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Guillain-Barre Syndrome
Background & Definition
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Described in 1916 by Guillain, Barre, and Strohl
Acute-onset immune-mediated disorder of the peripheral nervous system
Aka acute inflammatory demyelinating polyradiculoneuropathy (AIDP)
Clinical Features and Diagnosis
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Incidence rates are 1-2 per 100,000 population
Lifetime likelihood of any individual acquiring BGS in 1:1000
M=F; occurs at any age
Often predated by unremarkable infection (i.e. URTI/GI infections) by 10-14
days (examples include Campylobacter jejuni, CMV, Mycoplasma pnemonia,
EBV, influenza virus)
Usually begins with abrupt distal, relatively symmetrical onset of
paresthesias, followed by progressive limb weakness
Rapid progression with ~50% of patients reaching clinical nadir by 2 weeks
and >90% by 4 weeks
80-90% of patients will become non-ambulatory during illness
pain is prominent in ~50%
Examination
o Ascending dsistal and often proximal relatively symmetrical weakness
o Sensory exam often normal in early phase
o Widespread areflexia or hyporeflexia is the rule
o Often develop cranial nerve weakness—facial or pharyngeal
weakness
Diaphragmatic weakness due to phrenic nerve involvement
1/3 of hospitalized patients require mechanical ventilation
Autonomic dysfunction seen in >50%--usually manifest as tachycardia but
may included arrhythmias, hypotension, hypertension, and GI dysmotility
Diagnosis
o Clinical suspicion
o Elevated CSF protein (with normal cell count) found in ~50% of
patients initially, but occurs in >90% at clinical nadir
o EMG demonstrates features of demyelination (temporal dispersion,
significantly slow conduction velocities, prolonged distal and F-wave
latencies)
 Very low compound muscle action potentials (CMAP) is
associated with poor long-term outcome
o MRI of Spine/Brain
 useful to rule out mimics of GBS (myelopathy or infiltrative or
compressive causes of polyradiculoneuropathy)
 may support diagnosis by showing enhancement of involved
nerve roots or cranial nerves
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o no diagnostic value in antiganglioside antibody values
Signs/Symptoms suggestive of alternate diagnoses
o Intact reflexes despite generalized weakness
o Asymmetric weakness
o Fever during the initial presentation
o Electrodiagnostic freatures inconsistent with an acquired
demyelinating polyneuropathy
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Variants
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Axonal injury occurs to some degree in many cases of GBS
In severe GBS, significant secondary axonal damage will develop and impact
the degree of residual damage and thus long-term outcome
Variations of GBS include:
o Severe axon loss
o One particular fiber type (sensory or autonomic) is predominantly
affected
o Regional or markedly asymmetric distribution
o Differences in abruptness or onset and time to reach nadir
Miller-Fisher Syndrome
o Classically present with external ophthalmoparesis, areflexia, ataxia
o Generally a benign self-limiting condition
o Almost all treated and untreated patients return to normal activities
within 6 months of disease onset
Acute axonal neuropathy form of GBS
o Accounts for 5-10% of cases in North America
o Characterized by immune attack directed at axons rather than
Schwann cells and myelin
o Course protracted with poor outcome; most patients require
mechanical ventilation within a few days of symptom onset and only
~20% ambulating at 1 year
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Mimics
Pathophysiology
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Acute Inflammatory Demyelinating Polyradiculoneuropathy
o Most common form of GBS
o Pathologic characteristics of demyelination, lymphocytic infiltration,
and macrophage-mediated clearance of myelin
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o Epitopes on surface of infectious agents (C. jejuni, CMV, mycoplasma
pneumonia, influenza virus) are similar to those on surface of
peripheral nerves
o Complement-fixing IgG antibodies bind to peripheral nerve
gangliosides inducing autoimmune injury
o Demyelination may occur throughout the length of the nerve; nerve
terminal axons are also damaged
Acute Axonal Neuropathy
o Often follows infection with C. jejuni
o AgG and complement mediated disorder (like AIDP); target epitopes
are surface of axolemma of motor fibers
o Antibody binding may cause conduction block, and thus may recover
quickly if this antibody binding reversed before the development of
significant axonal degeneration
Miller Fisher Syndrome
o Key difference from AIDP or acute motor axonal neuropathy is
activation of anti-GQ1b and anti-GT1a antibodies that target
oculomotor and bulbar nerves
Management
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Immunotherapy
o Plasma exchange
 Administered as one plasma volume, 50mL.kg, on five separate
occasions over 1-2 weeks
 Shown to be cost-effective given decreased hospital stay
 Should be administered to nonambulant patients with GBS
within 4 weeks and for ambulant patients within 2 weeks of
symptom onset
 Data supports 2-4 plasma exchanges depending on severity
 Side Effects: hypotension, speticemia, pneumonia, abnormal
clotting, complications from central venous access,
hypocalcemia
 Contraindications: major hemostatic disorders, unstable
cardiovascular status, active infection, pregnancy
o IVIg
 Administered 2g/kg totatl divided over 2-5 days
 Give to patients with GBS who require aid to walk within 2
weeks or 4 weeks of neuropathic symptom onset
 Significant adverse effects: renal failure, myocardial infarction,
vomiting, meningismus, ATN, thromboembolic events,
anaphylactic reaction in those with IgA deficiency (risk
1:1000)
o Steroids
 No role
 Choose PE or IVIG, but not both
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Supportive Care
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Mortality from GBS is ~5%; up to 20% for ventilated patients
o Causes: Pneumonia, ARDS, sepsis, PE, cardiac arrest
Relapses in ~10%; consider repeat EMGs to check for CDIP (chronic
demyelinating inflammatory polyneuropathy)
Respiratory
o Mechanical ventilation required in 20-30% of GBS patients
o Predictors of imminent respiratory arrest (“20/30/40 rule”):
VC<20mL/kg, max inspiratory pressure <30cm H2O, or max
expiratory pressure >40cm H2O
o Need for mechanical ventilation associated with
 Time from onset to admission <1 week
 Facial weakness
 Inability to cough
 Inability of lift head off of pillow
 Atelectasis on CXR
 Autonomic dysfunction
o Mean duration of mechanical ventilation is 2-6 weeks
Autonomic Dysfunction
o Symptoms of cardiac, hemodynamic, GI, bladder
o Most common pattern is sympathetic overactivity with
parasympathetic underactivity
o Urinary retention in up to 1/3
o Gastrointestinal motility disorder in 15%
Long-term Issues
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40% of hospitalized patients will require inpatient rehabilitation
Persistent Symptoms and Disability
o Recover is slow and can take years; majority of recover occurs over
the first 6 months
o Persistent disability in 20-30%; 2/3 will report significant disturbed
sensation/loss of power at 1 year
o Erasmus GBS Outcome Score (EGOS)
Immunization
o May increase risk of GBS by 1-2 per million
o For patients who have GBS, immunizations are not recommended
during the acute phase of GBS and porbalby not during a period,
possible of 1 year, after onset of GBS; decisions about future
immunization should be made on a case-by-case basis
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References
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Burns, TM. Guillan-Barre Syndrome. Seminars in Neurology. 28(2):152-67,
2008 Apr.
Green, DM. Weakness in the ICU: Guillain-Barre syndrome, myasthenia
gravis, and critical illness polyneuropathy/myopathy.. Neurologist.
11(6):338-47, 2005 Nov.
Hall & Schmidt. Critical Care: Just The Facts. 2007. pp218-220.