Disease

Pathophysiology

Signs and Symptoms

Diagnostic Tests

Therapeutic management

MYASTHENIA GRAVIS

Affects the neuromuscular

transmission of impulses to the
voluntary muscles, primarily
skeletal muscles, and the muscles
innervated by the cranial nerves.
Acetylcholine (ACh) which is
released at the neuromuscular
junction does not appear to produce
an action potential in the muscle
group. The defect in the
transmission of impulses from
nerve to muscle is due to the loss of
available receptor sites on the post
synaptic membrane of the NMJ. It
is thought to be an autoimmune
disease in which antibodies (ACh
receptor antibody- ACh RAb) are
directed at ACh receptor sites and
impair the transmission of impulses
from nerve to muscle. A high
percentage of patients have a
thyrotoxic or other autoimmune
disease ( i.e. RA). Most patients
have an enlarged thymus. ACh
antibodies are found in the
postsynaptic membrane which
decreased the formation and release
of acetylcholinesterase. Although
the disease is not hereditary, some
infants born to mothers with the
disease exhibit transient signs and
symptoms of the disease which
disappear once the maternal Abs
disappear from the fetal blood in 714 days.

The onset is insidious,

unpredictable and characterized by
remissions and exacerbations
(precipitated by illness, stress,
menses, etc. or with medications
which can cause crises). Primarily
found in young women or older
men.
CLINICAL
MANIFESTATIONS:
1. Extreme muscular weakness that
is increased by repeated use of the
muscles at any one time.
2. Easy fatigablility that becomes
worse with effort and improves
with rest. Patients tire on slight
exertions such as combing hair,
chewing, walking, and must
frequently stop and rest.
3. Shows symmetrical muscle
involvement with those muscles
affected by the cranial nerves being
affected first. This results in
diplopia, ptosis, sleepy mask facies,
with the smile becoming a snarl.
They c/o a weak larynx and
pharynx which results in a weak
voice, swallowing difficulties, and
aspiration.
4. Manifest weak shoulder and neck
muscles and are unable to hold up
their head.
5. Progressive weakness leads to
diaphragmatic and intercostal
involvement and eventual
respiratory distress, poor ventilation
and ultimately altered gas exchange
and respiratory failure.

History is most important. Have

patient look at the ceiling for two
minutes and watch for drooping of
the eyelids (ptosis).
Tensilon Test: drug challenge
study. Given IV, IF patient shows
marked improvement within 30
seconds, the test is positive for MG.
If increased weakness, test is
negative. Especially useful for
cranial nerve involvement.
Prostigmin Test: Drug challenge
study to diagnose extremity
involvement. Given IM. Diagnosis
positive for MG if marked
improvement in 30 mins, negative
if increased weakness.
Atropine and code cart should be at
bedside for risks of cholinergic
crisis, v-fib and cardiac arrest for
both tests.
EMG: electromylogram and nerve
conduction studies to document
abnormal action potentials.
CXR/CT: looking for enlarged
thymus (tumor of thymus).
Anti-ACh RAb: is positive in 8595% of persons with MG. No false
positives in the test but a negative
test does not exclude the disease.
Lab Studies: include ACh RAb,
SLE prep, protein electrophoresis,
thyroid function tests.

Focused on maintenance of optimal

respiratory function and muscle
strength.
Medications: AnticholinergicMestinon (less SEs); Mytelase,
Prostigmin. Should be given 45
mins AC, exactly on time each day.
Give with crackers and milk. Check
patients swallowing capability
before giving medication.
Side effects: see pharm book.
Atropine may be given in small
doses to help control SEs but may
mask S/S of impending cholinergic
crisis. Watch for increased muscle
weakness after receiving
medication (usually an hour) and
respiratory distress. These are
signs of impending cholinergic
crisis.
Corticosteroids
Immunosuppressives:
Drugs containing magnesium, MS,
quinine, quinidine, procainamide,
hypnotics, sedatives, certain
antibiotics (neomycin, kanamycin,
streptomycin, polymixin B, and
certain tetracyclines) should be
avoided as they may increase S/S.
Therapeutic Regimens:
Plasmaphoresis: cleanses the blood
of anti-ACh RAb. Temporary
method to control symptoms.
Watch patient for S/S of impending
cholinergic crisis, electrolyte
imbalance, dehydration, fluid
overload, and give meds at a time
when they will not be remove by
plasmaphoresis.
Thymectomy: Removal deceases
the level of anti ACh RAb.

A progressive neuromuscular
condition characterized by general
weakness and fatigue of the skeletal
muscles.

Disease

Pathophysiology

Signs and Symptoms

Diagnostic tests

Therapeutic M anagement

M ULTIPL E SC LER OS IS

A degenerative disorder of the CNS

in which the myelin sheath of axons
in the brain and spinal cord become
inflamed causing patchy
destruction of myelin sheath. When
the inflammation subsides, the
nerve regains some function but
eventually the myelin sheath is
destroyed and replaced by scat
tissue. This accounts for the
exacerbations and remissions
pattern and why function is never
restored to the level as prior to an
exacerbation. S/S vary from person
to person and depend on the area of
brain or spinal cord that is
involved. It eventually spreads to
most myelinated areas of the brain.
Characterized by exacerbations and
remissions that extend over many
years. Exacerbations are
precipitated by cold, stress, changes
in temperature, illness, etc. It is a
disease that affects young adults,
females 2X that of males, with an
average age of onset of S/S at 2040 years of age. There is a familial
tendency and occurs most often in
Caucasians born and raised in their
1 st 15 years in a colder climates
(Europe, Canada, Northern US).
Thought that cause is a disruption
of the immune system where a
virus attacks the T-lymphocytes
that is responsible for suppressing
antibody production.

1. Impaired sensory and motor

coord ination, stiffness, weakness
and clumsiness.
2. Decreased mo tor ability after a
hot bath, neuritis, neuro pathy,
numbness, and tingling.
3. Visual changes, gait and
extremity ataxia, decreased
muscle tone, tremo rs, spastic
paralysis and pa resis.
4. Inappropriate euphoria, wide
mood sw ings, manipula tive (M S
personality due to a loss of
control between the cortex and
the basal ganglia), vertigo, N/V.
5. Bowel, bladder, and sexual
dysfunction.
6. Charcots Triad: Nystagmus,

1. CSF shows elevated proteins,

colloid golds, elevated lymph s,
elevated gamma globulins, and
positive serology.
2. Visual evo ked resp onse
potential will produce nystagmus
when a light is shone into the eye.
3. Elevated IgG and oligoclonal
bands.
4. M RI currently the most
accurate in seeing the MS plaques
in the brain and spinal cord.

There is no cure but certain drugs

are use d to p revent or try to
overcome the exacerbations and
manage the symptoms. A CT H is
used during acute exacerbations
to try and decrease the
inflammation and shorten the
exacerbation period. Prednisone
or other high dose steroid s (Solu
Med rol) are used for short term
therap y.
Other drugs that been used
experimentally are
immunosuppressive drugs like
Imuran, alkylating agents and
antimetabo lites.
Muscle relaxants such as Valium,
quinine and baclofen for sp asms.
Plasmaphoresis has been tried
with little success.

Diagnostic tests

Therapeutic M anagement

Disease

Pathophysiology

intentional tremor (a tremor on

performance of precise willed
movements), and scanning
speech.
7. Hyperreflexia and positive
Babinski reflex (typical S/S of
upper mo tor neu ron d isease).

Signs and Symptoms

ALS- Amyotrophic Lateral

Sclerosis. A.K .A. Lo u Ge hrigs
Disease.

The cause of this disease is

unknown. There is degeneration
and demyelination of the motor
neuro ns in the cord and the brain
that innervate striated muscle and
degeneration of the ventral horn
causing asymmetric muscle
involvement and muscle atrop hy.
There is a steady dow nhill course
with a 3 year life expectancy from
diagnosis.
Males are affected 2X as much as
females. Associated with athletic
men or men with exposure to
heavy metals.

Three aspects of the disease.

1. Progressive muscular atrophy
2. Progre ssive bulbar paralysis
3. Increased neuromuscular
deficits
The chief S /S are:
1. Fatigue, weakness, muscular
atrophy and fasiculations. Tends
to start with the extremities then
progresses to the trunk and finally
to the cranial nerves.
2. The patient has hem iparesis,
paraparesis, muscular spasm s,
dysarthria, dysphagia, dysphasia,
aphonia.
3. Respiratory and intercostal
involvement. The patient
eventually ends up with a
tracheostomy because they cannot
handle their secretions, and
gastrostomy tube because they
cannot swallow.
4. Eventually with bulbar
paralysis (destruction of nerve
centers of the m edulla oblongata
and paralysis of the parts
innervated fro m the m edulla with
interruption of their functions (as
swallowing or speech)
5. Known to have wide mood
swings fro m eup horia to
involuntary weeping.
6. Intellectual ability is not
affected . Senso ry intact, on ly
motor is involved.
7. T hey nee d diversional activity

H&P
Muscle biopsy
EM G
CK is elevated

No specific treatme nt. Prim arily

supportive.
Trach
GT
Lengthy hospitalizations and
eventually decision needs to made
abo ut hom e ventilatory sup port.

Disease

Pathophysiology

Signs and Symptoms

Diagnostic tests

Therapeutic M anagement

Guillian Barre

An inflamma tory disease

processes involving
demyelination and degeneration
of the myelin sheath and cylinder
of peripheral nerves, the anterior
(ventra l) and p osterio r (dorsal)
roots of the spinal cord.
Characterized b y rapid ly
ascending motor and sensory
paralysis along with cranial nerve
involvement and decreased motor
function with respiratory
involvement a distinct possib ility.
If respiratory involvement, patient
will need ventilatory supp ort.
Paralysis can stop at any level. It
can take weeks to months for
complete recovery. 95% will have
com plete re covery.
Cause is unknown but thought to
be an autoimmune response to a
previous viral illness or
immunization. 50% o f patients
have a history o f a mild
respiratory o r GI illne ss 1-3
weeks prior to the appearance of
the symp toms.

1. Paresthesia, numbness, tingling,

or other unusual sensations
typically starting in the toes and
feet. Pain, temp, proprioception,
vibration and light touch sensation
diminished in affected areas due to
degeneration of dorsal nerve roots
of spinal cord.
2. Paralysis with flaccidity,
decreased or absent DTRs and
hypotonia or atonia of muscles. The
motor involvement usually
corresponds to the areas involved in
the sensory deficits and progresses
in the same pattern- weakness then
paralysis. Progression to cranial
nerves usually takes 1-3 weeks.
Paralysis in phrenic and intercostal
nerves is leading cause of death in
GB.
3. Cranial nerve dysfunction
resulting in weakness and paralysis
of facial muscles, bulbar paralysis,
nasal, dysarthric speech, dysphagia,
impaired gag and cough reflexes.
Diplopia, non-conjugate eye
movement, ptosis, impaired
shoulder shrug, and turning head
side to side difficulty. They may be
extremely hypersensitive and have
tremendous pain.
4. Sympathetic dysfunction with
postural with postural hypotension,
flushing, sweating, and tachycardia.
- They are fully alert, in pain and
often terrified. Their weak facial
muscles mask their terror. They are
overwhelmed by their distorted
sensations and paralysis that
relentlessly progresses.

1. The diagnosis of Guillian Barre

Syndrome is based on the clinical
history, clinical presentation,
progression of S/S, and clinical
course.
2. Two main diagnostic tests:
EMG; LP for CSF examination.
Leukocyte count is normal and
protein level is high (called
albuminocytological dissociation).
The levels appear elevated several
days after onset of S/S and reach a
peak at 4-6 weeks (75-200 mg).
Thought to be due to inflammation,
degeneration and damage of the
nerve roots.
3. Electrolytes, CBC, coagulation
tests, UA, cultures, CXR, EKG,
pulmonary function tests (PFTs).

Plasmaphoresis has been quite

successful in stopping the
progression of the paralysis but
does not decrease the duration of
the disease process.
Symptomatic treatment otherwise.

Disease

Pathophysiology

Signs and Symptoms

Diagnostic tests

Therapeutic M anagement

Parkinso ns Disease
Progressive neurological
characterized by degenerative
changes in the basal ganglia.
Presents age 40-70 years if age
affecting women and men
equally.

Cause Unknown
Possible ca uses:
Viral agents
Genetic disposition
Premature aging
Do pam ine (made and sto red in
basal ganglia) pro vides a
homoeostatic balance of
inhibitory and excitatory actions.
Degenerative changes associated
with Parkinso ns interfere with
production and storage of
dopam ine and thus reflects the
imbalance of the excitatory and
inhibitory actions.

Clinical Manifestations: gradual

onset with unilateral involvement
progressing to total dependence.
Resting tremors, pill rolling
motio n of hands when at re st,
slowness and rigidity of
movement. Flexion posturestooped appe arance, shuffling
propulsive gait, loss of autom atic
coo rdinated movement.
Fatigue- alert but slow to respond
and irritable.
Expressionless mask-like facies.
Dro oling, oily skin, dysphagia
Urinary hesitancy
Depression but no loss of mental
function
Heat sensitivity

History and clinical findings.

EM G, CT, M RI to R/O other
pathology
Urine and CSF to document level
of homov anillic acid (metabolite
of dopamine)
Parkinsons Disease
Classifications:
0= N o sign of disease
1= U nilateral disease
2= B ilateral disease without
balance impairment
3= M ild to moderate bilateral
disease with postural instability
but physically independent
4= Severe disability, still able to
stand and w alk
5= Wheelchair dependent or
bedridden

Artane, Cogentin
Levodopa/Carbidopa combination
therap y (Sinem et)
Man other medicatio ns as agents
that decrease the destruction and
enhance production of dopam ine
Exp erimental and highly
controversial is the placement of
fetal tissue inside the brain of the
patient to mak e dopam ine. T his
practically eliminates the side
effects of dop amine production in
the blo odstream.

Disease

Pathophysiology

Signs and Symptoms

Diagnostic tests

Therapeutic M anagement

Muscular Dystro phy

Genetic origin, gradual

degeneration of muscle fibers and
characterized by progressive
muscle weakness and wasting of
symmetric groups of skeletal
muscles and increasing disability
and deformity.

(Duchennes)
- Muscle weakness 3-5 years (Hx of
delayed motor development)
- difficulty rising from sitting to
standing
- May have enlarged calves
- Waddling gait and characteristic
way of rising from sitting to
standing- turns on side or abd with
knees flexed, kneeling then
gradually pushes self to upright by
extending knees and walking hands
up knees.
- Muscles in thighs and upper arm
enlarged from fatty infiltration, feel
firm or woody.
- Profound muscular atrophy in
later stages and as the disease
progresses, contracture and
deformities of large and small joints
are common.
- Ambulation becomes impossible
by age 12
- Facial, oropharyngeal, and
respiratory muscles are spared until
the terminal stage of the disease.
Ultimately, the heart
(cardiomegaly), the diaphragm, and
auxiliary muscles of respiration
become involved.
- Cause of death is usually
respiratory infection or failure, or
cardiac failure.

Serum enzymes- CK, SGOT,

aldolase all elevated until end
stages of disease.
Muscle biopsy shows
degeneration of muscle fibers
with fibrosis and fatty tissue
replacement
EM G- decrease in amplitude and
duration of m otor unit potentials

No effective tre atment. Go al is to

maintain function in unaffected
muscles for as long as possible. If
this is don e, wheelchair
dep endency is delayed .
Maintenance if function is
includes: RO M, surgery to release
contractures, bracing.
Gene tic counseling for pare nts,
female siblings, au nts and female
offspring.

The most severe a nd mo st

impo rtant single group of m uscle
diseases in children.
Basic defect unknown but seems
to be caused by m etabo lic
disturbance unrelated to the
nervous system.
CK always increased.

P seudohyp ertro ph ic MD
(Duchenne): M ost severe and
most common. X linked
inheritance in 50% of cases.
(Males almost exclusively)

Clinical Course:
- Early onset 3-5 years of age
- Progressive m uscular weakness,
wasting and contracture
- Calf mu scle hyp ertrop hy in
most cases
- Loss of independent ambulation
by 9-12 years of age
- Slowly progressive generalized
weakness during teenage years
- Progression until death from
respiratory or cardiac failure

Complications:
Contractures of knees, hip and
ankles, scoliosis
Disuse atrophy
Resp infection
Obesity
Cardiac failure