GUILLAIN-BARRE SYNDROME

 Definition 
 Epidemiology 
 Pathogenesis 
 Neurophysiological testing 
 CSF/LCS 
 Clinical feature 
 Clinical subtypes 
 GBS in children 
 Autoimmune process 
 Treatment 
 Prognosis 
 Diagnosis Banding 
 GUILLAIN-BARRE SYNDROME
• 2
DEFINITION
GUILLAIN-BARRE SYNDROME
 Clinical entity characterized by rapidly
progressing limb weakness and the loss
of tendon reflexes
 Affects children and adults of all age,
sexes, men>women
 Preceded by viral or bacterial ilness,
upper respiratory tract infections or
gastroenteritis in 60-70% cases
Kuwabara, 2004. • 4
GUILLAIN-BARRE SYNDROME
 Is an autoimmune disorder
 encompassing heterogenous group of
pathological and clinical entities.
 Antecedent infections are thought to
trigger an immune response, which
subsequently cross-react with nerves
leading to demyelination or axonal
degeneration.
Seneviratne, 2000 • 5
EPIDEMIOLOGY
GBS EPIDEMIOLOGY
 0,6-4 cases/100.000 population throughout the
world
 Europe : 1,2-1,9/100.000

 Fisher’s syndrome 0,1/100.000

 Men > women (1,5:1)

 Increase steadily with advancing age

 China : 0,66/100.000 in all ages

Hughes & Comblath, 2005

• 7
 Guillain-Barrésyndrome (GBS) is described
most accurately as a collection of clinical
syndromes manifested by an acute
inflammatory polyradiculoneuropathy with
resultant weakness and reflex changes.
(Cha-Kim, 2004)

• 8
GBS EPIDEMIOLOGY
 Annual incidence 0,4-4,0 ( median 1,3 ) cases per
population of 100.000.
 1,15 cases per population 100.000 in Japan
Kuwabara, 2004

• 1-3/100.000 population in Europe, USA and Australia

Seneviratne, 2000

• 0,5-1,5 /100.000 in individual less than 18 years of age

Sladky, 2004

• 9
GBS EPIDEMIOLOGY
 Occurs in all ages
 Slight peak in late adolescence and young adulthood 
CMV and C jejuni infection
 Elderly  susceptible for autoimmune disorders  decrease
immune suppressor mechanism
 Men > women ( 1,25 : 1 )
Kuwabara, 2004
 Males affected more commonly
 Bimodal distribution : peak in young adult and elderly
 No consistent geographical variation
 Lower during pregnancies, increases after deliveries
 Infants : the lowest risk
• 10
Seneviratne, 2000
GBS EPIDEMIOLOGY
 the overall death rates range from 2-12% of
 increase markedly with age.

 In the United States, the case-fatality ratio ranges from

0.7% less than 15 years to 8.6% more than 65 years.
 In age 60 years or more, the risk of death increases 6-
fold compared with persons aged 40-59 years and
increased 157-fold compared with persons aged less than
15 years.
 Males have a death rate 1.3 times greater than females
after the age of 40 years.
Cha-Kim, 2004 • 11
GBS EPIDEMIOLOGY
 outcome of GBS more favorable in children than adults.
Deaths are rare and 75-90% achieve full recovery. The
recovery period is longer than the duration of the acute
illness, often weeks to months, with a median estimated
recovery time of 7 months. In another series, the
median time from onset of symptoms to initial recovery
was 17 days; to walk unaided was 37 days; and to be
symptom free, 66 days.

• 12
 The most common serious complications are weakness of the
respiratory muscles and autonomic instability. Pneumonia,
adult respiratory distress syndrome, septicemia, pressure
sores, and pulmonary embolus are also important potential
complications. During the acute progressive phase of the
disease, close attention should be paid to respiratory status.
Measurements such as vital capacity provide objective data to
follow and compare.

 Recurrence of GBS occurs in approximately 5% of cases,

often many years after the initial bout. Recurrence is relatively
uncommon in children.
 Some patients experience a chronic progressive course,
known as chronic inflammatory demyelinating • 13
polyradiculoneuropathy (CIDP).
• 14
DIFFERENTIAL DIAGNOSIS OF ACUTE
FLACCID PARALYSIS
PATHOGENESIS
PATHOGENESIS GBS
AUTOIMUNE OF GBS
 Molecular mimicry refers to the situation where the pathogen and
host share nearly identical antigens, which induces an antibody and
T cell immune response that is cross reactive.

 Two-thirds of GBS cases are associated with prior acute infection of

several bacterial species and viruses. Campylobacter jejuni,
cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae,
Haemophilus influenzae, and Varicella-zoster virus have been found
in patient serum after the onset of GBS
PATHOPHYSIOLOGY 1
PATOPHYSIOLOGY 2
 Autoantibodies cross the barrier and bind to gangliosides of neural
tissue, they can activate complement cascades and the resident
macrophages by their FcIII receptors inducing cytokine production
and inflammation within the nerve tissue.
 Endoneural macrophages had the capacity to express CD1 (CD1a, b,
and c), which allows them to present glycolipids such as
gangliosides to some T cell subsets along with dendritic cells
(Hughes et al., 2006)
PATOPHYSIOLOGY 3
The inflammation due to cytokines and causes recruitment of
leukocytes and damage to the nerve tissue by one of four
mechanisms:
1. CD8 T cell lysis,
2. complement-mediated attack,
3. cytokine and free radical damage via phagocytes,
4. antibody-mediated interference of nerve conduction (Ho et al.,
1998)
 There are several places in the peripheral nervous system
where the inflammation response of GBS: dorsal root ganglia,
nodes of Ranvier, and schwann cell myelin (Ho et al., 1998).
Locations of GBS peripheral nerve attack
in peripheral nervous system:
a) Dorsal root ganglia can be the
target of an antibody response in
MFS.
b) Nodes of Ravier are a target of
immune response in AMAN.
c) Schwann cell myelin surface
proteins can be the target of
antibody binding in AIDP.
d) Neuromuscular junction (not known
to be involved with GBS)
CLASSIFICATION & PATHOLOGY OF

• 24
NEUROPHYSIOLOGICAL TESTING
NEUROPHYSIOLOGICAL TESTING

• 26
SUMMARY ENMG PATIENT

• 27
ELECTROPHYSIOLOGIC CRITERIA OF GBS (ANY
3 OF 4 CRITERIA)(ASBURY 1990)
Reduction in conduction velocity of two or more motor nerves
< 80% LLN if amplitude > 80% of LLN;
> 150% of LLN if amplitude < 80%
Prolonged distal latencies in two or more nerves
> 125% of ULN if amplitude >80% of LLN; >150% of ULN if amplitude
<80%
Absent or prolonged minimum F-waves in two or more motor nerves
> 120% of ULN if amplitude > 80% of LLN; > 150% of ULN if amplitude
is < 80% of LLN
 Conduction block or abnormal temporal dispersion (> 20% drop in
amplitude or > 15% change in duration between proximal and distal sites)
in one or more nerves
--------------------------------------------------------------------------------------
--
LLN=lower limit of normal; ULN=upper limit of normal
ENMG demielinisasi dan aksonopati (Hughes, 2002)
DD PRIMARY AXONAL VS PRIMARY DEMYELINATING NP
(BROMBERG, AAN 2003)

Limits of axonal Limits of demyelinating

pathology pathology
------------------------------------------------------------------------------------------------------
Distal latency < 120% ULN > 130% ULN
Conduction velocity > 70% ULN < 70% ULN
Prox : distal amplitude < 50% > 50%
Abn.temporal dispersion Smooth wave form Irregular wave form
F-wave latency < 130% ULN > 130% ULN
-----------------------------------------------------------------------------------------------------
 Aksonopathy VS Myelinopathy
(Potts, 2001)
Study Axonal Segmental
degeneration demyelination
Motor-nerve conduction studies
a b
CMAP amplitude Decreased Normal
Distal latency Normal Prolonged
Conduction velocity Normal Slow
Conduction block Absent Present
Temporal dispersion Absent Present
F wave Normal Prolonged or absent
H reflex Normal Prolonged or absent
Sensory-nerve conduction studies
SNAP amplitude Decreased Normal
Distal latency Normal Prolonged
Conduction velocity Normal Slow
Needle electromyography (spontaneous activity)
Fibrillations Present Absent
Fasciculations Present Absent
Recruitment
Number of motor units Decreased Decreased
ELECTROMYOGRAPHY AND NERVE CONDUCTION STUDIES
(FLAHERTY 2000)

-----------------------------------------------------------------------------------------------------------------------------------------
Disease NCV Ampli- F-H Distal Fibril-
tude Latency Latency lations
---------------------------------------------------------------------------------------------
Axonal NP > 70  mild  N 
 
Demyel.NP < 50 mild   mild  Variable
 
LMD disease > 70  motor mild  N 
UMN disease N N N N None
 
Radiculopathy > 80 mild   N 
 
Neuromusc N N/  N N None
junction defect
 
Myopathy N mild  N N None
---------------------------------------------------------------------------------------------
NEUROPHYSIOLOGICAL TESTING
 Sufficient data required from
 at least three sensory nerves
 at least three motor nerves with multisite stimulation
 F waves
 Bilateral tibial H-reflexes

Sign of demyelination finding probability increase as more nerves

were studied, including late responses, F waves, and H-reflexes

 There is still no consensus on neurophysiological criteria for

classification
• 33
Hughes & Cornblath, 2005
NEUROPHYSIOLOGICAL TESTING
 USA, Australia, and Europe: early electrodiagnostic
study abnormality showing demyelination in 85% cases
 13% remains normal

 Motor conduction studies were abnormal earliest,

sensory later
 Early abnormalities : prolonged distal and F-wave

latencies, reduced conduction velocities, partial motor

conduction block
 Feature of axonal degeneration developed over time

including reduced evoked amplitude and abnormal

electromyography • 34
NEUROPHYSIOLOGICAL TESTING
Sensory conduction:
 Sural Action Potential is frequently normal

 Median SAP is abnormal

 “normal sural-abnormal median pattern“

 No particular best time to do nerve conduction studies

 Better be done as soon as possible

 Repeated after 1 or 2 weeks

• 35
PARAMETERS IN ENMG
 Distal latency
 Nerve conduction velocity (NCV)
 CMAP amplitude
 CMAP duration
 F-waves
 Sensory conduction studies
 H-reflex
 Needle EMG

• 36
DISTAL LATENCY
 DL- latency from stimulus onset to appearance of
CMAP
 Depends on
 NCV of distal segment
 Neuromuscular Jn. And muscle membrane transit time

 Abnormal ?
 > 125 % ULN if CMAP amplitude is normal
 > 150% ULN if CMAP amplitude is < 80%

• 37
NERVE CONDUCTION VELOCITY
 Slowing of NCV is one of the hallmarks of
demyelinating neuropathy
 Normal
 UL > 50 m/s
 LL > 40 m/s

 Abnormal?
 <80% of LLN if CMAP >80% of LLN
 <70% of LLN if CMAP < 80% of LLN

• 38
CMAP AMPLITUDE
 Amplitude depends on the no. Of “functioning”
motor axons with “secure conduction”

 So, low amplitude can occur with both demyelination

and axonopathy

 Amplitude < 20% of normal  axonopathic if there

are no features of demyelination

• 39
CMAP DURATION
 Depend on the range of conduction velocities of
conducting fibers

 Abnormal ?
 >15% increase in the negative peak duration of the proximal
evoked CMAP compared to distal CMAP -called Temporal
Dispersion

 CMAP area: Amplitude X duration

• 40
EVOLUTION OF ENMG FEATURES
 Most proximal and most distal segments are affected
early
 NC Velocities are often normal early
 Motor NCV slowest-3rd week
 Sensory NCV slowest-4th week
 Change in NCV - often the last to recover
 When patient improves, NCV may paradoxically slow

• 41
ELECTRODIAGNOSTIC CRITERIA (AIDP)

Albers Albers Cornbl Ho et al Dutchg Italy

et al & Kelly ath roup group
(CIDP)
CV <95 <90 80% <90 <70 <80
(Low amp)
(85) (80) (70%) (85) (70)
DL >110 >115 >125% >110 >150 >125
CB 30 30 20% 30 30 30
TD 30 30 20% 30 - 30
F-wav >120 >125 >120% >120 >150 120-150

43 pts 72% 37% 21% 58% 63% 56%

• 42
CRITERIA FOR ELECTROPHYSIOLOGICAL
CLASSIFICATION
 Primary Demyelinating
 At least 1 of the following in 2 nerves or 2 in 1 nerve if others are
of low amplitude/ in-excitable

 MCV <90% LLN (85% if amp. <50% LLN)

 DML >110% ULN (120% if amp. < 20%LLN)

 C.Block 50% fall proximally if CMAP >20% LLN

 F-latency >120% ULN

• 43
CLASSIFICATION CONTD…

 Primary Axonal [AMAN/AMSAN]

 None of the features of demyelination in any nerve
 Distal CMAP amp <80% LLN in at least 2 nerves

 Inexcitable
 Distal
CMAP absent in all nerves
 OR present in only 1 nerve with amp.<10%LLN

• 44
CLASSIFICATION CONTD…
 Equivocal
 Does not exactly fit criteria for any group
 Follow up studies will help in reclassifying the Inexcitable
and Equivocal group into axonal/demyelinating
[GBS study Group. Ann Neurol 1998]

• 45
EARLY GBS ENMG FEATURES
 Early diagnosis is important
 CSF is often normal in early stages
 Gordon & Wilbourn, 2001
 31 patients studied within 7 days
 H-reflex absent 97%
 Absent or Low amplitude SNAPs in UE-61%
 Abnormal Median & Normal Sural SNAP 48%
 Abnormal F-waves 84%

• 46
EARLY GBS CONTD…
 Prolonged DL 65%
 Low CMAP amp 71%
 Temporal dispersion 58%
 Conduction Block 13%
 Slowed Motor conduction velocity 52%
 Definitive diagnosis in 55% usually by 5th day
[Gordon et al.Arch Neurol 2001;58:913]

• 47
AMNS RESPONSES
 Median: Wrist-finger
 Sural: Calf-Lat mall

 In GBS most distal and prox.

Segments are affected early
 In true sense AMNS is an
artifactual finding

• 48
ISOLATED ABSENT F-WAVES IN
GBS
 Kuwabara et al. studied 62 pts (Japan)
 12 had Isolated F-wave absence
 Follow up conduction revealed 2 patterns
 Rapid restoration of normal F-waves ! Normal parameters in

other sites too [Rapid clinical recovery]

 Evolution into AMAN!!

• 49
PATHOPHYSIOLOGY OF ISOLATED
ABSENT F-WAVE IN GBS

1. Demyelinative
conduction block in
proximal segment
2. Acute axonopathy in
proximal segment
3. Reversible conduction
failure at nodes of
Raniver (AMAN)
4. Impaired excitability
[Kuwabara JNNP 2000;68:191]

• 50
INEXCITABLE?
 Nerve may have
conducting axons
but inexcitable by
conventional
stimulation

• 51
EMG

 Preferably done in all cases

 Denervation features may
occur as early as first week
of illness
 Indicate axonopathic
process

• 52
• 53
MILLER FISHER SYNDROME
 Sensory
 Axonal loss
 Reduced SNAPs
 Can be completely normal

 Motor: Usually Normal

 F-waves: Prolonged; Dispersed; Absent

 Serial conduction studies- more useful

• 54
PROGNOSTIC FACTORS
 CMAP amplitude 0-20% LLN -poor outcome
 Other parameters-do not predict

 Recurrent GBS Vs CIDP?

 No electrophysiological features
 Rely more on clinical features
 A documented normal study between relapses may help

• 55
CONCLUSION
 Electro-clinical diagnosis
 No universally accepted EP criteria

 Majority 56-87% -AIDP

 Early GBS - normal study unlikely with significant

deficit
 Axonal GBS diagnosed in the absence of
demyelination features
 Low CMAP –only prognostic indicator

• 56
Main pathologic events of primary segmental demyelination in
immune-mediated inflammatory polyneuropathies (Potts,
2001)

• 57
Normal peripheral motor nerve anatomy and
responses to injury (Quan, 1999)

• 58
ENMG demielinisasi dan aksonopati (Hughes, 2002)

• 59
Conduction Block (Mossa, 2002)

• Difference of CMAP amplitude between distal

and proximal stimulation
• >15% increase in the negative peak duration
of the proximal evoked CMAP compared to
distal CMAP -called Temporal Dispersion
• Amplitude fall >30% in proximal stimulation
compared to distal irrespective of change in
the duration [Temporal dispersion]
• Both TD and CB signify the same process-
i.e., segmental demyelination

• 60
F-WAVES (MOOSA, 2002)

Antodromic impulse from the motor nerve  proximal nerve root

AHC motor nerve  elicits a delayed small action potential called F-
wave
Delayed or absent F wave showing root demyelination

• 61
H-REFLEX (MOOSA, 2002)

 Electrophysiological correlate of areflexia

 Monosynaptic spinal reflex  Sensory N  Dorsal Root  Synapse Motor
root  Motor nerve  H Reflex
 Abnormal : Absence of H-reflex
 Almost an universal finding in early GBS

• 62
Aksonopathy VS Myelinopathy(Potts, 2001)

Study Axonal Segmental

degeneration demyelination
Motor-nerve conduction studies
a b
CMAP amplitude Decreased Normal
Distal latency Normal Prolonged
Conduction velocity Normal Slow
Conduction block Absent Present
Temporal dispersion Absent Present
F wave Normal Prolonged or absent
H reflex Normal Prolonged or absent
Sensory-nerve conduction studies
SNAP amplitude Decreased Normal
Distal latency Normal Prolonged
Conduction velocity Normal Slow
Needle electromyography (spontaneous activity)
Fibrillations Present Absent
Fasciculations Present Absent
Recruitment
Number of motor units Decreased Decreased
• 63
GBS INVESTIGATION

• 64
CSF/LCS
GBS INVESTIGATION: CSF FINDINGS
 Progressive motor weakness prime
↑ protein
 ≤ 10 mononuclear cells/mm3

 CSF protein N in first week

 Pleocitosis raises doubt, associated with HIV

• 66
LCS
The Normal Findings What abnormal findings may indicate
Evaluation
Pressure Less than 200cm H2O tumors, hydrocephalus, intracranial bleeding
Color Clear and colorless Cloudy-bacteria, WBCs
Red-tinged--subarachnoid bleeding
Blood None Cerebral hemorrhage or Traumatic tap (inadvertant rupturing a
blood vessel )
Cells No Red blood cells, Red blood cells-- blood within the spinal canal,
<5 lymphocytes/mm2 White blood cells--infection
Culture & No organisms present Bacterial or fungal infection
Sensitivity
Protein 15 - 45 mg/dl Meningitis, encephalitis, myelitis, tumors, inflammatory processes
up to 70mg/dl for
elderly and children
Glucose 50 - 75 mg/dl Meningitis, neoplasm
or 60 to 70% of blood
glucose level
Chloride 700 - 750 mg/dl Meningeal infections, tubercular meningitis
(not routinely
evaluated) • 67
Dissosiasi sitoalbuminique

Reaksi inflamasi dan edema menimbulkan kompresi.

Terjadi transudasi protein serum ke dalam ruang
subarachnoid dan CSS.
Hal ini menimbulkan kenaikan karakteristik kadar protein
dalam CSS.
Hiperemi dan dilatasi pembuluh darah yang terjadi akibat
inflamasi menyebabkan pasokan protein lebih besar ke CSS

• 68
CSF FINDINGS IN GBS
 Elevated protein (higher than 0,5 g/dl)
 No pleocitosis (abnormal cell number in CSF)

 CSF often normal in less than 48 hours, but by the end of

one week the protein level is elevated.
 Pleocitosis (cell count 10-100/mm3) with typical GBS
symptom increase the possibility of Lyme disease, HIV,
and other disease.

• 69
CLINICAL FEATURE
DIAGNOSIS KRITERIA FOR TYPICAL GBS
GBS FEATURE
 Acute/sub acute onset
 Gradual recovery after plateau phase

 Mean time nadir; improvement; recovery : 12;

28; 200 days
 Plateau phase 4 wks from onset

Seneviratne, 2000

• 72
 CLINICAL FEATURES

 Most patients are essentially well

 Lack systemic symptoms, including fever, when PNS symptoms
begin
 Initial neurological symptoms vary from patient to patient
 Cardinal features of GBS include:
 Paresthesias
 Weakness
 Diminished or absent DTRs

• 73
PARESTHESIAS

 Distal, usually symmetrical paresthesias involving the toes,

fingers, or both herald the onset of the disorder in at least 50% of
patients
 Typically spreads proximally but seldom extends beyond the
ankles and wrists
 Substantial sensory abnormalities are found infrequently on
exam
 In contrast with the high incidence of sensory symptoms
 Typically, vibration and proprioception are the most severely
affected
 Sensory modalities mediated over large myelinated fibers

• 74
 WEAKNESS

 Weakness is often first noted a few days after the onset of

paresthesias
 Typically, it begins in the lower extremities, especially in the
proximal muscles
 Patients may experience difficulty climbing stairs and rising from chairs
for a day or two before they realize that they are ill
 Weakness soon spreads (ascends) to the upper extremities
 Less often, weakness begins simultaneously in the upper and lower
extremities
 Lower extremities usually more severely affected

• 75
DEEP TENDON REFLEXES

 On clinical examination, one of the earliest findings is

decreased or absent DTRs
 These may either precede or follow by a few days the
demonstration of weakness on physical exam
 In some cases, profound proprioceptive loss results in
sensory ataxia and pseudoathetosis

• 76
DISEASE PROGRESSION

 Progressive phase of the illness lasts from a few days to a month

 ~ 50% of patients reach the nadir of clinical function by 2 weeks and 80%
by 3 weeks
 Flaccid weakness is ultimately present and varies considerably in severity
and distribution
 Often is profound, involving all four limbs, the respiratory muscles, and the face
 Facial diplegia, or bilateral facial weakness, is seen in ~ 50% of the patients
 Occasionally, fasciculations are noted

• 77
PAIN

 Although the prominent features are motor in nature, pain

occurs in over 75% of patients with acute GBS
 Usually, it is most severe in the shoulder girdle, back, and
posterior thighs
 Notoriously more severe at night
 Diagnosis of pain in children is particularly difficult due to
limited history and cooperation during the neurological
exam
 Most often misdiagnosed and under-treated

• 78
GBS ANTECEDENT EVENTS
 Two third patient of GBS
 URTI or GE

 Resolved at onset

 Interval preceding infection : 1-3 wks (mean 11 days)

Kuwabara, 2004

• 79
C JEJUNI
 Major cause of bacterial GE throughout the
world
 Most frequent antecedent infection of GBS

 Commonest pathogen identified : 20% diarrhoea

 Eur & USA 26%-30% culttured (+)

 Japan 45%

Kuwabara, 2004; Seneviratne, 2000

• 80
C. JEJUNI AND SEROTYPE
 AMAN and AMSAN
more often; AIDP less
often
 Most frequent in MFS
 Associated with slow
recovery, severe
residual and axonal
degeneration
In America Risk 1:1058
After inf O:19 1:158
• Serotype & susceptibility
 important role
• Japan: Penner serotype
O:19 ( 18% GBS)
• USA and German 29%
seropositive for O:19
• South Africa : O:41
• MFS : O:2
• 81
Seneviratne, 2000
C JEJUNI PATHOGENESIS
 Mollecular mimicry
 Gangliosides: important surface molecule in nervous
system
 Antibodies formed against ganglioside-like epitope in
lypopolysacharida C jejuni cross react with peripheral
nerves causing damage
 High titre of antibodies against : GM1, GM1b, GD1a or
Ga1NAc-GD1a.
 Host susceptibility : important

 GBS & enteritis similar ganglioside like epitopes

• 82
Kuwabara, 2004; Seneviratne, 2000
C JEJUNI

• 83
C. JEJUNI AND GBS FACT

• 84
C. JEJUNI AND GBS FACT

• 85
CMV AND GBS
 Second commonest infection
 Japanese 5%; European: 11-13%; Belgium 13%
 ♀>♂ ; Young age
 Severe course initially + respiratory difficulties
 Often with cranial nerve palsy (bilateral facial palsy) and
severe sensory loss
 ↓ SNAP
 NCV, conduction blocks, denervation activities ~ others
 Recovery delayed
 Liver function disturbance  ↑ liver enzymes
 Molecular mimicry : possible
 Host factor important  individu with ↑ antibodi anti GM2.
• 86
Seneviratne, 2000
HAEMOPHILUS INFLUENZA
 13% serological evidence in 41 cases in Japan
 Antiganglioside antibodies (+)

 AMAN ~ C jejuni

 Presence of ganglioside GM1-like structure on the

surface
Seneviratne, 2000

• 87
OTHER INFECTION AND GBS
 EBV
 Mycoplasma pneumonia
 Parainfluenza type 1 virus
 Influenza A & B virus
 Adenovirus
 Varicella zoster virus (VZV)
 Parvovirus B19
 HIV
 Lyme disease
 Hepatitis A,B,C, and D
 Typhoid
 Plasmodium falciparum
Seneviratne, 2000 88
•
GBS AND VACCINE
 A/New Jersey (Swine Flu) vaccination programme in USA
1976-1977↑ GBS
 RR 4-7,8 in 6 wks

 8.6 cases/million in Michigan

 9.7 cases/million in Minnesota

 1978-1979 RR1.4

 1980-1988 RR 1.1

 1992-1993 RR 1.7 ~ 1-2/million age < 45

 1999 10/million

 Other virus : not clear

 Immunization continued  risk and benefit

• 89
Seneviratne, 2000
GBS AND VACCINE
Finland
 ↑ GBS during Nationwide Oral Polio Vaccine
 Failed to prove case-effect relationship

Latin America
No temporal association between the mass oral polio
vaccination campaign and GBS in 1989-1991

 TT not significant
 MMR & Measles  anecdotal case records; not significant
in South America 1992-1993.
 HBV immunization: 9/850.000 • 90
Seneviratne, 2000
GUILLAIN BARRE SYNDROME FOLLOWING
INFLUENZA VACCINATION JAMA, 2004.

• 91
CLINICAL SUBTYPES
 • 93

American Academy of Family Physician, 2004

CIDP
ACUTE INFLAMMATORY
DEMYELINATING POLINEUROPATHY
 Most common form  85-90%
 GBS ~ AIDP

 Lymphocyte infiltration of peripheral nerve & macrophage

mediated segmental demyelination
 Infiltration of T Cells in endoneurium

 Immune target: Schwann cells surface or myelin. Molecule

target not known
 Axonal loss may also occur in severe case as secondary event

 Mediated by humoral and cellular immunity

 EP : segmental demyelination

 Recovery : remyelination
• 95
Seneviratne, 2000; Kuwabara, 2004; Hughes & Cornblath, 2005
AIDP IMAGE

• 96
AMAN
 Majority case in China 1991-1992
 76% seropositive for C jejuni
 Antiganglioside antibody anti GM1, GM1b, GD1a, GD1b,
Ga1NAc-GD1a
 CAMP ↓
 Motor distal latencies, motor conduction velocities, SNAP, F
Wave  Normal
 Wallerian degeneration of motor axon
 Earliest pathologic feature:

- lengthening of node of ranvier

- distortion of paranodal myelin
- dissection of axon from Schwann cell adaxonal plasmalemma
by extending macrophage processes • 97
- may be reversible
AMAN IMAGE

• 98
AMAN
 Tendon reflexes could be preserved or
exaggerate
 Hyperreflexia in 1/3 cases esp early phase
occasionally acute phase  anti GM1 antibody
 less severe case
 Characterized by rapidly progressive weakness
often with respiratory failure
 Usually good recovery

Seneviratne, 2000; Kuwabara, 2004; Hughes & Cornblath, 2005 • 99

AMSAN
 EP  inexcitable motor nerves and evidence of sensory &
motor axonal dysfunction
 Axonal degeneration with no demyelination or inflammation
 Wallerian degeneration sensory and motor fibre with little
demyelination or lymphocytic infiltration
 Could follow C jejuni infection
 Numerous macrophage in periaxonal and intraaxonal
space epitope in such space
 The course typically fulminant
 Slow and incomplete recovery
 The worst form of GBS

• 10
Seneviratne, 2000; Kuwabara, 2004; Hughes & Cornblath, 2005 0
MILLER FISHER SYNDROME (MFS)
 Associated wit C jejuni infection
 Penner Serotype 2 and Lior Serotype 4

 IgG autoantibody against GQ1b

 GQ1b in

- N III, IV, VI  ophtalmoplegia

- dorsal root ganglia  areflexia
- interfere neuromuscular transmission 
weakness
• 10
Seneviratne, 2000; Kuwabara, 2004; Hughes & Cornblath, 2005 1
ATAXIA IN MFS
Peripheral mechanism
 Abnormal joint position sense

 Abnormal muscle spindle proprioception

Fisher : out of proportion to the degree of sensory loss

Central mechanism
 Based on MRI and EP test

 Stain of the cerebellar molecular layer with IgG anti

GQ1b antibodies

• 10
Seneviratne, 2000; Kuwabara, 2004; Hughes & Cornblath, 2005 2
MFS NEUROPATHOLOGICAL
 Scanty,
rare disorder
 Demyelination and inflammation of N III& VI

 Demyelination and inflammation of spinal ganglia

 Demyelination and inflammation peripheral nerve

 No axonal damage

Seneviratne, 2000; Kuwabara, 2004; Hughes & Cornblath, 2005

• 10
3
MFS ELECTROPHYSIOLOGY
↓ or absent SNAP
 Motor and sensory nerve conduction velocity N
or ↓
 Absent tibial H reflex

 Absent denervation changes In limb muscle

• 10
4
OTHER VARIANT OF GBS
 Pure sensory
 Pure dysautonomia

 Pharyngeal-brachial-cervical

 Paraparetic variant

• 10
5
PURE SENSORY VARIANT GBS
 Symmetric sensory loss
 Areflexia

 Mild or no weakness
 CSF and EP ~ GBS

 Necropsy : demyelination with mononuclear cell

infiltration of nerve and posterior roots

• 10
6
DYSAUTONOMIA VARIANT GBS
 Vary in feature
 Cardiovascular involvement

 ↑ plasma cathecolamine and cortisol  hypertension,

tachycardia
 ECG : ST depression, T inverted, tall T wave, prolonged
QTc interval in 1/3 case
 Lymphocytic infiltration of autonomic ganglia and
perivascular lymphocytic infiltration in hypothalamus
and brainstem
 Fatal case : wide fluctuation of BP

 Vagal overactivity : arrhythmia, • 10

7
GBS IN CHILDREN
GBS IN CHILDREN
 0,5-1,5 cases/million
 Most common cause of acute paralysis

 Affects all ethnic group

 Incidence among countries variable

 Unclear genetic susceptibility

 potential pathogens infections

 Associated with antecedent infection

 EBV, CMV, Hepatitis, VZV, HSV

 M. pneumonia, Campilobacter
 Role of immunization  anecdotal  never concincingly
establihed • 10
Sladky, 2004 9
CLINICAL FEATURES CHILDREN WITH
GBS

Sladky, 2004• 11
J Child Neurol;0 116
CLINICAL COURSE CHILDHOOD GBS
J CHILD NEUROL, 2004;116

Onset and progression of symptoms

 Evolves rapidly from mild to mechanical ventilators over
hours
 Nadir 2 wks (small group 4 wks)

 Immune mediated attack on myelin and axon

 Followed by plateau phase

Plateau phase
 Variable duration

 Peripheral nerve damage slows

• 11
 Regeneration process 1
CLINICAL COURSE CHILDHOOD GBS
J CHILD NEUROL, 2004;116
Recovery
 Weeks or months
 Severity at nadir quite variable
 Mean disability grade : 3.5-4
(Hughes criteria)
 45% score 2-3
 40% score 4
 15% score 5
 Mortality is rare with high
quality supportive management
 90-95% completely recovered
within 6-12 months
• 11
 Minor Residual deficit 2
MANAGEMENT CHILDHOOD GBS
J CHILD NEUROL, 2004;116
 Hospitalization until maximal degree of disability

 Fulminant fashion and respiratory failure can developed

rapidly
 Pain : often under-treated

 Autonomic complication

 Careful attention to nutrition requirement

 Early introduction of physical and occupational therapy

• 11
3
TREATMENT CHILDHOOD GBS
J CHILD NEUROL, 2004;116
Plasma Exchange
 Descriptive reports
 Enhances time of recovery and shortening time to discharge from
hospital
 Mostly for severe case
 Dose and schedule have not been determined
 Generally safe in children weighing 10 Kg or more
 Cumulative total 250 ml/kg exchange or roughly triple volume exchange

IVIG
 Similar with PE
 Total dose 2g/kgBW (0.4kg/kgBW 5 days; 1g/kgBW 2days, 0,5g/kgBW
4 days ?? )
Steroid
 No potential role • 11
4
PROGNOSIS OF CHILDHOOD GBS
RUST&FLEMMING, 1996

Good prognosis:
 Young age

 No need for respiratory assistance

 Slow progression of illness

 Normal EP study

 Treatment with PE or IVIG

• 11
5
CLINICAL EVIDENCE CHILDHOOD GBS

• 11
6
CLINICAL EVIDENCE CHILDHOOD GBS

Koul, et al, 2003 • 11

7
CLINICAL EVIDENCE CHILDHOOD GBS

• 11
8
Graaf, et al, 1999
CLINICAL EVIDENCE CHILDHOOD GBS

• 11
Shanbag, et al, 2003
9
CLINICAL EVIDENCE CHILDHOOD GBS

• 12
0
CLINICAL EVIDENCE CHILDHOOD GBS

• 12
1
CLINICAL EVIDENCE CHILDHOOD GBS

• 12
2
CLINICAL EVIDENCE CHILDHOOD GBS

• 12
3
AUTOIMMUNE PROCESS
AUTOIMMUNITY & AUTOIMMUNE DISEASE
LANCET, 2003

• 12
5
AUTOIMMUNITY & AUTOIMMUNE DISEASE
LANCET, 2003

• 12
6
AUTOIMMUNITY & AUTOIMMUNE DISEASE
LANCET, 2003

• 12
7
MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)

Pengertian:
MHC = seperangkat gene yang menghasilkan protein yang mempunyai peran
penting dalam imunologi
MHC molecule = molekul yang dihasilkan oleh MHC

Molekul MHC :
MHC I diekspresikan oleh semua sel somatik; fungsinya mempresentasikan
antigen kpd limfosit Ts membunuh sel
MHC II diekspresikan hanya oleh fagosit dan beberapa sel lain; fungsinya
mempresentasikan antigen kpd limfosit Th produksi antibodi – penting pada
manipulasi kekebalan spesifik

• 12
8
MHC

• 12
9
Presentasi antigen kepada sel T
Gb. atas oleh fagosit : fagosito-sis – proses
penghancuran – presentasi Ag kepada sel
T bersama MHC II
Gb tengah oleh sel B : internalisasi antigen –
presentasi kepada sel T bersama MHC II
Gb bawah oleh sel dendritic : pinositosis (?)
– presentasi kepada sel T bersama MHC
II

• 13
0
• 13
1
• 13
2
• 13
3
• 13
4
• 13
5
• 13
6
• 13
7
TREATMENT
 GBS TREATMENT : SUPPORTIVE
 Respiratory assistance  significantly improve outcome
 Intubation and mechanical ventilation required for 25-33%
 Measurement of maximal expiratory vital capacity  VC ≤
15ml/kg  intubation & mechanical ventilation
 Bulbar palsy : intubation required to prevent aspiration
 Continuous monitoring of BP and HR
 Hypotension associated with dysautonomia in 10% severe
cases  iv infusion & vasopressor agents
 Hypertension  short acting anti-hypertensive medication
 Prevention of thromboembolic and pulmonary embolism 
heparin
 Respiratory infection  minimal sedation in ICU
• 13
 Pain  analgesics and early rehabilitation 9
GBS TREATMENT
IMMUNOMODULATING
Plasma exchange
 Improved more rapidly
 Weaned from ventilators more quickly
 Able to walk unaided in shorter period of time
 Improve long-term outcome
 Adverse events more often according to number of session
 Severe case : 4 session; mild case 2 session
 Secondary worsening after PE n 10% cases
 Acceptable safety profile when patient condition carefully
monitored  haemodynamically unstable patients and
infection complication
 Limited facilities, high cost  need to discover alternative • 14
treatment 0
PLASMA EXCHANGE
 Requires skilled personnel and specialized
equipment
 May not be available in all hospitals
 May increase the risk of infection and hemorrhage
due to the removal of immunoglobulins and clotting
factors
 Complications and side effects : hypotension,
septicemia, pneumonia, cardiac arrhythmias,
malaise, hypoprothrombinemia with
bleeding/abnormal clotting, and hypocalcemia

• 14
1
MECHANISM OF PE
Plasma exchange or plasmapharesis -- The
mechanism of plasmapheresis is the
removal of immunoglobulins and
antibodies from the serum by removing the
blood from the body, separating cells from
the plasma, and replacing the cells in fresh
frozen plasma, albumin, or saline. Adult
Dose3-5 exchanges of 50 mL/kg of plasma
over 1-2 wk via central venous catheter • 14
suggested 2
CORTICOSTEROIDS
 No benefit in GBS
 124 patients treated with methyl prednisolone 500
mg for 5 days compared with 118 control (Lancet,
1993): no significant difference
 Cochrane evidence based review 2003 :
corticosteroid alone should not be used in the
treatment of GBS

• 14
3
•  Corticosteroid

•  A recent meta-analysis of all the available

• randomized studies has concluded that
• corticosteroid treatment is not beneficial
•  A pilot study of IVIg 0,4 gm/kg/day combined
• with iv. Methylprednisolone 500 mg daily for
• 5 days has suggested that this combination
• regimen may be more effective than IVIg alone
Ropper 1992 :
Efek kortikosteroid adalah :
1. Menghamabat Respon seluller-hambatan
migrasi adheren, aktifasi fagosit & sitokin
2. Menghamabat IL-1 & IL 6

3. Antiinflamasi : menstabilkan membran lisosom,

mencegah aktifasi fosfolipase A2, mencegah
motilitas neutrofil, dan menurunkan
permeabilitas vaskuler
                                                           

From Cochrane Review Abstracts                                                                                                                                                                            

Corticosteroids for Guillain &hyphen; Barr é syndrome

Posted 10/01/2005                                                                                                                                                                            
RAC Hughes 

Introduction
Date of Most Recent Substantive Amendment: 2000 02 03
Background
   
The cause of Guillain – Barr é syndrome (GBS) is inflammation of the peripheral nerves which corticosteroids would be expected to benefit.
Objectives
   
To
  examine   the efficacy of corticosteroids in hastening recovery and reducing the long term morbidity from Guillain – Barr é syndrome (GBS).
Search
  strategy
 
Search
  of  the Cochrane Neuromuscular Disease Group register for randomised trials and enquiry from authors of trials and other experts in the field.
Selection
    criteria
Types of studies: quasi – randomised or randomised controlled trials Types of participants: patients with GBS of all ages and all degrees of severity Types of interventions: any
form of corticosteroid or adrenocorticotrophic hormone Types of outcome measures: Primary: improvement in disability grade on a commonly used seven point scale four weeks
after randomisation Secondary: time from randomisation until recovery of unaided walking, time from randomisation until discontinuation of ventilation (for those ventilated),
mortality,
  proportion of patients dead or disabled (unable to walk without aid) after 12 months, improvement in disability grade after six months, improvement in disability grade
after 12 months, proportion of patients who relapse, and proportion of patients with adverse events related to corticosteroid treatment
Data collection and analysis
We identified six randomised trials. One author extracted the data and the other checked them. We obtained some missing data from investigators.
Main results
The six eligible trials included a total of 195 corticosteroid treated patients and 187 control subjects. One trial of intravenous methylprednisolone accounted for 243 of the total
382 subjects studied (63%). This trial did not show a significant difference in any disability related outcome between the corticosteroid and placebo groups.
There was no significant difference between the corticosteroid and control groups for the primary outcome measure, improvement in disability grade four weeks after
randomisation. The weighted mean difference of the three trials for which this outcome was available showed no significant difference. The actual figure was – 0.06 (95% CI –
0.32 to 0.19) grade in favour of the control group.
There was also no significant difference between the groups for most of the secondary outcome measures. However in the largest trial hypertension developed less often in the
intravenous methylprednisolone group (2/124, 1.6%) than in the control group (12/118, 10.2%), a significant difference in favour of corticosteroid treatment (relative risk 0.20,
95% CI 0.04 to 0.66).
Authors' conclusions
Corticosteroids should not be used in the treatment of Guillain – Barr é syndrome. If a patient with Guillain – Barr é syndrome needs corticosteroid treatment for some other
reason its use will probably not do harm. The effect of intravenous methylprednisolone combined with intravenous immunoglobulin in Guillain – Barr é syndrome•is being 14 tested
with a randomised trial. 6
COCHRANE DATABASE SYST REV. 2006 APR 19;(2):CD001446.
CORTICOSTEROIDS FOR GUILLAIN-BARRÉ SYNDROME.
HUGHES RA, SWAN AV, VAN KONINGSVELD R, VAN DOORN PA.

 AUTHORS' CONCLUSIONS:

 Limited evidence shows that oral corticosteroids

significantly slow recovery from Guillain-Barré
syndrome. Substantial evidence shows that intravenous
methylprednisolone alone does not produce significant
benefit or harm.
 In combination with intravenous immunoglobulin,
intravenous methylprednisolone may hasten recovery but
does not significantly affect the long-term outcome.
More research is needed and more effective treatments
• 14
for Guillain-Barré syndrome should be sought. 7
• 14
8
• 14
9
INTRAVENOUS IMMUNOGLOBULIN
 IVIG is an immunomodulating agent that has multiple
activities. These include modulation of complement
activation; suppression of idiotypic antibodies; saturation
of Fc receptors on macrophages; and suppression of
various inflammatory mediators, including cytokines,
chemokines, and metalloproteinases (Dalakas, 2002).
 The Fc region of IgG facilitates interaction with and
signaling through Fc receptors on phagocytes, B cells,
and other cells and with Fc-binding plasma proteins (eg,
components of the complement system) (Kazatchkine,
2001).
• 15
0
MECHANISM OF ACTION OF IVIG

• 15
1
Mekanisme aksi Ig terapi (Kazatchkine, dkk, 2001)

• 15
2
Mekanisme kerja IG (Abe, 1996)

• 15
3
Pharmacology

Intravenous immune globulin contains a broad

spectrum of antibodies against bacterial, viral,
and parasitic antigens that are capable of
opsonization of as well as neutralization of
microbes and toxins.
Appropriate doses can restore low IgG levels to
normal range.

• 15
4
 Pharmacokinetics

Important features are as follows:

 Bioavailability is 100% after intravenous injection

 A five-fold rise of serum IgG following intravenous
injection with a decline to 50% in 3 days and
return to normal in 3 to 4 weeks
 A two-fold rise of CSF level of IgG following
intravenous injection and return to normal
within a week
 The half-life of intravenous immune globulin varies
from 2 to 4 weeks
• 15
5
KONTRA INDIKASI IVIG
 Prior anaphylactic reaction with IVIG; anaphylactic reactions may
occur in patients with IgA deficiency with anti-IgA antibodies; when
present, IVIG treatments can be performed with low-level IgA
preparations; renal complications can be minimized by diluting the
IVIG preparation, slowing the rate of infusion, and ensuring
adequate hydration of the patients; in severe congestive heart
failure, complications can be reduced by slower rates of infusion to
minimize risk of rapid fluid overload

• 15
6
EFEK SAMPING IVIG
 Adverse reactions to IVIG usually
are minor (eg, headache, fever,
chills, malaise, myalgia); less
common side effects may include
migraines, aseptic meningitis,
pulmonary edema, skin reactions
(eg, urticaria, pruritus, petechia),
and renal complications; serum
viscosity increases with IVIG
therapy, which can result in rare
cases of stroke, PE, and myocardial
infarction

• 15
7
FACT ABOUT IVIG
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2005; 142.

• 15
8
GAMIMUNE
 Gamimune-N (Miles; Elkhart, Ind; Bayer)
 Sterile solution in 5% and 10% concentrations
 Sodium content in mEq/mL considered trace amount
(incompatible in saline)
 Not sugar-glycine based
 Advanced viral removal and inactivation technologies used in
manufacturing; solvent detergent treated
 Contraindicated in patients with history of prior systemic
allergic reaction to IVIG products or a history of IgA
deficiency
 pH of 4-4.5
 Additives in 5% solution include 9-11% maltose; in 10%
solution, 0.16-0.24 M glycine • 15
 IgA content of 270 mcg/mL 9
IVIG USE IN GBS : EXPERT CONSENSUS
GBS with significant or severe involvement seen within 2
weeks
 Patient require aid to walk
 Impaired bulbar or require ventilation
 Rapidly deteriorating
 Individuals in difficulties in performing ADL
 Treatment should be initiated early within 2 weeks of onset.

Mild GBS/ GBS seen more than 2 weeks after onset

 Consider potential benefit versus clinical risks
 Mild GBS usually recovers well without treatment
 May be considered if deterioration continue
• 16
0
RECOMMENDED DOSE AND
DURATION OF INFUSION
 Standard total dose 2 g/kgBW
 Conventionally given 0,4g/kgBW for 5 consecutive days

 Many centers use 1g/kgBW for 2 days for faster and more
convenient administration
 Side effect ~ shorter course of infusion

• 16
1
EVIDENCE OF IVIG IN GBS

• 16
2
EVIDENCE OF IVIG IN GBS

• 16
3
PROGNOSIS
PROGNOSIS GBS

• 16
5
• 16
6
• 16
7
• 16
8
DIAGNOSIS BANDING
 • Approach to Evaluation of Peripheral Neuropathies (Bosch & Smith
2000)
• History and Examination

• 1. Mononeuropathy • 3. Peripheral Neuropathy

• EMG • EMG

•• Focal •• Widespread •• Axonal

Axonal
Focal Widespread changes
changes

• Compression • Subclinical neuropathy

Consider diabetes or • Acute • Subacute • Chronic
• Entrapment •
• other systemic disease
Porphyria
• • Systemic diseases • Consider:
• Axonal GBS • Deficiency states • Hereditary
• 2. Multifocal Mononeuropathy • Tick paralysis • Toxins • neuropathies
• Toxins • Amyloid • CMT II
• Critical illness NP • Carcinoma • Dysproteinemias
• EMG
•• Demyelination
Demyelination

•• Axonal
Axonal •• Demyelination
Demyelination • Uniform slowing, • Non-uniform slowing
•• Conduction
Conduction block
block • chronic • Conduction block
• Systemic, nonsystemic • Multifocal variant • Hereditary neuropathies
• vasculitis • of CIDP • CMT I,III, CMTX
• Diabetes
• Multifocal motor • Refsum disease • Acute • Relapsing or chronic
• Sarcoidosis
• Leprosy
• neuropathy • Leukodystrophies
• CIDP
• HNLPP • GBS • Dysproteinemia
• Diphteria • Osteosclerosis
• myeloma
DIFFERENTIAL DIAGNOSIS OF
GUILLAIN-BARRE SYNDROME
 Hysteria/conversion reaction  Vasculitis
 Hexacarbons  Rabies
 Malingering
 Neuromuscular transmission
 Diphtheria
disorders
 Brain stem infarction
 Enteroviruses
 Drugs
 Botulism
 (Locked-in syndrome)
 Acute myelopathies
 Lyme disease
 Tick bite paralysis

 Peripheral neuropathies
DIFFERENTIAL DIAGNOSIS OF
GUILLAIN-BARRE SYNDROME (CONT.)
 Critical illness
 Poliomyelitis
 Transverse myelitis
 Myasthenic syndrome
 Focal compression
 Myasthenia gravis
 Cauda equina lesions
 Snake venom
 Acute intermittent porphyria
 Sea urchin venom
 Heavy metals; arsenic;
thallium, gold
 Hypermagnesemia
 Muscle disorders
 Alcohol
 Hypokalemia
 Organophosphates
 Hyperkalemia
 TRANSVERSE MYELITIS
 Superficially resembles GBS if
 Spinalshock has occurred
 Lower extremity DTRs are absent

 Distinctions:
 Asymmetrical involvement
 Definite sensory level
 Complete absence of upper extremity weakness
 Urinary incontinence
 CSF pleocytosis
 HEAVY METAL INTOXICATION
 Heavy metal intoxication mimics GBS clinically
 Principally subacute arsenic or acute thallium poisoning
 In the initial phase of arsenic poisoning, both the CSF and EDX findings
may be identical to typical GBS
 Distinctions:
 Always with preceding bouts of gastroenteritis
 Associated central nervous system involvement
 particularly with thallium poisoning
 Oftenmore than one person is affected simultaneously, strongly
suggesting a common source
 VASCULITIC NEUROPATHIES
 Vasculitic neuropathies occasionally are mistaken for
GBS
 Distinctions:
 Systemic signs, including fever, are common
 Sensory and motor involvement in the limbs usually is both distal in
location and asymmetrical
 Cranial nerve involvement, respiratory complications, and sphincter
dysfunction are uncommon
 CSF typically is normal (except with systemic lupus erythematosus)
 NCS reveal changes suggestive of axon loss, rather than SD
ACUTE INTERMITTENT PORPHYRIA
 Acute intermittent porphyria can produce a PNS disorder that can
be mistaken for GBS
 Distinctions:
 Longer evolution
 Abdominal pain, constipation, and altered mental status
 Motor deficits begin in the upper extremities
 Preserved achilles DTRs
 Proximal sensory loss
 Seizures may occur
 CSF protein typically is normal
 NCS demonstrate axon loss rather than SD
 BOTULISM
 Botulism in adults, nearly always food borne, has a clinical
presentation that resembles that of GBS
 Distinctions:
 Frequently several cases occur simultaneously
 Immediately preceding gastrointestinal symptoms are prerequisite with
constipation throughout the course
 Blurred vision, dry mouth, and ptosis
 Dilated pupils that poorly respond to both light and accommodation
 Weakness descends from the bulbar region
 neck weakness and respiratory muscle weakness may be far more prominent than
limb weakness
 Raresensory loss and a normal CSF
 NCS changes include motor unit disintegration
DRUGS CAUSING NEUROPATHIES (MASSON
1992)
Axonal Axonal Demyelinating
Vincristine Lithium Amiodarone
Paclitaxel Alfa interferon Chloroquin
Nitrous oxide Dapsone Suramin
Colchicine Phenytoin Gold
Isoniazid Cimetidine
Hydralazine Disulfiram Neuronopathy
Metronidazole Chloroquin Thalidomide
Pyridoxine Amitriptyline Cisplatin
Didanosine Pyridoxine