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Guillain-Barré syndrome in adults: Clinical features and diagnosis

Author: Francine J Vriesendorp, MD

Section Editors: Jeremy M Shefner, MD, PhD, Ira N Targoff, MD
Deputy Editor: April F Eichler, MD, MPH

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: May 2018. | This topic last updated: Aug 21, 2017.

INTRODUCTION — The acute immune-mediated polyneuropathies are classified under the eponym Guillain-Barré
syndrome (GBS), after the authors of early descriptions of the disease. GBS is a heterogeneous condition with several
variant forms. Most often, GBS presents as an acute, monophasic paralyzing illness provoked by a preceding
infection.

The clinical features and diagnosis of GBS in adults will be reviewed here. Other aspects of GBS are discussed
separately. (See "Guillain-Barré syndrome in adults: Treatment and prognosis" and "Guillain-Barré syndrome in
children: Epidemiology, clinical features, and diagnosis" and "Guillain-Barré syndrome in children: Treatment and
prognosis".)

PATHOGENESIS — The pathogenesis of Guillain-Barré syndrome (GBS) is reviewed here briefly and discussed in detail
elsewhere. (See "Guillain-Barré syndrome: Pathogenesis".)

GBS is thought to result from an immune response to a preceding infection that cross-reacts with peripheral nerve
components because of molecular mimicry. The immune response can be directed towards the myelin or the axon of
peripheral nerve, resulting in demyelinating and axonal forms of GBS. (See "Guillain-Barré syndrome: Pathogenesis",
section on 'Mechanisms'.)

Campylobacter jejuni infection is the most commonly identified precipitant of GBS. Cytomegalovirus, Epstein-Barr
virus, human immunodeficiency virus (HIV), and Zika virus have also been associated with GBS. (See "Guillain-Barré
syndrome: Pathogenesis", section on 'Antecedent events'.)

A small percentage of patients develop GBS after another triggering event such as immunization, surgery, trauma, and
bone-marrow transplantation. (See "Guillain-Barré syndrome: Pathogenesis", section on 'Other triggering events' and
"Guillain-Barré syndrome: Pathogenesis", section on 'Vaccination'.)

EPIDEMIOLOGY — Guillain-Barré syndrome (GBS) occurs world-wide with an overall incidence of 1 to 2 cases per
100,000 per year [1,2]. While all age groups are affected, the incidence increases by approximately 20 percent with
every 10-year increase in age beyond the first decade of life. In addition, the incidence is slightly greater in males than
in females.

CLINICAL FEATURES — The cardinal clinical features of Guillain-Barré syndrome (GBS) are progressive, fairly
symmetric muscle weakness accompanied by absent or depressed deep tendon reflexes. Patients usually present a
few days to a week after onset of symptoms. The weakness can vary from mild difficulty with walking to nearly
complete paralysis of all extremity, facial, respiratory, and bulbar muscles.

Studies from the United States and Europe, reflecting primarily patients with acute inflammatory demyelinating
polyneuropathy (AIDP), show that GBS is associated with the following clinical features [3,4]:
 ● The weakness usually starts in the legs, but it begins in the arms or facial muscles in about 10 percent of
patients.

● Severe respiratory muscle weakness necessitating ventilatory support develops in 10 to 30 percent [5].

● Facial nerve palsies occur in more than 50 percent, and oropharyngeal weakness eventually occurs in 50 percent.

● Oculomotor weakness occurs in about 15 percent of patients.

● Decreased or absent reflexes in affected arms or legs are found in approximately 90 percent of patients at
presentation and in all patients with disease progression [4].

● Paresthesias in the hands and feet accompany the weakness in more than 80 percent of patients, but sensory
abnormalities on examination are frequently mild.

● Pain due to nerve root inflammation, typically located in the back and extremities, can be a presenting feature
and is reported during the acute phase by two-thirds of patients with all forms of GBS [6,7].

● Dysautonomia occurs in approximately 70 percent of patients [8]. In a study of data from the US Nationwide
Inpatient Sample during 2010-2011, manifestations of autonomic dysfunction that were more common in
patients with GBS (n = 2587) compared with controls (10,348) included diarrhea/constipation (16 versus 5
percent), hyponatremia (15 versus 7 percent), bradycardia (5 versus 3 percent), urinary retention (4 versus 2
percent), tachycardia (3 versus 1 percent), reversible cardiomyopathy (1 versus 0 percent), and Horner syndrome
(1 versus 0 percent) [9]. Severe autonomic dysfunction is important to recognize since this is occasionally
associated with sudden death [10].

● The syndrome of inappropriate antidiuretic hormone secretion (SIADH), which may be due to autonomic
involvement, is another complication of GBS [9,11,12]. In the US Nationwide Inpatient Sample data, SIADH was
significantly more frequent in hospitalized patients with GBS compared with controls (5 versus <1 percent) [9].

Unusual features of GBS include papilledema, facial myokymia, hearing loss, meningeal signs, vocal cord paralysis,
and mental status changes [13]. In addition, posterior reversible encephalopathy syndrome, also known as reversible
posterior leukoencephalopathy syndrome (see "Reversible posterior leukoencephalopathy syndrome"), has been
associated with GBS in adults and children, likely related to acute hypertension from dysautonomia [14-16].

GBS usually progresses over a period of about two weeks. By four weeks after the initial symptoms, >90 percent of
GBS patients have reached the nadir of the disease [4]. Disease progression for more than eight weeks is consistent
with the diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). (See "Guillain-Barré
syndrome in adults: Treatment and prognosis", section on 'Clinical course and prognosis' and 'Chronic inflammatory
demyelinating polyneuropathy' below.)

Laboratory features — The typical finding with lumbar puncture in patients with GBS is an elevated cerebrospinal fluid
(CSF) protein with a normal white blood cell count. This finding, called albuminocytologic dissociation, is present in
up to 66 percent of patients with GBS at one week after onset of symptoms. (See 'Cerebrospinal fluid analysis' below.)

Electrodiagnostic studies (ie, electromyography and nerve conduction studies) may show evidence of an acute
polyneuropathy with predominantly demyelinating features in acute inflammatory demyelinating
polyradiculoneuropathy (AIDP), or predominantly axonal features in acute motor axonal neuropathy (AMAN) and
acute sensorimotor axonal neuropathy (AMSAN).

Glycolipid antibodies may be associated with different forms or aspects of GBS (see "Guillain-Barré syndrome:
Pathogenesis", section on 'Molecular mimicry'). However, aside from the GQ1b antibody associated with the Miller
Fisher variant of GBS, antibody testing has little or no role in the diagnosis of the more common GBS variants.

Laboratory testing for patients with GBS is discussed below. (See 'Diagnostic evaluation' below.)
GBS VARIANTS — Historically, the Guillain-Barré syndrome (GBS) was considered a single disorder. It now is
recognized as a heterogeneous syndrome with several variant forms. Each form of GBS has distinguishing clinical,
pathophysiologic, and pathologic features.

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) is the most common form in the United States and
Europe, representing approximately 85 to 90 percent of cases. The clinical variant Miller Fisher syndrome (MFS),
characterized by ophthalmoplegia, ataxia, and areflexia, occurs in 5 percent of cases in the United States and 25
percent of cases in Japan [17].

Acute motor axonal neuropathy (AMAN) and acute sensorimotor axonal neuropathy (AMSAN) are primary axonal
forms of GBS. These forms are frequently observed in China, Japan, and Mexico, but they also comprise an estimated
5 to 10 percent of GBS cases in the United States [18].

Other, less frequent, clinical variants are recognized and listed below. (See 'Other variants' below.)

Acute inflammatory demyelinating polyneuropathy — As noted above, AIDP is the most common form in the United
States and Europe, representing approximately 85 to 90 percent of cases. The typical clinical features are a
progressive, fairly symmetric muscle weakness accompanied by absent or depressed deep tendon reflexes. (See
'Clinical features' above.)

Peripheral nerve myelin is the target of immune attack in AIDP. The immunologic basis of peripheral nerve
demyelination in AIDP is discussed separately. (See "Guillain-Barré syndrome: Pathogenesis", section on
'Mechanisms'.)

Inflammatory demyelination is thought to start at the level of the nerve roots, leading to electrophysiologic conduction
slowing and conduction blocks with resultant muscle weakness and back pain. Multifocal, patchy, widespread
peripheral nerve demyelination follows, causing increasing paralysis. Peripheral nerve remyelination occurs relatively
rapidly over several weeks to months. However, in a small percentage of patients, there is superimposed significant
axonal degeneration with markedly delayed and incomplete recovery.

The earliest abnormalities seen on electrodiagnostic studies in patients with AIDP are prolonged or absent F waves
and absent H reflexes, reflecting demyelination at the level of the nerve roots [19,20]. Increased distal latencies and
conduction blocks with temporal dispersion of motor responses follow [21,22]. Significant slowing of nerve
conduction velocities is usually not seen until the third or fourth week [22]. Sensory nerve conduction studies (NCS)
reveal absent responses or slowed conduction velocities. In the first days after the onset of weakness, some patients
with AIDP have a sural sparing pattern in which the sural nerve sensory response is normal, while median and ulnar
nerve sensory responses are affected [20,23,24]. Sural sparing has a low to moderate sensitivity and a high specificity
for AIDP compared with a diagnosis other than GBS.

Needle electromyography (EMG) of weak muscles shows reduced recruitment. Ancillary studies, such as facial NCS
and blink reflexes, are occasionally helpful.

A small percentage of AIDP patients develop severe secondary axonal degeneration, and electrodiagnostic studies in
these patients at three to four weeks after GBS onset show loss of motor and sensory responses on NCS with
extensive denervation on needle examination.

Acute motor axonal neuropathy — An acute axonal form of GBS, now known as AMAN, was first recognized in 1986
[25]. Most cases are preceded by Campylobacter jejuni infection. AMAN occurs frequently in Japan and China,
particularly in young people [26,27]. AMAN has a seasonal incidence, being more frequent in the summer.

Deep tendon reflexes are occasionally preserved in patients with AMAN [28]. Sensory nerves are not affected. It
progresses more rapidly, but the overall prognosis is not worse than AIDP [29]. The presenting clinical features and
recovery of AMAN are otherwise similar to those of AIDP.
This disorder is distinguished from AIDP by its selective involvement of motor nerves and by an electrophysiologic
pattern of axonal involvement. In AMAN, distal motor amplitudes are low initially but may increase rapidly with
recovery of function; these findings may reflect reversible conduction failure, possibly at the motor nerve terminal or
node of Ranvier [30-32]. There is no sensory nerve involvement and no peripheral nerve demyelination. F waves may
be absent but are not significantly prolonged. There is no significant slowing of conduction velocities or increase in
distal latencies. There is no temporal dispersion.

The development of AMAN and AMSAN has been associated with antibodies to the gangliosides GM1, GD1a, GalNac-
GD1a, and GD1b that are present in peripheral nerve axons. These anti-ganglioside antibodies can be induced by
Campylobacter jejuni infection. The pathophysiology is that of antibody and complement mediated axonal nerve
damage without significant axonal degeneration. (See "Guillain-Barré syndrome: Pathogenesis", section on
'Mechanisms'.)

Acute motor and sensory axonal neuropathy — AMSAN is a more severe form of AMAN, in which both sensory and
motor fibers are affected with marked axonal degeneration, causing delayed and incomplete recovery [33]. Clinically,
AMSAN resembles the AMAN variant but has more sensory symptoms. The pathology is predominantly axonal
lesions of both motor and sensory nerve fibers.

In AMSAN, motor and sensory responses are frequently severely reduced or absent on electrodiagnostic studies.
Axonal degeneration in these patients is demonstrated by extensive denervation on follow-up electromyography
studies.

Miller Fisher syndrome — The typical presentation of MFS is that of ophthalmoplegia with ataxia and areflexia
[17,34]. About one-quarter of patients who present with MFS will develop some extremity weakness, clearly linking
this disorder to GBS. Incomplete forms include acute ophthalmoplegia without ataxia, and acute ataxic neuropathy
without ophthalmoplegia [1,35]. Some patients with MFS develop fixed, dilated pupils [36].

Antibodies against GQ1b (a ganglioside component of nerve) are present in 85 to 90 percent of patients with MFS
[37,38]. The GQ1b antibody is strongly associated with involvement of oculomotor nerves and is also found in most
patients with prominent oculomotor weakness and GBS.

Electrodiagnostic studies in patients with MFS reveal reduced or absent sensory responses without slowing of
sensory conduction velocities [39]. When there is associated weakness, the motor nerve conduction abnormalities of
AIDP may be present.

Only a few pathological studies of MFS are available. Two case reports of MFS showed extra-axial oculomotor nerve
demyelination [40].

Bickerstaff encephalitis — Bickerstaff encephalitis is a brainstem encephalitis characterized by encephalopathy and

hyperreflexia with features of Miller Fisher syndrome (MFS) such as ophthalmoplegia and ataxia. It is not only
clinically linked to MFS, but is associated with anti-GQ1b antibodies and can respond to intravenous immune globulin
(IVIG) and plasma exchange [41,42]. Some experts consider MFS, Bickerstaff encephalitis, and pharyngeal-cervical-
brachial weakness with anti-GQ1b antibodies to be overlapping expressions of the anti-GQ1b antibody syndrome [43].

Pharyngeal-cervical-brachial weakness — The pharyngeal-cervical-brachial variant of GBS is characterized by acute

weakness of the oropharyngeal, neck, and shoulder muscles with swallowing dysfunction [44,45]. Facial weakness
may be present as well. Leg strength and leg reflexes are usually preserved. This form may overlap with Miller Fisher
syndrome [45,46]. It is thought to represent a localized form of axonal GBS [1,44,45]. Some patients with pharyngeal-
cervical-brachial weakness have IgG autoantibodies to GT1a, GQ1b, or less often to GD1a.

Paraparesis — The paraparetic variant is a relatively mild type of GBS characterized by weakness limited to the lower
limbs at presentation [44,47]. A minority experience some arm weakness over the course of the illness. However,
most patients with this variant have reduced or absent arm reflexes and approximately 90 percent have abnormalities
in the upper extremities on electrodiagnostic studies.
Other variants — There are a number of additional uncommon variants of GBS, including the following:

● Acute pandysautonomia, which may respond to intravenous immune globulin [48,49]. Symptoms include
diarrhea, vomiting, dizziness, abdominal pain, ileus, orthostatic hypotension, urinary retention, pupillary
abnormalities, an invariant heart rate, and decreased sweating, salivation, and lacrimation. Reflexes are absent or
diminished and sensory symptoms may be present.

● Pure sensory GBS, with involvement of large sensory fibers leading to significant sensory ataxia [50]. Reflexes are
absent and there may be minor motor involvement. An association with antibodies to GD1b has been noted [50].

● Facial diplegia and distal limb paresthesia [46,51,52]. This is considered a variant of acute inflammatory
demyelinating polyneuropathy [1].

● Acute bulbar palsy with areflexia, ophthalmoplegia, ataxia, and facial palsy; neck and limb weakness are absent
[53]. This form overlaps with both the Miller Fisher syndrome and the pharyngeal-cervical-brachial variant of GBS.

● Sixth nerve palsy and distal paresthesia [46].

DIAGNOSTIC EVALUATION — The initial diagnosis of Guillain-Barré syndrome (GBS) is based upon the clinical
presentation. The cardinal clinical features of GBS are progressive, mostly symmetric muscle weakness and absent
or depressed deep tendon reflexes. The weakness can vary from mild difficulty with walking to nearly complete
paralysis of all extremity, facial, respiratory, and bulbar muscles. (See 'Clinical features' above.)

The clinical diagnosis of GBS is supported if cerebrospinal fluid (CSF) and electrodiagnostic studies show typical
abnormalities [54]. Therefore, lumbar puncture and electrodiagnostic studies are performed in all patients with
suspected GBS. These tests are also helpful in excluding an alternative diagnosis. Examination of the CSF is
especially important to exclude causes of weakness that are associated with a CSF pleocytosis [55].

Cerebrospinal fluid analysis — In patients with GBS, lumbar puncture often reveals an elevated CSF protein with a
normal CSF white blood cell count. This finding, known as albuminocytologic dissociation, is present in 50 to 66
percent of patients with GBS in the first week after the onset of symptoms and ≥75 percent of patients in the third
week [1,13,56]. The elevated protein may be due to increased permeability of the blood-nerve-barrier at the level of the
proximal nerve roots. A normal CSF protein is found in one-third to one-half of patients when tested earlier than one
week after symptom onset and therefore does not exclude the diagnosis of GBS [4]. Furthermore, a mild increase in
CSF count occurs in some patients with GBS.

● In the Massachusetts General Hospital (MGH) prospective series of 110 patients with GBS, initial CSF protein
elevations varied from 45 to 200 mg/dL (0.45 to 2.0 g/L) in 73 percent of patients, but protein elevations as high
as 1000 mg/dL (10 g/L) have been described [13].

● The CSF cell count is typically normal, ie, <5 cells/mm3. However, a minority of patients with GBS have mildly
elevated CSF cell counts. In a review of 494 adult patients with GBS, a mild CSF pleocytosis of 5 to 50 cells/mm3
was present in 15 percent, and none had a pleocytosis >50 cells/mm3 [4]. In the earlier MGH series, the cell count
was <5 cells/mm3 in 87 percent of patients, 5 to 10 cells/mm3 in 9 percent, and 11 to 30 cells/mm3 and >30
cells/mm3 in 2 and 2 percent of patients, respectively [13].

● A CSF pleocytosis is common in patients who have GBS and concurrent human immunodeficiency virus (HIV)
infection [57].

Electrodiagnostic studies — Nerve conduction studies (NCS) and needle electromyography (EMG) are valuable for
confirming the diagnosis of GBS and for providing some information regarding prognosis. In addition,
electrodiagnostic studies are useful in classifying the main variants of GBS as demyelinating (eg, acute inflammatory
demyelinating polyneuropathy) or axonal (eg, acute motor axonal neuropathy) [54]:
 ● Demyelinating forms of GBS are supported by features of demyelination, including decreased motor nerve
conduction velocity, prolonged distal motor latency, increased F wave latency, conduction blocks, and temporal
dispersion [58].

● Axonal forms of GBS are supported by decreased distal motor and/or sensory amplitudes [58]. Transient motor
nerve conduction block (ie, reversible conduction failure) can be present [32].

Since the nerve conduction abnormalities progress over time, serial electrodiagnostic studies are frequently helpful
[59]. Findings can be normal early in the course of GBS, and are typically most pronounced approximately two weeks
after the onset of weakness [58].

Electrodiagnostic findings in patients with specific GBS variants are also discussed above. (See 'GBS variants' above.)

Antibodies — In clinical practice, commercially available testing for serum IgG antibodies to GQ1b is useful for the
diagnosis of Miller Fisher syndrome (see 'Miller Fisher syndrome' above), having a sensitivity of 85 to 90 percent.
Antibodies to GQ1b may also be present in GBS with ophthalmoparesis, Bickerstaff encephalitis, and the pharyngeal-
cervical brachial GBS variant (see 'GBS variants' above), but not in disorders other than GBS [37,38].

MRI — Spinal MRI (image 1) may reveal thickening and enhancement of the intrathecal spinal nerve roots and cauda
equina [60-63]. The anterior spinal nerve roots only may be involved, or both the anterior and posterior spinal nerve
roots can be involved. In exceptional cases of Miller Fisher syndrome, abnormalities of the spinal cord posterior
columns have been described [61]. In the brain (image 1), enhancement of the oculomotor, abducens, and facial
nerves may be seen [62-64].

Laboratory testing for antibodies to glycolipids other than GQ1b is not performed routinely because of limited clinical
utility.

Diagnostic criteria — Diagnostic criteria for GBS, originally proposed in 1978 from the National Institute of
Neurological Disorders and Stroke (NINDS) [65] have an important role in research and are widely used in clinical
practice. These criteria are based on expert consensus and have been modified over time to reflect advances in the
understanding of GBS [54,66].

Required features include:

● Progressive weakness of the legs and arms (sometimes initially only in the legs), ranging from minimal weakness
of the legs to total paralysis of all four limbs, the trunk, bulbar and facial muscles, and external ophthalmoplegia

● Areflexia or decreased reflexes in weak limbs.

Supportive features include:

● Progression of symptoms over days to four weeks (80 percent reach nadir in two weeks)

● Relative symmetry

● Mild sensory symptoms or signs

● Cranial nerve involvement, especially bilateral facial nerve weakness

● Recovery starting two to four weeks after progression halts

● Autonomic dysfunction

● Pain

● No fever at the onset

 ● Elevated protein in CSF with a cell count ≤50/mm3 (usually <5 cells/mm3)

● Electrodiagnostic abnormalities consistent with GBS

The following features make the diagnosis of GBS doubtful:

● Sensory level (decrement or loss of sensation below a spinal cord root level as determined by neurologic
examination)

● Marked, persistent asymmetry of weakness

● Bowel and bladder dysfunction at onset

● Severe and persistent bowel and bladder dysfunction

● Severe pulmonary dysfunction with little or no limb weakness at onset

● Severe sensory signs with little or no weakness at onset

● Fever at onset

● CSF pleocytosis with a white cell count >50/mm3

Versions of these diagnostic criteria have been used for years in research studies and are applicable to about 80 or
90 percent of patients with GBS in North America and Europe, particularly those with the AIDP form. Patients with
GBS who do not meet the required criteria will typically have one of the other GBS variants such as AMAN, in which
reflexes can be retained, MFS, or a regional variant (see 'GBS variants' above). In support of this observation, an
epidemiologic study in Italy found that 84 percent of patients with GBS fulfilled the NINDS criteria and 16 percent had
a variant syndrome [67].

The World Health Organization recommends use of the Brighton criteria (table 1) for the case definition of GBS in
regions affected by Zika virus transmission [68]. The Brighton criteria are developed for research studies and exclude
most clinical variants of GBS. (See "Zika virus infection: An overview".)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of Guillain-Barré syndrome (GBS) includes other acute
polyneuropathies, chronic inflammatory demyelinating polyneuropathy, and diseases of the spinal cord,
neuromuscular junction, and muscle (table 2).

Chronic inflammatory demyelinating polyneuropathy — There is a temporal continuum between acute inflammatory

demyelinating polyneuropathy (AIDP), the demyelinating form of GBS, and chronic inflammatory demyelinating
polyneuropathy (CIDP).

● AIDP is a monophasic subacute illness that reaches its nadir within three to four weeks (see 'Acute inflammatory
demyelinating polyneuropathy' above)

● CIDP continues to progress or has relapses for greater than eight weeks (see "Chronic inflammatory
demyelinating polyneuropathy: Etiology, clinical features, and diagnosis")

● Subacute inflammatory demyelinating polyneuropathy (SIDP) is the term used by some authors for disease that
reaches its nadir between four and eight weeks

This arbitrary temporal delineation of inflammatory demyelinating polyneuropathy can occasionally be difficult to
ascertain in practice. Only observation of the patient over time can clarify whether the clinical course is that of AIDP
or CIDP.

In addition to chronicity, other features may be useful to distinguish GBS (including AIDP) from CIDP:
 ● While the onset of GBS is usually easily identified, the precise onset of CIDP is typically less clear

● Antecedent events are more frequent with GBS (where they occur in approximately 70 percent of cases) than
with CIDP (where they are found in ≤30 percent of cases) (see "Guillain-Barré syndrome: Pathogenesis", section
on 'Antecedent events')

● Certain features are more consistent with an increased likelihood of CIDP in the first weeks after onset of
symptoms, including three or more episodes of clinical deterioration, a mild disease course with retained ability
to walk independently, lack of cranial neuropathies, and less frequent respiratory involvement [69]

About 2 to 5 percent of patients initially diagnosed with AIDP will develop the chronic relapsing weakness of CIDP.
(See "Guillain-Barré syndrome in adults: Treatment and prognosis", section on 'Relapses'.)

Other polyneuropathies — Acute polyneuropathies that may mimic GBS include those due to acute severe vitamin B1
(thiamine) deficiency, acute arsenic poisoning, n-hexane (in glue sniffing neuropathy), vasculitis, Lyme disease, tick
paralysis (mostly in children), porphyria, sarcoidosis, leptomeningeal disease, paraneoplastic disease, and critical
illness.

The combination of data from the clinical setting, appropriate screening laboratory tests (including thiamine level,
rheumatologic testing, Lyme titer, spot urine for porphyria), as well as electromyography with nerve conduction
studies and cerebrospinal fluid analysis, are usually sufficient to rule out these other causes of polyneuropathy. A spot
urine test for porphobilinogen in a sample obtained at the time of symptoms will identify the majority of patients with
acute porphyria. (See "Acute intermittent porphyria: Pathogenesis, clinical features, and diagnosis".)

Peripheral nerve vasculitis is a potentially life-threatening illness that can be difficult to diagnose. The pattern is that
of a mononeuritis multiplex involving sensory and motor fibers in the distribution of individual peripheral nerves.
Although the pathology of the disease is asymmetric, the clinical picture can mimic GBS with fairly symmetric
ascending weakness when the vasculitis is rapidly progressive with confluent nerve involvement. (See "Clinical
manifestations of vasculitic neuropathy".)

Severe pain is present in the majority of patients with peripheral nerve vasculitis. The most frequently associated
conditions include polyarteritis nodosa, rheumatoid arthritis, eosinophilic granulomatosis with polyangiitis (Churg-
Strauss), and connective tissue disorder not otherwise specified. Systemic features of weight loss and fever as well
as other organ involvement may be present [70]. Serological testing, detailed clinical electrophysiologic testing, and
biopsy of nerve and muscle lead to the diagnosis.

Spinal cord disorders — Acute myelopathies due to spinal cord compression or acute transverse myelitis can be
confused with GBS, since reflexes can be depressed in the acute stage of spinal cord disease. Early bowel and
bladder dysfunction and a sensory level point to a myelopathy. MRI is usually helpful in diagnosing acute myelopathy
by demonstrating a focal spinal cord lesion and distinguishing myelitis from GBS. (See "Transverse myelitis" and
"Disorders affecting the spinal cord".)

Motor neuron disorders may mimic GBS including poliomyelitis, West Nile virus myelitis, amyotrophic lateral sclerosis,
and progressive spinal muscular atrophy. (See "Polio and infectious diseases of the anterior horn" and "Clinical
manifestations and diagnosis of West Nile virus infection" and "Clinical features of amyotrophic lateral sclerosis and
other forms of motor neuron disease" and "Diagnosis of amyotrophic lateral sclerosis and other forms of motor
neuron disease" and "Spinal muscular atrophy".)

Severe low back pain in patients with GBS is common and frequently leads to imaging of the lumbar spine;
practitioners should be aware that prominent contrast enhancement of the nerve roots on MRI may occur in GBS [71].

Neuromuscular junction disorders — Diseases of the neuromuscular junction including botulism, myasthenia gravis,
and Lambert-Eaton myasthenic syndrome can all present with acute weakness, but sensory signs or symptoms are
lacking. Botulism is associated with large, unreactive pupils and constipation, though similar pupillary abnormalities
may occur in a subset of patients with Miller Fisher syndrome. Electromyography with repetitive nerve stimulation and
appropriate laboratory tests help clarify the diagnosis. (See "Diagnosis of myasthenia gravis" and "Lambert-Eaton
myasthenic syndrome: Clinical features and diagnosis" and "Botulism".)

Muscle disorders — Acute polymyositis, critical illness myopathy, and critical illness neuropathy can occasionally
mimic GBS. The myopathy and neuropathy of critical illness present as an acute paralysis, typically in patients
receiving intensive care. High-dose intravenous corticosteroids, neuromuscular blocking drugs, sepsis, and
multiorgan failure are thought to play an important role, but the pathophysiology is not well understood. (See
"Neuromuscular weakness related to critical illness".)

In critical illness neuropathy, clinical electrophysiological testing shows markedly reduced motor and sensory
responses with widespread active denervation. In critical illness myopathy, the sensory responses are spared.

Differential diagnosis of Miller Fisher syndrome — On initial presentation, Miller Fisher syndrome (MFS) may be
mistaken for a brainstem stroke (see 'Miller Fisher syndrome' above). However, the gradual onset of MFS in particular
distinguishes this syndrome clinically from an acute stroke. The differential diagnosis of MFS includes Wernicke
encephalopathy and brainstem encephalitis, but these are associated with altered mental status. In addition, patients
with Wernicke encephalopathy usually have nystagmus, a feature not associated with MFS. Neuroimaging studies
can be helpful to exclude stroke and to demonstrate the acute lesions of the diencephalon, midbrain, and
periventricular regions that are sometimes found in patients with Wernicke encephalopathy. (See "Wernicke
encephalopathy".)

Other entities to consider in the differential diagnosis of MFS are myasthenia gravis and other neuromuscular junction
disorders. Appropriate laboratory and electrodiagnostic testing with repetitive nerve stimulation helps differentiate
MFS from a neuromuscular junction disorder. (See "Clinical manifestations of myasthenia gravis" and "Diagnosis of
myasthenia gravis" and "Electrodiagnostic evaluation of the neuromuscular junction".)

The combination of absent or reduced sensory responses on electrodiagnostic testing [39] and elevated CSF protein
lead to the diagnosis of MFS. The diagnosis of MFS can be confirmed by positive anti-GQ1b antibody testing [37].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and
regions around the world are provided separately. (See "Society guideline links: Guillain-Barré syndrome".)

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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics
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● Basics topics (see "Patient education: Guillain-Barré syndrome (The Basics)")

SUMMARY AND RECOMMENDATIONS — The Guillain-Barré syndrome (GBS) is an acute monophasic illness causing
a rapidly progressive polyneuropathy with weakness or paralysis.

● The cardinal clinical features of GBS are progressive, mostly symmetric muscle weakness and absent or
depressed deep tendon reflexes. The weakness can vary from mild difficulty with walking to nearly complete
paralysis of all extremity, facial, respiratory, and bulbar muscles. Severe respiratory muscle weakness
 necessitating ventilatory support develops in about 30 percent, and dysautonomia occurs in 70 percent of
patients. GBS usually progresses over a period of about two weeks. (See 'Clinical features' above.)

● GBS is a heterogeneous syndrome with several variant forms. Acute inflammatory demyelinating polyneuropathy
(AIDP) is the most common variant of GBS in North America, Europe, and most of the developed world. The Miller
Fisher syndrome (MFS) is a GBS variant characterized by ophthalmoplegia with ataxia and areflexia. (See 'GBS
variants' above and 'Acute inflammatory demyelinating polyneuropathy' above and 'Miller Fisher syndrome'
above.)

● Axonal forms of GBS include acute motor axonal neuropathy (AMAN), most common in Japan and China, and
acute motor and sensory axonal neuropathy (AMSAN). (See 'Acute motor axonal neuropathy' above and 'Acute
motor and sensory axonal neuropathy' above.)

● The initial diagnosis of GBS is based upon the clinical presentation. The certainty of the diagnosis is supported if
cerebrospinal fluid (CSF) analysis and electrodiagnostic studies show abnormalities typical of GBS. Therefore,
these studies should be performed in all patients with suspected GBS. (See 'Diagnostic evaluation' above.)

● An increased CSF protein with a normal CSF white blood cell count (albuminocytologic dissociation) is found in
50 to 66 percent of patients with GBS in the first week after the onset of symptoms and in ≥75 percent of patients
in the third week. An alternative diagnosis, including human immunodeficiency virus, should be considered in
patients with a CSF cell count >50/mm3. (See 'Cerebrospinal fluid analysis' above.)

● Electrodiagnostic studies are very useful in confirming the diagnosis and in classifying the main variants of GBS,
which are demyelinating GBS (AIDP) and axonal GBS (AMAN). (See 'Electrodiagnostic studies' above and 'GBS
variants' above.)

● Testing for serum IgG antibodies to GQ1b is useful for the diagnosis of MFS. Testing for other glycolipid
antibodies has no clinical role. (See 'Antibodies' above.)

● The differential diagnosis of GBS includes other acute polyneuropathies, chronic inflammatory demyelinating
polyneuropathy, and diseases of the spinal cord, neuromuscular junction, and muscle. The differential diagnosis
of the MFS variant of GBS includes brainstem stroke, Wernicke encephalopathy, and brainstem encephalitis. (See
'Differential diagnosis' above and 'Differential diagnosis of Miller Fisher syndrome' above.)

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Topic 5137 Version 24.0

GRAPHICS

Magnetic resonance imaging of 51-year-old woman with Guillain-Barré syndrome

(A) Coronal brain T1 MRI with Gd images showing bilateral facial nerve enhancement (arrows).
(B) Sagittal lumbar spine T1 MRI with Gd showing enhancement in the medullary cone (arrow).
(C) Axial lumbar-spine T2 MRI showing increased signal intensity in the spinal ganglia bilaterally (arrowheads).
(D) Axial lumbar-spine T1 MRI (fast scanning) with Gd showing enhancement of the spinal ganglia (arrowheads) and cauda equina roots (dashed
arrows).

Gd: gadolinium contrast; MRI: magnetic resonance imaging.

From: Neuroradiology, Magnetic resonance imaging findings in Guillain-Barré syndrome caused by Zika virus infection, Vol. 58, 2016, p. 837, Fontes CA, Dos
Santos AA, Marchiori E, © Springer-Verlag Berlin Heidelberg 2016. With permission of Springer.

Graphic 114440 Version 1.0

Brighton criteria for case definition of Guillain-Barré syndrome

Level 1 of diagnostic certainty Level 2 of diagnostic certainty Level 3 of diagnostic certainty

Bilateral and flaccid weakness of the
limbs; AND
Decreased or absent deep tendon reflexes
in weak limbs; AND
Monophasic illness pattern; and interval
between onset and nadir of weakness
between 12 hours and 28 days; and
subsequent clinical plateau; AND
Absence of identified alternative diagnosis
for weakness; AND
Cytoalbuminologic dissociation (ie,
elevation of CSF protein level above
laboratory normal value and CSF total
white cell count <50 cells/microL; AND
Electrophysiologic findings consistent
with GBS
Bilateral and flaccid weakness of the
limbs; AND
Decreased or absent deep tendon reflexes
in weak limbs; AND
Monophasic illness pattern; and interval
between onset and nadir of weakness
between 12 hours and 28 days; and
subsequent clinical plateau; AND
Absence of identified alternative diagnosis
for weakness; AND
CSF total white cell count <50
cells/microL (with or without CSF protein
elevation above laboratory normal value);
OR electrophysiologic studies consistent
with GBS if CSF not collected or results
not available
Bilateral and flaccid weakness of the
limbs; AND
Decreased or absent deep tendon reflexes
in weak limbs; AND
Monophasic illness pattern; and interval
between onset and nadir of weakness
between 12 hours and 28 days; and
subsequent clinical plateau; AND
Absence of identified alternative diagnosis
for weakness

CSF: cerebrospinal fluid; GBS: Guillain-Barré syndrome.

Reproduced from: Sejvar JJ, Kohl KS, Gidudu J, et al. Guillain-Barré syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis,
and presentation of immunization safety data. Vaccine 2011; 29:599. Table used with the permission of Elsevier Inc. All rights reserved.

Graphic 107091 Version 2.0

Differential diagnosis of Guillain-Barré syndrome

Differential diagnosis
Cerebral

Acute disseminated encephalomyelitis (ADEM)

Bilateral strokes

Psychogenic symptoms

Cerebellar

Acute cerebellar ataxia syndrome

Posterior fossa structural lesion

Spinal

Anterior spinal artery syndrome

Compressive myelopathy

Neuromyelitis optica

Poliomyelitis

Transverse myelitis

Other infectious causes of acute myelitis (eg, West Nile virus, coxsackieviruses, echoviruses)

Peripheral nervous system

Acute onset chronic inflammatory demyelinating neuropathy (CIDP)

Critical illness polyneuropathy

Cytomegalovirus-related radiculitis

Diphtheria

HIV-related radiculitis

Leptomeningeal malignancy

Lyme disease

Metabolic and electrolyte disorders (eg, hypoglycemia, hypophosphatemia)

Porphyria

Thiamine deficiency (beriberi)

Tick paralysis

Toxic neuropathy

Vasculitis

Neuromuscular junction

Botulism

Myasthenia gravis

Neuromuscular blocking agents

Muscle disease

Acute inflammatory myopathies (eg, dermatomyositis, polymyositis)

Acute viral myositis

Acute rhabdomyolysis

Critical illness myopathy

Metabolic myopathies (eg, hypokalemic, hyperkalemic)

Mitochondrial myopathies

Periodic paralysis
Data from:
1. Evans OB. Guillain-Barré syndrome in children. Pediatr Rev 1986; 8:69.
2. Jones HR. Childhood Guillain-Barré syndrome: clinical presentation, diagnosis, and therapy. J Child Neurol 1996; 11:4.
3. Yuki N, Hartung HP. Guillain-Barré syndrome. N Engl J Med 2012; 366:2294.
4. Willison HJ, Jacobs BC, van Doorn PA. Guillain-Barré syndrome. Lancet 2016; 388:717.

Graphic 80040 Version 7.0