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 "Pathogenesis, clinical
manifestations, and diagnosis of acute intermittent porphyria".)

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].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education

materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces
are written in plain language, at the 5th to 6thgrade reading level, and they answer the
four or five key questions a patient might have about a given condition. These articles
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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 to your patients. (You can also locate patient
education articles on a variety of subjects by searching on "patient info" and the
keyword(s) of interest.)

●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
up 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.)

Treatmrnt and prognosis

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 an acute monophasic paralyzing illness usually
provoked by a preceding infection.

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

APPROACH TO INITIAL CARE — Supportive care for patients with Guillain-Barré

syndrome (GBS) is extremely important due to the associated risk of respiratory failure
and autonomic dysfunction with potentially severe cardiovascular involvement. Patients
in the progressive phase of GBS require close monitoring of respiratory and
cardiovascular function, often in the intensive care unit. (See 'Supportive care'below.)

Treatment with plasma exchange or intravenous immune globulin (IVIG) is indicated for
most patients with GBS because these treatments accelerate recovery. We
recommend treatment with plasma exchange or IVIG for nonambulatory adult patients
with GBS who are within four weeks of symptom onset. In addition, we suggest
treatment with plasma exchange or IVIG for ambulatory adult patients with GBS who
are not yet recovering within four weeks of symptom onset. The choice between
plasma exchange and IVIG is dependent on local availability and on patient preference,
risk factors, and contraindications. (See 'Disease-modifying treatment' below.)

SUPPORTIVE CARE — Supportive care is extremely important in Guillain-Barré

syndrome (GBS) since up to 30 percent of patients develop neuromuscular respiratory
failure requiring mechanical ventilation [1]. In addition, autonomic dysfunction may be
severe enough to require intensive care unit (ICU) monitoring [2]. Thus, many patients
with GBS are initially admitted to the ICU for close monitoring of respiratory, cardiac,
and hemodynamic function. Less severely affected patients can be managed in
intermediate care units, and mildly affected patients can be managed on the general
ward with telemetry, along with monitoring of blood pressure and vital capacity every
four hours.

Prophylaxis for deep vein thrombosis, bladder and bowel care, physical and
occupational therapy, and psychological support are essential. Low molecular weight
heparin and support stockings are recommended until patients are able to walk
independently [1]. Bedbound patients should have frequent repositioning to avoid
pressure ulcers. Adequate pain control is necessary. (See 'Pain control'below.)

Issues related to the respiratory management of patients with neuromuscular

weakness are also discussed separately. (See "Respiratory muscle weakness due to
neuromuscular disease: Clinical manifestations and evaluation".)

Respiratory failure — Vigilance is essential when caring for a patient with GBS, since
deterioration due to progression of muscle weakness can occur rapidly.

Respiratory failure in GBS is common, and 15 to 30 percent of patients need ventilatory

support. Thus, close respiratory monitoring with frequent measurement (eg, every four
hours) of vital capacity and negative inspiratory force (NIF) should be instituted initially
in all patients [1]. Bulbar dysfunction with swallowing problems and inability to clear
secretions may add to the need for ventilatory support.

Succinylcholine should be avoided when invasive airway management becomes

necessary. The techniques and medications for rapid sequence intubation in adults are
discussed separately. (See "Rapid sequence intubation for adults outside the operating
room".)

The following parameters warn of impending respiratory arrest and are an indication for
intubation [3]:

●Forced vital capacity <20 mL/kg

●Maximum inspiratory pressure <30 cmH2O
●Maximum expiratory pressure <40 cmH2O

Specific clinical findings and measurements on admission predict a high risk for
respiratory failure. In a French prospective study of 722 patients with GBS not
ventilated at admission, mechanical ventilation was needed in 313 (43 percent) [4]. The
following factors were identified as predictors of respiratory failure:

●Time of onset to admission less than seven days

●Inability to cough
●Inability to stand
●Inability to lift the elbows
●Inability to lift the head
●Liver enzyme increases

In patients with at least four of these six predictors, mechanical ventilation was required
in >85 percent.

In the subgroup of 196 patients whose vital capacity was measured on admission,
three factors predicted mechanical ventilation [4]:

●Time from onset to admission less than seven days

●Inability to lift the head
●Vital capacity <60 percent of normal predicted mechanical ventilation

In patients with all three of these predictors, mechanical ventilation was required in 85
percent.

Another report of 397 patients with GBS found that independent predictors of the need
for mechanical ventilation on admission were as follows [5]:

●Fewer days between onset of weakness and admission

●Presence of facial or bulbar weakness
●Severe muscle weakness

An online prognosis model (https://gbstools.erasmusmc.nl/prognosis-tool) uses these

parameters to estimate the risk of respiratory failure in the first week after admission
[5].

Weaning from mechanical ventilation should be guided by improvement in strength and

serial pulmonary function tests (PFTs) [1]. Tracheostomy should be performed after
two weeks if PFTs do not show any significant improvement from baseline, but can be
deferred for another week if PFTs do show improvement [1].

Autonomic dysfunction — Autonomic dysfunction is a well-recognized feature of

GBS and is a significant source of mortality [6]. Dysautonomia occurs in 70 percent of
patients and manifests as symptoms that include tachycardia (the most common),
urinary retention, hypertension alternating with hypotension, orthostatic hypotension,
bradycardia, other arrhythmias, ileus, and loss of sweating.

Severe autonomic disturbances occur in about 20 percent of patients, mostly (but not
always) in patients who develop severe weakness and respiratory failure.
Consequently, close monitoring of blood pressure, fluid status, and cardiac rhythm is
essential to the management of patients with GBS.

Cardiovascular management — Cardiovascular complications of GBS are an

important cause of morbidity. Common manifestations include paroxysmal fluctuations
in blood pressure, and tachy and bradyarrhythmias, while less frequent manifestations
include myocardial involvement ranging from myocarditis to heart failure [7]. Therefore,
we recommend cardiac rhythm and blood pressure monitoring for patients in the
progressive phase of GBS [1,8]. Monitoring should be instituted at time of admission
and continued until ventilatory support is no longer necessary or until recovery is
underway in patients not needing mechanical ventilation.

Practical tips for the management of patients with GBS include the following [9]:

●Quadriplegic patients should not be left unattended in the sitting position without
assessment of orthostatic hypotension
●Intravascular volume should be maintained, particularly during positive-pressure
ventilation
●Drugs with hypotensive side effects should be avoided if possible
●Arrhythmias frequently occur during suctioning
●Plasma exchange can cause hypotension and electrolyte disturbances

Blood pressure — Both paroxysmal hypertension and orthostatic hypotension are

frequent, occurring in 24 and 19 percent of patients with GBS, respectively, while
sustained hypertension occurs in 3 percent, as described in a series of 169 patients [9].

Intraarterial monitoring should be instituted in the presence of significant blood

pressure fluctuations. Hypotension can usually be treated with fluids, but low-
dose phenylephrine can be used if fluids are not effective. In the presence of
dysautonomia, only low doses of carefully titrated short-acting vasoactive agents
should be used for treatment of hypotension and hypertension because of the potential
to overshoot the target blood pressure in the setting of possible denervation
hypersensitivity [10].

Episodes of severe hypertension (mean arterial pressure >125 mmHg) can be treated
with labetalol, esmolol, or nitroprusside [9,10]. In cases of autonomic cardiovascular
dysfunction, other conditions must be excluded, such as pulmonary thromboembolism,
hypoxemia, sepsis, gastrointestinal bleeding, and fluid and electrolyte disturbances [2].

Arrhythmias — Sustained sinus tachycardia is the most common cardiac arrhythmia,

affecting 25 to 38 percent of patients with GBS, and usually requires no treatment
[7,10-12]. Bradyarrhythmias are also fairly common. Additional arrhythmias and
electrocardiogram (ECG) changes that have been reported with GBS include atrial
fibrillation, atrial flutter, paroxysmal tachycardia, ventricular tachycardia, elevated or
depressed ST segments, flat or inverted T waves, Q-T interval prolongation, axis
deviation, and various conduction blocks [2]. Causes of cardiovascular disease other
than GBS need to be excluded if these abnormalities are observed.
Serious or life-threatening cardiac arrhythmias, including atrioventricular block and
asystole, can occur with GBS and require intervention with administration
of atropine and cardiac pacing [7]

Bowel and bladder care — Additional autonomic problems associated with GBS
include adynamic ileus and urinary retention. Daily abdominal auscultation to monitor
for bowel silence and the development of adynamic ileus is recommended, as is
monitoring of opioid administration.

For treating ileus, erythromycin or neostigmine may be effective [1].

Pain control — Pain occurs in about two-thirds of patients during the course of GBS
and often requires treatment. (See "Guillain-Barré syndrome in adults: Clinical features
and diagnosis", section on 'Clinical features'.)

Gabapentin or carbamazepine may be used for intensive care unit pain control during
the acute phase of GBS [1,13]. Simple analgesics or nonsteroidal anti-inflammatory
drugs (NSAIDs) may be tried, but they often do not provide adequate pain relief.
Appropriate narcotic analgesics may be used but require careful monitoring for adverse
effects in the setting of autonomic denervation. Epidural morphine also can be useful
[10].

For the long-term management of neuropathic pain, tricyclic

antidepressants, gabapentin, carbamazepine, or pregabalin may be useful.

Rehabilitation — Acute-phase rehabilitation should include an individualized program

of gentle strengthening, involving isometric, isotonic, isokinetic, and manual resistive
and progressive resistive exercises [1]. Rehabilitation should emphasize proper limb
positioning, posture, and orthotics as well as nutrition. A device to help with
communication may be necessary.

After the acute phase, disabled patients should be treated by a multidisciplinary

rehabilitation team [14]. An exercise program may be beneficial for persistent fatigue
[1].

DISEASE-MODIFYING TREATMENT — The main modalities of therapy for Guillain-

Barré syndrome (GBS) are plasma exchange (also called plasmapheresis) and
administration of intravenous immune globulin (IVIG). These treatments hasten
recovery from GBS, as shown in randomized controlled trials. Patients recover sooner
when treated early. The beneficial effects of plasma exchange and IVIG are believed to
be equivalent, while combining the two treatments is not beneficial [15,16].

We recommend treatment with plasma exchange or IVIG for nonambulatory adult

patients with GBS who are within four weeks of symptom onset. In addition, we
suggest treatment with plasma exchange or IVIG for ambulatory adult patients with
GBS who are not yet recovering within four weeks of symptom onset. The choice
between plasma exchange and IVIG is dependent on local availability and on patient
preference, risk factors, and contraindications. Patients who are mildly affected and
already recovering do not require disease-modifying therapy. These recommendations
are in general agreement with guidelines from the American Academy of Neurology
[15,16]. When both therapies are equally available and there are no contraindications
for either, we suggest treatment with IVIG.

Plasmapheresis is thought to remove circulating antibodies, complement, and soluble

biological response modifiers. The precise mechanism of action for IVIG in GBS is
unknown but may include providing anti-idiotypic antibodies, modulating expression
and function of Fc receptors, interfering with activation of complement and production
of cytokines, and interfering with activation and effector functions of T and B cells [17-
19]. The roles of the immune response, molecular mimicry, and antiganglioside
antibodies in the pathogenesis of GBS are discussed separately. (See "Guillain-Barré
syndrome: Pathogenesis".)

Aside from plasma exchange and IVIG, no other pharmacologic agents have been
found to be effective for GBS [20]. In particular, glucocorticoids are not beneficial
[21,22]. In a systematic review and meta-analysis of six trials with 587 participants,
glucocorticoid-treated patients with GBS showed no significant difference in disability
grade compared with patients who were not treated with glucocorticoids [23].
Furthermore, in four small trials, patients treated with oral glucocorticoids had
significantly less improvement than patients who were not treated with oral
glucocorticoids.

Plasma exchange — Large, randomized multicenter trials have established the

effectiveness of plasma exchange in patients with severe GBS [24-27]. Earlier
improvement in muscle strength, reduced need for mechanical ventilation, and better
recovery have been demonstrated.

In an updated (2012) meta-analysis of six randomized controlled trials and 649 patients
with GBS, treatment with plasma exchange was superior to supportive care [28]:

●The median time to recover walking with aid was shorter in the plasma exchange
group than the control group in two trials that reported this outcome measure.
●The time to onset of motor recovery in mildly affected patients was significantly
shorter in the plasma exchange group in the one trial that reported this outcome
measure.
●Plasma exchange was associated with a significantly increased proportion of
patients who improved by one or more disability grades at four weeks in five trials.
Additionally, plasma exchange treatment compared with control was associated
with significant improvement as assessed by the time to recover walking without
aid, the percentage of patients requiring mechanical ventilation, the duration of
ventilation, full muscle strength recovery after one year, and severe sequelae after
one year.
●Plasma exchange was most effective when started within seven days of
symptom onset. However, in the North American study that allowed enrollment up
to 30 days after symptom onset, there was still an improvement in outcome in the
plasma exchange group compared with controls.
 ●Four exchanges were superior to two in patients with moderately severe GBS.
However, in subjects with severe disease requiring mechanical ventilation, six
exchanges were not superior compared with four.
●The methodologic quality of the trials was generally good. However, none were
patient-blinded, as sham apheresis was considered unethical. Furthermore, none
of the trials were observer-blinded, and only two trials [24,25] used centralized
review of cases in an attempt to minimize unblinded outcome assessment.

Dosing and side effects — Plasma exchange is usually given for four to six
treatments over eight to 10 days. The main complications are hypotension, sepsis, and
problems with intravenous access. The implementation of therapeutic plasma
exchange, including techniques and regimens, is discussed in detail separately.
(See "Therapeutic apheresis (plasma exchange or cytapheresis): Indications and
technology".)

Intravenous immune globulin — IVIG is as effective as plasma exchange for the

treatment of GBS. This conclusion was reached by a 2014 systematic review and
meta-analysis [29] and by a 2012 American Academy of Neurology guideline on IVIG in
the treatment of neuromuscular disorders [16].

As an example of these reports, a 2012 meta-analysis found no significant difference in

the primary outcome measure, the change in a seven-grade disability scale at four
weeks, with IVIG compared with plasma exchange (weighted mean difference -0.02,
95% CI -0.25 to 0.20) [29]. In addition, there were no statistically significant differences
in other outcome measures.

There are no randomized controlled trials comparing IVIG with placebo for the
treatment of GBS; rather, the trials have compared IVIG with plasma exchange [30-32].
A 2014 meta-analysis found that patients assigned to IVIG were significantly less likely
to discontinue treatment than patients assigned to plasma exchange (relative risk 0.14,
95% CI 0.05-0.36) [29].

Though unproven, patients with more severe clinical disease possibly may benefit from
longer duration of IVIG treatment.

A retrospective analysis of randomized trial data found that the increase in serum
levels of IgG after IVIG treatment compared with baseline varied considerably among
patients with GBS, and that patients in the lowest two quartiles of increase in serum
IgG levels two weeks after treatment had a worse clinical outcome compared with
those in the highest two quartiles [33]. These data suggest that a higher dose or a
repeat course of IVIG may be useful in patients with only a small increase in serum
IgG, but this hypothesis requires confirmation [34].

Combining IVIG with plasma exchange does not appear to be beneficial for patients
with GBS [16]. Supporting evidence comes from a trial of 379 nonambulatory patients
with severe GBS who were within two weeks of symptom onset and were randomly
assigned to treatment with five or six plasma exchanges, or five days of IVIG, or
plasma exchange followed by IVIG [32]. There were no significant differences in
measures of recovery among patients treated with plasma exchange, IVIG, or the
combination of plasma exchange and IVIG.

Dosing and side effects — Intravenous immune globulin is given for five days at
0.4 gram/kg per day. Side effects include aseptic meningitis, rash, acute renal failure
(mostly related to sucrose containing products), and (rarely) hyperviscosity leading to
stroke. IgA deficiency can lead to anaphylaxis [19]. (See "Overview of intravenous
immune globulin (IVIG) therapy".)

CLINICAL COURSE AND PROGNOSIS — The natural history of Guillain-Barré

syndrome (GBS) is illustrated by a retrospective series of 162 patients who were
evaluated in the era before the advent of disease-modifying treatment [35]. Most (74
percent) showed continued progression for up to two weeks, followed by a plateau
phase of two to four weeks, and then recovery of function. At four weeks after onset,
recovery was underway in 67 percent of patients.

The time period to onset of recovery is shortened by about 40 to 50 percent by

treatment with plasma exchange or intravenous immune globulin (IVIG). Data from the
North American plasma exchange trial that studied 245 patients treated within 30 days
after onset of motor deficit illustrates the degree of improvement with disease-
modifying therapy [24].

●The median time to improve one grade in the plasma exchange and control
groups was 19 and 40 days
●The median time to walking unaided in the plasma exchange and control groups
was 53 and 85 days
●Improvement by at least one grade at one month in the plasma exchange and
control groups occurred in 59 and 39 percent of patients

Prognostic factors — Factors associated with a poor prognosis for recovery from
GBS include [36-40]:

●Older age
●Rapid onset (less than seven days) prior to presentation
●Severe muscle weakness on admission
●Need for ventilatory support
●An average distal motor response amplitude reduction to <20 percent of normal
●Preceding diarrheal illness

Several of these factors influencing prognosis in GBS have been incorporated in a

useful prognostic scoring system available online
at https://gbstools.erasmusmc.nl/prognosis-tool. This scoring system can be used at
one or two weeks after admission to estimate the risk of being unable to walk at six
months [38,41]. At one week after admission, the score incorporates patient age, the
presence or absence of preceding diarrhea, and strength as measured by the Medical
Research Council (MRC) sum score [38]. At two weeks, a GBS disability score
replaces the MRC score [41]. The higher the score, the higher the risk of being unable
to walk at six months. As an example, for a patient evaluated at one week with the
highest score of 12, the estimated risk of being unable to walk at six months is 66
percent. The limitation of the scoring system is that the data are derived from a Dutch
Caucasian population and may not be applicable to other populations.

Electrodiagnostic studies — Electrodiagnostic studies can have prognostic value,

especially when repeated over the first five weeks. Axonal degeneration and poor
prognosis (ie, slower recovery and/or severe residual disability) are suggested by
markedly reduced distal motor response amplitude (<20 percent of normal) and
profuse fibrillation potentials on needle examination, starting at two to four weeks after
disease onset [42,43]. In contrast, demyelination and a good prognosis are associated
with a pattern characterized by preservation of the distal motor response amplitude
above 20 percent of normal, conduction block, and temporal dispersion.

Relapses — Relapses with increased weakness occur in up to 10 percent of patients

with GBS [44,45].

●Occasional patients diagnosed with GBS may continue to deteriorate after initial
treatment with plasma exchange or IVIG. This may reflect the natural history of the
disease or an error in diagnosis [34,46]. Thus, it is useful to confirm that the
diagnosis of GBS is correct prior to deciding about retreatment. (See "Guillain-
Barré syndrome in adults: Clinical features and diagnosis", section on 'Differential
diagnosis'.)
●A minority of patients with GBS will have initial improvement after treatment with
plasma exchange or IVIG followed by a secondary deterioration, a situation
termed a "treatment-related fluctuation" or TRF [47,48]. In one report of 147
patients with GBS who received therapy with plasma exchange or IVIG, treatment-
related fluctuations (ie, relapses) occurred in 10 percent of patients at a median of
21 days (range 10 to 60 days) after the start of treatment [47]. The relapses were
typically not as severe as the initial progressive phase of GBS prior to treatment.
Similar findings were noted in a prospective study of 170 patients with GBS, which
reported that treatment-related fluctuations occurred in 9 percent of patients [48].
No patient with GBS had more than two treatment-related fluctuations.

There are no data from randomized trials to guide retreatment for patients with poor
response or relapse after initial treatment for GBS. We suggest observing the patient
for one to two weeks after finishing treatment. For very severely affected patients only
who show no improvement or further deterioration at two weeks, we suggest retreating
(no more than once) with the same modality (plasma exchange or IVIG), under close
observation for side effects. We suggest not switching from IVIG to plasma exchange
because it will remove the potentially beneficial circulating IVIG. However, retreatment
is controversial and should not be given routinely. It is considered inappropriate by
some experts because evidence is lacking [49]. A clinical trial to evaluate this issue is
underway [50].

About 2 to 5 percent of patients initially diagnosed with GBS will develop the chronic
relapsing weakness of chronic inflammatory demyelinating polyradiculoneuropathy
(CIDP) [12,48,51,52]. Distinguishing between GBS with treatment-related fluctuations
and acute-onset CIDP can be difficult (see "Guillain-Barré syndrome in adults: Clinical
features and diagnosis", section on 'Chronic inflammatory demyelinating
polyneuropathy'), but several clinical patterns may point to the diagnosis of CIDP rather
than GBS [48]:

●Deterioration after eight weeks from onset of weakness

●Deterioration occurs ≥3 times
●No loss of independent ambulation
●Absence of cranial nerve involvement

CIDP is reviewed in detail separately. (See "Chronic inflammatory demyelinating

polyneuropathy: Etiology, clinical features, and diagnosis".)

Long-term outcome — The proportion of patients with GBS who walk independently
at six months and 12 months after diagnosis is approximately 80 and 84 percent,
respectively [39]. At one year, full recovery of motor strength occurs in about 60
percent of patients, while severe motor problems persist in about 14 percent.
Approximately 5 to 10 percent of patients with GBS have a prolonged course with
several months of ventilator dependency and very delayed and incomplete recovery
[53].

Within one year of diagnosis, approximately 3 to 7 percent of patients with GBS die
despite intensive care [39,40,54]. Of patients who become ventilator dependent, about
20 percent will die. Causes of death include acute respiratory distress syndrome,
sepsis, pulmonary emboli, and unexplained cardiac arrest [55]. Mortality appears
highest in the recovery phase after neurologic improvement [40].

Immunizations — The risk of vaccine-associated GBS is very low (one to two excess
cases of GBS per million people vaccinated) and is substantially less than the overall
health risk posed by naturally occurring influenza. This issue is discussed separately.
(See "Guillain-Barré syndrome: Pathogenesis", section on 'Vaccination'.)

In general, vaccination in patients with GBS should be considered on an individual

basis. The following recommendations are in agreement with a 2005 expert review of
supportive care for patients with GBS, and are based on observational studies and
expert opinion [1]:

●Immunizations are not recommended during the acute phase of GBS and are not
suggested for a period of one year after the onset of GBS
●After one year, immunizations need not be withheld, but the need for the
immunization should be reviewed on an individual basis
●Future avoidance is suggested for any particular immunization that is followed
within six weeks by the onset of GBS

For the majority of patients who have risk factors for severe influenza complications
and who have a history of GBS not provoked by influenza vaccination, the established
benefits of influenza vaccination justifies yearly vaccination. The utility of influenza
vaccination in adults is discussed separately. (See "Seasonal influenza vaccination in
adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education

materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces
are written in plain language, at the 5th to 6thgrade reading level, and they answer the
four or five key questions a patient might have about a given condition. These articles
are best for patients who want a general overview and who prefer short, easy-to-read
materials. Beyond the Basics patient education pieces are longer, more sophisticated,
and more detailed. These articles are written at the 10th to 12th grade reading level and
are best for patients who want in-depth information and are comfortable with some
medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage
you to print or e-mail these topics to your patients. (You can also locate patient
education articles on a variety of subjects by searching on "patient info" and the
keyword(s) of interest.)

●Basics topics (see "Patient education: Guillain-Barré syndrome (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Supportive care is extremely important in Guillain-Barré syndrome (GBS) since

up to 30 percent of patients develop neuromuscular respiratory failure requiring
mechanical ventilation. In addition, severe autonomic dysfunction occurs in about
20 percent and warrants intensive care unit (ICU) monitoring. (See 'Supportive
care' above.)
●Close respiratory monitoring with frequent measurement of vital capacity and
negative inspiratory force should be instituted in all patients with GBS on
admission and continued while weakness is progressing. Patients with a forced
vital capacity <20 mL/kg, maximum inspiratory pressure <30 cmH2O, or maximum
expiratory pressure <40 cmH2O are at high risk of impending respiratory failure
and should undergo urgent intubation and mechanical ventilation.
(See 'Respiratory failure' above.)
●For patients with GBS and progressive weakness, we recommend cardiac and
blood pressure monitoring. (See 'Cardiovascular management'above.)
●For patients with GBS and progressive weakness, we recommend daily
abdominal auscultation to monitor for bowel silence and the development of
adynamic ileus. (See 'Bowel and bladder care'above.)
●Pain occurs in about two-thirds of patients during the course of GBS and often
requires treatment. (See 'Pain control' above.)
●The main modalities of disease modifying therapy for GBS are plasma exchange
and intravenous immune globulin (IVIG). The treatments are equivalent and
improve outcome. Treatment shortens the time to walking independently by 40 to
50 percent. (See 'Disease-modifying treatment'above.)
●For nonambulatory adult patients with GBS who are within four weeks of
neuropathic symptom onset, we recommend treatment with plasma exchange or
IVIG (Grade 1A). For ambulatory adult patients with GBS who are not yet
recovering within four weeks of neuropathic symptom onset, we suggest treatment
with plasma exchange or IVIG (Grade 2B). The choice between plasma exchange
and IVIG is dependent on local availability and on patient preference, risk factors,
and contraindications. When both therapies are equally available and there are no
contraindications for either, we suggest treatment with IVIG (Grade 2B).
(See 'Disease-modifying treatment' above and 'Plasma exchange' above
and 'Intravenous immune globulin' above.)
●For adult patients with GBS, we recommend nottreating with glucocorticoids
(Grade 1A). (See 'Disease-modifying treatment' above.)
●Most patients with GBS have continued progression (ie, worsening) for up to two
weeks, followed by a plateau phase of two to four weeks, and then gradual
recovery of function. (See 'Clinical course and prognosis' above.)
●A minority of patients with GBS will have initial improvement after treatment with
plasma exchange or IVIG followed by a secondary deterioration, a situation
termed a "treatment-related fluctuation" or TRF. There are no data from
randomized trials to guide retreatment for patients with poor response or relapse
after initial treatment for GBS. We suggest observing the patient for one to two
weeks after finishing treatment. For very severely affected patients only who show
no improvement or further deterioration at two weeks after initial treatment, we
suggest retreating (no more than once) with the same modality (plasma exchange
or IVIG), under close observation for side effects (Grade 2C). We suggest not
switching from IVIG to plasma exchange because it will remove the potentially
beneficial circulating IVIG. However, retreatment is controversial and is
considered inappropriate by some experts because evidence is lacking. It should
not be given routinely. (See 'Relapses'above.)
●At one year after onset and treatment of GBS, full recovery of motor strength
occurs in about 60 percent of patients, while severe motor problems persist in
about 14 percent. Approximately 5 to 10 percent of patients have a prolonged
course with very delayed and incomplete recovery, and 3 to 7 percent die despite
intensive care. (See 'Clinical course and prognosis' above.)