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Etiology
The Guillain-Barre syndrome (GBS) and its variants are considered post-infectious, immune-
mediated neuropathies. Evidence from animal models suggests a key role of molecular mimicry.
In Campylobacter jejuni gastrointestinal infections, a lipooligosaccharide present in the outer
membrane of the bacteria is similar to gangliosides that are components of the peripheral nerves.
[5] Therefore, an immune response triggered to fight infection can lead to a cross-reaction on
host nerves.
Many infections have been linked with GBS. The most common are gastrointestinal or
respiratory illnesses. Up to 70% of patients have reported an antecedent illness in the 1 to 6
weeks before the presentation of GBS.[6] During the Zika virus outbreak, many GBS cases were
described.[7] Case reports detail many other possible etiologies linked to GBS including
medications and surgeries. (Evidence level III)
In 1976, flu vaccination against the influenza A/H1N1 antigen led to a well-documented,
increased incidence of cases of GBS; however, further surveillance data of flu vaccinations in
subsequent years have described only one additional case of GBS for every 1 million vaccines.
Subsequent studies estimate that developing GBS after a flu infection is up to 7 times more likely
than developing GBS after a vaccination.[8][9][10][11][12] (Evidence level IV)
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Epidemiology
Although rare, with an incidence of 0.4 to 2 per 100,000, Guillain-Barre syndrome (GBS) has
major effects on the health care system. The cost of medical care for a patient with GBS has been
estimated at up to $318,966. Overall, the cost of treating patients with GBS has been estimated at
$1.7 billion dollars per year. Males are affected at a slightly higher incidence than females. Each
year, it is estimated 100,000 patients worldwide would contract GBS.[13][14] (Evidence level
III)
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Pathophysiology
Antecedent infections are reported in up to 70% of patients with Guillain-Barre Syndrome
(GBS).[15] Therefore, molecular mimicry plays a substantial role in our understanding of GBS,
particularly the axonal variant. The lipooligosaccharide of Campylobacter jejuni is similar to the
gangliosides of peripheral nerve membranes.[5] Passive immunization of rabbits with these
ganglioside-like lipooligosaccharides have led to similar clinical syndromes of flaccid
tetraplegia, similar to the acute motor axonal neuropathy variant of GBS.[16][17] Ganglioside
antibodies have been shown to have different peripheral nerve targets. Anti-GD1a antibodies
bind to paranadol myelin, nodes of Ranvier, and neuromuscular junction.[18][19]  GM1 and
GQ1B antibodies bind to a peripheral nerve or neuromuscular junction.[20][21] These different
peripheral nerve targets may play a role in the heterogeneity of the clinical presentation of GBS.
Additionally, complement cascade is activated and plays a key role in the disease’s pathogenesis.
[22]
Certain gangliosides are more likely to be associated with specific presentations. For example,
Miller-Fisher syndrome is associated with the anti-GQ1B antibody.[23] The axonal motor
neuropathy form may be associated with anti-GM1 antibodies.[24] The pharyngeal-cervical-
brachial variant of GBS may be associated with anti-GT1A antibodies.[25] However, besides
Miller-Fisher syndrome’s association with anti-GQ1B antibodies, sensitivity and specificity of
all antibodies for specific subtypes are low-to-moderate yield for clinical utility.
Given that not all patients test positive for anti-ganglioside antibodies, further research is needed
to elucidate the roles of anti-ganglioside antibodies in GBS, as causal or epiphenomenon. Less is
known about the pathophysiology behind the acute inflammatory demyelinating polyneuropathy
variant (AIDP) of GBS, despite the fact that it is considered the most common variant in the
United States.
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History and Physical

Guillain-Barre syndrome (GBS) patients describe a fulminant course of symptoms that usually
include ascending weakness and non-length dependent sensory symptoms. By definition, the
nadir is usually reached within 4 weeks. Symmetric involvement is a key feature of GBS.
[6] GBS is usually considered monophasic; therefore, a relapsing or remitting course at
presentation would be considered atypical.[26] Additionally, a prior GBS event (recurrent GBS)
is also unusual, occurring in < 10% of all patients.[27] If the patient reports progression beyond 8
weeks, other diagnoses should be considered.
GBS often presents (up to 70% of patients) within 1 to 6 weeks of antecedent illness.[28] Other
antecedent events that have been linked with GBS include vaccinations (specifically a 1976
strain of swine flu vaccine), surgery, trauma, or other infections. [28][11] 
Classically, patients with GBS will have a pattern of proximal and distal weakness, which is
flaccid and often profound if hospitalized. Significant neck flexion weakness may be present and
can portend the need for intubation. Areflexia or hyporeflexia is usually present. (Rare cases
without hypo/areflexia have been described, mostly in the AMAN variant of GBS).[29] Besides
the flaccid weakness and areflexia, patients experience non-length-dependent sensory symptoms;
therefore, unlike more common chronic neuropathies such as diabetic neuropathy, patients may
report dysesthesias in the hands followed by the feet. Patients can develop facial diplegia due to
the involvement of both facial cranial nerves. They can also develop dysphagia due to the
involvement of the glossopharyngeal, vagus, and hypoglossal cranial nerves.[6] Autonomic
nerves can lead to significant morbidity; therefore, most physicians recommend monitoring in an
intermediate or intensive care unit for cardiac arrhythmias or blood pressure lability.
Dysautonomia is a primary etiology of the morbidity and mortality attributable to GBS.
Additionally, the involvement of the lower cranial nerves (glossopharyngeal, vagus, and
hypoglossal nerves) or involvement of the nerves to the muscles of respiration may lead to the
need for artificial ventilation. Respiratory failure can occur in up to 30% of patients, usually
leading to prolonged hospitalization and recovery.[30]
Besides the classic GBS presentation described above, many variants of GBS have been
described. There is a variant with pure motor involvement called "AMAN (acute motor axonal
neuropathy)" that is more common in Asian countries.[31] Rarely,  these patients can have
normal reflexes.[29] There is also a regional variant involving primarily the pharyngeal, neck,
and upper extremity muscles called the "pharyngeal-cervical-brachial" variant).[32] Some
variants can involve the central nervous system, termed "Bickerstaff Encephalitis."[33] There is
also a variant that presents with paraparesis.[34] Arguably, the most famous variant is the Miller
Fisher syndrome.[35][36] This is classically described as a triad of ophthalmoplegia, areflexia,
and ataxia; however, other cranial nerves besides the oculomotor nerves have been reported in
this variant.[36]
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Evaluation
Guillain-Barre syndrome (GBS) is considered a clinical diagnosis; therefore, a diagnosis can be
made with confidence at the bedside in most cases. For atypical cases or unusual subtypes,
ancillary testing can be useful.[26]
Electromyography and nerve conduction studies may be helpful in distinguishing GBS from its
mimics. Nerve conduction studies (NCS) utilize technology to help distinguish between
demyelinating and axonal forms of neuropathy. Needle electromyography may help to determine
the acuity of a patient’s symptoms. In some cases, these studies may be helpful in evaluating for
other considerations in the differential diagnosis such as neuromuscular junction disorders or
diabetic neuropathy. Classically, electrodiagnostic studies should be undertaken at 10 to 14 days
after symptom onset due to the time for Wallerian degeneration of sensory and motor nerve
fibers; however, there have been many studies that reveal that early, nonspecific findings may be
helpful in diagnosing GBS as early as 3 to 7 days after symptom onset.[37][38] 
The more common early electrodiagnostic findings in GBS include absent or prolonged H-
reflexes and/or F-wave latencies.[39][38] The sural sparing pattern is considered specific for
GBS as compared to other polyneuropathies.[40] This pattern would show an intact sural sensory
response with abnormal upper extremity sensory responses. Other findings would depend on the
variant of GBS. Acute inflammatory demyelinating polyneuropathy would be more likely to
have partial motor conduction block, temporal dispersion, slow conduction velocities,
prolonged/absent F-wave latencies, and prolonged distal latencies.[41][31] AMAN would
usually show a pattern of low, compound muscle action potential amplitudes or even inexcitable
motor nerves; however, partial motor conduction block or complete conduction block can be
seen in AMAN nerve conduction study (NCS). This phenomenon is explained by “reversible
conduction failure.”[42] Complement is deposited in nodes of Ranvier and paranodal regions on
peripheral nerves. Subsequently, the nerves can undergo Wallerian degeneration leading to
significant and prolonged axonal damage or can reverse, deemed conduction failure.[43]
[22] This phenomenon explains the relatively rapid recovery of some severely weak patients
with AMAN. Sensory nerves would be spared both clinically and electrodiagnostically in
AMAN. Acute motor and sensory axonal neuropathy (AMSAN) would show low amplitude
motor and sensory potentials. Miller Fisher syndrome is more often described with reduced or
absent sensory nerve action potentials.[44] 
Cerebrospinal fluid (CSF) shows a classic pattern of albuminocytologic dissociation. This term
means that spinal fluid shows a normal amount of white blood cells and an elevated CSF protein
level.[4][26] However, this pattern is only present in 80% of patients at 2 weeks following
symptom onset. Therefore, the absence of this classic finding does not exclude the diagnosis. If
the white blood cell count is elevated, this should prompt consideration of other infectious GBS
mimics, such as HIV seroconversion.[6] 
A number of ganglioside antibodies have been associated with GBS. Antibodies include anti-
GM1, anti-GD1A, anti-GT1A, and anti-GQ1B. These range in sensitivity from up to 60% (anti-
GM1 antibodies in acute motor axonal neuropathy) to up to more than 90% (anti-GQ1B
antibodies in Miller Fisher syndrome). However, these laboratory studies usually require
some time to obtain results and, therefore, may not be as helpful in decision making at the time
of patient admission.[45][46][47]
Imaging studies such as magnetic resonance imaging (MRI) spine may show enhancement of the
nerve roots, indicating a breakdown of the blood-nerve barrier due to inflammation in GBS.
However, MRI utility in GBS is most useful to rule out other etiologies of quadriparesis or facial
diplegia such as transverse myelitis or intracranial disease.[48][49]
A negative inspiratory force (NIF) should be performed on patients with suspected GBS.  Serial
NIFs should be followed in patients with a high risk of respiratory compromise.  Patients that are
unable to perform a NIF of -20 to -30 cm H2O should be considered at very high risk.  
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Treatment / Management
In randomized controlled trials, there are two treatment options currently considered the standard
of care in Guillain-Barre syndrome (GBS). These include either intravenous immunoglobulin
(IVIG) or plasma exchange. IVIG is thought to act by its immune-modulating action; however,
the exact mechanism remains to be elucidated. IVIG is given 2 grams/kilogram divided over 5
days. (Evidence level I)[50]) Plasma exchange is thought to act by removing pathogenic
antibodies, humoral mediators, and complement proteins involved in the pathogenesis of GBS.
Similar to IVIG, its exact mechanism of action in the treatment of GBS has not been proven.
Plasma exchange is generally given as a volume of exchange over five sessions. Plasma
exchange and IVIG have been shown to be equally efficacious. (Evidence level I)[51] The effect
is present if either treatment is given within 4 weeks, but the stronger effect may be present if
treatment is administered within two weeks. (Evidence level II)[52][53][54][52] Surprisingly,
corticosteroids (both oral prednisone and intravenous methylprednisolone) have not shown
benefit over placebo or in combination with IVIG and plasma exchange over either modality
alone. Overall, treatment is generally considered to shorten the course of recovery of GBS.
Treated patients in one study achieved independent ambulation 32 days faster than untreated
patients. (Evidence level I)[55][56][53][51][57][58]
 Overall, most patients with GBS do well, with up to 85% of patients achieving independent
ambulation with recovery; however, there is a significant proportion of patients (20%) with
morbidity. (Evidence level III) Further studies of plasma exchange followed by IVIG and IVIG
concurrent with steroids have not shown significant improvement. (Evidence level I)[59][60] An
ongoing trial of 2 courses of IVIG should have results within the next year. (Evidence level
III) [61] There are also ongoing trials of complement inhibitors in patients with refractory GBS.
(Evidence level II)[62][63][64]
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Differential Diagnosis
Following the eradication of poliovirus, Guillain-Barre syndrome (GBS) is the most common
cause of acute or subacute, flaccid neuromuscular weakness worldwide; however, other disorders
may mimic GBS. If the flaccid weakness occurs in a critically ill patient with multiorgan
involvement, critical illness neuropathy and myopathy should be considered. Other etiologies
that may mimic GBS include tick paralysis. There would be an initial presentation of
neuromuscular junction disorder, acute intermittent porphyria, HIV infection, spinal cord
disorders, toxic neuropathies and even infections (such as West Nile virus or rabies). Some
atypical clinical features should lead providers to consider other diagnoses. These include early
bowel and bladder involvement, asymmetric features, and hyperreflexia or normal reflexes.
Distinguishing GBS from its mimics would require a thoughtful evaluation of history, clinical
presentation, and ancillary data. Regarding the clinical presentation, the presence of dilated
pupils may be more suggestive of tick paralysis or botulism. Ancillary testing such as
electromyography and nerve conduction studies may distinguish GBS from critical illness
neuropathy/myopathy along with history and clinical context. Cerebrospinal fluid testing
showing pleocytosis rather than the classic albuminocytologic dissociation may lead to further
consideration of infectious etiologies such as HIV or West Nile Virus infection.
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Prognosis
After the acute phase of illness, Guillain-Barre syndrome (GBS) patients tend to do well. More
than 80% achieve independent ambulation after 6 months.[30] Mortality during the acute phase
of the illness is less than 5%.[65] However, there is a subset of patients, less than 20%, who
continue to have significant disability despite receiving the standard of care for GBS. Studies are
underway to try to identify these patients early. Early identification of poor prognostic factors
could lead to trials of further treatment specific to this subgroup. In a cohort of Dutch patients, a
prognostic tool, Erasmus GBS Outcome score, utilizes the patient’s physical examination, age,
and presence of diarrhea to predict the patient’s ability to walk in the near future.[66] Patients
with a significant likelihood of residual disability would be most amenable to further therapeutic
trials.
Studies to assess whether plasma exchange followed by IVIG would have an additional benefit
were not significant.[60] Additionally, a number of studies regarding the addition of
corticosteroids to IVIG were also not significant; however, there may have been a benefit in
patients with worse prognostic factors (such as age and GBS disability score).[59] According to
a small case series, two courses of IVIG has been suggested as a possible intervention.[67] There
may be some limitations of IVIG use based on adverse effects, however.[68] Currently, there is
an ongoing randomized controlled trial of 2 courses of IVIG with patients with refractory GBS.
[61] Additionally, there is much interest in the key role of complement activation in the
pathogenesis of GBS; therefore, a randomized controlled trial of eculizumab in patients with
GBS is being studied.[63]
Other clinical features have been shown to predict the need for ventilation during the illness.
These include fulminant course (onset to admission < 7 days), bulbar weakness, and neck flexion
weakness. These predictive factors would suggest triage to an intensive care unit rather than a
stepdown unit.[69]
Following recovery, patients may continue to contend with residual fatigue, pain, and
paresthesias for up to several years. (Evidence level III)[70][71]
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Complications
The most feared complications are respiratory compromise and bulbar palsies.
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Consultations
 Neurology
 Pulmonology/Intensive Care
 +/- Infectious Disease
 +/- Immunology
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Enhancing Healthcare Team Outcomes

The care of the patient with Guillain-Barre syndrome (GBS) requires all members of the
healthcare team. Nurses are integral in recognizing and preventing complications, including
decubitus ulcers, dysautonomia, and infection prevention. Pharmacists should be well-versed in
the adverse effects that may occur with the administration of treatments for GBS, such as IVIG.
Respiratory therapists can assist with preventing atelectasis and aspiration pneumonia. Physical
and occupational therapists are crucial as the patient begins to regain function and strength.
Following recovery, patients often may find it helpful to enlist in support groups available
through the GBS foundation.
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