripheral vascular disease DHPCCB can be tried
Absolute Contraindication of β-Blocker Oxygen
• Signs • Augmentation of fraction of O2 in inspired air does not elevate
1. Heart failure O2 delivery significantly in the infarcted area in patient who
2. Evidence of low output state are not hypoxemic
3. Increased risk for cardiogenic shock Moreover it causes peripheral vasoconstriction so afterload
Metoprolol rises which decreases COP
• Injection metoprolol—5 mg IV × 3 dose at 5 minutes interval • Patient with STEMI with arterial hypoxia (O2 saturation <90%).
→ patient is observed for 5 minutes in between the doses for O2 is delivered at the rate of 2–4 L/min as 100% moist O2 by
BP/ pulse/rales → if no contraindication appears after three nasal prong or mask for 6–12 hours
IV bolus • For severe hypoxia or in pulmonary edema endotracheal
↓ intubation and PEP-ventilation may be required

Flowchart. 10.4: Outline of management of acute myocardial infarction


94 Essentials of Internal Medicine

REPERFUSION THERAPY (flowchart 10.5) Indications for Primary Fibrinolysis


When ST-elevation of at least 2 mm in two contiguous •• Early presentation (within 3 hours).
precordeal lead 1 mm in two adjacent limb lead is present, •• PCI not favorable as
the patient should be considered candidate for reperfusion −− Laboratory is occupied/not available.
therapy. −− Vascular access is difficult.
Although late spontaneous reperfusion occurs in some •• Delay in invasive strategy
patients, persistent thrombotic occlusion in majority −− Prolonged transport.
of STEMI patients causes necrosis of the ischemic −− Door to balloon (D–B)—Door to needle (D–N) time
myocardium. So to limit the infarct size. > 1 hour.
•• Two major procedure are available
−− Door to balloon (D–B) time >90 minutes.
−− Fibrinolysis
−− Primary PCI.
•• Extent of myocardial salvage is large when reperfusion
Choices of Agents in Fibrinolytic Therapy
is achieved by PCI and is less time- dependent than •• Patient presenting within 4 hours of symptom onset
fibrinolysis. It is due to the fact that— −− High intensity fibrinolytic regimen (accelerated t-PA)
−− Full restoration of blood flow occurs in PCI (>90%) is preferred except in some low-risk individuals.
in comparison to fibrinolysis ~ 70%. −− In low-risk individual—streptokinase and acceler-
−− Time makes coronary thrombi mature on which ated t-PA are equivalent.
fibrinolytic agent cannot act or act very poorly. •• Patient presenting between 4–12 hours of onset
−− Speed of reperfusion is of lesser importance. So
Indication for Primary PCI streptokinase and t-PA are equivalant.
−− In low-risk patient but having a high chance of ICH/
•• Skilled PCI laboratory is available with surgical backup.
bleeding, streptokinase is preferable to t-PA in cost-
•• Door to balloon (D-B) time <90 minutes.
benefit consideration.
•• Door to needle (D-N) time >1 hour.
Candidates appropriate for fibrinolytic therapy with
•• High-risk STEMI case where cardiogenic shock has
t-PA should better be treated with bolus thrombolytic
developed.
like reteplase/tenecteplase because
•• Contraindication to fibrinolysis in present (past history
–– Easy administration
of bleeding and past history of ICH).
–– Low chance of application error
•• Late presentation >3 hours from the onset of symptoms.
–– Less noncerebral bleeding
•• Diagnosis of STEMI is in doubt.
–– Potential for prehospital treatment.

Flowchart. 10.5: Reperfusion therapy


Ischemic Heart Diseases 95

• Late therapy/treatment for patient presenting 12 •• Antiplatelet agents


hours or later −− Nonenteric coated aspirin should be chewed by
−− No mortality benefit was demonstrated in patient patient who have not taken ASA prior to presentation
with fibrinolytic therapy when started between 12–24 with STEMI—initial dose 162–325 mg followed by
hours after onset of symptoms. 75–162 mg/day.
−− But still fibrinolytic therapy is reasonable to consider −− If true ASA allergy is present
in patient with –– Clopidogrel (P2Y12 receptor antagonist)→ 300–
–– Persistent symptoms 600 mg followed by 75 mg/day.
–– Persistent ST-elevation in ECG –– Prasugrel and ticagrelor are more effective than
–– Persistent chest pain. clopitogrel in preventing ischemic complication
−− Patient >65 years treated with fibrinolytic therapy but associated with increased-risk of bleeding.
after 12 hours has a higher chance of cardiac rupture −− Efficacy and safety of the routine combination of
hence late fibrinolytic reperfusion therapy is better ASA with clopidogrel in patient with STEMI specially
to restrict in young patient < 65 years of age. those receiving fibrinolytic therapy have been
−− So elderly patient with ongoing ischemic symp- toms established (prevent death, reinfarction and stroke).
> 12 hours—PCI is the ideal treatment. −− In patient <75 years with low-risk of bleeding and
−− All patients with suspected STEMI should receive anterior wall MI. Combination reperfusional
aspirin regardless of fibrinolytic therapy and should therapy with abciximab and half dose reteplase/
be continued indefinitely. tenecteplase can be considered to prevent
−− Patient requiring PCWP measurement and trans- reinfarction/other complications.
venous pacemaker lead (temporary) should be
introduced before starting fibrinolytic therapy or it • Combination reperfusion regimen facilitate the rate and
extent of fibrinolysis by—
can be given after fibrinolytic therapy, only when it
i.  Inhibiting platelet aggregation
is crucial for patients survival. ii.  Weakening the clot structure
−− Doses— iii.  Allowing fibrinolytic agent to deeper into the clot.
–– Streptokinase → 1.5 mU within 30–60 minutes • But this combination should not be used in patient >75 years
dissolved in 100 mL N saline. of age because of chance of ICH and have similar efficacy with
–– Reteplase → 10 U × 2 (each over 2 minutes) each bolus fibrinolytics.
at 10 minutes apart in short push.
–– Tenecteplase → 30–50 mg/kg IV bolus. −− For patient planned to be treated with PCI should
receive GP-IIb/IIIa inhibitors either alone or in
LATE HOSPITAL CARE combination with reduced dose of fibrinolytic may
be considered.
•• Antithrombin/anticoagulant therapy •• β-blocker—If the 1st dose is given in the emergency
−− Patient undergoing PCI/surgical intervention → then continue and titrate the daily dose according to
UFH. BP and heart rate.
−− Patient undergoing reperfusion therapy either with
t-PA or streptokinase → UFH. • Metoprolol—50–100 mg twice daily.
– Bisoprolol (10 mg daily) timolol and alprenolol can also be
used alternatively.
– In diabetic patient carvedilol (αβ both blocker) can be
• Dose—UFH 60 U/kg (maximum 4000 U). Initially followed by
considered.
infusion of 12 U/kg/hour (maximum 1000 U/hour) adjusted
– In presence of absolute contraindication to β-blocker, it
to maintain INR 1.5–2 times of control.
should be avoided and replaced by non-DHP-CCB.
– It is not unreasonable to consider intra-venous UFH therapy
to all patient receiving streptokinase therapy specially for
those who are at high-risk for systemic embolization. −− In presence of relative contraindication, β-blocker
– LMWH/Fondaparinux—It can be considered as an
should be started at a lower initial dose and titrated
alternative to UFH for patient <75 years of age receiving
fibrinolytic therapy without significant renal dysfunction weekly to reach the optimal target dose.
but still superior to UFH. •• ACEI/ARB —It reduce mortality and morbidity after
• Enoxaperin—30 mg IV bolus followed by 1 mg/kg SC BD. STEMI and the mortality benefits are additive to those
• Patient more than 75 years of age should not receive LMWH. achieved with β-blocker and aspirin.
• Patient with known heparin-induced thrombo- cytopenia → −− It should be started within 24 hours in all patient
bivalirudin (direct antithrombin) can be given.
with STEMI specially to—
96 Essentials of Internal Medicine

–– Elderly patient −− Dobutamine—Though it has the inotropic effect but


–– Anterior wall infarction chronotropic effect is minimal. Starting dose—2.5
–– Prior infarction mg/kg/min–10 mg/kg/ min.
–– Globally depressed LV function/large RWMA Doses must be monitored to maintain it HR >100–
–– Hypertensive. 110/min.
•• Nitroglycerin—Injection NTG by IV root should be −− Levosimendan.
continued in patient of STEMI with CHF, HTN and −− Milrinon—Inotropic agent as well as vasodilator.
persistent chest pain (SBP >90 mm Hg). Dose—Starting dose—0.5 mg/kg/min over 10 minutes.
•• Statin (atorvastatin—80 mg PO/day). ↓ Followed by
•• Absolute bed rest. Maintenance infusion—0.375–0.75 mg/kg/min.
•• Nothing per month except sips of water—later low •• Digitalis—Digitalis in STEMI patient is unimpressive.
salt, low fat, low cholesterol diet should be intro- duced Arrhythmias can be increased by digitalis specially if
slowly. given within first few hours of STEMI. So digitalis is
•• Stool softener and PPI—To be added. mainly reserved for atrial flutter/atrial fibrillation or
•• Continuous monitoring of vital sign every 1.5 hour till in case of refractory HF nonresponsive to diuretics,
the patient becomes stable. vesodilator and β-agonist.

MANAGEMENT OF COMPLICATION ARRHYTHMIAS


HEART FAILURE (HF) •• Ventricular premature beats—
The therapy mostly consist on −− Prophylactic antiarrhythmic agent is contraindicated
a. Avoidance of hypoxemia by high flow O2 in absence of clinically important sustained
b. Diuresis ventricular arrhythmia.
c. Afterload reduction −− β-blockers are useful in patient with ventricular
d. Inotropic support. ectopic and for prevention of ventricular fibrillation
•• Diuretics—Frusemide (10–40 mg repeated at 3–4 hours and should be used routinely unless contraindicated.
interval if necessary). It reduces LV filling pressure and −− Hypokalemia and hypomagnesemia should be
pulmonary congestion resulting in improvement of corrected and to be kept around 4.5 mmol/L and 2.0
orthopnea, dyspnea. Reduction of EDV and myocardial mmol/L respectively.
wall tension reduces myocardial O2 requirements. •• VT and VF—Routine prophylactic antiarrhythmic drug
•• Vasodilator therapy is recommended in HF when HF therapy is no longer recommended.
is unresponsive to diuretic or when HF in STEMI is −− Sustained VT if well-tolerated hemodynamically
associated with HTN/MR/VSD. should be treated with—
−− In those above situation the vasodilators increase –– Injection amiodarone IV (bolus IV 150 mg over
the stroke volume and may reduce myocardial O2 10 minutes followed by 1 mg/min for first 6 hours
demand. It decrease the preload by vasodilation and then 0.5 mg/min.)
without decreasing plasma volume. »» Alternatively
−− Commonly used vasodilators are nitroglycerin, –– Injection procainamide IV (bolus—15 mg/kg
nitropruside, ISDN. All decrease the preload over 20–30 min) followed by 1–4 mg/minutes.
without much lowering of plasma volume and thus −− If VT causes hemodynamic deterioration or develops
advantageous to diuretic. The dose of NTG infusion VF then unsynchronized DC shock with 200–300 J
(commonly used) is adjusted in such a way that— (monophasic wave form approximately 50% energy
–– PCWP—to be maintained at 20 mm Hg. with biphasic wave-form) for prompt cardioversion.
–– BP—to be maintained above 90/60 mm Hg. −− VT or VF unresponsive to cardioversion become
•• ACE inhibitors or ARB are used as ideal therapy for responsive after treatment with
long-term management of heart failure but can be –– Injection epinephrine (1 mg intracardiac) diluted
started on the first day. to 10 mL (1 : 10000) via a intracardiac catheter.
•• Isotropic support—It is given by –– Injection amiodarone 75–150 mg bolus.
β-agonist—When heart failure is severe and manifested −− Patient who developed VF secondary to pump failure
as marked reduction of cardiac index (<2 L/min/m2) face a poorer prognosis—they should be managed
and PCWP > 20 mmHg with diuretics then β-agonist with implantation of ICD.
dopamine and dobutamine is indicated. −− Torsades-de-pointes may occurs in patient of
−− Dopamine—Started with 1–2 mg/kg/min and should STEMI as a consequence of hypoxia, hypokalemia
be increased stepwise from 2–10 mg/kg/min with or following electrolyte disturbances, digoxin or
strict monitoring of SBP, PCWP and COP. quinidine therapy. A search for the cause to be
Ischemic Heart Diseases 97

undertaken. Withdrawal of such treatment (digoxin Clinical Features


and quinidine) and correction of electrolyte
•• Signs of severe RV failure—Kussmaul’s sign, engorged
disturbance is the treatment of choice in that
JVP, hepatomegaly, hypotension, clear lung field,
situation.
jugular venous distension.
•• SVT
•• ST-elevation of the right-sided precordial lead
−− Digoxin is the treatment of choice, if SVT is associated
(particularly V4R).
with HF.
•• Positive cardiac biomarker.
−− If HF is absent then β-blocker, verapamil or
•• 2-D echo shows RV dysfunction with RWMA.
diltiazem are suitable alternatives.
•• Catheterization of right-side of heart show distinctive
−− If abnormal rhythm persists > 2 hours with ventricular
hemodynamic pattern resembling cardiac tamponade/
rate >120 bpm or tachyarrhythmia induces HF,
constrictive pericarditis.
shock, ischemia—synchronized. DC shock with
(100–200 J) energy (monophasic wave-form) is used.
•• Bradyarrhythmias and heart blocks—Temporary Therapy
electrical pacing is the procedure of choice in •• Volume expansion by normal saline infusion to
management of any type of bradyarrhythmias except maintain RV preload.
sinus bradyarrhythmia in which atropin and iso- •• Measure taken to decrease pulmonary arterial pressure
prenaline is of some help. Initial dose of atropin is 0.5 and PCWP by improving LV function.
mg, additional dose 0.2 mg up to 2.0 mg may be given. •• Avoidence of β-blocker – (heart block may be there).
•• Cautious consideration of streptokinase (to avoid risk
CARDIOGENIC SHOCK (CS) of hypotension).
Shock usually develops following severe multivessel
coronary artery disease. OTHER COMPLICATIONS OF AMI
Goal of therapy—Mean BP >60 mm Hg. •• Recurrent chest discomfort—It develops in 25% of
•• To maintenance of SBP >90 mm Hg. STEMI patient. It is due to extension of original infarct
•• To maintain PCWP 20 mm Hg. or reinfarction. It should be evaluated thoroughly by
•• Correction of hypoxia and acidosis. coronary angio and managed accordingly.
Prompt reperfusion to reduce the infant size and •• Pericarditis—Pericardial friction rub or pains are
treatment of ongoing ischemia have reduced the inci- dence frequently encountered in STEMI patient. It is important
of shock from 20–7% only. to differentiate pain of pericarditis from pain of
•• Management of cardiogenic shock according to SBP extension of original infart/reinfarct which does not
−− SBP <70 mm Hg with signs and symptoms of shock. radiates to trapezius. Pain of pericarditis are usually
Injection norepinephrine 0.5–30 μg/min IV managed by aspirin 650 mg 6 hourly.
infusion. •• Thromboembolism—Thromboembolism is clinically
−− SBP 70–100 mmHg with sign and symptoms of shock. detected in 10% of STEMI cases and 20% by autopsy. It
Injection dopamines 2–20 μg/kg/min IV infusion. occurs in association with large anterior wall infarct, LV
−− SBP 70–100 mg Hg without signs and symptoms of thrombus is usually detected by echocardiography but
shock. rare with inferior or posterior wall infarction.
Injection dobutamine 20 μg/kg/min IV infusion. When thrombus is detected by echocardiography or
−− SBP >100 mm Hg. large area of RWMA is present, systemic anticoagulation
Injection nitroglycerine 10–20 μg/min IV infusion. with warferin should be started prophylactically and to
•• Intraaortic balloon pump (IABP)—Rapidly stabilizes be continued for 3–6 months.
the patient with cardiogenic shock prior to PCI or prior •• Left ventricular aneurysm—This term is usually used
to surgery for MR or VSD in AMI. It is contraindicated to describe ventricular dyskinesia or local expansile
in AR or aortic root dissection. paradoxical wall motion. Clinically it is detected
•• Reperfusion/revascularization—Patient who deve- lop by double or diffuse or displaced apical impulse. It
cardiogenic shock within 36 hours myocardial infarction. is readily diagnosed by echocardiography and may
Primary PCI/CABG is class-I recommendation of usually contain mural thrombus. When it is associated
ACC/AHA guidelines. with localized myocardial rupture it should be treated
surgically.
RIGHT-VENTRICULAR INFARCTION
Postinfarction Risk Stratification and Management
•• Patient with inferoposterior wall infarction may
demonstrate minor to extensive right ventricular High-risk patient are identified by the following points
infarction ( rarely limited primarily to right ventricle). •• Age >75
98 Essentials of Internal Medicine

•• Presence of diabetes mellitus 3. Write on updated Jone’s criteria for diagnosis of acute
•• Prolong sinus tachycardia rheumatic fever (ARF).
•• Symptomatic ventricular arrhythmia 4. Write on treatment and prophylaxis of ARF.
•• Hypotension 5. Write on clinical features of bacterial endocarditis.
•• ST-segment changes at rest without angina 6. Write on diagnosis of bacterial endocarditis by Duke’s
•• Complete heart block criteria.
•• New interventricular conduction disturbances 7. Write on prophylaxis against bacterial endocarditis.
•• Rales above the lung bases 8. Write on clinical features of mitral stenosis.
•• EF <40% 9. Write on management of mitral stenosis.
•• Persistent ischemia. 10. Write on peripheral signs of aortic regurgitation (AR).
And due attention must be paid in the management of 11. Write on auscultatory finding of AR.
the above-mentioned condition. 12. Write on types of aortic stenosis (AS).
13. Write on clinical features of AS.
ADVISE AT DISCHARGE (FOR SECONDARY 14. Write on clinical features of mitral regurgitation
PREVENTION) 15. Define heart failure.
16. Write on etiology of heart failure.
These are given for improvement of long-term mortality
17. Write on types of heart failure.
and morbidity.
18. Write on clinical features of heart failure.
•• Antiplatelet—Aspirin 75–150 mg daily or clopidogrel
19. Write on Framingham’s criteria for diagnosis of heart
75 mg/day who are intolerant to aspirin.
failure.
•• ACE inhibitors—To be continued indefinitely who have
20. Write on stages of heart failure and therapeutic
the following features:
measures at different stages.
−− Heart failure.
−− Moderate decrease in global ejection fraction 21. Write on refractory heart failure and its management.
(<40%). 22. Write on diastolic heart failure.
−− Large RWMA. 23. Write on management of acute left ventricular failure.
•• β-blocker—Chronic routinue use of β-blocker after 24. Define hypertension, labile hypertension, malignant
STEMI for at least 2 years reduces total mortality, hypertension and isolated systolic hypertension.
sudden death and reinfarction. 25. Classify hypertension (by JNC and European society)
•• Warferin—It lower the risk of late mortality and 26. Write on types of hypertension.
reinfarction after STEMI. Warferin with aspirin 75 mg 27. Write on investigation for hypertension.
for 3–6 months is more effective than aspirin along 28. Write on treatment of essential hypertension.
for prevention of recurrent MI and cerebrovascular 29. Write on drug therapy of accelerated hypertension.
embolism below the age of 75. 30. Write on causes of secondary hypertension and its
•• Lifestyle modification—To control the risk factor for investigation.
atherosclerosis the recommendations are as follows— 31. Write on types of atrial septal defect (ASD).
−− Cessation of smoking. 32. Write on hemodynamic alteration and clinical features
−− Moderation of alcohol use. of ASD.
−− Reduction of body weight with attainment of 33. Write on types of VSD.
optimum BMI (18.5–25). 34. Write on pathophysiology, complication and clinical
−− DASH diet. features of VSD.
−− Control of hypertension (if not properly con- trolled 35. Write on clinical features of tetralogy of Fallot’s (TOF).
by β-blocker or ACEI). 36. Management of TOF.
−− Control of hyperlipidemia (target LDL <100 mg/ 37. Clinical features of patent ductus arteriosus (PDA).
dL with help of HMG CoA reductase inhibitor 38. Define and write on diagnosis of acute coronary
(atorvastatin). syndrome.
−− Regular aerobic physical exercise. 39. Write on differential diagnosis of central or precordial
chest pain.
EXERCISE 40. Write on management of STEMI in the first half an hour.
1. Draw and label a schematic diagram of the conducting 41. Write on thrombolysis in STEMI.
system of heart. 42. Write on late hospital care and management of
2. Draw and describe physiological and clinical cardiac complications of STEMI.
cycle. 43. Write on management of UA or NSTEMI in early hours.
SECTION  II
CENTRAL NERVOUS SYSTEM

•• Coma and Related Disorders


•• Meningitis
•• Epilepsy
•• Hemiplegia
•• Cerebrovascular Accident
•• Spinal Cord Disease (Paraparesis and Quadriparesis)
•• Guillain-Barré Syndrome
•• Peripheral Neuropathy
•• Myasthenia Gravis
•• Myopathy and Myotonia
•• Parkinsonism
•• Motor Neuron Diseases
•• Multiple Sclerosis
•• Polymyositis–Dermatomyositis–Inclusion Body Myositis
Chapter 11
Coma and Related Disorders

COMA initiate activity and is due to lesion of frontal lobe and its
connection.
It is a deep sleep like state from which arousal is not pos-
sible (whatever may be the intensity of stimulus).
CATATONIA
STUPOR It is characterized by hypomobility and mute syndrome that
occurs in schizophrenia and major depression. They make
It is a lighter from of coma from which arousal is possible
few voluntary or responsive movement although they blink
transiently and accompanied by motor activity that leads
and swallow. Eyelid elevation is actively resisted, blinking
to avoidance of uncomfortable stimulus.
occurs in response to visual threat and conjugate eye
DROWSINESS movement to opposite direction occurs on head rotation
(Doll’s eye).
It simulates light sleep and is characterized by easy arousal It is also characterized by cataplexy or waxy flexi- bility
and the persistence of alertness is for a brief period. in which the limbs retain the postures in which they are
Drowsiness and stupor is accompanied by some degree placed.
of confusion.
LOCKED-IN-STATE
Vegetative state (awake coma)
It is a type of pseudocoma in which an awake patient can-
It is an awake but unresponsive state where the patient not produce any speech or voluntary movement but retain
have emerged from coma, he is wakeful but unresponsive. vertical eye movement and lid elevation. The pupil are of
Eyelids are open, yawning, coughing, swallowing and normal size and reactive. The usual cause is infarction or
limb and head movement persist but there is no response hemorrhage in the ventral pons that transect all corticospi-
to external or internal stimulus. This is accompanied by nal or corticobulbar pathway.
decerebrate or decorticate limb posturing and is due to A similar state can result from total neuromuscular
extensive damage to both cerebral hemisphere as a result paralysis in Guillain-Barré syndrome, critical illness
of— neuropathy and pharmacological neuromuscular
•• Cardiac arrest with cerebral hypoperfusion. blockade.
•• Head injury.
STRUCTURE RELATED TO COMA
AKINETIC MUTISM
The pathogenesis of diminished alertness in coma is either
It signify partially or fully awake state in which the patient is
due to —
able to from impression and think as demonstrate by later
•• Widespread abnormality of cerebral hemisphere
recalling of events but remain virtually immobile and mute.
•• Reduced activity of reticular activating system (RAS).
This condition results from lesion of the medial nucleus
The causes of coma are—
of thalamus or deeper orbitofrontal surface of frontal lobe
•• Lesion that damage the RAS in upper midbrain or its
from extreme hydrocephalus.
projection.
•• Suppression of reticulocerebral function by drugs, toxin,
ABULIA metabolic derangement like hypoglycemia, anoxia,
It is a milder form of akinetic mutism characterized by uremia and hepatic encephalopathy.
mental and physical slowness and diminished ability to •• Destruction of a large portion of cerebral hemisphere.
102 Essentials of Internal Medicine

As the RAS ascends through midbrain which control This herniation can cause compression of ventricular
pupillary light reaction, its size with vertical and adduction system causing acute hydrocephalus.
movement of eye, preservation of pupillary light reflex and −− Central transtentorial herniation cause downward
eye movement suggest that the lesion is not in the midbrain displacement of thalamus through tentorial opening
but due to widespread structural lesion of cerebral cortex or with compression of upper midbrain cause miotic
metabolic suppression of the cerebral hemisphere. Whereas pupil and drowsiness due to progressive compression
loss of pupillary light reflex and eyeball movement suggest of brainstem (midbrain, pons and medulla).
lesion is in the midbrain. A direct relationship between transtentorial herniation
and coma is not always established.
ETIOLOGY OF COMA
Other herniation that usually does not produce coma:
•• Group of diseases that have no focal or lateralizing a. Transfalcine herniation—Displacement of cingulate gyrus
neurological sign with normal CT scan, CSF and under falx, across the midline.
brainstem function. b. Foraminal herniation—Downward displacement of cerebellar
tonsil into the foramen magnum which cause compression of
−− Intoxication by alcohol, sedative and opiates.
medulla with respiratory arrest and death.
−− Metabolic disturbances like anoxia, hypo or
hypernatremia, hypercalcemia, diabetic ketoacidosis Acute horizontal displacement of pineal calcification
or HONK, hypoglycemia, uremia, hepatic coma, of 3–5 mm is associated with drowsiness.
hypercarbia, hypo and hyperthyroid coma, 6–8 mm displacement of pineal calcification is
addisonian crisis hyper and hypothermia.
associated with stupor.
−− Severe systemic infection like septicemia, pneumo-
>9 mm displacement of pineal calcification is asso-
nia and malaria.
ciated with coma.
−− Postseizure and subclinical status epilepticus.
−− Hypertensive encephalopathy and eclampsia.
−− Acute hydrocephalus. Coma due to Widespread Damage to
−− Concussion of brain. hemisphere
•• Group of diseases with CSF abnormality with or
•• Hypoxic ischemia—Cause coma due to reduced supply
without fever but no focal or lateralizing neurological
sign and normal CT/MRI. of energy substrate which initially cause diffuse slowing
−− Acute meningitis of EEG similiar to metabolic coma ultimately brain
−− Viral encephalitis metabolic activity ceases.
−− Subarachnoid hemorrhage. •• The mechanism of coma in metabolic diseases like
•• Group of disease that cause focal or lateralizing hypoglycemia, hyponatremia, hyperosmolarity, hyper-
neurological sign with abnormal CT/MRI with or capnia, hypercalcemia, hepatic and renal failure is ill
without changes in CSF. understood and the reversible effect of this condition
−− Cerebral, pontine or cerebellar hemorrhage with on the brain may be due to impaired energy supply,
secondary brainstem compression. changes in ion fluxes across neuronal membranes,
−− Cerebral or brainstem infarct. neurotransmitter abnormalities and decrease blood
−− Brain abscess. brain barrier (BBB).
−− Brain tumor. •• Epileptic coma is probably due to exhaustion of energy
−− Epidural or subdural hemorrhage and brain contusion. reserve or due to accumulation toxic molecule or large
transcellular shift of sodium and water in brain which
MECHANISM OF DAMAGE TO COMA PRODUCING produces generalized slowing of background EEG
structure activity.
•• Structural compression of midbrain by herniation. •• Coma in systemic metabolic disorder like diabetic
−− Transtentorial herniation—Uncal herniation ketoacidosis, nonketotic hyperosmolarity, hyponatremia
(anterior medial temporal gyrus) cause coma is due to large shift of water and sodium balance in the
due to compression of midbrain against opposite brain.
tentorial edge by the displaced parahippocampal Na level <125 mmol/l induce confusion.
gyrus with ipsilateral pupillary dilatation. Lateral Na level <115 mmol/l induce coma and convulsion.
displacement of midbrain may compress opposite Serum osmolarity >350 mosmol/l induces coma.
(cerebral peduncle) producing extensor plantar and •• Toxic drug-induced coma—They produce coma by
hemiparesis contralateral to original hemiparesis depressing both brainstem nuclei including RAS and
known as Kernohan-woltman sign. cerebral cortex.
Coma and Related Disorders 103

Combination of brainstem sign and cortical sign which •• Bilateral asterixis is a sign of metabolic encephalopa-
occurs in certain drug overdose may lead to incorrect thy and drug intoxication.
diagnosis, i.e. drug that have atropin-like action produce •• Decorticate rigidity (posturing)—It is indicated
dilated pupil, tachycardia, dry skin whereas opiates by flexion of elbow and wrist and supination of arm
analog produce bilateral pinpoint pupil < 1 mm in suggested bilateral damage rostal to midbrain.
diameter. •• Decrebrate posturing is indicated by extension of
•• TTP, malaria and hyperviscosity—Cause coma by elbow and wrist with pronation of forearm. Suggest
diffuse occlusion of small blood vessel. bilateral damage to motor tract in midbrain or caudal
•• Cranial trauma and inflammatory demyclinating diencephalon.
disease—Cause coma by diffuse white matter damage. •• Extension of arm with leg flexion or flaccid leg is
associated with pontine lesion.
APPROACH TO DIAGNOSIS IN A PATIENT OF •• Acute widespread disorder of any type regardless
COMA of location cause limb extension and all extensor
posturing become predominantly flexor in course of
History of trauma, cardiac arrest, use of illicit drug, alcohol, time.
fever, seizure, double vision, vomiting, chronic liver disease, •• Flexor posturing in response to noxious stimulus
chronic kidney disease, heart disease or COPD or any HTN indicate severe damage to corticospinal tract.
and diabetes should be searched for as cause of coma. •• Abduction avoidance movement of limb indicate intact
corticospinal system.
GENERAL SURVEY •• Brainstem reflexes are— (a) pupillary size, (b) light
In general survey the following points helps in diagnosis reflex, (c) spontaneous or elicited eye movement, (d)
of coma are cor- neal reflex, (e) oculovestibular response and (f)
•• Fever—Suggest meningitis, encephalitis, heatstroke, respiratory pattern.
malignant hyperthermia, neuroleptic malignant It helps to localize the site of damage in coma.
syndrome, anticholinergic drug overdose or central •• Pupil size—Normal size pupil 2.5–5 mm with normal
fever and vigorous convulsion as a cause for coma. light reflex exclude primary midbrain damage or
•• Hypothermia in comatosed patient suggest alcohol, secondary compression.
barbiturate, sedative, phenothiazine, hypoglycemia, −− Unilateral dilated pupil > 6 mm with poor light
peripheral circulatory failure and extreme hypothyroid reflex signify compression or stretching of ipsilateral
state as etiology of coma. Core temperature below < 31°C 3rd nerve due to mass lesion above.
itself can cause coma. −− Oval or eccentric pupil is a early sign of 3rd nerve
•• Tachypnea—Indicate acidosis (DKA), pneumonia or compression.
infiltration of brain by lymphoma as a cause of coma. −− Bilateral dilated and unreactive pupil—Indicate
•• Hypertension—Suggest hypertensive encephalopathy severe damage to midbrain due to compression from
but it may be secondary to raised ICP (Cushing supratentorial mass, mydriatic eyedrop, direct ocular
response) in cerebral hemorrhage or head injury. trauma, anticholinergic drug.
•• Hypotension in comatosed patient suggest alcohol, bar- −− Unilateral miosis is occasionally seen in large
biturate, AMI, sepsis, internal hemorrhage, hypothyroid cerebral hemorrhage that compress the thalamus.
and Addisonian crisis as an etiology of coma. −− Bilateral small (1–2.5 mm) but reactive pupil seen
•• Fundoscopy—Can detect subhyaloid hemorrhage in in metabolic encephalopathy or deep bihemispheral
subarachnoid hemorrhage, hypertensive and diabetic lesion such as hydrocephalus or thalamic hemorrhage.
changes in comatosed patient and helps in diagnosis. −− Smaller reactive pupil (<1 mm) is characteristic
•• Cutaneous petechiae—Suggest TTP and meningococ- of narcotic overdose, e.g. (barbiturates and opiates)
cemia or bleeding disorder as a cause of coma. and extensive pontine hemorrhage. In case of
•• Cyanosis and pallor—Suggest other systemic disease opiates it will dilate with naloxone. Presence of reflex
as the etiogoly of coma. eye movement also helps to differenciate sedative
from pontine hemorrhage as a cause of coma. Reflex
NEUROLOGIC SIGN eye movement is absent in pontine hemorrhage where
Tossing in the bed, crossing of leg, yawning, coughing and it will be present in sedative overdose.
swallowing suggest drowsiness. •• Ocular movement—Eyes are observed after elevating
•• Lack of movement on one side suggest hemiplegia. the eyelid and note the resting position and spontaneous
Multifocal myoclonus indicate metabolic disorder like movement.
uremia, anoxia or prion disease, lithium or haloperidol −− Horizontal divergence of the eye at rest is normal
toxicity. in drowsiness.
104 Essentials of Internal Medicine

−− Ocular axes become parallel in deep coma. •• CNS-depressant drug—(a) First, paralyses reflex eye
−− Conjugate horizontal roving of eyeball in comatosed movement, (b) then loss of corneal reflex and (c) pupil
patient exclude damage to the pons and midbrain. become unreactive at last.
−− Conjugate ocular deviation to one side indicate •• Respiration
damage to pons on the opposite side or frontal lobe −− Shallow, slow but regular breathing suggest
lesion on the same side. “The eye looks towards the metabolic cause or drug as a cause of coma.
hemispheral lesion and moves away from brainstem −− Cheyne-Stokes respiration suggest bihemispheral
lesion.” damage or metabolic suppression associated with
−− Eye turn down and inward in thalamic and upper light coma.
midbrain lesion (hemorrhage). −− Kussmaul breathing (rapid and deep breathing)
−− “Ocular bobbing” means brisk downward and slow indicate metabolic acidosis or pontomesencephalic
upward movement along with loss of horizontal lesion.
movement in diagnostic of bilateral pontine damage −− Tachypnea suggest CNS lymphoma.
usually due to thrombosis of basilar artery (also −− Agonal gasp or terminal respiratory pattern seen in
known as down beating nystagmus). severe brain damage.
−− “Ocular dipping” slower arrhythmic downward Laboratory Investigation in a comatosed patient
movement and faster upward movement along with •• Toxicological screeming of blood and urine.
normal light reflex and horizontal gaze indicate •• CT/MRI of brain.
diffuse anoxic cortical damage (also known as •• ECG.
upbeating nystagmus). •• CSF study.
−− Oculocephalic reflex or Doll’s eye movement is •• Blood glucose, Na +, K +, calcium osmolarity, urea,
the conjugate movement of the eyes opposite to the creatinine NH3 pH, PCO2 HCO3.
movement of the neck (both vertical and horizontal) ECG: High voltage slow (d or triphasic) have over frontal
depends on the intregity of the midbrain, pons and lobe is lypical of metabolic coma (hepatic coma).
medulla and oculomo- tor nuclei which is absent in Wide-spread fast (B) activity indicate sedative drug.
awake patient. Alpha coma (wide spread) 8–12 H2 activity not altered
−− Presence of Doll’s eye indicate lesion or dysfunction by environmental stimuli results from pontine or diffuse
of cerebral hemisphere with intact brainstem cortical damage associated with poor prognosis.
pathway. EEG is also diagnostic of subclinical status epilepticus.
−− Absent oculocephalic reflex (Doll’s eye) indicate
Brain death: Criteria for brain death are:
either brainstem damage or overdose of certain
•• Widespread cortical damage as suggested by deep coma
drug. Pupillary size and light reaction differentiate
unresponsive to all form of stimulus.
drug-induced coma from structural brainstem
•• Global brain stem damage as suggested by
damage.
−− Absent pupillary light reflex
•• Normal caloric response or oculovestibular reflex to
−− Absent corneal reflex
thermal stimulus indicate normal function of frontal
−− Absent oculovestibular reflex.
lobe and brainstem and their interconnection and
•• Destruction of medulla as suggested by complete apnea.
indicate hysterical coma.
An Isoelectric EEG is confirmasy for total cerebral
•• Normal corneal reflex along with reflex eye move- ment
damage.
indicate normal pontine function.
Chapter 12
Meningitis

DEFINITION •• Group B Streptococcus (Streptococcus agalactiae) was


previously responsible for meningitis in neonates but
Inflammation of meninges is called meningitis.
now it is seen with increased frequency >60 years age
Bacterial meningitis is an acute purulent infection
group.
within subarachnoid space.
•• Listeria monocytogenes is an important causative agent
It is associated with CNS inflammatory reaction that
in neonates <1 month, pregnant woman, >60 years
results in complications like—
age group and in immunocompromised individuals of
•• Impaired consciousness, even loss of consciousness
all ages. The infection is acquired by consumption of
•• Seizure
contaminated food (specially milk products).
•• Stroke
•• Staphylococcus and coagulase negative streptococcus
•• Raised ICT
are important causes of meningitis that follow
•• Death.
neurosurgical procedure and head injury.
•• Meninges, subarachnoid space, brain parenchyma all
are involved in this inflammatory reaction that is why
PATHOPHYSIOLOGY
it is sometime called meningoencephalitis by some
authors. S. pneumoniae and N. meningitidis colonize in the
nasopharynx.
ETIOLOGY ↓
In community-acquired bacterial meningitis the common Invade blood vessel by membrane-bound vesicle
pathogen are discribed in Table 12.1. through nasopharyngeal epithelial cell or by creating
separation in the apical tight junction of columnar
nasopharyngeal epithelial cells.
Table 12.1: Common pathogen in meningitis

Age of onset Common Less common Avoid phagocytosis by neutrophil and complement-
Neonates Gram-negative bacili L. monocytogenes mediated bactericidal activity due to presence of LPS
(E. coli, Proteus) capsule.
Gr B Streptococci ↓
Preschool children H. influenzae M. tuberculosis Bloodborne bacteria reach the intraventricular choroid
N. meningitidis plexus and penetrates its capillary endothelial cell and enter
S. pneumoniae the CSF space.
Older children and S. pneumoniae L. monocytogenes ↓
adults N. meningitidis M. tuberculosis They multiply very rapidly because of almost absence of
WBC, complement and immunoglobulin in CSF.
Streptococcus pneumoniae—50% ↓
Meningococcus—25% Lysis of bacteria liberates cell wall components
Gr B Streptococcus—15% composed of LPS, teichoic acid and peptidoglycan.
Listeria monocytogenes—10% ↓
H. influenzae~ <10%. (incidence drastically. Fall after Stimulate immune competent cell in the vicinity
introduction of Hib vaccine). (microglia, astrocyte, endothelium and monocyte) to
•• Streptopneumonia is the causative agent in the adult in produce cytokines like TNF and ILs which subsequently
the age group 20–55 years. induces a massive inflammatory response liberating various
•• N. meningitis accounts for 60% of case in between 2–20 cytokine and chemotactic factors, excitatory amino acids,
years.
106 Essentials of Internal Medicine

Table 12.2: Typical csf changes in different forms of meningitis


Bacterial meningitis Viral meningitis Tubercular meningitis
• Appearance → Turbid/purulent Clear/turbid Turbid/viscus with cobweb coagulation on
standing
• Cell → Total cell 500–10000 cmm
Lymphocyte— <50 cmm PMN 10–100 cmm 100–500 cmm
→ >500 cmm Nil 0–200
• Protein → 0.5–2 g/l 0.05–0.1 g/l 0.1–0.4 g/L
• Glucose → <50% of blood glucose >50% of blood glucose <50% of blood glucose

reactive oxygen and nitrogen species. The results of which 2. Rickettsial disease (RCMF)
are— 3. Subdural and epidural empyema
•• Brain cell death. 4. Brain abscess
•• Obliterative endarteritis of leptomeningeal arteries 5. Subarachnoid hemorrhage (SAH).
causing secondary cerebral infarction. Less common differentials
1. Chemical meningitis.
CLINICAL FEATURES 2. Drug-induced hypersensitivity.
3. Carcinomatous or lymphomatous meningitis (sarcoid).
•• The course of the disease may be acute fulminant 4. SLE.
rapidly progressive or subacute slowly progressive. 5. Behçet’s disease.
•• Classical triad—Fever, occipitocervical headache, 6. Meningism caused by apical pneumonia, enteric
nuchal rigidity present in 90% of patients. Patient lies on fever, empyema thoracis, diphtheria, acute pyogenic
side, curled up attitude and resistive if disturbed. tonsillitis, viral encephalitis, leukemia, lymphoma and
•• Mental obtundation starting from lethargy to coma Weil’s disease.
present in >75% of patients (due to raised ICT). 7. Neck rigidity/retraction is also present in tetanus/
•• Nausea, vomiting, photophobia are other accompany- strichnine poisoning.
ing symptoms.
•• Seizure present in 20–40% of patients, may be focal or DIAGNOSIS
generalized, may be an early or a late presentation.
•• Other features of raised ICP are papilledema, •• Routine blood examination and blood sugar
dialated and poorly reacting pupil, VIth nerve estimation—Before starting antimicrobials.
palsy, decerebrate posturing and Cushing’s reflex •• Blood culture.
(bradycardia, hypertension, irregular respiration due to •• LP with CSF study (Table 12.2)—To confirm the
cerebral herniation) may be present. bacterial meningitis.
ƒƒ Diffuse erythematous maculopapular rash, spreading PCR for N. meningitidis, E.coli, L. monocytogenes, N.
over trunk, lower extremity, mucous membrane, influenzae, S. agalactae, S. pneumoniae to confirm
conjunctiva, palm and sole, resembling viral exanthem etiological diagnosis.
but rapidly turns into petechiae is specific clinical •• CT of brain shows diffuse meningeal enhancement.
features of meningococcal meningitis. •• MRI (superior to CT is differentiating meningitis from
•• Kernig’s sign—Inability to extend the knee when the encephalitis) shows meningeal enhancement with
thigh is flexed to a right angle over the abdomen. gadolinium and FLAIR and DNI from orbitofrontal,
•• Brudzinski’s sign. anterior and medial-temporal lobe and insular cortex
•• Brudzinski’s neck sign—When the head is passively in 90% patient.
flexed over the chest there will be active flexion of the •• EEG—Important in differentiating bacterial meningitis
hips and the knees even there may be flexon of upper from viral encephalitis by periodic sharp and slow
limb. wave complexes originating in one/ both temporal lobe
•• Brudzinski’s leg sign—Passive flexon of one hip with repeating at regular interval of 2–3 seconds in between
extension of knee of one side, cause active flexon of hip 2nd–15th day of HSV meningoencephalitis.
and knee on the other side.
TREATMENT (tables 12.3 and 12.4)
DIFFERENTIAL DIAGNOSIS •• Bacterial meningitis is a medical emergency.
Common differentials are: •• Start antibiotic therapy within 60 minutes of
1. Viral meningoencephalitis (HSV) patient’s arrival in emergency.
Meningitis 107

Table 12.3: Empirical antibiotic in case of meningitis according to age


Indications Drug and dose
• Infant <1 month → Injection ampicillin IV (200 mg/kg/day) → dose to be divided and given 4 hourly.
+
Injection cefotaxime IV (200 mg/kg/day) → dose to be divided and given 4 hourly. Same (in
• Infant 1–3 months → place of cefotaxime, ceftriaxone may be added)
• Infant 3 months to 55 years Injection cefotaxime/ceftriaxone (100 mg/kg/day → dose to be divided (55 years →) and
given 12 hourly. Adult → 2 g BD)
+
Injection vancomycin → 2 g/day → dose to be given 12 hourly and infused over 1 hour +
rifampicin
• Adult >55 years → Ampicillin + Cefotaxime / Ceftriaxone + Vancomycin + Rifampicin
(alcoholics or other debilitating illness) (3 g 4 hourly) (2 g 6 hourly) (2 g 12 hourly) (1 g 12 hourly)

• Nesocomial/posttraumatic/ Ampicillin + Ceftazidime + Vancomycin


postsurgery → (3 g 4 hourly) (2 g TDS) (1 g 12 hourly)

Table 12.4: Antibiotic therapy for meningitis—based on culture sensitivity


Pathogen Regimen of choice Alternative agents
• N. meningitidis →
Penicillin-sensitive Benzylpenicillin Ampicillin
Penicillin-resistant Ceftriaxone/cefotaxime Ampicillin
• S. pneumoniae →
Penicillin-sensitive Penicillin G Chloramphenicol
Penicillin-intermediate Cefotaxime/ceftriaxone Chloramphenicol
Penicillin-resistant Cefotaxime/ceftriaxone + vancomycin Vancomycin + Rifampicin
• Pseudomonas aeruginosa → Ceftazidime/cefepime/Meropenem
• H. influenzae → Cefotaxime/ceftriaxone Chloramphenicol
• Streptococcus agalactiae → Penicillin/ampicillin
• L. monocytogenes → Ampicillin + Gentamicin Ampicillin + Cotrimoxazole (25
mg/kg BD)
• Staphylococcus →
Methicillin-sensitive Nafcillin
Methicillin-resistant Vancomycin
• Bacteroides/Furobacterium → Metronidazole

•• Empirical antibiotic therapy is to be initiated in bacterial •• Hypotension—Fall of BP should be corrected with


meningitis after sending the blood and CSF for IV fluid and vasopressor (dopamine/dobutamine/
examination and culture. noradrenaline).
•• Treatment of complication—
General and Symptomatic Management −− Hydrocephalus—May occur in acute phase. If
not regress after conservative treatment, ventri-
•• Nursing care culoperitoneal or ventriculoatrial shunt (VP/VA)
•• Maintenance of nutrition and bladder-bowel care shunt is required.
•• Management of raised ICT—Injection mannitol −− Subdural empyema—Drainage with appropriate
(20%)—250 ml 4–6 hourly IV for 3 days. Alternatively antibiotic therapy.
oral glycerine—20–30 ml 6 hourly. −− Patient with typical meningococcal rash →
•• Convulsion—Lorazepum (0.1 mg/kg IV maximum Benzylpenicillin (2.4 g IV 6 hourly).
5 mg. If not controlled phenytoin 10–20 mg/kg IV −− Patient with history of anaphylaxis to β-lactam
subsequently 5 mg/kg orally. → Chloramphenicol (25 mg/kg IV 6 hourly) +
•• Fluid and electrolyte—Restricted (two-third of Vancomycin (1 g IV BD).
maintenance dose) fluid intake as there is chance of –– A 7-day course of IV antibiotic is adequate
SIADH. for meningococcal meningitis whereas for
108 Essentials of Internal Medicine

pneumococcal meningitis it requires 2 a week Contd...


antibiotic therapy. g. Sedation by (Morphine, propofol or midazolam) add
–– When reports of culture and sensitivity of CSF are neuromuscluar paralytic agent if necessary (patient may
available, the antibiotic regimen can be modified require endotracheal intubation and mechanical ventilation
accordingly. h. Pressor therapy to raise SBP and CPP (cerebral perfusion
•• Adjunctive dexamethasone therapy pressor) >60 mm Hg by phenylephrine, dopamine and
−− Dexamethasone → 10 mg IV 6 hourly for 4 days. norepinephrine
i. Consider second line therapy for refractory ICP
i. High dose barbiturate therapy or pentobarbital coma
The available evidence on adjunctive dexamethasone therapy ii. Aggressive hyperventilation PaCO2 < 30 mmHg
confirms benefit for H. influenzae and S. pneumoniae in reducing
iii. Craniotomy
sensory neural deafness and death. Dexamethasone therapy
j. Ventriculoatrial/ventriculoperitoneal shunt
should commence 20 minutes before or at least with the
k. Carbonic anhydrase inhibitor in communicating hydroc­
parenteral antibiotic but it is useless to start dexamethasone 6
hours after commencing antibiotic therapy ephalus.
Dexamethasone exerts its beneficial effects
1. inhibiting the synthesis of 1L–1 and TNF at the level of mRNA.
2. by decreasing the CSF outflow resistance
3. by stabilizing the bloodbrain barrier
• Dexamethasone should not be used with vancomycin as it PROGNOSIS
decreases the penetration of vancomycin into the CSF and
•• Mortality is in the range of 3–7% for H. influenzae,
delays sterilization, in that condition vancomycin can be
administered by intraventricular route
Gr. B Streptococcus, N. meningitidis.
Management of raised intracranial pressure •• L. monocytogenes mortality is 15%.
To maintain ICP <20 mm Hg. •• S. pneumoniae mortality is 20%.
a. Drain CSF via ventriculostomy.
b. Elevation of patient’s head to 30–45° in midline position CHEMOPROPHYLAXIS OF CLOSE CONTACTS
c. Intubation and hyperventilation (PaCO2→ 25–30 mm Hg) MENINGOCOCCAL MENINGITIS
d. IV Mannitol (20%) —25–100 g every 4 hourly
e. Hypertonic saline 3.4%—30 ml bolus Rifampicin (600 mg BD) for 2 days in adults or in child (10
f. Dexamethasone 4 mg every 6 hourly for vasogenic edema mg/kg BD for 2 days).
from tumor, abscess avoid glucocorticoid in head trauma, Rifampicin → Not given in pregnant women.
ischemic and hemorrhagic stroke Alternative → One dose of ciprofloxacin (750 mg) or
Contd... azithromycin (500 mg) or ceftriaxone (250 mg) IM stat.
Chapter 13
Epilepsy

Seizure—It is due to paroxysmal (abnormal, excessive) •• Alcohol withdrawal


hypersynchronous electrical discharge from a group of •• Metabolic disease
neuron in CNS, resulting in clinical manifestation ranging −− Liver failure
from dramatic convulsion to features not readily detected −− Renal failure
by the observer. −− Hypoglycemia
Epilepsy: It is a condition in which the person has −− Hypocalcemia
recurrent seizure due to chronic noncorrectable cause. −− Hyponatremia
•• When a person has single seizure or recurrent seizure −− Hypomagnesemia.
due to correctable or avoidable circumstances that does •• Infection
not necessarily called epilepsy. −− Meningitis
•• Two or more unprovoked seizure is called epilepsy. −− Encephalitis
−− Abscess
CLASSIFICATION OF SEIZURE −− Toxoplasma
−− Tuberculoma.
•• Partial seizure: •• Inflammatory
−− Simple partial seizure (without unconsciousness)— −− Multiple sclerosis
(i) sensory, (ii) motor, (iii) autonomic and (iv) psychic. −− SLE
−− Complex partial seizure (with loss of consciousness). −− Vasculitis.
−− Partial seizure with secondary generalization. •• Degenerative
•• Primary generalized seizure −− Alzheimer’s disease
−− Absence (petit mal) seizure −− Creutzfeldt-Jakob disease.
−− Tonic clonic (grand mal) seizure
−− Tonic seizure CLINICAL FEATURES OF DIFFERENT TYPES
−− Atonic seizure OF EPILEPSY
−− Myoclonic seizure.
•• Unclassified seizure Simple Partial Seizure
−− Neonatal seizure May present with the following symptomatology:
−− Infantile spasm •• Motor symptom—Typically clonic movement (2–3 Hz),
−− Febrile convulsion. but may be of pure tonic variety.
•• Sensory symptoms:
CAUSES OF GENERALIzED SEIZURE −− Paresthesia
•• Genetic −− Formed hallucination
−− Inborn error of metabolism −− Flashing of light
−− Storage disease. −− Disturbance of equilibrium.
•• Birth injury •• Autonomic symptoms
•• Cerebral anoxia −− Flushing
•• Hydrocephalus −− Sweating
•• Drugs −− Piloerection.
−− Antibiotic—Penicillin, INH and metronidazole •• Psychic symptoms
−− Antimicrobial—Chloroquine and mefloquine −− Higher cortical function disturbances
−− Antiarrhythmic—Lignocaine −− Hearing hallucination
−− Psychotropic—TCAD, phenothiazine and lithium. −− Olfaction hallucination
110 Essentials of Internal Medicine

−− Epigastric sensation •• EEG findings— 3 Hz spikes and wave pattern discharge


−− Feeling of Déjá vu’s phenomenon begin and end suddenly in a background of normal EEG.
−− Micropsia/macropsia.
FEATURES OF GTCS
EEG
This is the most common type of seizure
Ictal EEG shows abnormal discharge over a very limited Clinical stages of grand mal seizure (tonic/clonic
and appropriate area of cerebral cortex (If the epileptic foci seizure) are as follows :
is located on the medial temporal zygus or under aspect of a. Stage of aura.
frontal lobe then sphenoidal or intracranial electrode may b. Stage of cry and fall with loss of consciousness.
have to be applied to detect EEG abnormality). c. Tonic phase.
Three additional features of simple partial seizure— d. Tonic/clonic phase.
1. Jacksonian march—Spread of seizure impulse over a e. Stage of recovery and postepileptic automatism or
progressively larger area of motor cortex. Todd’s paralysis.
2. Postepileptic Todd’s paralysis—Temporary weakness or f. Postepileptic sleep.
paralysis of muscle due to exhaustion of neurotransmit- 1. Stage of aura—Some patient complain a vague
ter. premonitory symptom called aura which may be
3. Epilepsy partialis continua—Seizure may continue hours like higher cortical disturbances, hearing or visual
to days and may be refractory to medical therapy. hallucination and flashes of light.
2. Stage of cry and fall—Patient become unconscious with
loss postural control and fall occurs. Tonic contraction
FEATURES OF COMPLEX PARTIAL SEIZURE
of respiratory muscle starts in this stage cause prolong
•• Seizure activity is restricted to discrete areas of motor expiration and produce the epileptic cry.
cortex usually associated with structural abnormalities 3. Ictal phase—
of brain. −− Tonic phase—This phase persists for only 10–20
•• Transient impairment of patient’s ability to maintain seconds.
normal contact with the environment. –– Ictal cry (due to simultaneous tonic contraction of
•• Seizure is preceded by an aura. laryngeal and respiratory muscles).
•• Sudden behavioral arrest accompanied by automatism –– Impaired respiration.
(i.e. involuntary autonomic varied behaviors). –– Biting of tongue.
•• Antegrade amnesia. –– Hypertension.
•• Postictal aphasia. –– Tachycardia.
•• Confused state after the seizure persists for seconds to
–– Dilated pupil are seen in this phase.
hours.
−− Clonic phase—In this phase there is—
EEG Findings –– Superimposition of muscle relaxation period
in between tonic muscle contraction. Period of
•• May be normal or brief discharge of epileptiform spikes. relaxation progressively increases until the end
•• If the epileptic focus located on medial temporal of ictal phase, usually not more than 1 minute.
lobe—then use of sphenoidal/intracranial electrode is 4. 4th phase is the postictal period—This phase is
essential for detection of EEG changes. characterized by:
−− Unresponsiveness with muscle flaccidity
FEATURES OF PETIT MAL −− Excessive salivation
(ABSENCE) SEIZURE −− Stridorous breathing
•• Sudden loss of consciousness without loss of postural −− Bladder and bowel incontinence.
control is the cardinal sign. 5. Postictal confusion may persists for minute to hours.
•• The seizure activity lasts for a few seconds. Patient complains of headache, fatigue and muscleache
•• Consciousness returns as suddenly as it is lost without with impaired consciousness.
any postictal confusion. −− Duration of this phase may increase in:
•• May be associated with subtle motor sign (rapid –– Prolonged seizure
blinking, chewing and clonic movement of hand). –– Underlying CNS disease
•• May occur hundred times per day and begins in school –– Alcoholic cerebral atrophy.
life.
•• Evidenced by unexplained daydreaming and decline in EEG Findings
school performance.
•• Tonic phase—Progressive increase in generalized
•• Often associated with GTCS and responds well to
low voltage fast activity followed by generalized high
specific therapy.
amplitude polyspike discharge.
Epilepsy 111

•• Clonic phase—High amplitude activity typically EEG is not helpful in predicting or forecasting which
interrupted by slow waves to create spikes and waves patient is epileptic and when an epilepsy will develop.
pattern. If routine EEG is normal provocative measures like—
•• Postictal—Diffuse slowing of curve that gradually −− hyperventilation (3–4 minutes).
recovers as the patient awakens. −− photic stimulation.
−− sleep induction or sleep deprivation is performed in
VARIENTS OF GTCS an attempt to provoke abnormalities.
•• Pure tonic seizure •• Imaging—
−− CT is routinely performed to detect any structural
•• Pure clonic seizure
abnormality.
•• Atonic seizure
−− MRI is superior to CT in localizing the cerebral
•• Lennox-Gastaut syndrome.
lesion associated with epilepsy [e.g. tumor,
neurocysticercosis (NCC), tuberculoma, arterio-
DIAGNOSIS venous malformation, arterial aneurysm, cerebral
•• The first goal is to determine whether the event is truly diplegia, abnormality of cortical architecture,
a seizure and in depth history is essential as because hippocampal atrophy associated with mesial
in many cases diagnosis of seizure is based solely on temporal sclerosis apart from intracerebral
clinical ground. Examination and laboratory study are hemorrhage, infarction, abscess and encephalitis].
often normal. −− Functional imaging procedure (e.g. PET → Positron
•• Laboratory study—It includes— emission tomography) and single pho- ton
−− Estimation of blood glucose and urea creatinine. emission computed tomography (SPECT) and
−− Estimation of Na+, K+, Ca+2 and Mg+2. MR-spectroscopy are helpful to evaluate medically
−− Toxicological screening of blood and urine (in refractory seizure.
appropriate cases).
DIFFERENTIAL DIAGNOSIS OF SEIZURE
−− LP and CSF study if encephalitis or meningitis is
suspected. •• Syncope
•• EEG— −− Vasovagal attack
All patients who have a possible seizure disorder should be −− Orthostatic hypotension
evaluated with EEG. EEG measures the electrical activity of brain −− Cardiac arrhythmia
by recording from (electrode) monteg placed on scalp. The −− Valvular heart disease
potential difference between the pair of electrodes (monitoring) −− Heart failure.
is amplified and displayed on computer monitor or recorded on
paper •• Psychological disorders
  In normal awake adults lying quietly with eyes closed a −− Psychogenic seizure
α-rhythm 8–13 Hz is seen over occipital cortex intermixed with a −− Panic attack
variable amount of generalized faster β-rhythm (> 13 Hz) and it −− Hyperventilation.
is attenuated when the eyes are open
•• Metabolic disturbances
  During drowsiness α-activity is also attenuated. With light
sleep, slower activity in the range of θ rhythm (4–7 Hz) and δ −− Alcohol
rhythm (< 4 Hz) appear −− Delirium tremens
Abnormal repititive rhythmic activity having an abrupt −− Hypoglycemia
onset and termination establish the diagnosis of seizure. −− Hypoxia
Absence of EEG seizure activity does not exclude seizure disorder
−− Hallucinogenic drugs.
because partial seizure originating from the inferior frontal gyrus
and medial temporal gyrus is beyond the range of superficial •• Migraine
electrodes placed on scalp. So surgically placed intracranial •• Basilar artery TIA
electrode and sphenoidal electrodes are necessary for recording •• Sleep disorder
such seizure activity −− Nercolepsy
EEG are always abnormal during GTCS but routine −− Cataplexy
interictal EEG may be normal in 60% cases. Thus EEG −− Benign sleep disorder
cannot establish the diagnosis in many cases. −− Sleep walking
Interictal EEG showing bursts of abnormal discharge −− Night tremor.
containing spikes and slow wave (Delta wave) is highly •• Movement disorders
supportive but not specific. −− Tics
In general normal interictal EEG implies a better −− Myoclonus
prognosis whereas an abnormal background of profuse −− Chorea
epileptiform activity suggest a poorer outlook. −− Athetosis.
112 Essentials of Internal Medicine

•• In children •• Withdrawal of antiepileptic therapy—It seems rea-


−− Breadth holding spell sonable to attempt the withdrawal of the antiepileptic
−− Hemiplegic migraine therapy, if —
−− Abdominal pain and cyclic vomiting −− The patient remains seizure free for at least 2 years.
−− BPV (benign positional vertigo). −− Patient have single seizure type (either partial/
generalized).
TREATMENT (Table 13.1) −− Normal CNS examination (including investi- gation).
•• All patients with recurrent seizure should be put under •• In most cases it is wise to gradually reduce the dose
antiepileptic drugs. over 3–6 months—most recurrences occur within first
•• Single seizure with definite CNS abnormality like tumor, 3 months.
trauma, infarction, infection, hemorrhage must be given •• Surgery—
antiepileptic drugs. −− Approximately 20% patients are resistant to medical
•• Patient having single seizure without any clinical or therapy and some surgery is extremely effective in
investigational abnormality whether to be treated with substantially reducing the seizure frequency and
anticonvulsant is controversial. seizure control.
•• Risk factors for recurrent seizure −− Surgery is extremely valuable in focal seizure arising
−− Abnormal CNS examination from temporal lobe or from other parts of brain or
−− Abnormal EEG hemimegaloencephalopathy or other dysplastic
−− Patient presenting with status epilepticus abnormality.
−− Postictal Todd’s paralysis −− The surgical method of choices
−− Strong family history. –– Temporal lobectomy.
•• Patient having one or more than one of the risk factors –– Amygdalohippocampectomy.
should be treated. –– Subpial resection to disrupt the intracortical
•• The goal of antiepileptic therapy is to prevent seizure connections.
and to minimize the side effects which is done by –– Hemispherectomy or multilobular resection or
starting with a single antiepileptic drug with low dose corpus calosotomy.
and gradually building up the dose while monitoring »» 70% patients will become seizure-free.
the side effects and ideally the free drug levels in blood. »» 90% patient will have reduction in seizure
•• Add-on therapy—Monotherapy should be the goal frequency after surgical therapy.
whenever possible but if the seizure cannot be controlled
by one drug it is better to add a second drug without STATUS EPILEPTICUS
increasing the dose of 1st drug to the toxic range. •• It is defined as continuous seizure or repetitive discrete
Approximately 1/3rd patients require a combination of seizure with impaired consciousness in the interictal
two or more drugs to control the seizure. period for more than 15–30 minutes.
•• But practical definition of status epilepticus is a serious
condition where the duration of seizure prompts
emergency use of anticonvulsant therapy or when the
Table 13.1: Drugs in the management seizure seizure last for more than 5 minutes.
•• It is an emergency as cardiorespiratory dysfunction,
First line Second line/
hyperthermia and metabolic derangement prompts
Alternative
immediate therapy before irreversible neuronal injury
GTCS → 1. Valproic acid 1. Phenytoin occurs.
2. Lamotrigine 2. Carbamazepine Management of status epilepticus is described in
3. Topiramate 3. Zonisamide
4. Oxcarbazepine
Flowchart 13.1
5. Phenobarbital
CAUSES
Partial → 1. Carbamazepine 1. Levetiracetam
seizure 2. Phenytoin 2. Topiramate •• Common causes
3. Valproic acid 3. Tiagabine −− Anticonvulsant withdrawal.
4. Lamotrigine 4. Primidone −− Noncompliance to drugs.
5. Oxcarbazepine 5. Phenobarbital
−− Metabolic disturbance.
Absence → 1. Valproic acid 1. Lamotrigine −− Drug toxicity.
seizure 2. Ethosuximide 2. Clonazepum −− CNS—Infection.
Epilepsy 113

Flowchart 13.1: Management of status epilepticus

−− CNS—Tumor. uninterrupted seizure the feature become less prominent


−− CNS—Trauma. except mild clonic movements of the fingers, fine rapid
−− Refractory epilepsy. movement of the eyes, associated with tachycardia,
•• Typical features of status epilepticus is usually seen in hypertension and pupillary dialation. At that time EEG
initial period but after 30–45 minutes of uncontrolled, is the only method of diagnosis.
Chapter 14
Hemiplegia

DEFINITION CROSSED HEMIPLEGIA (NUCLEAR HEMIPLEGIA)


Weakness of one-half of the body is called hemiplegia. This rare type of clinical syndrome is seen in brainstem
lesion due to vertebrobasilar territory involvement. Here,
Paralysis and plegia indicates weakness that is complete or
the clinical feature is ipsilateral LMN motor cranial nerve
near complete and is usually due to LMN lesion whereas paresis
refers to weakness that is mild to moderate and is usually due to weakness with contralateral UMN type of weakness of
UMN lesion upper and lower limbs.
  Prefix ‘hemi’ refers to one-half of the body. Prefix ‘para’ means •• Motor cranial nerve involvement depends on the level
weakness of both the legs. Prefix ‘tetra’/‘quadri’ means weakness of brainstem lesion (midbrain, pons or medulla).
of all four limbs •• In midbrain lesion—3rd and 4th cranial nerves are in-
volved on the side of lesion with contralateral hemiplegia.
COMPLETE HEMIPLEGIA (capsular •• In pontine lesion—5th, 6th and 7th cranial nerve are in-
hemiplegia) volved on the side of lesion with contralateral hemiplegia.
•• In medullary lesion—Two types of syndrome are
Refers to paralysis/paresis of lower half of face along encountered.
with hand and leg on one side (contralateral to the side •• In medial medullary syndrome—12th cranial nerve is
of lesion). involved with contralateral UMN hemiplegia.
It is due to involvement of corticospinal tract on the •• In lateral medullary syndrome—9th, 10th and 11th cranial
opposite side at the posterior limb of internal capsule as nerves are involved with paresthesia over face on the same
a result of occlusion or hemorrhage of deep perforating
side of lesion with contralateral hemisensory loss.
branch of middle cerebral artery (lenticulostriate branch
of middle cerebral artery).
Capsular hemiplegia is contralateral to the side of lesion CAUSES OF HEMIPLEGIA
as because pyramidal tract has contralateral supply.
•• Acute onset (evolves over hours to days) hemiplegia
Pyramidal track crosses the midline at lower level of
medulla called great decussation of pyramid and supply −− Cerebral embolism.
the opposite half of body. −− Cerebral thrombosis.
−− Cerebral hemorrhage (atherosclerotic, head injury,
Motor cranial nerves (3rd, 4th, 5th, 6th, upper half of 7th and 9th, hemophilia, anticoagulation and hemorrhage within
10th, 11th and 12th) are not involved in complete hemiplegia ICSOL); Substance abuse (cocaine).
as because these nucleus have dual supply from corticonuclear −− Subarachnoid hemorrhage.
tract (pyramidal tract) of both sides except the lower half of facial −− Multiple sclerosis.
nerve nucleus which has unilateral supply from corticonuclear
tract of the opposite side. That is why all the motor cranial nerves
•• Subacute onset (evolves over days to weeks) hemiplegia
are speared except lower half of the face which is involved in −− Cerebral abscess
complete hemiplegia/capsular hemiplegia −− Subdural hematoma
−− Fungal granuloma
INCOMPLETE HEMIPLEGIA −− Meningitis
−− Parasitic infestation
It means weakness of upper and lower limb but there is no −− Primary/secondary neoplasm
involvement of cranial nerves. It is a very rare condition −− Toxoplasmosis in AIDS
and occurs due to hemisection of spinal cord between C1–4 −− Multiple sclerosis
(ipsilateral to the side of paralysis). −− Sarcoidosis.
Hemiplegia 115

•• Chronic onset (evolves over weeks to months) •• Deep tendon jerk are exaggerated (e.g. biceps, triceps,
hemiplegia: supinator, finger flexon jerk, Hoffman, knee and ankle
−− Chronic subdural hematoma. jerk) on the affected side.
−− Primary/secondary neoplasm. •• Plantar—Babinski’s sign positive (extensor plantar
−− Unruptured arteriovenous malformation. response).
−− Degenerative disease (primary spastic paraplegia, •• Gait—Classical hemiplegic gait (or circumduction
pseudobulbar palsy).
gait), i.e. flexion and adduction of upper limb,
−− Foramen magnum lesion.
with mid pronation of forearm and extension and
−− High cervical cord lesion.
abduction of hip with extension of knee and plantar
CLINICAL FEATURES OF HEMIPLEGIA flexion of ankle joint is seen at the stage of residual
paralysis.
Clinical features of hemiplegia can be divided into three
stages:
1. Stage of neurological shock CLINICAL FEATURES OF CROSSED HEMIPLEGIA
2. Stage of recovery
3. Stage of residual paralysis. In Midbrain Lesion (Fig. 14.1)
•• Dorsal midbrain lesion—Parinaud’s syndrome
Stage of Neurological Shock
−− Cause—Pinealoma/germinoma of pineal gland.
The patient is usually drowsy/comatosed in this stage: −− Involvement
•• All the muscles are flaccid. –– Superior colliculus and pretectal area of midbrain—
•• Muscle power grossly diminished. Lesion causes bilateral
•• All deep jerks are depressed. »» Paralysis of vertical gaze
•• Plantar could not be elicited/equivocal. »» Pupillary disturbances
•• Retention of urine and spontaneous defecation can occur.
»» Absence of convergence.
Stage of Recovery •• Paramedian midbrain lesion—Benedict’s syndrome
−− Oculomotor nerve, red nucleus, dentatothalamo
Recovery is usually in the following order:
rubrocortical path and medial lemniscus are involved.
1. Face—earliest.
2. Extensors of lower limb. –– Oculomotor nerve roots (ipsilateral intraaxial
3. Flexors of upper limb. fiber).
4. Plantar flexon of ankle joint. Lesion results in ipsilateral paralysis of all
5. Distal limb muscles and movement of the finger usually extraocular muscle, except
do not recover or recover very late. »» Superior oblique (IVth cranial nerve) and
lateral rectus (VIth cranial nerve).
»» Ptosis (paralysis of levator palpabrae
Stage of Residual Paralysis
superioris).
Features are seen on the affected side only and that is »» Dilated and fixed ipsilateral pupil (complete
opposite to the side of pyramidal tract lesion. internal ophthalmoplegia).
•• Nutrition—There is disuse atrophy of muscle more –– Dentatothalamic fibers and red nucleus lesion
on the distal part of the limb. No gross wasting and results in contralateral cerebellar dystaxia with
fasciculation is seen. intension tremor.
•• Tone—Clasp knife type of spasticity is present on the –– Medial lemniscus—Lesion results is contralateral
affected side. Specially in antigravity group of muscle,
loss of tactile sensation over trunk and extremities.
i.e. flexor and adductor in upper limb, extensor and
abductor in lower limb. •• Medial midbrain lesion—Weber’s syndrome
•• Power—Loss of power is more in the distal limb muscle, −− Intraaxial fibers of IIIrd nerve and cerebral peduncle
i.e. fingers and toes. Power is comperatively preserved are involved. Results are as follows:
in proximal group of limb muscle. –– Ipsilateral IIIrd nerve palsy
•• Superficial reflex—Lost on the affected side (abdominal –– Contralateral UMN type of facial weakness
and cremasteric). –– Contralateral hemiparesis (UMN type).
116 Essentials of Internal Medicine

Fig. 14.1: Lesions in the midbrain (at the superior colliculus)

Fig. 14.2: Lesions in the caudal pons

Lesion of Pons (Fig. 14.2)


Table 14.1 Medial superior pontine syndrome (paramedian branches of upper basilar artery)
On the side of lesion Opposite to the side of lesion
1. Cerebellar ataxia—due to superior and middle cer- ebellar 1. Paralysis of face, arms and leg due to pyramidal tract lesion
peduncle lesion
2. Internuclear ophthalmoplegia due to lesion of—MLF 2. Loss of touch, vibration and position sense due to medial lemniscus
involvement
3. Myoclonus of palate, pharynx, vocal cord face, respiratory or fa-
cial muscle—central tegmental bundle, dentate projection and
inferior olivary nucleus
Hemiplegia 117

Table 14.2 Lateral superior pontine syndrome (superior cerebellar artery)


On the side of lesion Opposite to the side of lesion
1. Ataxia of limb and gait falling to the side of lesion due to involv- 1. Impairment pain and thermal sense on face, limb and trunk—
ment of superior and middle cerebellar peduncle, superior sur- spinothalamic tract involvement
face of cerebellum and dentate nucleus
2. Dizziness, nausea, vomiting, horizontal nystagmus due to vestibu- 2. Impaired touch, vibration, position sense more in leg than in the arm
lar involvement nucleus due to medial lemniscus involvement
3. Paralysis of conjugate gaze due to pontine contralateral gaze nu-
cleus involvement
4. Horner’s syndrome due to descending sympathetic fiber involve-
ment

Table 14.3 Medial midpontine syndrome (paramedian branch of midbasilar artery)

On the side of lesion Opposite to the side of lesion


1. Ataxia of limb and gait due to bilateral pontine nuclei involvement 1. Paralysis of face, arms and leg—corticobulbar and corticospinal
tract

2. Variable loss of touch and proprioceptions— medial lemniscus

Table 14.4 Lateral midpontine syndrome (short circumferential artery)


On the side of lesion Opposite to the side of lesion
1. Paralysis of muscle of mastication—due to Vth cranial nerve and its 1. Impaired pain and temperature sensation over limb and trunk—
fiber involvement spinothalamic tract involvement
2. Impaired sensation over face—due to Vth cranial nerve and its
sensory fiber involvement

Table 14.5 Medial inferior pontine syndrome (paramedian branch of basilar artery)
On the side of lesion Opposite to the side of lesion
1. Paralysis of conjugate gaze center for conjugate lateral gaze 1. Paralysis of face, arms and leg—pyramidal tract
2. Nystagmus due to vestibular nucleus lesion 2. Loss of touch and proprioception over the half of body—medial
lemniscus
3. Ataxia of limb—middle cerebellar peduncle involvement
4. Diplopia on lateral gaze VIth cranial nerve lesion

Table 14.6 Lateral inferior pontine syndrome (anterior inferior cerebellar artery)
On the side of lesion Opposite to the side of lesion

1. Horizontal and vertical nystagmus, vertigo nausea, vomiting, os- 1. Impaired pain and temperature sensation over body and limb in-
cillopsia due to vestibular nerve and nucleus lesion cluding face due to spinothalamic tract involvement
2. Facial paralysis due to VIIIth cranial nerve, nucleus and nerve
lesion
3. Paralysis of conjugate gaze center for conjugate gaze lesion
4. Deafness and tinnitus due to VIIIth cranial nerve and its nucleus
involvement
5. Ataxia due to—middle cerebellar peduncle and cerebellar hemi-
sphere lesion
6. Impaired sensation over face due to Vth cranial nerve and its
descending tract lesion
118 Essentials of Internal Medicine

Fig. 14.3: Lesions in the medulla oblongata

Lesion of Medulla (Fig. 14.3) Contd...

Table 14.7 Medial medullary syndrome (due to occlusion of vertebral Ipsilateral features Contralateral features
or basilar artery or its paramedian branch) • Hoarseness of voice due
to Xth CrN involvement –
Ipsilateral features Contralateral features paralysis of vocal cord
1. XIIth nerve lesion causes 1. Paralysis of arm and leg
→ paralysis and atrophy of except face due to pyramidal 3. VIIIth nerve (vestibular
same half of the tongue tract lesion div) nystagmus, diplopia,
oscillopsia, vertigo, nausea
2. Medial lemniscus involvement
and vomiting
causes → numbness and loss
of proprioceptive sense over 4. Horner’s syndrome—due
the opposite half of the body to descending sympathetic
tract involvement—(a)
Crossed pattern of sensory disturbances in which one side of ptosis, (b) miosis, (c)
the face and opposite half of the body are affected due to lesion hemianhydrosis, (d)
localized to the lateral medulla as a result of involvement enophthalmos and (e) loss
of ipsilateral descending trigeminal tract and ascending of ciliospinal reflex are the
spinothalamic tract subserving opposite half of body. features of Horner syndrome
5. Loss of taste sensation →
Table 14.8 Lateral medullary syndrome (wallenberg syndrome) due Due to nucleus of tractus
to occlusion of vertebral pica, (posterior inferior cerebellar solitareous (NTS) lesion
artery) superior, middle, inferior lateral medullary artery 6. Numbness of arm and trunk
due to nucleus cuneate and
Ipsilateral features Contralateral features
graciles involvement
1. Vth nerve involvement 1. Anterior spinothalamic
(descending tract and sensory tract involvement causes
nucleus) causes loss of • Loss of pain and •• Foville’s syndrome—Dorsal pontine injury causes
sensation over same side of thermal sense over the lesion of VIth and VIIth nerve nucleus and involve-
the face. opposite half of the
body (contralateral to ment of corticospinal fiber which results in ipsilateral
the side of lesion) lateral gaze palsy with LMN type of facial weakness and
2. IX, X, XI, nerve involvement – contralateral hemiparesis.
• Dysphagia with nasal intona- •• Millard-Gubler syndrome—Ventral pontine injury
tion and nasal regurgitation resulting in almost same feature of Foville’s syndrome
due to IX and cranial root of XI
th cranial nerve involvement
except lateral gaze palsy which is replaced by lateral
causing paralysis of palate rectus weakness (because abducent fascicle is injured
and pharyngeal muscle rather than abducent nuclei).
Contd...
Chapter 15
Cerebrovascular Accident

STROKE MEANS STRUCK BY HAND OF GOD •• Arteritis—SLE and PAN.


•• Hypercoagulable state—Sickle-cell diseases,
It is the most common cause of hemiplegia and is defined
polycythemia, myeloma, APLA syndrome and myelo-
as abrupt onset neurodeficit [most commonly hemiplegia
proliferative disorder.
with/without higher cerebral dysfunction (aphasia,
hemisensory loss, visual field defect or brainstem defect) MECHANISM OF STROKE
which lasts for >24 hours] and is due to focal vascular cause.
•• The common mechanisms of stroke are as follows—
CEREBROVASCULAR DISEASE (CVD) −− Arterial embolism fromed at a distant site [carotid
RESPONSIBLE FOR STROKE bifurcation (most common), aortic arch, common
carotid, internal carotid, vertebral, basilar artery and
•• Thromboembolic infarct (80%) heart] dislodges from its primary site of formation
•• Cerebral and cerebellar hemorrhage (10%) and ultimately caught in the cerebral artery in the
•• Subarachnoid hemorrhage (5%) dominant cause of CVA.
•• Dissecting carotid/vertebral aneurysm (3%) −− Atheromatous occlusion of carotid or vertebral artery
•• Cranial venous sinus thrombosis (<1%) or their branches (anterior, middle or pos- terior
•• Subdural/extradural hemorrhage/hematoma (1–2%). cerebral and basilar artery) and subsequent brain
infarction.
TYPES −− Primary hemorrhage into the brain parenchyma.
−− The other uncommon mechanisms of stroke are as
•• Completed stroke—Persistent neurodeficit which has
follows—
become maximum usually within 6 hours.
–– Venous sinus thrombosis.
•• Stroke in evolution—Progression (progressive increase)
–– Multiple sclerosis (MS).
of neurodeficit during the first 24 hours.
–– Mass effect from the tumor, abscess and subdural
On other words neurodeficit is coming in step ladder
hematoma.
fashion.
–– Arteritis in SLE and PAN.
•• Minor stroke—When the patient recovers without any
–– Hypercoagulable state → e.g. thrombophilia, APLA
significant residual neurodeficit within a week.
syndrome and hyperhomocysteinemia.
•• Transient ischemic attack (TIA)—Focal neurodeficit
(e.g. → monoparesis, aphasia and hemianopia) lasts
PATHOPHYSIOLOGY
from few seconds to 24 hours and leaving no residual
neurodeficit after 24 hours regardless of whether there There are some compensatory changes that can prevent
is imaging evidence of new permanent brain injury. stroke even in case of occlusion of a carotid artery from
having any apparent clinical effects. These compensatory
mechanisms are as follows—
CAUSES OF CEREBRAL EMBOLISM OR TIA
•• After occlusion of a cerebral artery, the opening of
•• Artery to brain embolization— anastomotic channels from other arterial territories may
−− Intracerebral—Anterior communicating and poste- restore perfusion of its territory.
rior communicating, basilar and vertebral. •• Furthermore, a reduction in perfusion pressure leads
−− Extracerebral—Arch of aorta, common carotid, to other homeostatic changes to maintain oxygenation
bifurcation of common carotid and internal carotid. to the brain.
•• Heart to brain embolization—Left atrium, mitral valve When this compensatory mechanism fails, the clinically
and left ventricle. apparent effects appear.
120 Essentials of Internal Medicine

Normal brain requires 70–100 ml blood/100 g of brain CAUSES OF ISCHEMIC STROKE


tissues/min.
•• Blood flow <16–18 ml/100 g of brain tissue/min causes Common Cause
infarction within 1 hour.
•• Blood flow <20 ml/100 g of brain tissue/min may causes •• Thrombosis
ischemia without infarction unless prolonged for several hours −− Large vessel thrombosis.
to days. The area is called ischemic penumbra. −− Lacunar stroke (small vessel thrombosis— usually
•• But a fall in cerebral blood flow to zero causes brain death associated with dehydration or hypotension/
within 4–10 minutes. hypercoagulable state).
•• If blood flow is restored prior to significant brain cell death •• Embolism
and patient goes to TIA.
−− Artery to brain embolism
•• Tissue surrounding the core region of infarction is ischemic
but reversibly dysfunctional is called ischemic penumbra and
–– Aortic arch.
can be easily detected by perfussion-diffusion MRI. –– Carotid bifurcation.
Ischemic penumbra will eventually develop infarct if no –– Arterial dissection of aorta, carotid and vertebral
improvement in blood flow occurs within few hours. artery.
•• Neuronal death occurs via the following two distinct −− Heart to brain embolism (cardioembolic)
pathways— –– Left atrium—Mitral stenosis and atrial fibrillation.
−− Necrotic pathway –– Mural thrombus— Myocardial infarction and
−− Apoptotic pathway. dilated cardiomyopathy.

Fig. 15.1: Schematic diagram of pyramidal tract


Cerebrovascular Accident 121

–– Valvular lesion—Mitral stenosis, prosthetic valve •• Cerebral hemorrhage—In these patient with posi-
and bacterial endocarditis. tive history of hypertension, diabetes and accentuated
–– Paradoxical embolus—Fallot’s tetralogy and atrial atherosclerosis at the height of excitement suddenly
septal defect. develops headache, vomiting, unconsciousness,
Rare causes convulsion and neurodeficit—everything coming within
•• Hypercoagulable disorder half to one hour time.
−− Protein C, S, or antithrombin–III deficiency and •• Cerebral thrombosis—In the background of hyper-
dysproteinemia. tension, diabetes, accentuated atherosclerosis
−− Antiphospholipid antibody (APLA) syndrome and neuro- deficit coming in step-ladder fashion over few
SLE. hours specially in situation of sluggish circulation/
−− Factor V leiden and prothrombin G 20210 hemo- concentration due to diarrhea, hypotension,
mutation. cardiac arrhythmia, myocardial infarction and
−− Sickle cell, b-thalassemia and polycythemia vera. anesthesia.
−− TTP and DIC. •• Subarachnoid hemorrhage—Sudden onset headache,
−− Nephrotic syndrome, inflammatory bowel disease. vomiting persisting for few hours with meningeal signs
−− Oral contraceptive. (neck rigidity) followed by slowly evolving neuro- deficit
•• Vasculitis—PAN, Wegener’s, Takayasu’s and Giant cell (usually hemiparesis).
arteritis.
•• Meningitis—Syphilis, tuberculosis, fungal and bacterial. Clinical Features of CVA
•• Cardiogenic—Mitral valve calcification, atrial myxoma, •• Common abnormality due to occlusion of anterior
marantic endocarditis and Libman-Sacks endocarditis circulation (carotid territory—80%).
in (SLE). −− Hemiparesis—Due to pyramidal tract infarction at
•• Subarachnoid hemorrhage—Vasospasm. posterior limb of internal capsule.
•• Drugs—Cocaine and amphetamine. −− Hemisensory loss—Due to thalamocortical fiber
•• Eclampsia. infarction or ventral thalamic infarction.
•• Moyamoya disease. −− Aphasia—Due to infarction of Broca’s area, or
central speech area infarction.
RISK FACTORS FOR STROKE −− Hemianopic visual loss—Due to visual pathway
•• Systemic hypertension infarction (optic tract).
•• Diabetes −− Amaurosis fugax—Due to embolism of central artery
•• Dyslipidemia to the retina.
•• Hyperhomocysteinemia •• Common abnormality due to occlusion of posterior
•• Smoking; circulation (vertebrobasilar territory—20%).
•• Obesity −− Diplopia—Due to IIIrd, IVth and VIth cranial nerve
•• OCP nucleus or MLF infarction.
••
••
Hyperviscosity syndrome
Bleeding diathesis
−− Vertigo
}
−− Vomiting Due to VIIIth cranial nerve infarction
•• Trauma −− Chocking—Due to infarction of respiratory center.
•• Valvular heart disease with or without atrial fibrillation −− Dysarthria—Due to IXth, Xth, XIth and XIIth cranial
•• Vasculitis nerve infarction.
•• Bacterial endocarditis. −− Ataxia—Due to infarction of cerebellum and its
connection.
History in some form of cva −− Syncope—Due to pons and ascending reticular
system infarction.
Special features according to different etiology—
−− Hemisensory loss—Due to spinothalamic tract
•• Cerebral embolism—In the younger individual with
history of valvular heart disease/SABE neurodeficit infarction.
coming in lightening fashion over few seconds usually −− Hemianopic visual loss—Due to visual path or
in the form of monoparesis/aphasia. occipital cortex infarction.
  In the elderly individual the neurodeficit coming −− Transient global amnesia—Due to parieto-
in same lightening fashion with the background of temporal cortex infarction.
hypertension, diabetes, accentuated atherosclerosis, −− Tetraparesis—Due to infarction of great decus-
smoking and obesity. sation of pyramid.
122 Essentials of Internal Medicine

CLINICAL FEATURES DUE TO RISK FACTOR opercular syndrome). A combination of sensory


disturbance, motor weakness and nonfluent
•• Hypertension.
aphasia suggest occlusion of proximal part of
•• Difference of BP in two hands (subclavian stenosis) →
superior division of M2.
Coarction of aorta/Takayasu’s disease. −− Branches of inferior division of M2 supply the
•• Carotid bruit. inferior parietal and temporal cortex—occlusion of
•• Atrial fibrillation/other arrhythmia. which in the dominant hemisphere results in—
•• Valvular heart disease/endocarditis. –– Flucent aphasia, called wernicke’s aphasia
•• Recent MI. (jargon speech with inability to comprehend
•• Features of diabetes mellitus. written and spoken language).
•• Rarely features of arteritis, polycythemia, APLA –– Without any weakness but with.
syndrome, SLE and PAN. –– Contralateral homonymous superior quadran­
tanopia.
CLINICAL FEATURES ACCORDING TO Combination of acalculia, alexia, finger agnosia, right
VASCULAR TERRITORY left confusion called Gerstmann syndrome can develop due
to lesion of central and suprasylvian speech area as a result
Stroke syndrome can be subdivided into following three
of occlusion of inferior division of middle cerebral artery.
entities:
If the inferior division of M 2 in the nondominant
1. Large vessel stroke in anterior circulation
hemisphere is occluded hemineglect or spatial agnosia
2. Large vessel stroke in posterior circulation
without weakness results.
3. Small vessel stroke.
Complete MCA syndrome can occur when an embolus
Large vessel disease can be predominantly due to following occludes the steam of the artery. But cortical collateral
three causes: flow and differing arterial configurations are responsible
1. Embolism of artery for development of many partial syndromes which are
2. Atherothrombotic occlusion described above.
3. Dissection of artery.
Anterior Cerebral Artery Occlusion
STROKE IN ANTERIOR CIRCULATION It has following two divisions :
Clinical features according to arterial distribution: A1 segment—Extends from its origin from internal
carotid to anterior intercommunicating artery.
Middle Cerebral Artery (MCA) Occlusion A2 segment—Extends distal to anterior communicating
artery.
•• Proximal MCA (M1 segment—extend from origin A1 segment gives rise to several deep penetrating branch
to bifurcation in Sylvian fissure)—Gives rise to which supply anterior limb of internal capsule anterior
penetrating branches (lenticulostriate arteries) supply— perforate substance, amygdala, anterior hypothalamus and
outer globus pallidus, putamen, posterior limb of inferior part of the head of the caudate nucleus.
internal capsule, corona radiata, and most of the caudate Occlusion of proximal ACA is compensated by
nucleus. Occlusion of lenticulostriate branches produce collateral flow through MCA and PCA and anterior
lacunar stroke in the internal capsule which results in— communicating artery.
−− Pure motor stroke. If A2 segment of both sides arise from single anterior
−− Sensorimotor stroke contralateral to the side of cerebral artery (contralateral A1 segment atresia) occlusion
lesion, alternatively. of the patent A2 segment results in—
−− Contralateral hand may be ataxic. a. paraparesis with bilateral pyramidal sign
−− Dysarthria will be prominent. b. profound abulia (a delay in verbal and motor response).
−− Lacunar stroke in globus pallidus and putamen Occlusion of A 2 segment results in contralateral
may be asymptomatic but sometime Parkinsonism symptoms like—
and hemiballismus may be seen. •• Paralysis of opposite foot and leg due to motor leg area
•• Distal MCA (M2 segment)—MCA in Sylvian fissure is and corona radiata involvement.
divided into superior and inferior divisions. •• Cortical sensory loss over toes, foot and leg due to
−− Branches of superior division of M2 supply frontal lesion of sensory area for foot and leg.
and superior parietal cortex—occlusion of which •• Urinary incontinence due to involvement of sensory
results in— and motor area in paracentral lobule.
–– Arm and hand weakness (brachial syndrome). •• Contralateral grasp reflex, sucking reflex, gegenhalten
–– Facial weakness with nonfluent aphasia (paratonic rigidity) due to medial surface of posterior
(Broca) with or without arm weakness (frontal frontal lobe involvement.
Cerebrovascular Accident 123

•• Abulia (akinetic mutism) slowness, delay, intermittent which supply cerebellum, medulla, pons, midbrain,
interruption lack of spontaneity, whispering speech, hypothalamus, thalamus, hippocampus, medial temporal
reflex distraction to sound and sight due to cingulate and occipital lobes.
gyrus and inferior portion of medial frontal, temporal
and parietal lobe involvement. Posterior Cerebral Artery Occlusion
•• Impairment of gait and stance (gait apraxia) due to In 75% patients both posterior cerebral artery arises from
frontal cortex adjacent to motor leg area involvement. basilar artery.
•• Dyspraxia and tactila aphasia of left limb due to In 20% patients one arise from internal carotid.
corpus callosum lesion. In 5% patients both posterior cerebral arteries arise from
internal carotid (fetal posterior cerebral artery).
Anterior Choroidal Artery Occlusion P1 segment of posterior cerebral artery extends from
bifurcation of basilar artery to the union with posterior
The artery arises from internal carotid artery and
communicating artery. It supplies midbrain, thalamus,
supplies posterior limb of internal capsule and some
hypothalamus from its trunk or penetrating branches
geniculocalcarine fibers (visual path).
like thalamogeniculate, Percheron branch and posterior
Anterior choroidal stroke occurs due to thrombosis of
choroidal artery.
the vessel or during surgical clipping of aneurysm arising
Two clinical syndromes are observed with occlusion of
from internal carotid artery.
PCA, P1 and P2 segments.
Complete occlusion results in
1. P1 syndrome—It is due to infarction of medial thalamus,
•• hemiplegia
subthalamus, midbrain and cerebral peduncle.
•• hemianesthesia (hypesthesia)
Clinical features are the following:
•• homonymous hemianopia.
−− Weber’s syndrome—IIIrd nerve palsy with
Because this area is also supplied by M1 segment,
contralateral hemiplegia.
posterior communicating and posterior choroidal artery—
−− Claude syndrome—IIIrd nerve palsy with contralat-
minimal neuro deficit develop due to occlusion of anterior
eral ataxia (due to involvement of red nucleus or
choroidal artery and the patient recovers substantially.
dentatorubrothalamic tract), contraindic­ated hemi-
plegia is due to involvement of cerebral peduncle.
Internal Carotid Artery Occlusion
−− Hemiballismus—It is due to involvement of
It may be occluded by in situ thrombosis, embolism or subthalamic nucleus.
low-flow state. −− Paresis of upward gaze with drowsiness and
Occlusion of internal carotid may be asymptomatic if abulia—It is due to occlusion of artery of Percheron.
circle of Willis is competent but usually it produces features −− Coma with unreactive pupil, bilateral pyramidal
of proximal MCA occlusion. sign and decerebrate rigidity—It is due to bilateral
Sometime there is massive infarction of entire deep white proximal PCA occlusion causing extensive damage
matter and cortical surface. When origin of both MCA and to midbrain and subthalamus.
ACA are occluded:   Occlusion of penetrating branches to thalamic and
•• Abulia thalamogeniculate region causes less extensive
•• Stupor thalamic and thalamocapsular lacunar syndrome.
•• Hemiplegia −− Thalamic Dejerine—Roussy syndrome—consist of
•• Hemianesthesia contralateral hemisensory loss followed by agonizing
•• Aphasia burning pain (treatment by carbamazepine,
•• Anosognosia may occurs. gabapentin or TCAD).
2. P 2 segment of posterior cerebral artery—extends
In about 25% of patients of internal carotid occlusion transient distal to union with posterior communicating artery
recurrent monoocular blindness (amaurosis fugax) may be and supply medial, temporal and occipital lobes.
seen due to propagation of thrombus through ophthalmic Occlusion of P2 segment produces the followings:
artery which is a branch of internal carotid. Patient complains of
horizontal shades that sweeps down or up across the visual field
−− Contralateral homonymous hemianopia with
or transient blurring of lower or upper half of the field macular sparing.
−− Sometimes homonymous quadrantanopia can
occur, or
STROKE IN POSTERIOR CIRCULATION
−− Visual hallucination of brightly colored scenes and
Posterior circulation consist of—(a) two vertebral artery, (b) object (peduncular hallucination).
one basilar artery and (c) a pair of posterior cerebral artery. −− If the dominant hemisphere is affected and the
This arteries gives rise to—(a) deep penetrating infarct extends to involve the splenium of corpus
branches and (b) small or long circumferential branches callosum, the patient complains of
124 Essentials of Internal Medicine

–– Ataxia without agraphia. Medial medullary syndrome results from infarction


–– Visual agnosia for faces, objects, mathematical of pyramid of medulla causes contralateral hemiparesis of
symbol and colors. arm and leg sparing face with loss of joint and position sense
–– Anemia with paraphasic error (amnestic aphasia). (medial lemniscus) and ipsilateral LMN tongue palsy due
−− Medial temporal and hippocampal involvement may to involvement of XIIth nerve.
cause temporary acute disturbances of memory but it Cerebellar infarction initially leads to gait, unsteadiness,
passes away as memory has bilateral representation. headache, dizziness, nausea, vomiting, drowsiness,
−− Bilateral distal PCA occlusion produces cortical dysarthria, positive Babinski with bifacial weakness but
blindness (blindness with preserved pupillary light may suddenly develop respiratory arrest.
reaction), patient may not aware of it or even deny Initial symptom mimic viral labrynthitis but the main
it (Auton’s syndrome) or only peripheral vision is differentiating points are headache, neck stiffness and
lost and sparing central vision (gun barrel vision). unilateral dysmetria which favors stroke.
−− Balint’s syndrome—A disorder of orderly visual
scanning of surrounding due to low flow in the Basilar Artery Occlusion
watershed area between PCA and MCA territories.
Persistence of visual image for minutes despite It has the following three groups of branches—
1. Paramedian—7–10 in number supply anterior one-
shifting to another object (palinopia).
third of pons on each side of midline. Short paramedian
−− Asimultanagnosia—Inability to synthesize whole
branch of basilar artery occlusion causes infarction
image.
of a wedge-shaped area on one side of midline of pons
−− Embolic occlusion on the top of basilar artery
called medial pontine syndrome.
produces bilateral pupillary asymmetry with loss of 2. Short circumferential—5–7 in number supply lateral
light reflex and somnolence. two-third of pons with middle and superior cerebellar
peduncle.
Vertebral and Posterior Inferior Cerebellar Artery 3. Long circumferential—Anterior inferior cerebellar
Occlusion artery (AICA) and superior cerebellar artery (SCA) which
encircle pons and supply cerebellar hemisphere.
Vertebral artery has the following four segments—
In general basilar artery occlusion causes bilateral sign
•• V1—Extends from origin to the entrance to C6 transverse
and carries high mortality whereas occlusion of branch of
vertebral foramen.
basilar artery causes unilateral sign.
•• V2—Extends from C6–C2 vertebra. Complete basilar occlusion causes pontine and
•• V3—Extends from C2 to the point where the artery lower midbrain infarction produces ‘Locked in state’
pierces the dura at formen magnum. characterized by preserved consciousness with quadriplegia
•• V4—Extends from entry into the dura to join with other and cranial nerve sign and cerebellar dysfunction sparing
vertebral artery. IIIrd and sometime IVth cranial nerve (internuclear
V1 occlusion at origin is usually asymptomatic due ophthalmoplegia).
to collateral from other vertebral, thyrocervical trunk, Proximal basilar TIA produces vertigo or sensation
ascending cervical or occipital artery. of swimming, swaying, moving, unsteadiness and
When one V 1 is atretic and the other V 1 segment is lightheadedness. Other symptoms that herald basilar
occluded, a low-flow TIA can occur like vertigo, alternating occlusion include diplopia, dysarthria, facial or
hemiplegia and syncope. circumoral numbness and hemisensory loss. TIA
If subclavian artery is occluded proximal to origin of involving basilar artery or its branches are short-lived
vertebral artery, there is reversal in the direction of blood (5–30 min) and repetitive and are treated by intravenous
flow. At that time exercise of ipsilateral arm can produce heparin.
subclavian steal syndrome. Superior cerebellar artery occlusion causes severe
V 4 or PICA (posterior inferior cerebellar artery) ipsilateral cerebellar ataxia, nausea, vomiting, dysarthria,
occlusion causes ischemia of lateral medulla produce contralateral loss of pain and temperature sensation over
lateral medullary syndrome (Wallenburg syndrome) body and face (spinothalamic and trigeminothalamic
which consist of vertigo, numbness of ipsilateral face tract), partial deafness, ataxic tremor of ipsilateral upper
and contralateral limb, diplopia, hoarseness, dysarthria, extremity. Horner’s syndrome and palatal myoclonus
dysphagia and ipsilateral Horner’s syndrome. may occur.
Occlusion of medullary penetrating branch of V4 or PICA Anterior inferior cerebellar artery occlusion usually
results in partial syndrome. causes—
Quadriparesis may results from occlusion of the anterior •• ipsilateral deafness, facial weakness, vertigo, nausea,
spinal artery but hemiparesis is not a feature of vertebral vomiting, nystagmus, tinnitus, cerebellar ataxia,
artery occlusion. Horner’s syndrome, paresis of conjugate lateral gaze.
Cerebrovascular Accident 125

•• Contralateral loss of pain and temperature sensation •• Primary intracranial hemorrhage—Arteriovenous


(due to spinothalamic tract). malformation—MR angiography/CT angio.
Short circumferential branch of basilar artery •• Drug misuse—Drug screening for amphetamine and
occlusion causes infarction of lateral two-third of pons cocaine.
and middle and superior cerebellar peduncle called lateral •• Coagulopathy—PT, APTT and platelet count.
pontine syndrome. •• Subarachnoid hemorrhage:

}
−− Berry aneurysm
INVESTIGATION OF CVA −− Arteriovenous malformation MR angio and LP
Routine Examination −− Carotid-dissection/vertebral
artery dissection.
•• Routine blood count—for polycythemia and
thrombophilia. DIFFERENTIAL DIAGNOSIS OF CVA
•• Lipid profile.
•• Sugar, urea, creatinine or diabetes and uremia. •• Primary cerebral tumor.
•• Na+, K+, Ca+2 and Mg+2—Serum level estimation. •• Metastatic cerebral tumor.
•• Serologic test for syphilis. •• Cerebral abscess.
•• Noncontrast CT—Diagnostic of intracerebral •• Postepileptic Todd’s paralysis.
hemorrhage. •• Multiple sclerosis.
•• Metabolic encephalopathy, e.g. hepatic encepha-
• CT is important in excluding cerebral hemorrhage. But may
lopathy, hyperglycemic encephalopathy hypercal- cemic
not allow detection of small cerebral infarct in the early hours
and also cerebral tumor. After completed ischemic stroke it encephalopathy.
may take at least 12 hours or so before an area of low density •• Hemiplegic migraine.
appears (if at all) and by the end of 2 weeks an unenhanced
CT may appear normal even with substantial infarction due TREATMENT
to invasion by macrophage and blood vessel which renders it
isodense. But contrast enhanced CT (CECT) reveals at least a Immediate General Management
thin rim of lesion. → CT is preferable to MRI in acute stage
because intracranial hemorrhage may not be detected by MRI •• Hospital admission.
in first 48 hours. •• General medical measures
  MR angio is necessary for detection of vascular abnormality −− Care of unconscious patient.
and perfusion diffusion weighted. MRI have to be done for
−− Prevention of infection (pneumonia, UTI and skin
detection of cerebral ischemia.
infection).
•• Lumbar puncture (LP) mainly indicated for sub- −− Prevention of deep vein thrombosis and pulmonary
arachnoid hemorrhage. embolism by pneumatic compression stocking and
•• Chest X-ray may reveal cardiomegaly, valvular subcutaneous low molecular weight heparin.
calcification and bronchogenic carcinoma. −− BP check-up—Blood pressure should be lowered
•• ECG—Myocardial infarction and cardiac arrhythmias. if there is
–– Malignant hypertension.
SPECIAL EXAMINATIONS/INVESTIGATIONS IN CVA –– Concomitant myocardial ischemia.
–– If BP>185/110 and thrombolytic therapy is
Investigations for identification of risk factors are as follows: anticipated. Lowering of BP and heart rate is done
•• Cerebral embolism—Echocardiography (trans- by b-adrenergic blocker (esmolol).
esophageal) and carotid-doppler for identification of −− Fever is detrimental and should be lower by
source of emboli. paracetamol or surface cooling.
•• Arterial dissection—MR angiography. −− Anticonvulsive measures—Valproate/phenytoin (if
•• Premature atherosclerosis—Serum lipid profile and convulsion present).
measurement of carotid intimal thickening. −− Blood glucose to be monitored and to be kept < 110
•• Thrombophilia—Protein C, S and antithrombin III mg/dl by insulin infusion.
estimation. −− Brain edema—Approximately 10% of the patients
•• Homocystinuria—Urinary amino acid estimation and develop enough brain edema to cause brain
methionine loading test. herniation that peaks on 2–10 days for which
•• Anticardiolipin syndrome—APLA antibody. following measures are taken—
•• SLE—ANA and anti-ds-DNA detection. –– Water restriction—Also reduces the chance of
•• Vasculitis—ESR, C-reactive protein and ANCA SIADH.
estimation. –– IV Mannitol—20% Mannitol 300–400 ml IV. 4–6
•• Mitochondrial cytopathy—Serum lactate estima- tion hourly.
and muscle biopsy. –– Temporary craniotomy.
126 Essentials of Internal Medicine

Table 15.1: Eligibility/exclusion criteria for thrombolysis All SAH patients should be urgently investigated by
MR angio for taking decision about surgery or other
Eligibility criteria Exclusion criteria
measures like
1. Clinical diagnosis of 1. BP >185/100 despite proper −− Microembolization.
ischemic stroke treatment
−− Focal radiotherapy by γ-knife.
2. Age >18 years 2. Platelet count <1 lakh −− Insertion of stent at the site of aneurysm or
3. Onset of symptom 3. Hematocrit <25% arteriovenous malformation.
<3 hours •• Treatment of subdural hematoma and epidural or
4. Noncontrast CT 4. Glucose → <50 mg/dl >400 mg/dl extradural hemorrhage—Surgical evacuation.
excludes cerebral •• Long-term management—All risk factors should be
hemorrhage
identified and if possible treated—
5. Use of heparin within last 48 hours −− Antihypertensive therapy—DBP should be kept >100
6. Increased APTT/ INR mmHg at the onset. Later pressure should be lowered
7. Rapidly improving symptoms slowly to avoid sudden fall of cerebral perfusion
8. Major surgery/trauma in last 14 days pressure.
9. Myocardial infarction or pericarditis −− Antiplatelet agents—Long-term aspirin—150 mg/
in the recent past day, reduces infarction and thromboembolic
10. Neurosurgery/head trauma in last stroke tendency. Combination of aspirin 75 mg and
3 months, coma and stupor clopidogrel 75 mg is probably the best.
11. GI bleeding in last 3 weeks −− Anticoagulant agents—Heparin and warfarin to
be given with the background of atrial fibrillation/
•• Emergency plain CT—To differentiate between paroxysmal dysrrhythmia or vegetation in cardiac
ischemic stroke/hemorrhagic stroke/other causes. valve or cardiomyopathy and APLA syndrome. (but
intracranial hemorrhage, must be excluded before
Special Measure starting anticoagulant therapy).
•• Treatment for Cerebral Infarction (ischemic stroke) −− HMG-CoA reductase inhibitor for dyslipidemia.
−− If CT shows infarction—aspirin (300 mg/day) •• Other Measures
initially. −− Hyperhomocysteinemia → treated by folic acid.
−− Thrombolysis (Table 15.1)—In ischemic stroke or −− SLE, APLA syndrome → treated by prednisolone,
thromboembolic stroke consider r-TPA thrombolysis. mycophenolate motifil and cyclophosphonide and
[Dose → 0.9 mg/kg (max—90 mg) 10% of total dose by LMWH.
IV bolus over 1 minute, remainder by slow IV infusion −− Internal carotid endarteriotomy to be considered in
in 60 minutes] within 3 hours of onset of symptom. TIA/ischemic stroke, who have narrowing of lumen
−− Endovascular mechanical thrombectomy—It is the of internal carotid artery by 70% or more.
recent alternative method of treatment of acute stroke −− Rehabilitation, physiotherapy and speech therapy.
patient who are ineligible or have contraindications −− Cessation of smoking.
to thrombolytic therapy or have failed to vascular −− Moderation of alcohol consumption.
recanalization with IV thrombolytics. −− Reduction of body weight.
•• Treatment of cerebral hemorrhage (hemorrhagic −− Adoption of active lifestyle.
stroke)
−− If CT shows intracranial hemorrhage—Do not give TRANSIENT ISCHEMIC ATTACK
any therapy that interferes with clotting. Neurosurgery
is preferred for cerebellar hemorrhage >3 cm size.
DEFINITION of tia
−− For cerebral hemorrhage—Surgical decompression
can be done when a superficial hematoma in the It is a condition where transient focal neurological signs
putamen or cerebral white matter exerting mass and symptoms persist (typically for 5–15 min) but must be
effect. <24 hours due to embolic stroke.
•• Treatment for subarachnoid hemorrhage (SAH)—
Immediate treatment CAUSEs of tia
−− Bed rest
−− Supportive measure 1. Artery to brain embolism.
−− Control of BP 2. Heart to brain embolism.
−− Nimodipine—60 mg 4 times daily 3. Rarely sickle-cell anemia, polycythemia, SLE, APLA,
−− Paracetamol—for headache. myeloma and PAN.
Cerebrovascular Accident 127

CLINICAL FEATURES of tia •• Ataxia—Due to cerebellar involvement.


•• Dysarthria—Due to IXth, Xth, XIth and XIIth cranial
It can affect both anterior or posterior circulation. Clinical
nerve involvement.
feature depends on which artery has been involved.
•• Hemisensory loss—Due to spinal lemniscus involve-
ment.
FEATURES OF INVOLVEMENT OF ANTERIOR •• Hemianopic visual loss—Due to optic tract and lateral
CIRCULATION (CAROTID SYSTEM) geniculate body involvement.
Symptoms •• Transient global amnesia (loss of memory lasting for
several hours occurring commonly in aged person >65
•• Weakness of contralateral lower half of face, arm and years followed by complete recovery presumed to be
leg due to involvement of precentral gyrus or posterior due to vertebrobasilar insufficiency).
limb of internal capsule on the opposite side.
•• Paresthesia or impaired sensation of the opposite CLINICAL FEATURES IN OTHER SYSTEM
half of body due to involvement of postcentral gyrus or
posterior limb of internal capsule on the opposite side. •• Clinical evidence of source of embolism
•• Transient homonymous hemianopic loss of vision −− Carotid artery bruit
due to involvement of optic tract and radiation on the −− Atrial fibrillation or other arrhythmia
opposite side. −− Valvular heart disease
•• Dysphasia or aphasia due to involvement of Broca’s −− Endocarditis
area or its connection (arcuate fasciculus). −− Recent AMI
−− Difference in pressure in between right and left
Signs brachial artery.
•• Underlying condition that may be evident
•• UMN type of weakness on opposite half of body. −− Atheroma
•• Plantar extensor. −− Hypertension
•• Deep tendon reflex (DTR)—depressed in acute stage −− Postural hypotension
but brisk in the stage of recovery. −− Bradycardia or low cardiac output state
•• Ophthalmoscopy—retinal artery occlusion or −− Diabetes mellitus
embolism (confirmatory diagnosis) may be present. −− Rarely arteritis, polycythemia and APLA syndrome.
•• Amaurosis fugax—sudden transient loss of vision in
one eye due to passage of emboli through retinal artery DIAGNOSIS
which is sometime visible by ophthalmoscope.
Investigation is done to establish the followings:
FEATURES DUE TO POSTERIOR TERRITORY •• Clinical diagnosis.
•• Differentiate between hemorrhage or thromboembolic
(VERTEBROBASILAR SYSTEM) INVOLVEMENT
infarct from TIA.
•• Vertigo—Due to vestibular nucleus involvement. •• Look for the underlying cause of TIA and to direct
•• Chocking—Due to respiratory center involvement. therapy either medical and surgical accordingly.
•• Difficulty in speech—Due to central speech area −− Blood—CBC to exclude polycythemia, thrombophilic
(parietotemporal gyrus) or its connection involvement. disorder, syphilitic serology, clotting study,
•• Weakness of all 4 limbs—Due to involvement of autoantibodies (ANA, ds-DNA, APLA) and lipid profile.
pyramidal tract of both sides. −− Chest X-ray.
•• Transient loss of consciousness—Due to involvement −− ECG.
of pons or asending reticular system involvement. −− Echo with Doppler and transesophageal echo for
•• Transient loss of memory—Parietotemporal gyrus presence of thrombus or SABE in the left side of heart.
involvement. −− Carotid Doppler—For carotid atheroma.
•• Double vision—Due to IIIrd, IVth, VIth cranial nerve −− CT/MRI—To exclude hemorrhage or throm-
involvement. boembolic infarct.
−− MR angio of cerebral vessel.
Signs
MANAGEMENT
•• Quadriparesis—Due to involvement of pyramidal
tract of both side at the lower end of medulla (great •• Admit in multidisciplinary hospital.
decussation of pyramid). •• General medical measure.
•• Syncope—Due to involvement of pons or ascending •• Care of unconscious patient
reticular formation. −− Airway and breathing support.
128 Essentials of Internal Medicine

−− If bradycardia, decrease COP and absent pulse— •• Indication for anticoagulation therapy—
cardiopulmonary resuscitation. −− Valvular heart disease (especially MS)—Initially
•• O2 by mask LMWH and followed by warfarin.
•• BP—Check-up. −− Recent AMI (with intracardiac thrombus or atrial
•• Thorough clinical examination to find any source of fibrillation)—LMWH followed by warfarin sodium.
emboli. −− Acute thrombosis of internal carotid or basilar artery.
•• Aspirin (300 mg/day—initially by chewing) should −− Acute internal carotid/basilar artery dissection—
be given as antiplatelet treatment, provided no other heparin followed by warfarin.
contraindication present. −− Prothrombotic state—Thrombophilia and APLA
•• Appropriate drug for HTN, DM, heart disease or other syndrome—Anticoagulation.
medical conditions like dyslipidemia. −− Recurrent TIA on full antiplatelet therapy (Aspirin +
•• Carotid end arteriotomy if the condition requires. clopidogrel)—Anticoagulant is justified.
Chapter 16
Spinal Cord Disease (Paraparesis and Quadriparesis)

UMN—Upper moter neuron, LMN— Lower motor neuron, ALS—Amyotrophic latral sclerosis, MND—Motor neuron
disease.

Paraparesis—Weakness of both the lower limbs with or −− Mixed peripheral nerve, e.g. femoral or sciatic nerve
without sensory loss and sphincteric disturbances is called or its branches.
paraparesis. −− Myoneural junction and muscle are also included
Quadriparesis (tetraparesis)—Weakness of all four in LMN and lesion of which may cause paraplegia.
limbs is called quadriparesis.
CRANIAL CAUSEs OF PARAPLEGIA
TYPEs OF PARAPLEGIA OR PARAPARESIS Rarely some expanding mass in the interhemispheric fissure
causes compression of the paracentral lobule of motor
•• Spastic paraplegia—It is due to involvement of upper cortex of the frontal lobe on both the sides (which control
motor neuron, or pyramidal tract which arises from the lower limb muscle) causing paraplegia. These are—
large pyramidal cell of layer five of Brodmann’s area •• Parasagittal meningioma
four in the precentral gyrus and extend up to motor •• Superior sagittal sinus thrombosis
cranial nerve nucleus in brainstem or anterior horn •• Thrombosis of the unpaired anterior cerebral artery
cell in spinal cord (from cervical to coccygeal segment). •• Hydrocephalus.
•• Flaccid paraplegia—It is due to involvement of lower Spastic paraplegia in extension—In the initial stage of
motor neuron which consists of— spinal cord compression (compressive myelopathy) causing
−− Motor cranial nerve nucleus in brainstem and spastic paraparesis, the compression cause impairment
anterior horn cell in spinal cord. of pyramidal tract function only which leads to extension
−− Motor cranial nerve or motor fiber of mixed spinal of hip, knee and plantar flexion of ankle—called spastic
nerve. paraplegia in extension. In pure spastic paraplegia the lesion
−− Myoneural junction. involve pyramidal tract between D1–D9 vertebra containing
−− Muscle. T2– T12 spinal segment.
All are included in lower motor neuron. Spastic paraplegia in flexion—In the late stage of
•• Mixed paraplegia—It is due to involvement of both compressive myelopathy, there is compression of both
upper and lower motor neuron (e.g. ALS) (amyotrophic pyramidal and extrapyramidal tract which leads to
lateral sclerosis). unmasking of local spinal flexion reflexes from the higher
control and result in flexion attitude of lower limb (flex-
CAUSES OF PARAPLEGIA OR PARAPARESIS ion of hip, flexion of knee and dorsiflexion of ankle) called
paraplegia in flexion.
Causes of paraplegia: It lies in the spinal cord below T1 Flaccid paraplegia—In flaccid paraplegia, the lesion
spinal segment and is due to involvement of— is usually from D 10 vertebral body downward involved
•• Upper motor neuron (UMN) (i.e. lateral corticospinal structurs may be any one of the following—
tract lesion) causes spastic paraplegia. •• Anterior horn cell from L1 spinal segment downward
•• Lower motor neuron (LMN) lesion cause flaccid tocoxygealsegment.
paraplegia. The following structure of LMN are involved. •• Ventral nerve root arising from those anterior horn cell
−− Anterior horn cell below L1 spinal segment supplying including cauda equina.
lower limb muscle. •• Nerve plexus of both sides (lumbar and sacral plexus)
−− Ventral nerve root arising from those anterior horn •• Mixed peripheral nerve
cell of (L1 to coccygeal) segment. •• Myoneural junction
−− Nerve plexus (lumbar and sacral plexus). •• Muscle of lower limb.
130 Essentials of Internal Medicine

Fig. 16.1: Location of lesion in cranial causes of paraplegia

Mixed paraplegia—The muscles of the lower limb are a lesion involve the spinal cord in between D10–L1 vertebral
supplied by lumbar and sacral spinal segment and these bodies a mixed picture of UMN and LMN involvement is
spinal segments are situated within D10–L1 vertebra, when seen.

Table 16.1: in adults relationship of vertebral bodies with spinal segment


Vertebral body Spinal segment
Upper cervical vertebra contain Same spinal segment
Lower cervical vertebra contain One spinal segment below
D1to D5 vertebra contain Two spinal segment below
D6 to D9 vertebra contain Three spinal segment below
D6 vertebra contain T9 spinal segment
D7 vertebra contain T10 spinal segment
D8 vertebra contain T11 spinal segment
D9 vertebra contain T12 spinal segment
D10 vertebra contain L1+ L2 spinal segment
D11 vertebra contain L3 and L4 spinal segment
D12 vertebra contain L5 + few upper sacral segments (S1 + S2)
L1 vertebra contain Rest of the lower sacral and coccygeal segments (S3 + S4 + S5 + C)
(known as conus medullaris)

Table 16.2: Clinical differences between lmn and umn palsy


Features of UMN palsy Features of LMN palsy
a. Nutrition: Wasting is minimal called disuse atrophy a. Nutrition: Wasting and atropy is profound called LMN atrophy
b. Tone: Hypertonia— Clasp knife spasticity seen in antigravity group b. Tone: Gross hypotonia— flaccidity
of muscle, i.e. flexor plus adductor of upper limb and extensor plus
abductor in lower limb

Contd...
Spinal Cord Disease (Paraparesis and Quadriparesis) 131

Contd...

Features of UMN palsy Features of LMN palsy


c. Power: Diminished (grade 1/5–4/5) c. Power: Absent (grade– 0/5)
d. Involuntary movement: Absent d. Involuntary movement: Fasiculation may be present
[In slow degeneration of anterior horn cell, e.g. MND]
e. Reflex → Superficial reflex—lost e. Both superficial and deep tendon reflex are lost
deep tendon reflex → Hyperreflexia in recovery stage.
f. Plantar → Extensor f. Plantar: No response

CAUSEs OF ACUTE ONSET SPASTIC Other causes


PARAPARESIS •• Epidural abscess
Lesion located in between T1–T10 vertebra. •• Chronic arachnoiditis—TB, syphilis and sarcoidosis
•• Spinal cord compression •• Meningeal infiltration—Lymphoma and leukemia
−− Intervertebral disk prolapse. •• Extramedullary tumor
−− Subdural/epidural hematoma and abscess. •• Intramedullary tumor.
−− Vertebral fracture with dislocation due to trauma,
Noncompressive
TB and tumor.
•• Inflammatory and demyelinating lesion •• Inflammatory
−− Multiple sclerosis −− Multiple sclerosis
−− Devic’s neuromyelitis optica −− Devic’s disease.
−− Acute transverse myelitis (ATM) •• Vascular
−− Acute necrotic myelopathy. −− AV malformation
•• Ischemic causes −− APLA syndrome.
−− Anterior spinal artery thrombosis •• Infective
−− Disecting aneurysm. −− HTLV–1, HIV–1
•• Infective −− Progressive encephalomyelitis with rigidity.
−− Viral myelitis (acute transverse myelitis). •• Developmental
−− Syringomyelia
CAUSES OF ACUTE ONSET FLACcID −− Meningomyelocele.
PARAPARESIS •• Others
•• Lesion involving anterior horn cell—Poliomyelitis and −− MND (motor neuron diseases)
traumatic injury to vertebral column below T10 vertebra. −− Lathyrism
•• Lesion involving the anterior root of the spinal nerve −− Paraneoplastic myelitis.
or peripheral nerves— •• Metabolic
−− Lumbar disk prolapse −− Subacute combine degeneration of spinal cord
−− Lumbar plexus injury (psoas abscess or hematoma) −− Adrenomyeloneuropathy.
−− Guillain-Barré syndrome
CAUSES OF CHRONIC FLACCID PARAPLEGIA
−− Traumatic injury of peripheral nerve.
•• Chronic disk prolapse of lower lumbar region.
CAUSES OF CHRONIC ONSET SPASTIC •• Cauda equina syndrome and spinal canal stenosis.
PARAPLEGIA •• Myasthenia gravis and Lambert-Ealon syndrome.
Compressive •• Peripheral neuropathy including CMT (Charcot-Marie-
Tooth disease).
•• Metastatic deposit. •• Myopathies.
•• Cervical spondylosis.
•• Disk protrusion (chronic). CAUSES OF CAUDA EQUINA SYNDROME
•• Primary vertebral benign neoplasm—Sarcoma,
myeloma, osteoma, chordoma and hemangioma. •• Compressive—Ependymoma, neurofibroma, chor-
•• Vertebral infection—TB doma, lipoma, meningioma and spinal canal stenosis.
•• Craniovertebral anomalies •• Noncompressive—Arachnoiditis involving lumbo-
•• Atlantoaxial subluxation sacral region.
•• Thalassemia (by extramedullary erythropoiesis). •• Degenerative—Intervertebral disk protrusion.
132 Essentials of Internal Medicine

CLINICAL FEATURES OF SPINAL CORD INJURY In Higher Cord Lesion


(at a particular level) In case of paraplegia due to lesion of cervical or thoracic
When a lesion involves a segment of spinal cord, it destroys cord there is loss of higher control over lower spinal center.
both— In that condition sympathetic fiber takes the upper hand,
•• Peripheral white matter contain internal urethral sphincter remain contracted and there
−− Descending motor tract (both pyramidal and is retention of urine. But when the intravasical pressure
extrapyramidal). rises above the physiological limit of urethral sphincter,
−− Ascending sensory tract. the sphincter partially open and there is dribbling of urine
•• Central gray matter contains motor and sensory but bladder remain full. This condition is called Retention
neuron. overflow or overflow incontinence.
Outlines of clinical features of cord compression In Lumbar Cord Lesion
(Paraplegia)
•• Features at the level of lesion When lumbar sympathetic nerve (L 2–L4) is damaged in
−− Motor function—LMN type of motor weakness lumbar cord lesion and there will be loss of both cortical (or
(wasting, hypotonia, loss of muscle power grade higher) and sympathetic control on bladder. In this condition
(0/5). parasympathetic nerve takes the upper hand. As a result
−− Sensory function—All modalities of sensation are detrusor muscle remain contracted and the urethral sphincter
lost. But sometimes a girdle constricting pain due to remain open so there will be constant dribbling of urine but
nerve root irritation in extradural lesion or a burning the bladder remain empty. This is called true incontinence.
pain in intramedullary lesion may be present at the In Sacral Cord Lesion
level of lesion. When sacral parasympathetic nerve in damaged in sacral
−− Reflexes cord lesion, sympathetic will take the upper hand and there
–– DTR is lost at the level of lesion. will retention of urine with loss of voluntary contraction of
–– Superficial reflex is also lost at the level of lesion. detrusor but the detrusor muscle can be reflexly contracted
–– Plantar—not elicitable if the lesion involve S1 by stimulation of perinium which results in partial
segment but extensor when the lesion in above evacuation of bladder.
SI dermatome.
•• Features below the level of lesion CLINICAL FEATURES OF MYELOPATHIES
−− Motor function—UMN type of motor weakness
(disuse atrophy, spasticity, loss of muscle power Upper Cervical Cord (C1–C4)
grade 1/5–4/5). •• Sensory involvement of all four limbs and trunk.
−− Sensory function—Loss of all modalities of sensation •• Features of UMN lesion in all four limbs and trunk
(both large fiber and small fiber). (quadriparesis).
−− Reflexes •• Compromised diaphragmatic function.
–– DTR—Brisk below the level of lesion. •• Lesion in the region of foramen magnum (Arnold-Chiari
–– Superficial reflexes—Lost below the level of lesion. malformation) produces up beating nystagmus with
–– Plantar—Extensor. cerebellar ataxia.
•• Features above the level of lesion
−− Motor function—Normal. Lesion at the Level of C5–C6 Spinal Segment
−− Sensory function—A zone of hyperasthesia at the •• LMN atrophy and weakness of deltoid, biceps,
junction of normal with the diseased segments due to brachioradialis, supra-and infraspinatus and
loss of inhibitory impulse from the injured segment rhomboids.
below. •• UMN paralysis of remaining muscle of upper limb, trunk
−− Reflexes—Both superficial and deep sensation are and lower limbs.
normal. •• Biceps and triceps jerks are lost with inversion of
supinator jerk.
BLADDER AND BOWEL control in paraplegia •• Sensory loss of almost whole of the upper limb excluding
Bladder and bowel is controlled by sympathetic and some area over deltoid with loss of sensation over trunk
parasympathetic nurve which is coming from lumbar and leg.
(L2– L4) segment and sacral S3–S4 segment respectively.
Sympathetic supply internal urethral sphincter and function Lesion at the level of C8–T1 Spinal Segments
as a nerve of retention. Parasympathetic supply detrusor •• LMN atropy with weakness of flexors of wrist, fingers
muscle and act as nerve of evacuation. There is also a higher and small muscles of hands.
control which is coming from cerebral cortex. •• Horner’s syndrome.
Spinal Cord Disease (Paraparesis and Quadriparesis) 133

•• UMN paralysis of trunk muscle and lower limb muscle. •• Knee jerk depressed with exaggerated ankle jerk and
•• Sensory involvement of medial part of arm, forearm and extensor plantar response.
little finger with loss of sensation over trunk and legs. •• True incontinence of bladder.

Lesion at the Midthoracic Level Lesion at the level of S1–S2 Spinal Segments
•• LMN type paralysis with atrophy of the muscle confined •• LMN palsy of small muscle of the foot, calf, hamstring
to that intercostal space. and gluteus.
•• Diaphragmatic movement normal (root value—C3, C4 •• Sensory impairment over buttock, perineum, posterior
and C5). aspect of lower limb including sole.
•• UMN type palsy of muscles of abdomen and lower limb •• Knee jerk—preserved but ankle and plantar is lost.
below the level of lesion. •• Flexion of the hip, adduction of thigh, extension of knee
•• Loss of sensory function found at the corresponding and dorsiflexion of foot are preserved.
segment of lesion but some time.
Lesion Involving S3–S4 Spinal Segments
−− Root pain may be present—if the lesion compresses
the posterior root (extramedullary lesion). •• Large bowel, bladder is paralyzed with retension of
−− Dull aching pain may be present—over the segment urine and feces due to uninhibited action of sympathetic
in case of intramedullary lesions. supply.
−− A zone of hyperesthesia with sense of girdle con- •• External sphincter are paralyzed.
stricting pain just above the level of lesion. •• Anal and bulbocavernosus reflexes are lost.
−− Loss of all modalities of sensation below the level le- •• Sensory loss over perineum and buttock over a saddle-
sion. back distribution.
•• Lower limb is normal.
Lesions of the level of T9 , T10 and T11 Neural Segments
•• UMN palsy of lower limb and lower abdominal muscle. SOME SPECIAL PATTERNS OF SPINAL
•• Sensory loss below the umbilicus. CORD DISEASE
•• Beevor’s sign—Upward pulling of umbilicus when
the patient raises his head against resistance due to
Brown-Séquard Hemicord Syndrome (Fig. 16.2)
contraction of unaffected upper abdominal muscles. •• Classic forms of Brown-Séquard syndrome is rare—par-
•• Upper abdominal reflexes are preserved while those of tial forms commonly encountered.
lower abdomen is lost. Hemisection of the spinal cord produce Brown- Séquard
Special feature of T11 segment involvment. There will be syndrome with absent pain and temperature Sénsation
inguinal hernia due to involvment of lower oblique muscle contralaterally and loss of proprioception with motor power
of abdomen. ipsilaterally below the level of lesion. In simplified form we
can say.
Lesion at the level of T12–L1 Spinal Segments •• Maximum motor loss on same side.
•• Rectus abdominis are normal. •• Maximum sensory loss on the opposite side.
•• LMN lesion of lower fibers of internal oblique and −− Ipsilateral—UMN weakness (pyramidal sign) with
transverse abdominis causes—increased tendency of her- loss of joint, position and vibration sense (posterior
niation due to weakness of posterior wall of inguinal canal. column).
•• UMN palsy of lower limb. −− Contralateral loss of pain and temperature (lateral
•• Loss of all modalities of sensation over lower limb. spinothalamic tract)—below the level of lesion.
•• Abdominal reflex is preserved while cremasteric reflexes
are lost.
•• Lesion at any level above L1 segment will cause retention
overflow or overflow incontinence.

Lesion at the level of L3–L4 Spinal Segments


•• Mixed LMN, UMN lesion found in lower limb.
•• Flexion of hip is preserved through psoas and iliacus
(L1 and L2).
•• LMN wasting and weakness of lower part of quadriceps
and hip adductors.
•• UMN palsy of calf muscles and hamstrings.
•• Sensory loss starting from just above the knee whole of
the leg back of thigh and perineum. Fig. 16.2: Brown-Séquard hemicord syndrome
134 Essentials of Internal Medicine

Fig. 16.3: Schemic diagram of cross section of spinal cord at upper cervical level

−− Segmental signs, such as radicular pain, muscle Differentiation between intradural and Extradural
atropy, areflexia are unilateral at the level of lesion. Lesion
Difference between Intramedullary •• Extradural lesions due to malignant condition— gives
and Extrame- dullary Lesions a comparatively short history.
•• Intradural lesion due to benign tumor (neuro-
•• Extramedullary lesion—
fibroma)—have a long duration of symptom.
1. There is radicular pain at the level of lesion.
2. Saddle back anesthesia with early sacral sensory loss
Tetraparesis or Quadriparesis
due to involvement of lateral spinothalamic tract.
3. Spastic weakness of leg due to involvement of •• In case of compressive neuropathy involving upper
corticospinal tract with early involvement of cervical cord (C1–C5). The march of neuro deficit starts
hamstring due to superficial location of sacral fiber in the ipsilateral lower limb and then subsequently
in (hamstring) corticospinal tract (Fig. 16.3). ipsilateral upper limb, contralateral upper limb and
•• Intramedullary lesion—Poorly localizing. Burning pain contralateral lower limb are involved sequentially.
rather than radicular pain with sparing of sensation So the march of neuro deficit runs in an inverted
over perineal and sacral area (sacral sparing) reflecting U-shaped manner due to the laminated disposition of
the laminated configuration of spinothalamic tract. the pyramidal and spinothalamic tract in the lateral
Corticospinal tract sign appear later (Fig. 16.3). column of the cervical spinal cord (Fig. 16.3).
Spinal Cord Disease (Paraparesis and Quadriparesis) 135

Fig. 16.4: Subacute combined degeneration of spinal cord (B12 Fig. 16.5: Syringomyelia
neuropathy)

Subacute Combined Degeneration of Spinal Cord temperature sensation but relative preservation of light
(B12 neuropathy) (Fig. 16.4) touch, position sense and vibration sense.
•• Ventral horn involvement causes flaccid paralysis—
•• Associated with pernicious anemia. Specially of the intrinsic muscle of hand.
•• Dorsal column is involved—bilateral loss of tactile
discrimination position sense, muscle sense and
DIFFERENCE BETWEEN CAUDA EQUINA
vibration sense.
SYNDROME AND CONUS MEDULLARIS
•• Lateral corticospinal tract is involved—causing bilateral
spastic paraparesis with positive Babinski’s sign. SYNDROME (Table 16.3)
•• Spinocerebellar tract involvement—bilateral arm and Cauda Equina (Horsetail)
leg dystaxia.
•• Bunch of 40 nerve fiber (20 nerve on each side) with a
Friedreich’s Ataxia dural process (phyllum terminale) is called cauda equina
•• Spinal cord pathology is same as subacute combined which emerge from the terminal end of spinal cord
degeneration (due to B12 deficiency). below L1 vertebrae. It contains segmental nerve from L2
to coccygeal segment. Four nerve for lumbar segment
Syringomyelia (Usually Involve Cervical Cord) five nerve for sacral segment and one nerve for coccygeal
(Fig. 16.5) segment. Total ten segmental nerve on each side so
altogether 20 nerve. As the ventral and dorsal root arises
Formation of central cavitation or extension of the
from the spinal cord separately so there will 40 nerve fiber.
neurocele of the cervical cord of unknown pathology? It is
a degenerative disorder.
Conus Medullaris
•• Ventral white commissural fiber destruction causes
bilateral loss of pain and temperature sense. Dissociated •• Triangular cone-shaped lower end of spinal cord is
sensory loss with impairment of pinprick and called conus medullaris located within L1 vertebrae.

Table 16.3: Comparison between cauda equina and conus medullaris lesion
Points Cauda equina syndrome Conus medullaris syndrome
1. Involvement Spinal root from L2 to coccygeal spinal nerve Spinal cord segment (S3+ S4 + S5 coccygeal segment)
2. Onset Gradual and unilateral Sudden and bilateral.
3. Cause PID and nerve root tumor Intramedullary tumor
4. Pain Severe, unilateral and radicular pain Bilateral burning pain but not severe and
spontaneous sweating over sacral segment
5. Sensory loss Unilateral area around anus on the side of Bilateral dissociated sensory loss (symmetrical and
lesion saddle-shaped area around anus)
6. Muscle involvement Unilateral muscle atrophy Muscle changes are not marked
7. Reflexes Knee and ankle jerk are lost Ankle jerk is absent and usually knee jerk is also lost
8. Plantar response Lost Extensor plantar response
9. Bladder control and sexual function Involvement not marked Loss of bladder bowel control
Chapter 17
Guillain-Barré Syndrome

IMMUNE-MEDIATED NEUROPATHY −− Lymphoma—Both hodgkin and non-Hodgkin


lymphoma.
−− SLE.
DEFINITION All are increminated in the development of AIDP.
It is an acute fulminant polyradiculoneuropathy of
autoimmune nature associated with the clinical picture IMMUNE PATHOGENESIS
of rapidly developing ascending areflexic motor paralysis
1. Misdirected antibody targeted against nonself antigen
with/without sensory loss and sphincteric disturbances.
(vaccines and infectious agents) cross react with
glycoconjugates (specially gangliosides of the myelin
INCIDENCE sheath) due to molecular mimicry which plays the
Male and female are equally involved. central key pathogenic role in the development of GBS.
Adult >child. 2. Both humeral and cellular immune mechanism
contribute to tissue damage.
SUBTYPES   T-cell activation is suggested by the presence of IL-2,
IL-2R, INF-γ, TNF-α, IL-6 (Table 17.1).
•• Acute inflammatory demyelinating polyneuropathy
(AIDP)—90%. Table 17.1: Antibody in different, subtype of GB syndrome
•• Acute motor axonal neuropathy (AMAN).
•• Acute motor sensory axonal neuropathy (AMSAN). Clinical Target antibody Antibody type
•• Regional Gullain-Barré (GB) syndromes presentation
−− Miller-Fisher syndrome. AIDP GM1 IgG
−− Pure sensory form. AMAN GM1b, GM1, GD1a IgG
−− Ophthalmoplegia with anti-GQ–1b antibody.
−− GBS with severe bulbar or facial paralysis (antecedent Miller-fisher GQ1b IgG
CMV infection and anti-GM–2 antibody).
−− Acute pandysautonomia (disordered autonomic CLINICAL FEATURES
nervous system).
•• Usual clinical pattern is an ascending paralysis
accompanied by tingling disasthesia evolved over hours
ETIOLOGY
to days.
Immune responses to nonself antigen (infectious •• Legs are more frequently affected than arms.
agent and vaccines) misdirected to host nerve tissue due to •• Facial diaparesis occurs in 50% cases.
molecular mimicry. •• Lower cranial nerves are frequently involved resulting
75% cases of GB is preceded by an antecedent infec- tion in weakness of bulbar muscle, dysphagia, difficulty in
1–3 weeks. handling saliva and palatine palsy.
•• Respiratory infection by EBV, mycoplasma and CMV. •• 30% requires ventilatory support due to respiratoy
•• GI infection by Campylobacter jejuni (most common). muscle involvement.
•• Apart from infection— •• Muscle bulk is not grossly diminished.
−− Nerve tissue derived vaccine (NDV) in rabies. •• Gross hypotonia of the muscle—present.
−− Swine-influenza vaccine. •• Power may be grossly diminished (grade—0–II).
−− HIV seropositivity. •• Deep tendon reflex are absent.
Guillain-Barré Syndrome 137

•• Loss of pain and temperature are relatively insig- PROGNOSIS


nificant.
•• About 80–85% patient shows spontaneous usually
•• Posterior column senses (proprioceptions, vibration
complete recovery both in AIDP and axonal neuropathy
sense, position, fine touch and other cortical
group.
senses) are severely affected.
•• About 5% patient die of respiratory involvement and
•• Patient may complain of—
lung infection.
−− Dull aching pain from weakened muscle
•• About 15% patient recover partially and survive with
−− Low back pain from spinal cord and vertebral body residual neurodeficit.
−− Dysesthetic pain due to posterior column •• Patient with axonal neuropathy have a very good and
involvement. rapid recovery as the lesion is thought to be localized
•• Bladder dysfunction may be present but transient. Early in the preterminal neuron.
bladder dysfunction raises the question about diagnosis
and is possibly due to spinal cord disease. DIFFERENTIAL DIAGNOSIS
•• Autonomic involvement in the form of cardiac arrythmia
•• Acute transeverse myelitis (ATM) with prolong back
and postural hypotension may be found in severe cases.
pain and sphincter disturbances.
Once the clinical worsening stops and the patient
•• Botulinism (pupillary reaction lost early).
reaches a plateau within 4 weeks of onset, further
•• Diphtheria (Oropharyngeal paralysis).
progression is unlikely.
•• Porphyria (abdominal pain, seizure and psychosis).
•• Vascular neuropathy (raised ESR).
DIAGNOSIS •• Polio (child with fever and diarrhea) asymmetrical,
•• Diagnosis is mostly clinical—rapidly developing ascend- involvement of legs are more frequent.
ing, areflexic motor weakness usually starting from •• CMV polyradiculitis in immune-compromised patient.
lower limb with minimal sphincteric disturbances and •• Myasthenia gravis (cranial nerve and shoulder girdle
some amount of dysesthesia with/ without involvement and respiratory muscle are predominently involved).
of bulbar muscle is the hallmark of clinical diagnosis of •• Toxic peripheral neuropathy (thallium, arsenic and
GBS. organophosphorus).
•• CSF study—Changes are evident at the end of 1st week. •• Lyme polyradiculitis.
−− Classical picture—Cytoalbuminic dissociation. •• Tick-borne polyradiculopathy.
−− Protein—100–1000 mg/dl •• Critical illness neuropathy.
−− Cell count—10–100/ml.
Pleocytosis suggests CSF, viral/HIV myelitis. TREATMENT
•• Electrodiagnostic study (EDX)—Electrodiagnostic
Treatment should be initiated as soon as the clinical
features are mild or absent in early case of GBS and lags
diagnosis is made and the motor symptoms respond
behind clinical evolution.
maximally if treatment started within 2 weeks of onset of
EDX features of AIDP (demyelinating neuropathy) symptoms.
•• Slowing of conduction velocity. •• High dose intravenous immunoglobulin (IV Ig) → 0.4
•• Evidence of conduction block. g/kg/day for 5 days (total dose 2 g/kg) or 1 g IV on D1
•• Prolonged distal latency. and D3.
•• Temporal or lateral dispersion of compound action •• Plasmapheresis of 40–50 ml plasma/kg. 4 times a week
potential. is equally effective as IV Ig therapy. But combination
EDX features of axonal neuropathy (AMAN and therapy has no additional benefit.
AMSAN) •• Ventilatory support required in 30% patient → If
•• Reduced amplitude of compound action potential respiration is compromised.
without conduction slowing or prolongation of distal •• General care of paralyzed patient.
latencies. −− IV methylprednisolone has no role.
Chapter 18
Peripheral Neuropathy

• DM— Diabetes mellitus ETIOLOGY OF NEUROPATHY


• TOCP—Triorthocresyl phosphate
• CIDP—Chronic inflammatory demyelinating polyneuropathy •• Metabolic—Diabetes mellitus, renal failure, porphyria
• AIDP—Acute inflammatory demeylinating polyneuropathy and amyloidosis.
• GBS—Guillain Barré syndrome •• Infectious—Leprosy, diphtheria, HIV, cytomega-lovirus
• CMT—Charcot marie tooth disease and lyme disease.
• HMSN—Hereditary motor sensory neuropathy •• Immune-mediated—GBS, CIDP, MMCB and antibody
• MMN—Multifocal motor neuropathy with conduction block. to myelin-associated glycoprotein.
•• Hereditary—CMT.
•• Peripheral neuropathy is a general term indicating •• Drug—Anticancer drug, anti-HIV drug, metronida-
disorder of peripheral nerve. zole, ethambutol, dapsone, thalidomide and isoniazid.
•• The disorder may be due to affection of the anterior root •• Toxic—Alcohol and heavy metal, tick bite.
(radicle), nerve plexus, peripheral nerves, posterior root •• Vasculitis—PAN, Churg-Strauss syndrome and
ganglia and trigeminal ganglion. Cryoglobulinemia.
  Involvement of anterior horn cell gives the picture •• Paraneoplastic—Bronchogenic carcinoma.
similar to peripheral neuropathy but should be ideally •• Nutritional—Vitamin B1, B6 and B12 deficiency.
termed as neuronopathy. •• Miscellaneous cause—Celiac disease and hypothyroid
Peripheral neuropathy can be classified in various ways: Fabry disease.
•• According to number of nerve involved
−− Mononeuropathy MODE of onset of MAJOR TYPEs OF
−− Mononeuropathy multiplex POLYNEUROPATHY
−− Polyneuropathy
−− Plexopathy. Axonal
•• According to the type of nerve involved •• Acute (days to week)
−− Pure motor neuropathy −− Porphyria
−− Pure sensory neuropathy −− Massive intoxication with arsenics
−− Autonomic neuropathy −− Guillain-Barré syndrome.
−− Mixed neuropathy. •• Subacute (weeks to months)
•• According to clinical profile −− Mostly toxic and metabolic.
−− Acute onset neuropathy •• Chronic (months to years)
−− Subacute onset neuropathy −− <5 years—Toxic and metabolic
−− Chronic onset neuropathy. −− >5 years—hereditary, diabetes and dysproteinemias.
•• According to pathological type of involvement
−− Axonopathy Demyelinating
−− Demyelinating polyneuropathy.
•• According to region involvement •• Acute (days to week)
−− Proximal neuropathy −− Guillain-Barré all forms
−− Distal neuropathy. −− Diphtheria.
Peripheral Neuropathy 139

•• Subacute (weeks to months) •• Nerve conduction study—Amplitude of motor unit


−− Relapsing form of CIDP. potential is more affected than nerve conduction
•• Chronic (months to years) velocity.
−− Hereditary and inflammation •• Histopathology—Axonal degeneration and regenera-
−− Autoimmune tion can be demonstrated.
−− Dysproteinemia •• Prognosis—Very slow recovery.
−− Metabolic and toxic.
FEATURES OF NEURONAL DISEASE
ETIOLOGY ACCORDING TO MODE OF ONSET OF
NEUROPATHY •• Etiology—Pyridoxin defficiency, cisplatin toxicity and
SjÖgren’s syndrome.
•• Acute—GBS, porphyria, diphtheria, toxin like— TOCP, •• Onset—Rapid onset.
thallium and brachial neuritis. •• Pattern of involvement—Nonlength-dependent, upper
•• Subacute—Alcoholic, nutritional, angiopathic and limb, lower limb and face.
toxichexacarbon acrylamide. •• Symptoms—Gait ataxia and paresthesia.
•• Chronic—Diabetic, CIDP, paraneoplastic and •• Signs—
paraprotein. −− Sensory—Loss of vibration and proprioception
•• Hereditary—CMT and Friedreich’s ataxia. greater than pain and temperature, large fiber
•• Recurrent—CIDP, porphyria, refsum disease and HNPP. (postcolumn) involvement > small fiber (anterior
FEATURES OF DEMYELINATING NEUROPATHY column).
−− Motor—Proprioceptive weakness.
•• Etiology—GBS, CIDP, diphtheria, MMN (multifocal •• Reflexes—Areflexia.
motor neuropathy) with conduction block). •• Nerve conduction study—Sensory amplitude affected.
•• Onset—Acute or subacute. Affection of radial nerve greater than sural nerve. Axonal
•• Symptom—Paresthesia and weakness. degeneration but no regeneration.
•• Sensory sign—Loss of posterior column sensation (loss •• Prognosis—Poor recovery.
of vibration and proprioception is greater that loss of
pain and temperature). CLINICAL FEATURES OF PERIPHERAL
•• Motor loss—Weakness is equal on proximal and distal NEUROPATHY
group of muscle.
•• Reflex—Areflexia in both proximal and distal group of Demyelination affects motor and sensory fiber equally,
muscle. whereas axonal process involves sensory fiber > motor fiber.
•• Nerve conduction study—Nerve conduction velocity
is affected more than amplitude of motor unit action Large Fiber (Postcolumn) Neuropathy (Ataxic
potential. Neuropathy)
•• Nerve biopsy—Both demyelination and remyelina- tion
Large fiber polyneuropathy is characterized by loss of
is seen in HP examination.
vibration and position sense with absent tendon reflex,
•• Prognosis—Rapid recovery.
variable motor deficit and ataxia but preservation of most
cutaneous sensation. Band-like sensation with tingling
FEATURES OF AXONAL NEUROPATHY dyserthesia may be present.
•• Etiology—Toxic, metabolic (DM), HIV and CMT-2. •• Etiology—SjÖgren’s, cisplatin, pyridoxin deficiency and
•• Onset—Slow evolution. Friedreich’s ataxia.
•• Pattern—Distal involvement more than proximal •• Symptoms—Numbness, pins and needle sensation.
involvement and length-dependent. •• Signs—Decreased vibration sense, poor balancing,
•• Symptoms—Dysesthesia and distal weakness. decrease muscle, ligament and joint sense.
•• Signs— •• Investigations—
−− Sensory—Pain and temperature sensation affected −− Nerve conduction study
more that vibration and proprioception. Anterior −− Nerve biopsy and electromyography (EMG)
column or small fiber are affected more than pos- −− Lumbar puncture.
terior column or large fiber.
−− Motor—Weakness of distal group of muscle is more Small Fiber (Anterior Column) Neuropathy (Painful
than proximal group. Neuropathy with Dissociated Sensory Loss)
•• Reflexes—Areflexia of the distal group. Loss of ankle
and supinator jerk more than knee, biceps and triceps Small fiber neuropathy are characterized by burning, pain-
jerk. ful dysesthesia, reduced pinprick and thermal sensation but
140 Essentials of Internal Medicine

sparing proprioception, motor function and deep tendon ULNAR NEUROPATHY


reflexes. Touch sensation is variably involved when spared
called dissociated sensory loss which can also occur in
Causes
spinal cord lesion. •• At the elbow—by pressure palsy.
•• Etiology— •• Entrapment distal to elbow in cubital tunnel.
−− Hereditary sensory neuropathy •• Prolonged pressure over base of palm at wrist due to the
−− Leprosy use of hand tools and bicycling.
−− Diabetes
−− Amyloidosis Clinical Features
−− HIV and antiretroviral therapy •• Clawhand deformity owing to waisting and weakness of
−− Dysautonomia small muscle of hand which results in hyperextension
−− Fabry’s disease. of finger at MP joint and flexion at IP joint.
•• Symptoms—Pain-like-burning, shock-like shooting, •• Flexion deformity is most pronounced in 4th and 5th
lancinating, stabbing and prickling. finger.
•• Sign—Decreased pinprick and temperature sensa- •• Sensory loss occur over 5th and half of the 4th finger
tion. with ulnar border of the plam.
•• Investigations—Skin biopsy, nerve biopsy and •• Tinel’s sign at elbow.
quantitative sensory testing. •• Forment sign.

Motor Neuropathy Management

•• Etiology—Guillain–Barré syndrome, HMSN, dip- Surgical release, at cubital tunnel or anterior trans- position
htheria, diabetes, lead and acute intermittent porphyria. of the nerve at the elbow.
•• Symptoms—Wrist drop, foot drop, weak grip, muscle
cramp and twitching of muscle. CARPAL TUNNEL SYNDROME
•• Sign—Diminution of muscle power grade 1/5–4/5 with Causes
decreased DTR.
•• Investigations—Nerve conduction study and Median nerve at the carpal tunnel lies in a close space with
electromyography. nine tendons. So it can easily be compressed at that site.
•• Inflammatory—Osteoarthritis, rheumatoid arthritis and
tenosynovitis.
Autonomic Neuropathy •• Post-traumatic—Colles’ fracture.
•• Etiology— •• Endocrine—Myxedema, diabetes and acromegaly.
•• Metabolic—Amyloid and mucopolysaccharidosis.
−− Acute—Pandysautonomia, botulism, porphyria,
•• Idiopathic (most common).
GBS, amiodarone and vincristine.
−− Chronic—Amyloid, diabetes, SjÖgren, HSAn-I and Clinical Features
III and paraneoplastic disorder.
•• Symptoms— •• Nocturnal paresthesia of thumb, index and middle
−− Disturbances in sweating (decreased or increased). finger.
•• Weakness and atrophy of abductor policis brevis (thenar
−− Dryness of eye and mouth and erectile dysfunction.
eminence).
−− Gastroparesis and diarrhea.
−− Faintness and lightheadedness. Management
•• Sign—Orthostatic hypotension, unequal pupil size.
Surgical section of carpal ligaments.
•• Investigations—Valsalva, tilt table, R-R interval,
quantitative sudomotor axon reflex testing.
MONONEUROPATHY MULTIPLEX
•• Simultaneons or sequential involvement of indi-
MONONEUROPATHY
vidual noncontiguous nerve trunk, either partially or
•• Focal involvement of a single nerve trunk. completely evolving over days to years.
•• Ulnar neuropathy and carpal tunnel syndrome are the •• Since the disease process underlying mononeuritis
two most common varieties of mononeuropathy. multiplex affects peripheral nerve in multifocal and
•• Other mononeuropathies are—tarsal tunnel syndrome random fashion, progression of the disease gives the
and cranial mononeuropathy. picture of distal symmetric neuropathy.
Peripheral Neuropathy 141

•• So for diagnosis, attention to be paid on the early Contd...


symptom and the examination findings at the early C. Mononeuropathy multiplex—
stage of the disease. • Initial involvement like mononeuropathy
• Gradual involvement of different nerves of different limb
Cause • In late stage clinical feature stimulate polyneuropathy
• May or may not be painful
•• Leprosy • Isolated loss of DTR
•• DM • Etiology—Diabetes, vasculitis and pressure palsy
•• Vasculitis—PAN, SLE and SjÖgren’s
•• Sarcoidosis
•• HIV
•• RA −− Later weakness appears on dorsiflexor of wrist.
•• Amyloidosis. Extensors are more commonly affected than flexors.
There will be associated muscle atrophy and areflexia.
POLYNEUROPATHY •• Overall the nerve fibers are affected according to axon
length irrespective of route or nerve trunk distribution,
The typical picture of polyneuropathy is seen in acquired
that is why sensory loss appears in stocking and gloves
toxic and metabolic disorders.
pattern.
In polyneuropathies sensory deficit are generally
graded, distal and symmetric in distribution. The process
is usually nerve length-dependent and the neuro deficit is
PURE MOTOR PERIPHERAL NEUROPATHY
often described as glove and stocking type. It is due to the disease affecting anterior root and peri-
pheral nerve.
CLINICAL FEATUREs Clinically it is very difficult to distinguish this entity from
•• First symptom usually is sensory, consists of tingling, disorder of anterior horn cell (neuronopathy).
prickling, burning or band-like dysesthesia at the ball
of the feet or tips of toes or over the sole. Symptom Causes
is usually symmetric, graded distally and preceeds •• Lead poisoning.
objective sensory and motor sign. •• Dapsone.
•• As the disease progresses sensory loss moves cen- •• Porphyria.
tripetally and when it reaches the upper shin the •• MMCB (multifocal motor neuropathy with conduc- tion
dysesthesia usually involves the tips of fingers in the block).
hand. •• GBS (Guillain-Barré syndrome).
•• When the sensory loss reaches elbow and midthigh •• CIDP (chronic inflammatory demyelinating poly-
a tent-shaped area of hypoesthesia can be demon- neuropathy).
strated on lower abdomen with its apex directed rostally •• Hereditary motor neruopathy (Charcot-Marie-Tooth
towards xiphisternum. disease).
•• Motor
−− Usually weakness of the dorsiflexor of toe specially
Clinical Features
great toe.
−− Weakness of dorsiflexors of ankle. •• Weakness
•• LMN atrophy sign
Differential diagnosis of polyneuropathy/ plexopathy/
•• Fasciculation
mononeuropathy multiplex
A. Polyneuropathy— •• Areflexia.
• Symmetric distribution of symptoms (tingling dysesthesia)
• Initial symptoms over gloves and stocking area Electrodiagnostic Study (EMG and NCV)
• May or may not be painful
• Symmetric diminution of muscle power over both sides It also fails to localize the primary site of lesion (neuro-
• Symmetric diminution of DTR over both side pathic vs neuronopathic) unless the lesion is of demyeli-
B. Plexopathy— nating pattern.
• Asymmetric distribution of symptoms So the diagnosis is mainly done based on history and
• Usually painful onset
• Multiple nerve involvement in a single limb
clinical examination.
• Rapid asymmetric onset of muscle weakness and atrophy
• Asymmetric loss of DTR over limb PURE SENSORY NEUROPATHY
Contd... •• It is the most common form of peripheral neuropathy.
142 Essentials of Internal Medicine

•• It may be of three types involving primary sensations PLEXOPATHY


only—
•• The term reffers to either brachial/lumbosacral plexus
−− Large affarent fiber neuropathy (postcolumn
involvement.
involvement) with deficit of vibratory and
•• Brachial plexus involvement is more common—
proprioceptive sense (muscle sense and joint sense)
−− Upward jerk causes lower cord injury
with areflexia and sensory ataxia with/ without
−− Downward jerk causes upper cord injury.
tingling dysesthesia.
−− Small fiber neuropathy—lateral and anterior
Etiology
spinothalamic tract are involved resulting in
numbness and cutaneous hypoesthesia to pin- prick •• Direct trauma or downward jerk occure during lifting of
and temperature stimuli often with painful and heavy object—upper cord injury.
burning dysesthesia. •• Idiopathic brachial neuritis (neuralgia amyotrophy).
−− Both large and small fiber (pain sensory) •• Cervical rib or band.
involvement—the pattern of distribution although •• Infiltration by malignant tumor (Pancoast tumor).
variable but distal symmetrical involvement is •• Radiation therapy >60 Gy.
particularly seen for large fiber neuropathy. •• Lower cord injury occurs in upward arm jerk during
•• Severe and pure, widespread peripheral sensory catching running bus or train.
neuropathy with poor or no recovery suggest degen-
eration of dorsal root ganglia or trigeminal ganglia. Clinical Features
•• Mild to moderate form of peripheral sensory neuropathy •• Both motor and sensory signs are seen and which are
are potentially reversible. different from mono/polyneuropathies.
•• Involvement of upper part of brachial plexus C5–C7.
AUTONOMIC NEUROPATHY Leads to—
−− Weakness and atrophy of shoulder girdle.
It is usually a manifestation of more generalized poly- −− Weakness and atrophy of upper arm muscle.
neuropathy. −− Focal sensory deficit over shoulder girdle and lateral
aspect of arm.
Causes •• Involvement of lower part of brachial plexus C8–T1.
•• Diabetes mellitus (DM) Leads to—
•• Guillain-Barré syndrome (GBS) −− Distal arm weakness and atrophy.
•• Alcoholic polyneuropathy. −− Focal sensory deficit of forearm and hand—Medial
Symptoms of dysautonomia are mainly of two types— aspect.
1. Negative symptoms (loss of function) •• Lumbosacral plexopathy—less common.
−− Postural hypotension with faintness or syncope. Causes of lumbosacral plexus involvement
−− Anhidrosis. •• Trauma
−− Hypothermia. •• Intraoperative injury
−− Bladder atony—Neurogenic bladder. •• Retroperitoneal hemorrhage
−− Absolute constipation. •• Malignant tumor
−− Dry mouth and dry eyes—Failure of lacrimal and •• Infiltration and TB of lumbar spine
salivary glands. •• DM.
−− Blurring of vision (due to pupillary and ciliary
regulation loss). Diagnosis of Peripheral Neuropathy
−− Sex impotence in male.
Electrodiagnosis
2. Positive symptoms (hyperfunction)
−− Episodic hypertension Electromyography (emg)
−− Diarrhea
1. Myopathic disorders are marked by small, short du-
−− Hyperhidrosis
ration, polyphasic muscle action potential recruited in
−− Tachycardia/bradycardia.
excessive number for a given degree of voluntary muscle
contraction.
Management 2. Neuropathy shows features of denervation with posi-
It is mostly symptomatic and also directed at underlying tive sharp wave and complex repetitive discharges—
cause if it can be identified. followed by long duration, enlarged, polyphasic waves
Peripheral Neuropathy 143

in chronic phase indicating collateral innervation −− Surgery for entrapment neuropathy.


of denervated muscle fiber by axonal sprouts form −− Liver or bone marrow transplant for amyloid
surviving motor axons. neuropathies.
•• When disorder of neuromuscular junction is suspected −− Enzyme replacement for Fabry disease.
more specialized technique is used—muscle response Treatment of immune-mediated neuropathies.
to repetitive nerve stimulation (2–3 Hz) and single fiber
EMG study shows blocking and Jitter with normal fiber
density is confirmatory of MG. PAIN MANAGEMENT OF PAINFUL SENSORY
NEUROPATHY
Nerve conduction velocity (ncv)
Burning, aching, sharp, throbbing pain—Managed by
The axonopathy and demyelinating variety can be dis- TCAD— amitriptyline, imipramine and desiparamine.
tinguished by nerve conduction study. Neuropathic pain of diabetes—Managed by duloxetine
•• Features of demyelination— and tramadol.
−− Slowing of nerve conduction velocity. Lancinating pain—Managed by anticonvulsant like
−− Temporal (lateral) dispersion of evoked action phenytoin, carbamazepine, clonazepam, gabapentin,
potential. topiramate, venlafaxine and pregabalin.
−− Conduction block of nerve impulse. Focal neuropathic pain—Managed by lidocaine,
−− Marked prolongation of distal latencies. mexiletine and capsaicin isosorbide dinintrate spray.
•• Features of axonal injury— Severe refractory neuropathic pain—Managed by
−− Reduction of amplitude of evoked compound action narcotic analgesic.
potential.
−− Relative preservation of NCV (nerve conduction
HEREDITARY POLYNEUROPATHY
velocity).
(CHARCOT-MARIE-TOOTH DISEASE AND
Nerve Biopsy OTHER RELATED DISORDERS) (CMT)

•• Sural nerve at the ankle—Preferred site.


DEFINITION
•• Indications—
−− Asymmetrical and multifocal neuropathic disorder. Charcot-Marie-Tooth (CMT) neuropathy comprises a
−− One or more cutaneons nerve is thickened. heterogeneous group of inherited peripheral nerve disease.
−− Determination of genetically determined childhood
diseases. CLINICAL FEATUREs
•• In distal symmetrical polyneuropathy of acute/subacute
•• Onset is often during the 1st/2nd decade of life although
variety. Nerve biopsy should not be done as—
presentation in mid-adult life is not unusual.
−− No additional inference or information can be
•• Clinical presentation is exceptionally wide ranging from
gathered.
minimal or no distal muscle weakness with pes cavus
−− Yield is low, not worth of the risk as wound infection,
to severe distal atrophy most marked in hand and foot.
poor healing, persistent pain are the common
•• Common signs and symptoms are related to muscle
complication.
weakness initially involving feet and leg—later
progressing to hand and forearm.
TREATMENT OF PERIPHERAL NEUROPATHY
•• Pes cavas or high arched foot results from atrophy of
•• Pain management. intrinsic muscle of feet.
•• Supportive care to protect and rehabilitate damage •• History of abnormal high stepped gait with frequent
tissue. tripping and falling, due to foot drop.
•• Treatment of underlying disorder— •• Sensory—Subjective symptoms are unusual although
−− Diabetic neuropathy—Glycemic control. few objective signs may be present.
−− Vitamin deficiency neuropathy—By vitamin B1, B6 •• Deep tendon jerk (DTR)—Depressed or absent.
and B12. •• Transmission is most frequently autosomal dominant
−− Immune suppression for vasculitis. but may be autosomal recessive or X-linked.
144 Essentials of Internal Medicine

TYPES OF HEREDITARY MOTOR SENSORY DEJERINE SOTTAS Disease (DSD)


NEUROPATHY (HMSN)
•• Patient never ambulate or loose ambulation in early
It can be classified as— infancy—also known as congenital hypomyelinating
•• CMT–1 (demyelinating form) (HMSN–1) neuropathy.
•• CMT–2 (axonal degeneration) (HMSN–2) •• Clinical feature of DSD and congenital hereditary
•• CMT–3 (dejerine-Sottas disease) (HMSN–3) neuropathy overlap with CMT.
•• CMT–4 (autosomal recessive form) (HMSN–4) •• Laboratory diagnosis—
•• CMT–X (X-linked variety). −− CSF protein is eleveted.
[HMSN = Hereditary motorsensory neuropathy]. −− NCV—Substantially slow 10 m/sec.
Chapter 19
Myasthenia Gravis

It is a disorder of neuromuscular junction charecterized by •• Reduction in number of the AchR at the neuromuscular
progressive inability to repeated conduction of impulse to junction is brought about by three distinct mechanism—
sustain a maintained or repeated contraction of striated −− Accelerated turnover of AchR by a mechanism
muscle. involving crosslinking and rapid endocytosis of the
receptor.
ETIOLOGY AND PATHOLOGY (Fig. 19.1) −− Blockade of active site of AchR (acetylcholine
receptor), i.e. the normal binding site of acetylcholine.
•• The underlying defect is the decrease in the number −− Damage to the postsynaptic muscle membrane by
of acetylcholine (Ach) receptor in the postsynaptic antibody in collaboration with complement.
membrane of motor end plate. •• Thymus appears to play a major role in this process.
•• The neuromuscular abnormality in this disease is Thymus is abnormal in 75% of patient out of which 65%
brought about by a T-cell-dependent autoantibody of has hyperplastic thymus with the presence of active
IgG class against acetylcholine receptor (AchR). germinal center detected histologically. 10% of patients

Fig. 19.1: Schematic diagram of motor and plate with the pathophysiology of myasthenia and Lambert-Eaton syndrome
146 Essentials of Internal Medicine

have thymoma composed of muscle-like cell (myoid −− Speech have a nasal intonation due to weakness of
cell) within the thymus which bears AchR (acetylcholine muscle of tongue, palate and pharynx with difficulty
receptor) on their surface which serve as a source of in swallowing giving rise to nasal regurgitation (due
autoantigen and triger an antoimmune reaction. to weakness of muscle supplied by IXth, Xth, XIth
and XIIth cranial nerve).
CLINICAL FEATUREs −− Weakness of respiratory muscle may require
ventilatory support and then the patient is said to be
•• It can affect people of all age group. in myasthenic crisis.
•• Women are more frequently involved than men (M: −− In 85% patient, the weakness become generalized
F—2 : 3). Women are affected in the 2nd and 3rd decade affecting limb muscle as well. The limb weakness
while man are affected in 5th and 6th decade of their life. in MG is often proximal and asymmetric in nature.
•• Cardinal features are progressive weakness and easy Despite limb weakness the deep tendon reflexes are
fatiguability of muscle. preserved.
History—
−− Diplopia, ptosis and weakness. PHYSICAL EXAMINATION
−− Weakness increases during repetitive use (fatigue)
and may improve following rest, sleep or treatment. •• Presence of ptosis and diplopia.
−− Weakness may be generalized (85%) but cranial •• Motor power survey—quantitative testing of muscle
nerve muscle, shoulder girdle and respiratory muscle strength.
are specially involved. •• Forward arm abduction time (< 5 min).
•• Mode of presentation: •• Vital capacity measurement. Respiratory muscle
−− Ocular myasthenia gravis—Extraocular muscle weakness and respiratory failure is not an uncom-
involvement resulting in intermittent ptosis and mon cause of death—that should be checked by single
diplopia specially in the evening is the most common breath count test.
mode of presentation. •• Laryngeal and other muscle related to voice production
−− Other cranial nerve involvement— may be examined by continuous counting of number
–– Facial diaparesis due to bilateral LMN weakness and noting the slurring of speech.
of facial muscle. •• Absence of other neurological signs.
–– Weakness during chewing, swallowing, speaking
leading to nasal intonation, nasal regurgitation, DIAGNOSIS
aspiration and facial snarling due to Vth, IXth, Xth
•• Clinical—Diagnosis is made on the basis of weekness
and XIth cranial nerve involvement.
−− Weakness of limb movement specially those of and easy fatigability with typical distribution without
shoulder girdle as evident by fatigue during repetitive any loss of DTR and sensory impairment.
combing of hairs and diminution of forward arm •• Laboratory testing—
abduction time. −− Anti-AchR antibody assay—
•• The course of myasthenia gravis is often variable— –– Definitive diagnosis of myasthenia is done by the
exacerbation and remission occur particularly during presence of anti-AChR antibody but absence cannot
first few years of the disease. Remission is rarely exclude myasthenia gravis.
complete or permanent—unrelated infection or systemic –– Anti-AchR antibody is positive in 85% generalized
disorder usually leads to increased myasthenic weakness myasthenia gravis.
and may precipitate myasthenic crisis. –– Anti-AchR antibody is positive in 50% of ocular
•• The distribution of muscle weakness has a myasthemia gravis.
characteristic pattern –– 40% of anti-AchR negative patient with generalized
−− The cranial muscle particularly eyelid and extra- MG have anti-musk antibody.
ocular muscle (EOM) are involved early in the –– Anti-Musk antibody is rarely present in anti-
course, leading to diplopia and ptosis as a common AchR positive patient and myasthenia gravis
initial symptoms. If the weakness remain restricted limited to ocular muscle.
to extraocular muscle for 3 year, it is unlikely to –– There is evidence that myasthenia gravis patient
become generalized and the patient said to have without anti-AchR or MuSK antibody have other
ocular myasthenia. unidentified antibody.
−− Facial weakness produce a snarling expression −− Repetitive nerve stimulation—Anti-AchE medi-
with an attempt to smile (due to facial muscle cation is stopped 6–24 hours before testing. Test is
involvement). performed on proximal group of muscle. Muscle is
−− Patient may complain weakness during prolonged stimulated at 2–3 Hz. Rapid decrement of response
chewing (due to weakness of muscle of mastication). >15% is highly probable of myasthenia gravis.
Myasthenia Gravis 147

  As a further test a single dose of edrophonium generally administered over a period of 2 weeks.
may be given to prevent/diminish the decremental It is useful as a temporary measure in myasthenic
response. crisis condition or in preoperative preparation for
−− Edrophonium (tensilon) stimulation test—Intrave- thymectomy.
nous injection of 2 mg edrophonium initially given if −− Immunoglobulin (IV–Ig)—An alternative to plasma
no improvement occur a further 8 mg is given in two exchange in the treatment of myasthenic crisis.
divided dose just to reduce the unplasent cholinergic   Dose—400 mg/kg/day for 5 days. Improvement
side effects (diarrhea, abdominal pain, excessive occurs in 70% of patient.
salivation, lacrimation, fasciculation, bradycardia and   IV–Ig and plasmapheresis are reserved for immediate
syncope). If there is significant objective improvement relief in myasthenic crisis and bridge up therapy before
in muscle power seen within 30 seconds following surgery.
IV edrophonium and which last for 3–5 minutes, it is −− Corticosteroid—Improvement is commonly preceded
highly probable of myasthenia gravis. by marked exacerbation of myasthenic symptoms—
−− Single fiber EMG—Blocking and Jitter with normal treatment should be initiated in the hospital.
fiber density is confirmatory but not specific of MG. –– Initial dose is 15–25 mg/day and increase stepwise
−− For ocular myasthenia gravis/cranial myasthenia 5 mg/day at 2–3 days interval until there is marked
gravis—Exclude intracranial lesion by CT/MRI. clinical improvement or a dose of 50–60 mg/day
is reached.
DIFFERENTIAL DIAGNOSIS –– Dose should be given as a single morning dose to
reduce the side effects.
•• Congenital myasthenia syndrome (nonautoimmune). –– Dose is maintained for 1–3 months then slowly
•• Drug-induced myasthenia (aminoglycoside, procai- switch over to alternative day regimen over 1–3
namide, penicillamine). months patient.
•• Lambart-Eaton myasthenic syndrome (commonly in –– Patient on long-term glucocorticoid therapy
paraneoplastic disorder usually involve lower limb should be followed carefully for early detection
muscle, muscle power improve with repetitive use. of adverse side effects.
•• Hyperthyroidism. –– The most common side effect of glucocorticoid
•• Botulism. treatment is—
•• Intracranial mass lesion. »» Insufficient persistence—Improvement will be
•• Progressive external ophthalmoplegia. delayed and gradual.
•• Neurasthenia. »» Too early, too rapid and excessive tappering
of dose.
TREATMENT »» Lack of attention to prevent the adverse effect
of glucocorticoid.
Principles of treatment are as follows: −− Immunosuppressive drugs
•• To maximize the activity of acetylcholine at the –– Mycophenolate mofetil
remaining receptor of the neuromuscular junction— –– Azathioprine
C o m m o n l y u s e d a n t i c h o l i n e s t e r a s e d r u g i s –– Cyclosporine
pyridostigmine (30–120 mg orally divided 6 hourly). –– Tacrolimus
Muscarinic side effect include diarrhea, abdominal –– Cyclophosphamide.
colic, salivation, sweating and small pupil which can •• Mycophenolate mofetil—(Now the most preferred
be reversed by propantheline (15 mg). agent)
•• Immunological treatment of myasthenia 1–1.5 g bid inhibit the proliferation of lymphocyte but
−− Thymectomy—It should be done as soon as possible not other cells. Therefore clinical improvement may be
in patient between puberty to 55 years of age and delayed from months to years. The drug may be used
in antibody positive patient with symptoms not alone or with glucocorticoid.
confined to extraocular muscle, unless the disease •• Azathioprine
has been established >7 years. Initially 50 mg/day gradually increased to 2.5 mg/kg/
  85% patient experience improvement in symptoms day is of value in reducing the dose of steroid or allow
and of those 35% achieve drug-free remission which the steroid to be withdrawn.
requires a latent period of 9 months to 1 year. The   Effect of treatment on the clinical course of the disease
patient with Musk antibody positive may not may be delayed for several months, associated with
improve from thymectomy. fewer treatment failure, longer remission and lower side
−− Plasmapheresis—For removal of antibody from effects. However it is probably not useful as an initial
blood a course of 5 exchange (3–5 L/exchange) is immunosuppresant.
148 Essentials of Internal Medicine

  Side effects—Idiosyncratic reaction like fever, malaise •• Cyclophosphamide


bone marrow suppression and abnormal LFT. It is reserved for patient refractory to other drugs.
•• Cyclosporine High dose cyclophosphamide may induce long lasting
4–5 mg/kg/day in two equally divided dose either alone (possibly permanent) improvement by rebooting the
or in combination with glucocorticoids. immune system.
The beneficial effects appear to be more rapid than Causes of death
azathioprine. −− Respiratory failure—Due to myasthenic or
•• Tacrolimus cholinergic crisis.
0.1 mg/kg given in two equal divided dose. −− Aspiration—Due to weakness of pharyageal and
Side effects—Hypertension and nephrotoxicity. laryngeal muscle.
Chapter 20
Myopathy and Myotonia

MYOPATHY named as myotonia worsen with repetitive activity


is contrast to other myotonia which is eased with
It is a genetically determined disease of the muscle
repetitive activity.
characterized by degeneration of a group of muscle without
–– Drug-induced myotonia—Statin, fibrates,
involvement of nervous system. (Muscular dystrophy can
cyclosporine and chloroquine.
be defined as a group of hereditary progressive diseases
–– Myotubular/center nuclear myopathy.
of muscle each with unique phenotypic and genotypic
–– Chondrodystrophic myotonia.
feature).
–– Glycogen storage disorder (Pompe disease,
braching enzyme deficiency).
CLASSIFICATIONs –– Myofibrillar myopathies.
Myopathesis can be classified initially into two subgroups:
•• Muscular dystrophies DUCHENNE’S MUSCULAR DYSTROPHY
•• Mytonic disorder (autosomal dominant). •• It also known as pseudohypertrophy muscular
−− Progressive muscular dystrophies can be again dystrophy. Pseudohypertrophy is as a result of
subclassified according to their mode of inheritance. deposition of fibrofatty tissue within calf muscle, glutei,
–– Sex-linked recessive disorders quadriceps and deltoid.
»» Duchenne’s muscular dystrophy •• Duchenne dystrophy is caused by a mutation of the
»» Becker’s muscular dystrophy. gene that encodes dystrophin a 427 KDa protein located
–– Autosomal disorders— on the inner surface of the sarcolemma of the muscle
»» Limb girdle type (autosomal dominant/auto- fiber. Dystrophin gene is one of the largest human gene
somal recessive) dystrophy. located on the short arm of ‘X’ chromosome. Duchenne
»» Facioscapulohumeral (autosomal dominant) is caused by gene duplication or point mutation or
dystrophy. deletion. Diagnosis of Duchenne dystrophy is done by
»» Oculopharyngeal (autosomal dominant) western blot analysis of muscle biopsy for quantity and
dystrophy. molecular weight of dystrophin protein.
»» Congenital (autosomal recessive) dystrophy.   Immunocytochemical staining of muscle with
−− Myotonia—This condition is composed of two dystrophin antibodies can be used to demonstrate the
clinical disorder with overlapping phenotype and absence or deficiency of dystrophin to the inner surface
distinct genetic defect. of sarcolemma.
–– Myotonic dystrophy type–I (classical disease— •• Disease is present at birth usually become apparent by
originally described by Steinert)—DM1. the age of 3–5 with history of frequent fall.
–– Myotonic dystrophy type–II proximal myotonic •• On getting up from floor the patient needs his hands to
myopathy (PROMM). climb up his own leg (Gower’s sign positive).
–– Myotonia also seen in myotonia congenita-A •• Contracture of heal with tendo Achilles and iliotibial
chloride channel disorder but muscle weakness tract is apparent by the age of 6 when toe walking is
is not so prominent. associated with a lordotic posture.
–– Myotonia are also seen with sodium channel •• Initially there is weakness of proximal limb muscle
mutation, hyperkalemic periodic paralysis or and neck flexors. Leg involvement is greater than arm
potassium-sensitive myotonia. involvement.
–– Paramyotonia is associated with muscle stiffness •• By the age of 8–10 walking requires use of braces.
is also due to sodium channelopathy and is so •• By the age of 12 the patient is wheelchair-dependent.
150 Essentials of Internal Medicine

•• Chest deformity with scoliosis impairs pulmonary function •• 20% patient have progressive weakness of pelvic gridle
which is already compromised by muscle weakness. muscle.
•• Patient usually die in between 16–18 years due to fatal •• No other organ is involved.
pulmonary infection as a result of aspiration of food, or
acute gastric dialation or pulmonary infection. TREATMENT
•• Cardiomyopathy is seen in almost all patients but it is 1. Physiotherapy
not a cause of death. 2. Ankle foot orthosis
•• Intellectual impairment is common but non- progressive 3. Scapular stabilization to prevent winging of scapula.
and affects verbal ability.
•• ECG changes are : LIMB-GIRDLE TYPE
−− Increase RS in V1.
−− Tall R in V1. Prominent contracture of elbow and neck is the earliest
−− Deep narrow Q in the precordial lead. manifestation appear in the childhood or early teenage.
It precedes muscle weakness. Initial muscle weakness
TREATMENT involve humeral or peroneal muscle later spread to limb-
•• The disease cannot be cured at present. It may be cured gridle distribution. Dilated cardiomyopathy (DCM) is the
by gene therapy in future. cause of sudden death, apart from atrial fibrillation and AV
•• Prednisolone (0.75 mg/kg/day)—Significally slows the block.
progression of Duchenne up to 3 years but cannot cure TREATMENT
the disease or halt the progress of the disease.
•• Supportive care
BECKER’S MUSCULAR DYSTROPHY •• Management of cardiomyopathy and arrhythmia
•• Surgery for contracture.
•• Pattern of muscle wasting is Becker’s type closely
resemble Duchenne’s myopathy. MYOTONIA and OPhthalmoplegia
  Proximal group involvement > Distal group
involvement. •• It involves many system other than muscle.
  Lower extremity involvement > upper extremity •• Affected person have ‘hatchet’ facies due to atrophy and
involvement. weakness of temporalis, masseter along with frontal
•• Facial weakness is not a feature. baldness.
•• Hypertrophy in calves is a early prominent finding. •• Weakness and atrophy of neck muscles including
•• Onset of symptoms is between 5–15 years. Although it flexors, sternomastoid with distal limb muscles which
may be delayed up to 3–4 decade or even later. are involve early.
•• By definition the patient of Becker type can walk, beyond •• Weakness of wrist extensors, finger extensors and
the age of 15 while Duchenne is typically wheelchair- intrinsic hand muscle along with ankle dorsiflexor—
dependent by the age of 12. causing foot drop and wrist drop.
•• Cardiac involvement is in the form of CCF may be •• Proximal muscle remains stronger throughout the
present. course, except preferential atrophy of quadriceps
•• Patient usually survive upto 4–5th decade. muscle.
•• Mental retardation may occurs but less common than •• Palatal, pharyngeal and tongue muscle involvement
Duchenne. produce a dysarthric speech, nasal voice and swallow-
ing problem.
FACIOSCAPULOHUMORAL MYOPATHY •• In some patient, involvement of diaphragm and inter-
costal muscles results in respiratory insufficiency.
•• Onset in childhood/early adulthood. •• Myotonia which appears by the age of 5 is demonstrated
•• Facial weakness is a early manifestation in the form of by—
inability to smile, whistle or fully close the eye. −− Slow relaxation of hand grip after hand shaking.
•• Weakness of shoulder gridle usually draws medical −− Percussion on thenar eminence, tongue and wrist
attention. extensor produces a dimple which disappear slowly.
•• Biceps and triceps are severely affected with relative Precussion over thenar prominence produce
sparing of deltoid. dimpling along with peculiar movement of thumb
•• There is wrist drop and foot drop. (opponence movement).
•• Weakness is restricted to facial, upper extremity and •• In advance state muscle wasting makes myotonia more
distal lower extremity. difficult to detect.
Myopathy and Myotonia 151

Flowchart 20.1: Differential diagnosis of different group of muscle

Abbreviations: PM, Polymyositis; DM, Dermatomyositis; OPDM, Oculopharyngeal muscular dystrophy; FSHD, Facioscapulohumeral muscular
dystrophy; IBM, Inclusions body myositis; MG, Myasthenia gravis; ALS, Amyotrophic lateral sclerosis.

•• Cardiac involvement is common with DM–1 and ranges •• Other agents are quinine and procainamide but may
from 1st degree heart block to complete AV block and produce cardiac conduction defect.
sudden death, congestive heart failure, mitral valve •• Pacemaker can be applied.
prolapse and cor pulmonale can develop.
•• Other associated features are—
CAUSES OF PTOSIS AND OPHTHALMOPLEGIA
−− Intellectual impairment
−− Hypersomnia −− Peripheral nerve (neuropathy)
−− Posterior subcapsular cataract –– Guillain-barré syndrome
−− Insulin resistance –– Miller-Fisher syndrome.
−− Gonadal atrophy −− Neuromuscular junction
−− Decreased esophageal and colonic motility. –– Botulism
–– Eaton-Lambert syndrome
DM–2/ PROMM (PROXIMAL MYOTONIC –– Myasthenia gravis
MYOPATHY) –– Congenital myasthenia.
•• Patient usually have severe facial and bulbar weakness. −− Myopathy—
•• Transient neonatal respiratory insufficiency may develop. –– Mitochondrial myopathies.
•• Other distinctive features is involvement of proximal –– Oculopharyngeal/oculopharyngodistal muscular
group of muscle. dystrophy.
–– Myotonic dystrophy.
TREATMENT –– Congenital myopathy.
–– Graves disease.
•• Phenytoin is the preferred agent.
Chapter 21
Parkinsonism

DEFINITION TYPES
Parkinson’s disease (PD) is most common neuro- degenerative Primary parkinsonism
disorder characterized (biochemically by accumulation of
presynaptic protein α-syneuclein) and clinically by paucity •• Familial PD (5%)
and slowness of movement (bradykinesia), tremor at rest, •• Idiopathic PD (sporadic) [75%]
rigidity, shuffling gait, flexed posture with loss of postural •• Other neurodegenerative disease
reflexes. −− Striatonigral degeneration
Olivopontocerebellar atrophy.
−− Shy-Drager syndrome
PATHOLOGY
−− Motor neuron disease (MND) with Parkinson’s
•• Loss of normal dark melanin pigment due to degeneration feature.
of dopaminergic cell in the pars compacta of substantia −− Progressive supranuclear palsy.
nigra and mild frontal lobe atrophy. •• Genetically-mediated disorders
•• Microscopically there is presence of Lewy body (LB) −− Wilson’s diseases
which has high concentration of α-syneuclein, the −− Spinocerebellar atrophy (SCA–3)
pathological hallmark of the disease. −− Huntington’s disease.
•• Other areas of brain involvement are anterior olfac- tory
nuclei, IXth and Xth cranial nerve nuclei, locus ceruleus, Secondary parkinsonism
gigantocellularis, raphe magnus. These are reponsible •• Repeated head trauma.
for nonmotor symptoms (autonomic, sleep, emotional •• Postencephalitic Parkinsonism.
disturbances, cognitive disturbances) and refractory •• Neurosyphilitic Parkinsonism.
motor symptoms (postural instability, gait and bulbar •• Metabolic—Hypothyroidism.
disturbances). •• Drugs—neuroleptics, antiepileptic, antiemetics,
methyldopa, reserpine and lithium.
PATHOGENESIS •• Toxins—MTTP, manganese, cyanide, methanol and
Dopaminergic and other cells die due to combination of carbon monoxide.
many factors like
•• Genetic vulnerability CLINICAL FEATURES
•• Oxidative stress
•• Proteosomal dysfunction •• Resting tremor (4–6 Hz)—Typically appears
•• Environmental factor. unilaterally, initially distally (involving digits and
Endogenous oxidative stress comes from free wrists—giving the pill rolling character), some- time
radical generated by metabolism of dopamine and drum beating movement of finger are also seen. It
melanin and defect in the mitochondrial complex–1 of usually spreads ipsilaterally and proximally rarely to the
oxidative phosphorylation chain. This oxidative stress leg before crossing to other side which takes about 1 year
and proteosomal dysfunction leads to aggregation of α- or more. At this stage it is called hemiparkinsonism. It
syneuclein. may involve leap, jaw and tongue but sparing the head.
Parkinsonism 153

•• Bradykinesia—Interferes with both gross movement −− Coenzyme—Q10 (high dose) as free radical scavenger.
of big joints and fine motor activity (e.g. handwriting— −− Intrastriatal infusion of neurotrophic factors are
micrographia). investigational agents.
•• Rigidity—Lead-pipe rigidity is usually more marked on •• For motor symptoms—Treatment of choice is either
one side of the body and also present in the neck and levodopa or dopamine agonist. But the present trend
axial muscles. Rigidity increases in the examined arm is to start with dopamine agonist for the younger age
when the opposite arm is moved actively. When stiffness group while that in case of aged people > 70 years of
is combined with tremor, lead-pipe rigidity is broken up age with levodopa.
into jerky resistance to passive movement—known as   Early initiation and prolonged use of L-dopa-
cogwheel rigidity. It is more prominent in wrist joint Carbidopa mixture cause various side effects—
where the other wrist inactively moved. −− Weaning off phenomenon.
•• Postural changes and gait—A stoop is characteristic. −− On-off phenomenon.
The posture is sometimes called ‘simian posture’ to −− Increased chance of dyskinesia.
describe the ape-like forward flexion of knee, hip and −− Enhanced degeneration of nigrostriatal pathway.
spine with lack of facial expression. This side effects can be avoided by using dopamine
  Gait disturbances with shuffling short steps and agonist (D2A agonists). Moreover in case of complete
tendency to run enblock known as festinating gait—a degeneration of nigrostriatal pathway where L-dopa
classic parkinsonian sign results from flexed posture cannot produce any action then dopaminergic
and loss of postural reflexes. agonists act on postsynaptic dopaminergic receptors
Glabellar Tap sign—Tap over of middle of forehead and improves motor symptoms.
cause blinking which persists for 2–3 taps in normal •• Modalities of treatment of parkinsonism are as
man, but in case of parkinsonism blinking will continues follows:
as long the tap over Glabella is continued. −− Dopamine agonists
•• Nonmotor features of parkinsonism –– Nonalkaloid
−− Depression »» Pramipexole (1.5–4.5 mg/day in 3 divided
−− Anxiety doses).
−− Cognitive impairment »» Ropinirole (1.2–2.4 mg/day in 3 divided doses).
−− Sleep disturbances –– Alkaloid
−− Sensory abnormality »» Bromocriptine (7.5–15 mg/day in 3 divided
−− Loss of pain and smell sensation doses).
−− Autonomic dysfunction. »» Pergolide (1.6 mg/day in 2–3 divided doses)
(withdrawn from market).
TREATMENT (flowchart 21.1) »» Cobergoline—(Used in Europe).
−− L-dopa/carbidopa mixture
Aim of treatment is to improve the motor symptom and –– 100 : 25 mg—bid/tid
neuroprotection. –– 200 : 50 mg—continuous release (CR).
Motor symptoms (bradykinesia, rigidity and tremor) −− L-dopa augmentation
and abnormal posture respond well to medical therapy –– By MAO-B inhibitor—Selegiline and rasagiline
whereas cognitive symptoms, hypophonia, autonomic (they have additional neuroprotective role and
disfunction and balance difficulty respond poorly to medical weak symptomatic improvement).
therapy. –– COMT inhibitor—Tolcapone (50–200 mg tid)
•• Neuroprotective therapy Tolcapone is notorious for hepatotoxicity and
Dopamine breakdown product creates major free hematological disorders and withdrawn from
radicle which cause degeneration of dopaminergic market.
neuron. MAO-B inhibitor (selegiline and rosagiline) Entacapone (200 mg with each dose of
and COMT inhibitor (tolcapon and entacapon) prevent L-dopa and carbidopa mixture).
dopamine breakdown and cause neuroprotection. When they are coadministered with L-dopa they
−− Selegiline (MAO-B inhibitor)—2.5 mg/day to 5 mg increase the effect of L-dopa by 30%.
BD (breakfast and lunch). −− Anticholinergic drugs—Benzhexol (1–4 mg tid)—
−− Rosagiline. Useful for controlling resting tremor and dyskinesia.
−− Entacapone—COMT inhibitor 200 mg with each −− Amantadine—It can reduce drug-induced dyskinesia
dose of levodopa. up to 70%. Dose : 100 mg bid/tid.
154 Essentials of Internal Medicine

Flowchart 21.1: Flowchart of treatment Parkinsonism disease

•• For nonmotor symptoms •• The ablation of subthalamic nucleus (STN) results


−− Night-time awakening → L-dopa/carbidopa at night in dramatic reduction of all clinical features of
−− Depression—SSRI parkinsonism.
−− Psychological symptoms—Quiteapine/clozapine. Indications—
−− Idiopathic Parkinsonism
MANAGEMENT OF ‘ON-OFF’ PHENOMENON −− Poor response to L-dopa and carbidopa mixture
−− Significant intractable symptoms
•• Increased frequency of dosing. −− Weaning off phenomenon.
•• Occasional drug holiday. •• Bilateral deep brain stimulation of STN (subthalamic
•• Drug to be taken 1 hour before or 2 hours after food for nucleus) is more preferred now than thalamotomy.
maximum absorption. Stimulation is better than subthalamotomy as—
•• Protein restriction—Amino acid from high protein −− Less invasive and more reversible than ablation
meal—compete with L-dopa for transport and decrease −− Adjustable effect.
level of L-dopa at the site of action.
Both procedures improve patient’s quality of life and more
•• Addition of other drugs specially D2A agonist.
effectively than medical therapy in target population in patient
•• Administration of L-dopa or carbidopa in liquid form.
with advanced Parkinson’s disease particularly improve
•• Substitution of L-dopa or carbidopa with other drugs
troublesome dyskinesias, dystonia and motor fluctuation. But
like dopamine agonist/amantadine.
as a rule benefit from surgery unlikely to exceed the best result
obtain from dopaminergic therapy in early Parkinson’s disease.
SURGICAL TREATMENT
Signs and symptoms not responding to levodopa, e.g.
Resurgence of surgery in the treatment of parkinsonism is postural instability and falling, hypophonia, drooling of
motivated by the development of significant drug-induced saliva and autonomic dysfunction are unlikely to improve
side effects after 5 years of treatment. from surgery.
Chapter 22
Motor Neuron Diseases

Definition –– No sensory changes.


–– Loss of large pyramidal cells of layer five of
Motor neuron disease (MND) is a neurodegenerative
precentral cortex.
disorder and include all those diseases that involve
–– Survival 3 years.
selective structural or functional loss of upper motor
−− Familial spastic paraplegia (ad)
neuron and/or lower motor neurons innervating the
–– Adult onset.
voluntary musculature of limbs and bulbar regions.
–– Long survival due to late involvement of respiratory
muscle.
CLASSIFICATIONs –– Weakness starts from lower limbs.
•• Both upper motor neuron (UMN) and lower motor –– Bladder—Bowel involvement present.
neuron (LMN) involvement –– Sometimes associated with posterior column
−− Amyotrophic lateral sclerosis (ALS). involvement and Friedreich’s ataxia.
•• Pure LMN involvement −− Pseudobulbar palsy
−− Proximal hereditary motor neuropathy (PHMN). –– Bilateral lesion in the corticobulbar connections.
−− Multifocal motor neuropathy with conduction block –– Bilateral UMN tongue paralysis—nut in shell
(MMCB). tongue (small contracted and slowly moving
−− Motor predominant peripheral neuropathy (MPPN). tongue)
−− Motor neuropathy associated with paraproteinemia –– Brisk jaw jerk with risus sardonicus (exaggerated
(MNAP). emotional facial expressions).
−− Spinal muscular atrophy (SMA). −− Lathyrism.
–– Type–I—Infantile variety/Werdnig-Hoffman type. −− Konzo.
–– Type–II—Chronic childhood variety.
–– Type–III—Juvenile variety/Kugelberg-Welander Amyotrophic lateral sclerosis ALS
type.
−− Hereditary bulbar palsy •• It is the most devastating neurodegenerative disorder
–– With deafness (Brown-Vialetto-van-Laere) with progressive loss of both categories of motor neuron
–– Without deafness (Fazio-Londe). (UMN and LMN).
−− Tay-Sachs disease—Hereditary β-hexosaminidase •• In the absence of clear involvement of both UMN and
deficiency (X-linked recessive). LMN—the diagnosis of ALS is questionable.
−− Kennedy’s syndrome—Bulbospinal atrophy with •• LMN involvement is recognized clinically by gross muscle
androgen insensitivity (X-linked recessive)— atrophy and on muscle biopsy there is amyotrophy.
characterized by gynecomastia and reduced fertility. •• UMN involvement is recognized by loss of fibers of
−− Postpolio syndrome. lateral column of spinal cord with fibrillary gliosis—
−− Postirradiation syndrome. hence known as lateral sclerosis.
−− Monomelic and focal or segmental SMA.
•• Pure UMN involvement PATHOLOGY
−− Primary lateral sclerosis
Clinical features •• Early accumulation of pigmented lipid—Lipo- fuschin
–– Sporadic. with shrinkage of affected motor neuron.
–– Adult onset. •• Focal enlargement of proximal motor neuron due to
–– Spinal and bulbar involvement. early involvement of motor neuron cytoskeleton— due
–– Absent fasciculation. to accumulation of neurofilament forming spheroid-
–– Amyotrophy. like structure.
156 Essentials of Internal Medicine

•• Compensatory gliosis, i.e. hypertrophy of astrocyte and –– Exaggeration of motor facial expressions of
microglia. emotions (risus sardonicus) due to bilateral UMN
involvement of facial nerve nucleus.
PATHOGENESIS •• Whatever be the initial involvement UMN or LMN,
at a later stage of the disease, there will be symmetric
It is not well-defined—Several theory are proposed: involvement in all regions, with eventual implication of
•• Glutamate excitotoxicity both upper and lower motor neuron.
−− Due to diminished reuptake of synaptic glutamate •• In absence of clear involvement of both upper and lower
via astrocyte glutamate transporter, called EAAT-2 motor neuron the diagnosis of ALS is questionable.
(excitatory amino acid transporter-2). •• Until very late stage of the disease
•• Superoxide dysmutate (SOD-1) gene mut­ation— −− Sensory
Leading to— −− Cognitive
−− Aggregation of SOD protein. −− Ocular motility
−− Superoxide accumulation. −− Bladder (function is preserved).
−− Decreased ATP production and depressed
mitochondrial function. DIAGNOSIS
−− Impaired axonal transport.
−− Activation of cyclooxygenase pathway. •• Diagnosis of ALS mostly based on clinical findings and
–– All these effects ultimately leads to neuronal death the region of CNS involvement.
via caspases pathway. •• Diagnostic guidelines of ALS by WFN (World Federation
•• Diminished VEGF (vascular endothelial growth of neurologists).
factor) expression— −− Presence of simultaneous UMN-LMN involvement.
−− Increased risk of ALS mostly due to—Spinal −− Progressive increasing weakness.
cord hypoxia which is secondary to diminished −− Exclusion of all other possibilities, e.g. compressive
neurotropic influence of VEGF. myelopathy, syringomyelia, benign fasciculation.
•• Four regions of CNS are commonly involved in ALS—
−− Bulbar
CLINICAL FEATUREs
−− Cervical
Depends whether UMN or LMN is predominantly in- −− Thoracic
volved. −− Lumbosacral.
•• Features due to LMN involvement— 1. When 3 out of 4 regions are involved—Definitive of ALS
−− Features due to spinal anterior horn cell involvement: 2. When 2 out of 4 regions are involved—Probable of ALS
–– Asymmetric distal limb muscle involvement 3. When 1 out of 4 regions is involved—Possible of ALS.
leading to progressive, wasting, weakness and
fasciculation of limb muscle. Differential Diagnosis
–– Predominance of extensor weakness over flexor •• Compressive myelopathy involving cervical cord/
weakness. cervicomedullary junction.
–– Early involvement of respiratory muscle •• Syringomyelia.
responsible for early death before florid features •• Benign fasciculation of viral infection.
of MND develops.
•• Lymphoma/multiple myeloma.
−− Features due to bulbar motor cranial nerve nucleus
•• Chronic lead poisoning.
involvement
•• Thyrotoxicosis.
–– Weakness of muscle of mastication, facial muscle,
•• Multifocal motor neuropathy with conduction block.
difficulty in deglutition and tongue movement.
•• Features due to UMN involvement
TREATMENT
−− Corticospinal tract involvement
–– Tone—Spasticity. ALS is currently untreatable. No satisfactory treatment
–– DTR—Hyperreflexia. has yet come out. The commonly used drugs in ALS are
–– Nutrition (Without gross atrophy)—Disuse as follows:
atrophy. •• Riluzole—100 mg/day.
–– Extensor plantar response. (But prolongation of survival time using Riluzole is
–– Hyperreflexia and spasticity predominates over questionable/doubtful).
weakness.
−− Corticobulbar fiber involvement • Ceftriaxone }
• Insulin-like growth factor (1 GF – 1) Undergoing
clinical trial
–– Dysarthria • Physiotherapy and other rehabilitative measures.
Motor Neuron Diseases 157

Differential diagnosis OF MOTOR Multifocal Motor Neuropathy With Conduction


NEURON DISEASES (MND) Block (Mmcb)
•• High titer of mono and polyclonal antibody to
Lower MOTOR NEURON DISORDER ganglioside (GMI).
Kennedy’s Disease (X-Linked Spinobulbar Atrophy) •• Antibody cause selective focal paranodal demyeli-
nation of motor neuron.
It is an X-linked lower motor neuron disease charac- •• No pyramidal sign present.
terized by •• May respond dramatically with IV immunoglobulin or
•• A disease of the middle-aged male. chemotherapy.
•• There is progressive weakness and wasting of limb and
bulbar muscle. UPPER MOTOR NEURON DISORDER
•• Gynecomastia with reduced fertility is due to androgen
receptor insensitivity. Primary Lateral Sclerosis (PLS)
•• There is absence of pyramidal sign.
•• It is a disease of mid or late life and sporadic disorder.
•• Presence of subtle sensory neuropathy.
•• Progressive spastic weakness of limbs.
•• Molecular defect is in expanded trinucleotide repeat
•• Preceded or followed by spastic dysarthria or dys-
(– CAG –) is the first exon of androgen receptor.
phagia suggesting involvement of corticospinal and
•• Age of onset inversely correlates with the number of –
corticobulbar track.
CAG – repeat.
•• Fasciculation and LMN atrophy absent.
•• No sensory change.
Adult Tay-Sachs Disease •• EDX study does not show denervation.
•• Adult onset lower motor neuropathy due to deficiency •• Long-term survival is possible.
of enzyme β-hexosaminidase. •• Multiple sclerosis, adrenoleukodystrophy and HTLV–1
•• Slowly progressive dysarthria develops. comes in close differential separated by clinical and
•• Rarely spasticity may be seen. laboratory examinations.
•• Cerebellar atrophy—Seen in CT/MRI.
Familial Spastic Paraplegia (FPS)
Spinal Muscular Atrophy (SMA) Autosomal dominant form shows the following character-
istics:
Group characteristic of SMA
•• Usually starts in the 3rd or 4th decade but may start in
•• There is selected lower motor involvement. early life.
•• Age of onset is very early. •• Progressive spastic weakness involve distal part of lower
•• There is extensive loss of large motor neuron cell. limb.
•• Biopsy shows denervation atrophy. •• Long survival is possible as respiratory function is
•• Genetic defect is in the locus on chromosome-5 affected late.
encoding putative motor neuron survival protein. •• Urinary urgency and urinary and fecal incontinence are
−− Infantile SMA (Werdnig-Hoffman disease – seen in the late stage.
SMA-1). •• Sexual function is preserved.
−− Age of onset—early even before birth indicated by •• Often associated with loss of posteriar column sensation.
decreased fetal movement.
−− If born alive, baby is floppy (hypotonic) although Autosomal recessive form of FSP Shows
alert and die within 1 year.
−− Chronic childhood SMA •• Altered pyramidal and dorsal column function.
–– Slowly progressive course begins late childhood. •• Amyotrophy.
−− Juvenile SMA (Kugelberg-Welander disease) •• Mental retardation.
–– Begins at late childhood. •• Optic atrophy.
–– Runs an indolent course. •• Sensory neuropathy.
–– Weakness present in proximal muscle. •• Degeneration of corticospinal tract at the caudal part
–– EDX study and muscle biopsy show denervation of spinal chord.
which helps to differential the disease from •• Culprit gene of autosomal dominant form of fsp is
myopathic disorder. spastin which encode microtubule interacting protein.
Chapter 23
Multiple Sclerosis

It is a demyelinating disorder of CNS characterized oligoclonal antibodies are found. The pattern of oligoclonal
by inflammation, selective demyelination and gliosis band is different in each individual patient. Some band of
(scarring) of CNS. There is no associated systemic illness oligoclonal antibody are directed against EBV virus.
and the peripheral nervous system remains unaffected.
Genetic susceptibility with a subsequent triggering viral CYTOKINES
infection (probably EBV) stimulates a autoimmune reaction
that plays key role in the development of multiple sclerosis. Proinflammatory cytokine TH1 including IL2, TNFα and
•• Genetic susceptibility is proved by familial aggregation. INFγ injure oligodendrocyte or myelin membrane and plays
•• Susceptibility to MS is polygenic in nature. a key roles in inactivating and maintaining autoimmune
•• Each gene have little contribution in overall risk for MS. response.
•• Genetic heterogenisity is present in MS which means Activated microglia causes axonal injury through release
that different gene is responsible for MS in different of NO, oxygen radical and via glutamet which is toxic to
person. oligodendrocyte and neuron.
•• MHC (major histocompatibility complex gene) on
chromosome 6 is the strongest MS susceptibility region. CLINICAL FEATURES
•• Fine mapping shows class II region on MHC specially
DR2 alle is the culprit in most of the MS patient. Onset of MS may be abrupt or insidious. Symptom may vary
•• In others, the abnormality in the gene that encode from severe to trivial.
receptor for two proinflammatory cytokine, IL-7 Autopsy or MRI may show MS lesion in otherwise
receptor—a chain (CD 127) and IL-2 receptor—a chain healthy individual.
(CD 25) makes the person vulnerable to MS. Symptom of MS depends on the location and severity
•• Axonal damage is mediated by resident and migrated of lesion within CNS.
inflammatory cell, i.e. microglia, macrophage CD8 and
their toxic cytokine, NO and oxygen radical. SYMPTOMS OF MS
•• Autoimmune reaction: Autoimmunity is supported by
the study of immune system in MS patient. •• Sensory symtoms present in 37% of patients
•• Lhermitte’s sign present in 3% of patients
CELLULAR RESPONSE •• Optic neuritis present in 36% of patients
•• Pain present in symptoms 3% of patients
Myelin basic protein (MBP) is the T-cell antigen in MS MBP •• Motor symptoms present in 35% of patients
reactive T-cell found in blood and CSF. •• Dementia present in 2% of patients
•• Paresthesia present in 25% of patients
ABNORMALITY •• Visual loss present in 2% of patients
•• Diplopia present in 15% of patients
Abnormality in DR2 region causes high affinity binding of
•• Facial palsy present in 1% of patients
DR2 region with the fragment of MBP stimulating T-cell
•• Ataxia present in 10% of patients
response to self-protein.
•• Epilepsy present in 1% of patients
•• Vertigo present in 5% of patients
HUMORAL RESPONSE •• Impotence present in 1% of patients
Activated B-cell with antibody against myelin •• Bladder disturbances present in 5% of patients
oligodendrocyte glycoprotein (MOG) have been detected •• Onset and progression of the symptom vary from patient
in MS plaque. In CSF elevated levels of immunoglobulin and to patient.
Multiple Sclerosis 159

Four clinical pattern of onset of MS have been described. indicating that the lesions interrupt the afferent path of the
1. Relapsing and remitting MS (RRMS—85%)—This reflex are in the spinal cord.
type constitute 85% of MS patient at the beginning they Exercise-induced weakness is characteristic of MS.
have discrete attack that evolve over days to weeks but Spasticity—More than 30% of patients have moderate
usually complete recovery to severe spasticity which may be present at rest or during
takes place over months work. Muscle spasm may interfere with ambulation, work
in the initial stage. When or self-care and sometime may be painful.
ambulation is severely Ataxia—Manifest as cerebellar tremor or ataxia of
impaired during acute trunks, head and voice producing scanning speech (cer-
attack in the later stage of ebellar dysarthria).
the disease approximately half the patient fails to Optic neuritis (ON)—Symptom may be mild or may
improve completely leaving some residual neurodeficit progress to visual loss. Diminished visual acuity and
after each attack which are addictive. decreased color vision is the common symptom.
2. Secondary progressive •• Usually the symptoms are monocular but may be
MS (SPMS)—It appears to bilateral. Periorbital pain may proceed or accompany
be in the late stage RRMS. visual loss.
In the initial stage of the •• Defect in the affarent pathway of pupillary reflex may
disease the patients have the be present.
clinical course like that of •• Fundus may be normal or shows papillitis (swelling of
RRMS but at some point of optic disk) with pallor of optic disk which follows ON
time the patient have steady due to optic atrophy.
deterioration of clinical •• Visual blurring may result from diplopia or ON.
status unassociated with •• If blurring of vision disappears after covering one eye,
acute attack. Approximately then the symptom is due to diplopia.
2.5% of RRMS develop SPMS •• Diplopia is due either to internuclear ophthalmoplegia
each year. (INO) or from palsy of 6th cranial nerve and rarely from
3. Primary progressive MS IIIrd and IVth cranial nerves.
(PPMS—15%)—These •• INO (internuclear ophthalmoplegia) consists of
impaired adduction of one eye with prominent
patients do not have acute
nystagmus in the abducting eye along with small
attack but have steady
skew deviation is due to the lesion of MLF (medial
deterioration of the clinical
longitudinal fasciculus) of the side of adducting eye.
state from the beginning.
•• Bilateral INO is strongly suggestive of MS.
This type of clinical course is
Other gaze disturbances are—
usually seen among elderly
−− horizontal gaze palsy.
age >40 year with Male :
−− one and a half syndrome (horizontal gaze palsy
Female ratio (1 : 1) and
plus INO.
accounts for 15% of the patients.
−− acquired pendular nystagmus.
4. Progressive/Relapsing MS (PRMS—5%)—These pa- Bladder dysfunction like frequency, urgency, nocturia
tient experienced occasional acute attack superimposed incontinence, hesitancy, difficulty in initiation,
on the progressive course of the disease. It accounts for retension, overflow incontinence and UTI present in
5% or the patient. > 90% of MS patients.
Sensory symptoms are paresthesia, numbness, tingling, Constipation—Present in > 30% of patients.
prickling formication, burning and pins and needle sensa- •• Fecal urgency and bowel incontinence present in > 15%
tion, hyperesthesia and reduced sensation. of patients.
Unpleasant sensation like that the body parts are Cognitive dysfunction in the form of memory loss
swollen, wet, raw or tightly rapped may be present. Sensory impaired attention, euphoria. Difficulties is problem- solving,
impairment of trunk and leg below a horizontal line indicate slowed information processing is present in < 20% patient.
spinal cord disease. Depression may be endogenous or reactive and
Pain is present in > 50% of patient and can occurs any- contribute to fatigue and suicide.
where and can change location from time to time. Fatigue is present in > 90% can be exacerbated by
Motor symptom—Weakness of limb, i.e. loss of elevated temperature and depression.
strength, increased fatigue, disturbance of gait are usually Sexual dysfunction—Decreased libido, impotence-
associated with pyramidal sign like brisk DTR, Babinski impaired genital sensation in men and diminished vaginal
positive, spasticity. Occasionally DTR may be depressed secretion and adductor spasm in women.
160 Essentials of Internal Medicine

Facial weakness like Bell’s palsy but not associated DIAGNOSTIC


with loss of taste sensation and retroauricular pain may
•• Definite MS—All five criteria are present.
be present.
•• Probable MS—All five criteria is present except—
Vertigo—Due to brainstem lesion resembling acute
−− Only one objective abnormality despite two
labyrinthitis may present in minor percentage.
symptomatic episode.
Hearing loss—Uncommon.
−− Only one symptomatic episode despite two or more
Heat sensitivity and Uhthoff ’s symptom—Neurologic
objective abnormality.
symptom develop after elevation of ‘core’ body tem-
•• At risk for MS—criteria (1) + (2) + (3) + (5) fulfilled but
perature or during exercise or hot shower or after fever like
the patient have either only one symptomatic episode
unilateral visual blurring is called ‘Uhthoff ’s symptom’ is
or one objective abnormality.
due to transient conduction block.
Lhermitte’s sign—Electric shock like sensation down
DIFFERENTIAL DIAGNOSIS
the spine towards the leg rarely towards the arm on flexion
or movement of neck. This symptom can also occur in •• Acute disseminated encephalomyelitis (ADEM).
cervical spondylosis. •• APLA.
Paroxysmal symptoms—This syndrome include •• SLE and related collagen vascular disease and vasculitis.
Lhermitte’s symptom, tonic contraction of limb, face, •• Behçet’s disease.
trunk, paroxysmal dysarthria, ataxia, sensory disturbances. •• SjÖgren’ syndrome.
This is due to spontaneous discharge arising at the edge •• Congenital leukodystrophy (adrenoleukodystrophy and
of the demyelinated plague and spreading to adjacent metachromatic leukodystrophy).
white matter. They are of brief duration (10s–2 min) •• HIV.
high frequency 5–40 episode/day without alteration of •• Tropical spastic paraplegia (HTLV I and II).
consciousness or EEG change. •• Lyme disease.
Trigeminal neuralgia, hemifacial spasm, glos- •• Sarcoid.
sopharyngeal neuralgia—It can occur due to involvement •• CVA and vascular malformation.
of entry or exit of Vth, VIIth or IXth nerve. •• Neoplasm (lymphoma, glioma and meningioma).
•• Vitamin B12 deficiency.
DIAGNOSTIC CRITERIA FOR MS TREATMENT OF MULTIPLE SCLEROSIS
•• Two or more clinical attack or objective clinical evidence (Flowcharts 23.1 and 23.2)
of two or more lesion or objective clinical evidence of •• Treatment of acute attack
one lesion with history of one prior attack. •• Treatment with disease-modifying agent
•• Two or more clinical attack with objective clinical •• Symptomatic therapy.
evidence one lesion and T2 lesion of MRI in at least
one out of four MS typical site in CNS (paraventricular, Treatment of Acute Attack
juxtacortical, infratentorial or spinal cord). •• Methyl prednisolon—500–1000 mg/day IV × 3–5 day
•• One clinical attack with objective clinical evidence of without a tappering dose of prednisolone or with 60–80
two or more lesion or MRI evidence of two or more mg oral/day for 2 week.
lesion or appearance of new lesion on T2-MRI or wait •• Alternatively plasma exchange 40–60 ml/kg per
for a second clinical attack. exchange on every alternate day × 2 weeks (total 5–7 or
•• One clinical attack with objective clinical evidence of change) may benefit patient with fulminant attack who
one lesion with one T2-MRI lesion in at least two out are unresponsive to glucocorticoid. Glucocorticoid
of four MS typical site or wait for second clinical attack are used to manage either first attack or acute
at different CNS site and presence of asymptomatic exacerbation.
gadolinium enhancing on nonenhancing lesion or a −− They provide short-term benefit but regarding
new T2/gadolinium enhance lesion on follow up MRI long-term benefit is uncertain.
or wait for second clinical attack. −− That is why mild attack or pseudoexacerbation due to
•• Insidious progressive neurological lesion suggestive of fever, infection or rise in environmental temperature
MS with two out of three following criteria— are not treated with glucocorticoid.
T2-MRI lesion in the MS-specific area (paraventricular −− Side effects of glucocorticoid therapy are treated
juxtacortical, infratentorial). Two T2-MRI lesion is spinal accordingly.
cord. Positive CSF (oligoclonal band and elevated IgG −− Emotional lability and insomnia—Treated by lithium
index). carbonate— 300 mg bid
Multiple Sclerosis 161

Flowchart 23.1: Treatment of RRMS

Flowchart 23.2: Treatment of progressive MS


162 Essentials of Internal Medicine

−− Peptic ulcer—Ranitidine — 150 mg bid and panto- •• Cyclophosphamide—700 mg/m2 on alternate month.
prazole—40 mg bid. •• IVIG—1 g/kg monthly pulse for 2 years.
•• Methyl prednisolone—500 mg–1 gm monthly pulse.
Treatment with Disease-modifying Agent
Symptomatic Therapy
Disease-modifying therapy for relapsing from of MS—
Seven agents are approved by FDA. •• Heat-sensitive symptom—Potassium channel
•• INFB 1a blocker—4 aminopyridine 3–4 diaminopyridine—40–80
•• INFB 1b mg/day.
•• Glatiramer Side effect—Seizure.
•• Natalizumab •• Ataxia and tremor
•• Fingolimod Clonazepam—1.5–20 mg/day
•• Mitoxantrone Mysoline—60–200 mg/day
•• Cladribine. Propanolol—40–200 mg/day
These agents are used for treatment SPMS/RRMS and Ondansetron—8–16 mg/day.
have fewer clinical exacerbation and fewer new MRI lesion Physical measure—Wrist weight, thalamotomy, deep
compaired to placebo. brain stimulation, may be tried.
•• Interferon acts through its immune modulatory •• Spasticity
action— Lioresol—100–120 mg/day by a pump to deliver the
−− Down regulation of MHC molecule on APC cell. drug into CSF.
−− Inhibition of proinflammatory and stimulation of Diazepam—20–40 mg/day.
regulatory cytokines. Tizanidine—8–32 mg/day.
−− Inhibition of ‘T’ cell proliferation. Dantrolene—25–400 mg/day.
−− limiting the entry of inflammatory cells in CNS. Cyclobezapirine—10–60 mg/day.
•• Glatiramer acetate—A polypeptide composed of Physical therapy—Exercise, stretching and avoidence
L-glutamic acid, L-lysine, L-alanine and tyrosine acts by— of constipation and infection.
−− induction of antigen-specific suppressor ‘T’ cell. •• Pain
−− Binding to MHC molecule—thereby replacing bound Carbamazepine 100–1000 mg/day
MBP. Phenytoin—300–600 mg/day
−− Altering the balance between proinflammatory and Gabapentine—300–3600 mg/day
regulatory cytokines. Pregabalin—50–300 mg/day
•• Natalizumab—A humanized monoclonal antibody Amitriptyline—25–150 mg/day
against a cell adhesion molecule α4β1 integrin expressed Desipramine—100–300 mg/day
on the surface of lymphocyte which helps to penetrate Venlafaxine—75–225 mg/day.
BBB. Thereby prevent the lymphocyte from penetrating •• Bladder dysfunction—
BBB to enter CNS. Complication in PML with prolong −− Detrusor hyperreflexia
therapy. Propantheline bromide—10–15 mg/day
•• Fingolimod—Prevents the movement of lymphocyte Oxybutyrin—5–15 mg/day.
from spleen and lymph node to brain. It reduces the Hyoscyamine—0.5–0.75 mg/day.
attack rate and significantly improves all measures of Tolterodin—2–4 mg/day.
disease severity in MS. It can be administered orally Solifenacin—5–10 mg/day.
and well-tolerated and superior to low dose weekly Coadministration of pseudoephedrine 30–60 mg/day
INF-B. So, it is recommended for firstline therapy for may be beneficial.
MS by FDA. Complications are first degree heart block, −− Detrusor/sphincter dyssynergia—
bradycardia, elevated liver enzyme and lymphopenia. Phenoxybenzamine—10–20 mg/day
•• Cladribine—It is a purine analog inhibit DNA synthesis. Terazosin—1–20 mg/day Loss of reflex bladder con-
Easy oral dosing only 2 weeks/year makes it convenient. traction—Bethanicol 15–150 mg/day.
•• Mitoxantrone—12 mg/m2 every 3 months for 2–3 years •• Depression—Fluoxetin—20–80 mg/day sertaline—50–
for SPMS, PPMS and RRMS. 200 mg/day
Side effects—Permanent amenorrhea, cardiomyopathy Amitryptaline.
and leukemia. •• Fatigue is treated by—
Second line (disease-modifying) agent— Amantadine—200 mg/day
•• Azathioprine—2–3 mg/kg/day for SPMS. Methylphenidate—5–25 mg/day
•• Methotrexate—(7.5–20 mg/week for upper extremity Modafinil—100–400 mg/day.
dysfunction in SPMS. •• Cognitive problem—Donepezil—10 mg/day.
Chapter 24
Polymyositis, Dermatomyositis, Inclusion Body Myositis

Introduction −− Myalgia and tenderness are not seen in IBM and


polymyositis (PM).
•• These are inflammatory muscle disorder, consist of
three major disease:
SPECIAL FEATURES OF POLYMYOSITIS
1. Polymyositis (PM)—It is a rare disease affecting
adult. •• Rare subacutely progressive inflammatory myopa- thies
2. Dermatomyositis (DM)—Affects both child and affecting adults rarely children.
adult. Women are more often affected than men. •• No cutaneous rash seen.
3. Inclusion body myositis (IBM)—It is 3 times •• No involvement of extraocular or facial muscle.
common in men than women and whites are more •• No family history of neuromuscular disease.
commonly affected than black. •• Associated with systemic autoimmune or connective
tissue disease or viral or bacterial infection.
GROUP CHARACTERISTICS OF POLYMYOSITIS •• D-penicillamine or zidovudine may produce PM-like
syndrome.
•• PM and DM are subacutely progressive (over weeks
to months).
They are symmetric inflammatory myopathy involv- SPECIAL FEATURES OF DERMATOMYOSITIS
ing proximal group of muscle. Distal group of muscle
•• Skin rash may accompany or precede the onset of
which are required for fine motor movement are
muscle weakness.
affected late in the course of the disease of PM and DM.
•• Blue purple discoloration on the upper eyelid with
•• IBM is a very slowly progressive muscle disorder
edema—called heliotrope rash diagnostic of DM.
involving distal group of muscle but quadriceps
•• Flat red rash on the face and upper trunk and erythema
develop early in the course of the disease.
of the knuckles with raised violaceous scally eruption—
•• Ocular muscles are not involved in inflammatory myositis.
called Gottron’s sign seen in DM.
−− Facial muscles are unaffected in PM and DM.
•• Erythematous rash can also occur on knee elbow
−− Mild degree of facial involvement seen in IBM.
malleoli, neck, anterior chest (‘V’ sign), back and
−− Pharyngeal and neck flexors are involved in all forms
shoulders—worsen with sun exposer—called ‘Shawl’
of inflammatory myopathies causing dysphagia and
sign. Seen in DM.
head drop.
•• In some patients pruritic rash may be present on scalp,
−− Respiratory muscles are involved in late stage and
chest and back.
rarely in acute stage.
•• Dilated capillary loop at the base of finger’s nail.
−− Muscle wasting in associated with severe weakness.
•• Cuticles are irregular, thicker, distorted on lateral
−− DTR are preserved until very late stage but may be
and palmar aspect of the fingers which are rough and
absent in severly atrophied muscle specially in IBM
thickened, cracked with dirty horizontal line simulating
where atrophy of quadriceps and distal group of
mechanic’s hand.
muscle predominate.
•• Sometime muscle power may be normal in this disease
−− Sensation remains normal in inflammatory myo-
and is termed as dermatomyositis sine myositis.
pathies.
•• Perivascular and perimysial inflammation seen on
−− Myalgias and muscle tenderness seen in a small
muscle biopsy.
percentage of patient usually with DM which are
•• Dermatomyositis may overlap with scleroderma and
associated with connective tissue disorder like
MCTD.
scleroderma, MCTD and overlap syndrome.
164 Essentials of Internal Medicine

•• Chronic DM-like features are seen in eosinophilic some patients of DM and PM who have JO-1 antibody
myalgic syndrome associated with ingestion of con- positive.
taminated L–tryptophan. •• Subcutaneous calcification in DM patient sometime
•• Incidence of malignancy appear to increase with DM. project on skin and cause ulceration and infection.
•• Common tumors associated with DM are ovarian •• Dysphagia with GI symptoms due to involvement of
cancer, breast cancer, melanoma, colon cancer and oropharyngeal and esophageal muscle occurs specially
non-Hodgkin’s lymphoma. Nasopharyngeal cancer are in DM and IBM.
common association in Asian population. •• Cardiac symptoms like AV conduction disturbances,
•• Overlap syndrome in a patient of DM is characterized by tachyarrhythmias, DCM, low ejection fraction with CCF
features of systemic sclerosis or mixed connective tissue is due to involvement of heart. HTN can develop from
disease, e.g. sclerotic thickening of the dermis, contrac- glucocorticoid therapy.
ture, esophageal hypomotility microangiopathy and •• Pulmonary dysfunction is due to weakness of tho- racic
calcium deposit. They have specific antinuclear antibody, muscle, ILD, or drug-induced pneumonitis (from
Anti-PM/Scl 70 nuclear protein complex. methotrexate). Symptoms of pulmonary dysfunction
•• It is associated with rheumatoid arthritis, SLE and are dyspnea, nonproductive cough and aspiration
SjÖgren’s is rare. pneumonia. ILD may precede or accompany PM or DM
who have antibodies to tRNA synthetase.
SPECIAL FEATURES OF INCLUSION BODY—
MYOSITIS PATHOGENESIS
•• It is the most common inflammatory myositis. An autoimmune reaction is the reason behind inflam-
•• Age on onset is ≥ 50 years. matory myopathies and is supported by the following
•• It is a slow but steady progressive disorder require reasons—
walking assistance or wheelchair within several year. •• Overlap with scleroderma and MCTD.
•• Initial features are similiar to PM. •• Associated with specific MHC gene like—DR3 and
•• Weakness and atrophy of distal group of muscle DRW52. DR3 haplotype occurs in 75% of PM and IBM
specially long flexor of fingers and foot extensor which whereas in Juvenile DM there is increase frequency
develop very early and gives a clue to early diagnosis. DQA1.
•• Inability to perform fine movement like turning key or •• Presence of various antinuclear antibody-like anti-Jo-1.
knotting, holding object and stiching. •• Demonstrable ‘T’ cell-mediated myocytotoxicity and
•• Some patients present with history of repeated fall due complement-mediated microangiopathy.
to weakness of quadriceps. •• Response to immunotherapy.
•• Weakness and atrophy may be asymmetric and
selectively involve quadriceps, iliopsoas, triceps, biceps,
finger flexor mimic lower motor neuron disease. DIFFERENTIAL DIAGNOSIS
•• Dysphagia with chocking may be present in 60% Typical skin rash with proximal or diffuse skin rash is almost
patients. diagnostic of DM.
•• Sensory function is almost normal except mild Proximal muscle weakness without any skin rash which
diminution of vibration sense at lower limb in some is seen in PM and IBM have many differentials such as—
patient. Chronic progressive muscle weakness develop in the
•• The pattern of distal weakness makes it a close dif- following condition—
ferential diagnosis of MND or peripheral neuropathy, •• Spinal muscular atrophy.
systemic autoimmune or connective tissue disorder. •• Amyotrophic lateral sclerosis.
•• There is a subgroup called hereditary inclusion body •• Muscle dystrophy.
myopathy (h-IBM) which has familial aggregation. •• Collagen storage disease.
•• Lipid storage disease.
EXTRAMUSCULAR MANIFESTATION •• Endocrine myopathies—Cushing, hypo and hyper-
OF PM and DM thyroidism and hypoparathyroidism.
•• Systemic manifestation like, fever myalgia, arthralgia, •• Myoneural junction disorder—myasthenia and
weight loss, Raynaud’s phenomenon are present when Lambert-Eaton myopathy.
inflammatory myositis is associated with connective Acute muscle weakness develop in the following
tissue disorder. condition—
•• Arthralgia, synovitis or joint deformity or contracture •• GB syndrome.
with subluxation of interphalangeal joint can occur in •• Transverse myelitis.
Polymyositis, Dermatomyositis, Inclusion Body Myositis 165

•• Neurotoxin. In summery—
•• Neurotropic virus—polio and West Nile virus. •• In polymyositis—There is endomysial inflammation
•• Parasitic infestation—toxoplasma, trypanosoma and with CD8/MHC-I complex without vacuoles but
cysticerci. minimal inflammation.
•• Bacterial infection—Staphylococcus, Streptococcus •• In dermatomyositis—Perifascicular, perimysial or
yersinia, anaerobic bacteria, Legionella, pneu- mophilia, perivascular infiltrate and perifascicular atrophy.
Borrelia burgdorferi. •• Inclusion body myositis—Primary inflammation
•• Periodic paralysis—hypokalemia, hypophosphatemia, with CD8/MHC-I complex with vacuolated fibers and
hypomagnesemia, chronic alcoholic and parenteral β-amyloid deposit, cytochrome oxygenase-negative
hyperalimentation. fibers, sign of chronic myopathy.

Myofascitis TREATMENT
Parasitic infection, vasculitis, MCTD, hypereosinophilic 1. Glucocorticoids—Prednisolone—1 mg/kg/day for 4
syndrome and toxic exposure. weeks— reduced slowly over a period of 10 weeks to 1
mg/kg on alternate day—if the patient improves and
Drug-induced myopathies no serious side effects are seen then the dose is further
D-penicillamine, procainamide, AZT, contaminated reduced by 5–10 mg every 3/4 weeks until the lowest
L-tryptophan, cholesterol lowering agent, amphotericin, possible dose that controls the disease is reached.
heroin, growth hormone and glucocorticoids with pan-   If no objective benefit is noted after 3 months of high
curonium. dose therapy, prednisolone is rapidly withdrawn and
switched over to immunosuppressive drug.
DIAGNOSIS OF MYOPATHY IS CONFIRMED BY •• Immunosuppressive drug—75% patient requires this
type of drug when prednisolone fails to improve the
1. Serum muscle enzyme—CK which is always elevated patient within 3 months.
(up to fifty fold) in PM but may be normal in IBM and −− Azathioprine—2–3 mg/kg/day.
DM when associated with connective tissue disease. −− Methotrexate—7.5 mg/weekly for 3 weeks gradu- ally
  SGOT, SGPT, LDH and aldolase may also be elevated. increase the dose to 25 mg/week.
2. Needle EMG shows myopathic potential characterized −− Mycophenolate—Mofetil 2.5 mg/kg/day.
by short duration, low amplitude, polyphasic unit −− Rituximab (anti-CD–20).
on voluntary contraction and increased spontaneous −− Cyclosporine.
activity with fibrillation, complex repetitive discharge −− Cyclophosphamide 0.5–1 mg/IV for 6 months.
and positive sharp wave. −− Tacrolimus.
  EMG finding is not diagnostic but helps to differen- •• Immunomodulation—IV immunoglobulin (IV Ig)—2
tiate it from neurogenic disorder. gm/kg divided over 2/5 days can be repeated every 6– 8
3. Muscle biopsy is the gold standard for diagnosis weeks for sustained improvement for refractory DM.
Myositis inflammation is the histological hallmark for   Plasmapheresis or leukopheresis have no roll in PM
diagnosis. or DM.
 In PM—Inflammation is primarily located within the
muscle fascicles (endomysial) characterized by CD8 + Treatment protocol
T cell and MHC–I molecule expressed on sarcolema is
•• Step 1—High dose prednisone.
fundamental for confirming the diagnosis.
•• Step 2—Azathioprine, myeophenolate mofetil and
 In DM—Inflammation occurs around the muscle
methotrexate are used as steroid sparing agent.
fascicles instead of within the muscle fascicles
•• Step 3—IV immunoglobulin.
predominantly perivascular or in interfascicular septa.
•• Those who do not have optimal response with the above
  In IBM—There is endomysial inflammation with T-
agents for those patients.
cell infiltration with MHC-I expressing nonvacuolated
•• Step 4—Rituximab, cyclosporin, cyclophosphamide or
muscle fiber, basophilic granular deposit around the
tacrolimus can be tried.
edge of slit-like vacuoles, loss of fiber, hypertropic fiber,
angulated or round fiber, eosinophilic cytoplasmic
inclusion, abnormal mitochondria, ragged red fiber,
EXERCISE
cytochrome oxidase negative fiber, amyloid deposit, Write short notes on
filamentous inclusion are detected by congo red or 1. Draw schematic diagram of visual pathway and effect
crystal violet staining using fluorescent microscope. of lesion at different levels.
166 Essentials of Internal Medicine

2. Draw schematic diagram of pyramidal tract from cor- 19. Write in detail clinical features of generalized tonic-
tex to anterior horn cell/motor cranial nerve nucleus. clonic seizure (GTCS).
3. Write the clinical features of nuclear hemiplegia at the 20. Differentiate between complex partial seizure and petit
level of—(a) midbrain, (b) pons and (c) medulla. mal (absence) seizure.
4. Compare medial pontine syndrome with lateral 21. Write a short note on EEG.
pontine syndrome and medial medullary syndrome 22. Classify peripheral neuropathy.
with lateral medullary syndrome. 23. Write the etiology of peripheral neuropathy.
5. Write on thrombolysis in ischemic stroke. 24. Write short notes on carpal tunnel syndrome.
6. Compare the clinical features of LMN with the UMN 25. Write on etiology and clinical features of Guillain-Barré
type of lesion. syndrome.
7. Compare between the extramedullary with the intra- 26. Write on electrodiagnostic test and treatment of
medullary lesion. Guillain-Barré syndrome.
8. Write the clinical features of quadriparesis due to lesion 27. Write on diagnosis of myasthenia gravis (both clinical
at upper cervical cord.
and laboratory).
9. Write short notes on spastic paraplegia and flaccid
28. Write on drug therapy of myasthenia gravis.
paraplegia.
29. Write a short note on Duchenne myopathy.
10. Write the clinical features of compressive myelopathy
30. Write on clinical features of parkinsonism.
at the level of D8 vertebra.
11. Write short notes on subacute combined degeneration 31. Write on treatment of parkinsonism.
of spinal cord. 32. Classify motor neuron sclerosis.
12. Write the comparison between the clinical features of 33. Write on diagnosis of amyotropic lateral sclerosis
conus medullaris lesion with the cauda equina lesion. (ALS).
13. Write the bacteriological profile of pyogenic meningitis. 34. Write on polymyositis, dermatomyositis and inclusion
14. Write the clinical features of pyogenic meningitis. body myositis.
15. Write on management of pyogenic meningitis. 35. Write in short about the different clinical profile of
16. Define seizure and epilepsy. multiple sclerosis.
17. Classify seizure. 36. Write about diagnosis and treatment of multiple scle-
18. Write on management of status epilepticus. rosis.
SECTION  III
NEPHROLOGY

•• Acute Glomerulonephritis
•• Nephrotic Syndrome
•• Acute Renal Failure Acute Kidney Injury
•• Chronic Renal Failure
•• Urinary Tract Infection
•• Interstitial Nephritis
Chapter 25
Acute Glomerulonephritis

Introduction • Causes of microscopic hematuria


1. Benign prostatic hypertrophy
Acute Glomerulonephritis (AGN) is clinically character- 2. Interstitial nephritis
ized by abrupt onset of oliguria, hematuria, edema and 3. Papillary necrosis
hypertension. 4. Hypercalciuria
The clinical spectrum may range from very mild disease 5. Renal stone
which may go undetected, to severe anuria, hematuria, 6. Cystic kidney disease
hypertensive encephalopathy and heart failure. 7. Vascular injury
8. Malignancy of urinary tract
• Causes of gross hematuria
CAUSES 1. IgA nephropathy
•• Postinfections: 2. Sickle cell disease
−− Bacterial: • RBC cast, or dysmorphic RBC are found in glomerulonephritis
• Types of proteinuria:
–– Group A streptococci (most common)
1. Glomerular proteinuria >1 g/day
»» 4a, 12, 25 associated with pharyngitis a. Selective (MCD)
»» 49 associated with pyoderma b. Nonselective (nephrotic syndrome)
–– Staphylococci 2. Tubular proteinuria is due to failure of reabsorption of
–– Pneumococci low molecular weight plasma protein that are normally
–– Salmonella reabsorbed and metabolized by tubular epithelium < 1 g/
–– Subacute bacterial endocarditis. day. They consist of:
−− Viral: a. Tamm-Horsfall protein
b. β2-microglobulin
–– Hepatitis—B and C
3. Overflow proteinuria results from filtration of low molecular
–– Infectious mononucleosis (EBV) weight protein usuallyimmunoglobulin-light chain
–– Human immunodeficiency virus (HIV). (lambda) but that are present in low amount in normal
•• Glomerulonephritis of undetermined etiology: plasma usually seen in massive amount in plasma cell
−− Rapidly progressive glomerulonephritis (RPGN). dyscrasia.
−− Membranoproliferative glomerulonephritis (MPGN). In overflow proteinuria, Dip stick test is negative but
•• Systemic vasculitis: sulfosalicylate precipitation test is positive
−− Systemic lupus erythematosus (SLE) 4. Sustained proteinuria (1–2 g/24 hour) are associated with
glomerular disease
−− Henoch-Schonlein purpura (HSP)
5. Benign proteinuria (functional or transient proteinuria)
−− Hemolytic-uremic syndrome (HUS)
found in:
−− Polyarteritis nodosa (PAN) a. Fever
−− Wegener’s granulomatosis. b. Exercise
•• IgA nephropathy. c. Obesity
•• Familial glomerulonephritis: Alport syndrome. d. Sleep apnea
e. Emotional stress
POSTSTREPTOCOCCAL f. Congestive cardiac failure (CCF)
g. Orthostatic proteinuria
GLOMERULONEPHRITIS 6. Massive proteinuria found in:
•• Poststreptococcal glomerulonephritis (PSGn) is a. MCD
b. FSGS
common among the school going children >3 years.
c. Mesangioproliferative glomerulonephritis
•• AGN commonly develops following group-A-β-
hemolytic streptococcus infection. Contd...
170 Essentials of Internal Medicine

Contd... •• Boys are more commonly affected.


d. Diabetic nephropathy. It is nonselective proteinuria
•• Usually associated with streptococcus throat and skin
and composed of albumin with mixture of other infection which precedes AGN by 1–4 weeks.
protein •• It is a typical example of immune complex disease.
7. Selective proteinuria (mostly albumin) seen in minimal •• Streptococcal antigen-antibody complex is trapped in
change disease glomerular capillary where it activates complement and
• Pyuria is associated with: initiates inflammatory response.
a. Acute PSGN
b. MPGN PATHOLOGY
c. Urinary tract infection
• Causes of acute nephritic syndrome The disease is actually termed as acute diffuse proliferative
a. PSGN glomerulonephritis. Hence, it is characterized by:
b. SABE •• Diffuse (> 50% glomeruli involvement) proliferation and
c. Lupus nephritis marked hypercellularity of the glomeruli with occlusion
d. Antibasement membrane disease of capillary loop.
e. IgA nephropathy
•• Initial hypercellularity is due to neutrophil infiltration.
f. ANCA vasculitis, e.g. Wegener’s vasculitis
−− Proliferation involves mesangial and endothelial cell
g. Microscopic polyangiitis, Churg-Strauss syndrome
h. HSP
with infiltration of neutrophil in capillary lumen.
i. Membranoproliferative glomerulonephritis −− Occasional epithelial cell proliferation which may be
j. Mesangioproliferative glomerulonephritis extensive, forming crescents, could be seen.
k. Cryoglobulineuria •• Immunofluorescent study shows granular deposit of
• Causes of pulmonary renal syndrome IgG, IgM and C3.
a. Good pasture •• EM study shows subepithelial electron dense ‘lumpy’
b. ANCA vasculitis deposit.
c. HSP
d. Cryoglobulinemia
CLINICAL FEATURES
• Causes of basement membrane syndrome
a. Anti-GBM disease •• Age: Commonly children between 3–12 years.
b. Alport syndrome •• The disease usually starts with periorbital puffiness
c. Thin basement membrane disease with oliguria and hematuria. As the disease progresses
d. Nail- patella syndrome edema and hypertension appear.
• Causes of glomerular vascular syndrome
•• Pleural effusion and ascites are uncommon.
a. Atherosclerotic
•• Degree of oliguria, correlates with the severity of the
b. Hypertensive
c. Cholesterol embolic
disease and may progress to acute renal failure (ARF).
d. Sickel cell disease •• Urine is usually reddish-brown (smoky).
e. Thrombotic microangiopathies •• May present as hypertensive encephalopathy or acute
f. APLA syndrome congestive cardiac failure (CCF).
g. ANCA associated vasculitis
h. HSP DIFFERENTIAL DIAGNOSIS
i. Amyloidosis
j. Cryoglobulinemia Many primary and secondary glomerular diseases may
• Infections causing glomerulonephritis present for first time as AGN—however history, clinical
a. PSGN findings and course will help in differentiating PSGN from
b. SABE other progressive diseases like RPGN and MPGN.
c. HIV Persistence of microscopic hematuria, hypertension,
d. HBV nephrotic range proteinuria for > 4 weeks with progressive
e. HCV renal failure suggests the later situations.
f. Syphilis
g. Leprosy LABORATORY INVESTIGATIONS
h. Malaria
• Causes of nephrotic syndrome •• Urine:
a. MCD −− Proteinuria 1+ to 2+
b. FSGS −− RBC/RBC cast and granular cast
c. Membranous glomerulonephritis −− WBC—indicative of glomerular inflammation.
d. MPGN •• Blood—
e. Diabetes −− Normocytic anemia—due to hemodilution.
f. Amyloidosis
−− Raised ESR.
Acute Glomerulonephritis 171

−− Elevated urea, creatinine—depends on the degree −− Body weight—Should be weighed daily.


of renal impairment and oliguria. –– Patient should loose 0.5% of body weight per
−− Hyponatremia and hyperkalemia—due to day. A gain in weight suggests more severe fluid
continued oliguria and hemodilution. restriction is required
−− Complement level—Level of serum C3 and total B. Specific Management
hemolytic complement (CH–50) is low in 1st week. −− Diuretic
In 90% of cases C3 level returns to normal within 5–6 –– Not indicated if edema is not massive which
weeks. Persistent low level of C3 indicate other form of gradually disappears with return of renal function.
GN (glomerulonephritis). Normal C4 level. [If diuretic has to be given—loop diuretic should
•• Throat swab—Culture may rarely show β-hemolytic be used but never spironolactone—for fear of
streptococcus (40%). hyperkalemia due to ARF in AGN].
•• Serology—The following antibodies are present in –– In presence of severe volume overload and
PSGN. pulmonary edema IV frusemide (2–4 mg/kg/day)

}
−− ASO (30%) Rising titer is more and if not controlled then dialysis.
−− Anti-DNAase (40%) convincing −− Hypertension
−− Antihyaluronidase (40%) evidence of recent –– To be treated with antihypertensive like calcium
−− Rheumatoid factor (35%) streptococcus channel blocker/β-blockers —If there is severe
infection hypertension presenting as hypertensive en-
−− Cryoglobulin and circulating immunocomplex cephalopathy or acute congestive cardiac failure.
(65%). –– Malignant hypertension should be managed by
−− ANCA against myeloperoxidase (10%). IV labetalol or nitroprusside.
•• X-ray chest—Increased vascular marking suggestive of −− Left ventricular failure
hypervolemia. –– Frusemide IV (2–4 mg/kg/day).
•• Renal biopsy—Rarely indicated in PSGN. –– Venesection with removal of 100–200 mL of blood
Indications are but or rotating trourniquet to reduce venous return.
−− Severely impaired renal function for 2 weeks –– Respiratory support with positive end-expiratory
−− Decrease of serum C3 level for > 6–7 weeks pressure.
−− Persistence of hypertension and hematuria for > 3 −− Prolonged oliguria
weeks –– Dialysis is often required in children with severe
−− Features of systemic illness—rash, petechiae and renal failure and prolong oliguria with fluid
hepatomegaly overload and electrolyte disturbances.
−− Absence of elevated (anti-streptolysin O).
−− Age < 2 years. PROGNOSIS
•• PSGN patient usually have:
MANAGEMENT −− Excellent prognosis.
−− Subsidence of edema and fall of BP with return
•• Treatment of mild oliguria with normal BP can be of urine voloume within 7–14 days occurs in 95%
done at home but anuria, hypertension, CCF and patients.
hypertensive encepha- lopathy hematuria is best •• Microscopic hematuria, slight proteinuria may persist
managed at hospital settings. for several months and is of no significance.
A. General Management •• AGN with nonstreptococcal etiology have a variable
−− Rest—Absolute bed rest is not essential. and unpredictable outcome should be closely followed
−− Penicillin (for 10 days)—To eradicate skin/throat with regular checkup of BP, blood, urine. Kidney biopsy
infection and to prevent community spread. is usually necessary. It is to be managed according to
−− Diet etiology.
–– Protein restricted to 0.6 g/kg/day.
–– Water restriction (500 mL + urine volume of
COMPLICATIONS
previous 24 hours).
–– Salt (if severe hypertension and volume overload 1. Acute renal failure (ARF)
is present) should be restricted to <2 g/day. 2. Congestive cardiac failure (CCF)
172 Essentials of Internal Medicine

3. Hypertensive encephalopathy 3. Causes of pyuria


4. Pulmonary edema. 4. Causes of nephritic syndrome
5. Causes of nephrotic syndrome
6. Causes of pulmonary renal syndrome
EXERCISE
7. Causes of basement membrane syndrome
Write short notes on 8. Causes of glomerular vascular syndrome
1. Causes of hematuria 9. Clinical features of PSGN
2. Causes of proteinuria 10. Management of PSGN.
Chapter 26
Nephrotic Syndrome

Introduction Other components of the nephrotic syndrome and


the ensuing metabolic complications are all secondary to
Nephrotic syndrome (NS) is a clinical syndrome complex
urinary protein loss and may or may not occur in spite of
characterized by massive proteinuria [greater than 3.5
proteinuria.
g/1.73 m2/24 hours (3–3.5 g/day)] with hypoalbuminemia,
edema, hyperlipidemia, lipiduria and hypercoagulabil- MAJOR METABOLIC COMPLICATIONS
ity.
•• Hypoalbuminemia is due to:
ETIOLOGY −− Proteinuria
−− Increased renal catabolism of protein.
•• Primary/idiopathic (90%)
•• Edema—It is due to hypoalbuminemia, which results
−− Minimal change disease (MCD)
in decreased intravascular oncotic pressure, leading
−− Focal segmental glomerulosclerosis (FSGS)
to leakage of intravascular fluid into interstitium. As
−− Membranous glomerulopathy (MGN)
a result intravascular fluid volume falls which causes:
−− Membranoproliferative GN (MPGN).
−− Activation of RAAS
•• Secondary—
−− Activation of sympathetic nervous system
−− Infection—Endocarditis, malaria, syphilis, Hep-B,
−− Release of vasopressin
leprosy and HIV.
−− Suppression of ANP.
−− Connective tissue dissease—SLE and RA.
This neural and hormonal response, promote renal
−− Neoplasm—Hodgkin’s lymphoma, NHL, leukemia,
salt water retention restoring intravascular volume
carcinoma of lung, breast and ovary.
triggering further leakage of fluid into interstitium.
−− Drugs—Penicillamine, captopril, gold and mercury.
•• Hyperlipidemia is multifactorial in origin and is due to:
−− Metabolic—DM and amyloidosis.
−− Increased hepatic lipoprotein synthesis triggered by
•• Congenital—
decreased oncotic pressure.
−− Alport syndrome.
−− Increased urinary loss a protein which regulates lipid
Table 26.1: Urine assay for albumin/protein homeostasis.
−− Sympathetic overactivity leads to defective lipid
24 hour 24 hour Albumin: Cre- catabolism (TC and LDL will increase in majority
albumin protein atinine ratio
of cases whereas TG and VLDL will rise in severe
Normal 8–10 mg <150 mg <30 disease) hyperlipidemia leads to accentuated
Micro albuminuria 50–150 mg 150–300 mg 30–300 atherosclerosis which causes progression of renal
Proteinuria >150 mg >300 mg >300 disease.
•• Hypercoagulability is multifactorial in origin. It is due
PATHOGENESIS to:
−− Increased urinary loss of antithrombin-III.
Proteinuria results from increased permeability of glomeru- −− Altered level/activity of protein-c and protein-s.
lar filtration barrier for protein (namely GBM, podocyte and −− Hyperfibrinogenemia is due to increased hepatic
their slit diaphragm). synthesis of fibrinogen.
174 Essentials of Internal Medicine

−− Impaired fibrinolysis. •• Features of hypothyroidism.


−− Increased platelet aggregation. •• Features of steroid overdose (iatrogenic): Cushingoid
All these above-mentioned factors are responsible features, osteoporosis, subcapsular cataract, short
for hypercoagulability. stretcher and hypertension occasionally present.
•• Thromboembolic complication—It leads to peripheral
arterial and (superficial and deep) venous thrombosis INVESTIGATION
usually presents with— •• Urine
−− Pulmonary embolism. −− Routine examination of urine for quantification of
−− Renal vein thrombosis. proteinuria and demonstration of fatty cast, hyaline
−− Particularly seen (~ 40%) in membranous cast and granular cast.
glomerulonephritis, membranoproliferative −− Urine culture sensitivity in case of concomittent UTI.
glomerulonephritis and amyloidosis. −− 24-hour urinary protein estimation (Table 26.1).
−− Test for selectivity of protein loss (IgG:transferrin
ratio).
Clinical features of acute renal vein thrombosis seen in •• Blood
nephrotic syndrome.
−− Routine examination of blood
• Sudden onset flank pain
• Gross hematuria −− Total protein with albumin-globulin ratio
• Acute increase in proteinuria −− Serum lipid profile
• Acute decrease in GFR −− Serum urea and creatinine
• Left-sided vericocele in case of left testicular vein thrombosis −− Serum, Na+, K+, Ca++ and Po4––.
•• Serum immune electrophoresis for IgG, IgM and
compliment estimation.
•• Kidney biopsy—Usually not indicated in uncomplicated
MINOR METABOLIC COMPLICATIONS nephrotic syndrome (NS) but to be done when nephrotic
syndrome is associated with the following conditions—
•• Iron-resistant microcytic hypochromic anemia is due
−− Age of onset of nephrotic syndrome <1 year >10
to urinary transferrin loss.
years.
•• Hypocalcemia and secondary hyperparathyroidism is
−− Kidney biopsy is also indicated when nephrotic
due to vitamin D deficiency which results from urinary
syndrome is associated with hematuria, hypertension,
loss of cholecalcifeŕol binding protein.
impaired renal function, low compliment C3 level,
•• Low thyroxine level is due to loss of thyroxine binding
not responding to usual therapy, with frequent
globulin.
relapse and steroid dependance, before starting
•• Increased susceptibility to infection is due to urinary
cyclosporine therapy.
loss of IgG and their increased catabolism.
MANAGEMENT
CLINICAL FEATURES
•• General Management
It is common in child of 1–10 years of age. −− High protein diet.
•• Pedal edema—Usually with ascites and hydrothorax −− Infection in nephrotic syndrome to be treated with
(anasarca) and facial puffiness. appropriate antimicrobial.
•• BP—Usually normal but may be elevated. −− Diuretic in nephrotic syndrome is indicated only
•• Signs of infection—Especially spontaneous bacterial when ascites impede diaphragmatic movement.
peritonitis may be present. Frusemide 40–80 mg/day with aldosterone antago-
nist (spironolactone, triamterine and amiloride)
Features of Complication rapid loss of fluid should not be attempted.
•• Infection due to urinary loss and increased catabolism −− Statin therapy—For hypercholesterolemia.
of IgG. −− No role of prophylactic anticoagulation in NS.
•• Thromboembolic complication—Renal vein throm- •• Specific Treatment
bosis, pulmonary embolism and leg vein thrombosis. •• Before starting specific treatment of tuberculosis and
•• Oliguria and ARF. UTI to be excluded by proper investigation.
−− Classical nephrotic syndrome to be treated by:
Rarely –– 1st episode—Prednisolone 2 mg/kg/day ×
•• Anemia. 6 weeks, then 1.5 mg/kg on alternate day × 6
•• Features of hypocalcemia like tetany may be present. weeks.
Nephrotic Syndrome 175

–– For 2nd and 3rd relapse—Prednisolone 2 mg/ kg/ •• Immunofluorescence shows no immunoglobulin
day × 2 weeks followed by 1.5 mg/kg/on alternate deposit/C3. Occasional messengial hypercellularity.
day × 6 weeks. •• EM stydy shows diffuse effacement of foot process of
Before stopping steroid urine should be protein-free on visceral epithelial cell (foot process fusion).
three occasion.
For frequent relapse and steroid dependance. ETIOLOGY
•• Prednisolone—0.3–0.7 mg/kg × 9–12 months.
•• Levamisole—2–2.5 mg/kg + prednisolone 1.5 mg/kg on Exact etiology not known. Common association are:
alternate day × 1–2 years. Prednisolone may be tapered •• URTI
or discontinue. •• Immunization
•• Cyclophosphamide—2 mg/kg/day + prednisolone 1.5 •• Atopic subject (HLA B12)
mg/kg on alternate day × 12 weeks. •• Rarely NSAID and α-interferon.
•• Ciclosporin—5 mg/kg/day + prednisolone 1–1.5 mg/ •• Hodgkin’s disease.
kg on alternate day for 1–3 years. Selective proteinuria which is usually seen in children
composed of albumin and minimal HMW IgG. In conjunc-
Alkylating agents are reserved for patient tion with foot process effacement and loss of fixed negative
•• Who failed to achieve remission. charge in glomerular filtration barrier are responsible for
•• Relapse during/shortly after withdrawal of steroid increased permeability of basement membrane which is
(steriod-dependent). probably due to cytokine related to T-cell response.
•• Relapse > 3 times/year. Proteinuria is nonselective in adult suggesting more
extensive damage of membrane permeability in adult.
Side effects of cyclophosphamide and chlorambucil
1. Infertility
2. Hemorrhagic cystitis
COURSE AND PROGNOSIS
3. Alopecia •• Spontaneous remission occurs in 30–40% child which
4. Infection
5. Secondary malignancy
is less common in adult.
Frequent relapse—Four or more relapse per year. •• About 90% of child and 50% of adult enter remission
Infrequent relapse—Three or less relapse per year. following 8 weeks of high dose glucocorticoids.
Steroid-dependent—Remission phase lasts only when steroid •• Up to 90% of adult enters remission if therapy is
is continued and relapse occurs whenever steroid dose is extended to 20–24 weeks.
reduced or withdrawn. •• In 50% of cases—relapse occurs following withdrawal
Steroid-resistant—Either does not respond to initial treatment or
do so transiently.
of glucocorticoids.

MANAGEMENT
COMPLICATIONS OF NEPHROTIC SYNDROME
•• General management
1. Spontaneous bacterial peritonitis Same as management of nephrotic syndrome.
2. Pneumococcal septicemia •• Specific management
3. Renal vein thrombosis Same as management of nephrotic syndrome.
4. Deep vein thrombosis of leg
5. Thromboembolism of mesenteric artery.

MINIMAL CHANGE DISEASE


Complications of long-term steroid therapy
Silent features of minimal change disease (MCD) 1. Stunted growth
•• MCD is responsible for 80% of NS patients in children 2. GI hemorrhage and gastritis
< 16 years. 3. Osteoporosis and pathological fracture
•• MCD is responsible for 20% of adult (nephrotic 4. Posterior subcapsular opacity of lens
syndrome). 5. Glaucoma
6. Cushingoid feature
•• Peak incidence at 6–8 years of age. 7. Diabetes
•• Patients usually present with edema with benign 8. Hypertension and encephalopathy
urinary sediment but 20–30% patients have microscopic 9. Flairing of infection—TB, chickenpox and pneumococcal
hematuria. septicemia
•• Hypertension and renal insufficiency are very rare. 10. Steroid psychosis
•• Light microscopy shows no change (so-called minimal 11. Steroid myopathy
12. HP axis suppression
change disease).
176 Essentials of Internal Medicine

FOCAL SEGMENTAL •• Primary FSGS should be treated with renin angiotension


GLOMERULOSCLEROSIS system (RAAS) blocker.
•• Uncontrolled study suggests remission of nephrotic
Sclerosis with hyalinosis involving a segment of the range of proteinuria up to 35% may be achieved by
glomerulas (segmental) and fewer than 50% (focal) of glucocorticoid therapy for 24–36 weeks.
glomeruli in a tissue section is called focal segmental •• Cyclosporine induce partial/complete remission can
glomerulosclerosis (FSGS). be achieved in 50–60% of steroid responsive patient
The pathological changes are predominantly located but relapse frequently occurs after withdrawal of
at corticomedullary junction. cyclosporine.
•• FSGS accounts for 33% of nephrotic syndrome in adult •• Renal transplantation is complicated with recurrence
and 50% of nephrotic syndrome in black. in 35% cases and graft loss in10% cases.
•• FSGS can complicate a number of systemic disease •• Poor prognostic marker are:
and sustained glomerular capillary hypertension due −− Renal insufficiency at the onset
to nephron loss from any cause. −− Black race
−− Persistence of heavy proteinuria.
Pathogenesis •• 50% develop renal failure within 6–8 years.
•• T-cell-mediated circulating permeability factor. •• Chance of recurrence is high in patient:
•• TGF β-mediated cellular proliferation and matrix −− With short time interval between development of
systhesis. NS and ESRD.
•• Genetic mutation-mediated podocyte abnormality is −− Young age.
probably responsible for pathogenesis. −− Mesengial hypercellularity.

Etiology MEMBRANOUS GLOMERULONEPHRITIS


•• Idiopathic FSGS (66%). Membranous glomerulonephritis (MGN) accounts for 30%
•• Secondary FSGS due to nephrotic syndrome in adult.
−− HIV, HBV and parvovirus It is characterize morphologically by subepithelial
−− Hypertensive nephropathy immunoglobulin containing deposit along the GBM.
−− Drugs—Heroin, pamidronate and analgesic
−− Sickle cell nephropathy ETIOLOGY
−− Lymphoma
−− Radiation nephritis •• Idiopathic MGN (66%)
−− Charcot-Marie-Tooth disease. •• Secondary MGN (33%)
•• FSGS can also develop as a consequence of sustain −− Peak incidence at 30–50 years of age
glomerular hypertension in −− Male—Female ratio = 2:1.
−− Congenital oligonephropathy
−− Unilateral renal agenesis
ETIOLOGY OF SECONDARY MGN
−− Oligomeganephronemia •• Infection—Hepatitis B, syphilis, schistosomiasis,
−− Surgical resection leprosy, malaria and filaria.
−− Reflux nephropathy •• Malignant tumors—(25–30%) carcinoma of lung,
−− Alport syndrome breast, colon, stomach, kidney and lymphoma.
−− Tubulointerstitial nephritis. •• SLE and other autoimmune diseases.
•• Drugs—Penicillamine, gold, Hg and NSAID probenecid.
CLINICAL FEATURES
•• Idiopathic FSGS (66%) PATHOGENESIS
Initially presents with: •• Idiopathic MGN: Antibodies against M-type phosphate
−− Nonselective proteinuria (any level of proteinuria). A2 receptor (PLA2R) circulate and bind to receptor on
−− Hypertension. human podocyte is responsible for idiopathic MGN.
−− Renal insufficiency. •• Secondary MGN: Due to in situ formation of immune
−− Hematuria with abnormal urinary sediment— RBC complex against neutral endopeptidase expressed by
and pus cell. podocyte, HBV/HCV, H. pylori and tumor antigen.
•• Light microscope shows diffuse thickening of GBM
TREATMENT along the peripheral capillary loop.
•• Spontaneous remission is rare. •• Electron microscope shows subepithelial electron
•• Renal prognosis is poor. dense deposit against GBM and they are separated from
Nephrotic Syndrome 177

each other by small spike-like protrusion of GBM matrix −− Some patients present with hematuria and
which later on close over the deposit incorporating them proteinuria in subnephrotic range and other have
into GBM. combined nephrotic-nephritic picture.
•• Immunofluorescence shows typical granular deposit −− They are manifested histologically by alteration in
of IgG and complement (C3) along GBM. basement membrane and mesangium and proli-
feration of glomerular cells.
CLINICAL FEATURES OF MGN
•• Principal mode presentation is nephrotic syndrome Etiology
(80%). •• Type–I (most common)
•• Microscopic hematuria seen in 50%. −− Idiopathic
•• It may present, with acute nephritic syndrome. −− (a) SABE, (b) HCV, (c) SLE, (d) cryoglobulinemia,
•• Rarely it may begin with mild proteinuria. (e) HBV and (f) carcinoma of lung, breast and ovary.
−− Onset is insiduous in idiopathic variety without •• Type–II (dense deposit)
antecedent illness and the proteinuria initially may −− Idiopathic
not be in nephrotic range and nonselective in nature. −− C3-nephritic factor associated partial lipodystrophy.
Features of oliguria and uremia develop later. •• Type–III
−− It is necessary in all patients to rule out the secondary −− Idiopathic
cause first. −− Complement receptor deficiency.

COURSE AND PROGNOSIS PATHOLOGY


•• Spontaneous remission occurs in 33%.
•• Type–I—Proliferation and interposition of mesangium
•• In 33% patients, relapse and remission are seen without
in between endothelium and basement membrane
decline in renal function.
producing trams-track appearance. It is due to
•• Another 1/3rd die either due to renal failure or from
circulating or in situ formation of immune complex.
complications of nephrotic syndrome.
•• Type–II—Low serum complement (C3) with dense
•• Bad prognostic marker:
thickening of GBM containing ribbon of dense deposit
−− Male gender
and C3 is characteristic of Type–II disease.
−− Elderly age group
•• Type–III—Subepithelial laminated and dispersed
−− Hypertension
deposit with rare mesangial proliferation.
−− Severe proteinuria.
Type–II and III are due to nephritic factor which are
antibodies that stabilizes C3 convertase and allowes it to
TREATMENT activate serum C3.
•• Treatment of edema—Diuretics.
•• Treatment of dyslipidemia—Statin. CLINICAL FEATURES
•• Treatment of hypertension—CCB, ACEI and β- blocker.
•• Inhibitor of RAAS blocker. •• Fatigue and malaise more common in children.
•• Glucocorticoids fails to show consistent improvement •• Proteinuria, hematuria and pyuria seen in 30% patient.
in proteinuria and renal protection. •• Acute nephritic picture with RPGN and rapid
•• Cyclophosphamide, chlorambucil, cyclosporine and deterioration of renal function seen in 25% patient.
mycophenolate mofetil each has shown to reduce •• Serum complement is low.
the proteinuria and/or slow the decline in GFR in
patients with progressive disease. PROGNOSIS
•• Nonresponders to above drug are treated with Rituximab
(an anti-CD 20 antibody) with glucocorticoid. •• About 50% develop ESRD by 10 years.
•• Renal transplant is a successful treatment option. •• About 90% have renal insufficiency by 20 years.
•• Nephrotic syndrome, hypertension and renal insuf-
ficiency are poor prognostic parameter.
MEMBRANOPROLIFERATIVE
GLOMERULONEPHRITIS TREATMENT
•• Silent features in MPGN •• Inhibitors of renin-angiotensin-aldosterone axis.
−− Membranoproliferative (MPGN) accounts for 5–10% •• For primary or idiopathic MPGN in children— Steroid,
of idiopathic nephrotic syndrome in children and plasma exchange and immunosuppressive drugs are
adults. effective.
178 Essentials of Internal Medicine

•• In secondary MPGN—Treatment of primary disease, e.g. PATHOGENESIS


peginterferon and ribavirin for HCV and appropriate
•• Incompletely understood but probably due to:
treatment of carcinoma, e.g. SABE, SLE.
−− Increase production of IgA.
•• Warfarin and dipyredamol—not very effective.
−− Abnormal glycosylation of IgA.
•• Renal transplant—recurrence of disease is very
−− Impaired clearance of IgA is responsible for IGA
common.
nephropathy.
Although, IgA nephropathy is associated with altered
Immunoglobulin A NEPHROPATHY
mucosal defence, most IgA deposit in kidney are derived
(BERGER’S DISEASES) from bone marrow cell.
Immunoglobulin A nephropathy (IgAN) is the most
TREATMENT
common glomerulopathy worldwide and accounts for
10–40% glomerulonephritis in most cases. •• Wait and watch policy till GFR is not compromised and
Common in southern Europe and Asia, more common proteinuria <1 g/day.
in Black than White. Male > Female. •• ACE inhibitors—For renoprotection with more severe
The renal and serological abnormality in IgA nephropa- disease.
thy and Henoch-Schönlein purpura are indistinguishable. •• Glucocorticoid (high dose)—For 6 months when GFR
Most authorities consider these two as a spectrum of same is impaired and proteinuria >1 g/day.
disease. •• Cyclophosphamide and mycophenolate mofetil
are reserved for patients presenting with nephritic
Less commonly IgA nephropathy is found in association
syndrome, RPGN, aggressive crescent formation and
with systemic disease like chronic liver disease, Crohn’s dis-
marked glomerular inflammation on kidney biopsy.
ease, gastrointestinal adenocarcinoma, chronic obstructive
bronchiolitis and idiopathic interstitial pneumonia, derma-
COURSE AND PROGNOSIS
titis herpitiformis, mycosis fungoides, leprosy, ankylosing
spondylitis and Sjögren’s syndrome. In patient presenting with nephritic syndrome, RPGN,
In many of these conditions IgA is deposited in the aggressive crescent formation and marked glomerular
glomeruli without inducing inflammation. inflammation on kidney biopsy, the disease typically
smolder for decades with often exacerbation of hematuria
CLINICAL FEATURES and renal impairment during intercurrent infection.
20–50% patients develop ESRD within 20 years.
•• Gross hematuria—Often 24–48 hours after: •• Poor prognostic parameters are:
−− Pharyngeal and gastrointestinal infection −− Older age.
−− Vaccination −− Male sex.
−− Strenuous exercise. −− Hypertension.
•• Hypertension present in 20–30% of patients. −− Nephrotic range proteinuria.
•• Nephrotic syndrome present in 10% of patient. −− Renal insufficiency at presentation.
−− Crescent, immune attack into subendothelial space,
RENAL BIOPSY glomerulosclerosis, interstitial fibrosis and arteriolar
•• Mesangial expansion by increased matrix and cell. hyalinosis.
•• Diffuse epithelial proliferation leading to cellular
EXERCISE
crescent, interstitial inflammation and areas of
glomerular sclerosis. Write short notes on
•• Mesangial deposit is composed of IgA, C 3 and 1. Definition and etiology of nephrotic syndrome (NS).
occasionally IgG. 2. Major and minor metabolic complication of NS.
•• electron microscopy study shows electron-dense deposit 3. Management of NS.
in mesangium, paramesangium and subendothelial 4. Complications of NS.
space. 5. FSGS, MGN, MPGN and IGA nephropathy.
Chapter 27
Acute Renal Failure/Acute Kidney Injury

Introduction •• Causes of intrinsic renal ARF


−− Renal artery obstruction by atherosclerotic, plaque,
Acute renal failure (ARF) is a syndrome characterized by
thrombosis, embolism, vasculitis.
rapid decline in GFR (within hours to days) with retension
−− Renal vein obstruction by thrombosis/compression.
of nitrogenous waste product in the body.
−− Disease of the glomeruli and renal micro­-
vasculature:
TYPES OF ACUTE RENAL FAILURE –– Glomerulonephritis and vascul