Guillain-Barré syndrome (GBS)

What is GBS?
• Guillain-Barré syndrome (GBS) can be described as
a collection of clinical syndromes that manifests as
an acute inflammatory polyradiculoneuropathy with
resultant weakness and diminished reflexes.
• GBS is a heterogeneous condition with several
variant forms. 
• The symptoms usually present 2-4 weeks following
a relatively benign respiratory or gastrointestinal
illness.
 Pathogenesis
• GBS is a post-infectious, immune mediated disease.
• Most patients report and infectious illness weeks
prior to onset of GBS.
• GBS is thought to result from an immune response
to the 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.
 Pathogenesis
• 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.
• A small percentage of patients develop GBS
after another triggering event such as
immunization, surgery, trauma, and bone-
marrow transplantation. 
 Epidemiology
•  Guillain-Barré syndrome (GBS) occurs world-wide with
an overall incidence of 1 to 2 per 100,000 per year .
• No race related differences observed
• Male to female ratio: 1.5:1
• It has been reported in all age groups, however the
syndrome's age distribution seems to be bimodal, with
a first peak in young adulthood (ages 15-35 y) and a
second, higher one in middle-aged and elderly persons
(ages 50-75 y). Infants appear to have the lowest risk
of developing GBS.
 Clinical Presentation
• Progressive muscle weakness of lower limbs that may
progress from hours to days to involve the arms, truncal
muscles, cranial nerves, and muscles of respiration.
•  This 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.
• Paraesthesia, numbness and sensory changes.
 Clinical Presentation
• Cranial nerve involvement: facial droop, diplopias,
dysarthria, dysphagia, ophthalmoplegia, pupillary
disturbances
• Autonomic changes: tachycardia, bradycardia, facial
flushing, paroxysmal hypertension, orthostatic
hypotension, anhidrosis and/or diaphoresis, urinary
retention
• Pain, 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
 Diagnosis
•  Diagnostic criteria for GBS, originally proposed in 1978 from the National Institute of
Neurological Disorders and Stroke (NINDS):
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
 Diagnosis
• ●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
 Differential Diagnoses
• Botulism
• Cauda Equina and Conus Medullaris Syndromes
• Chronic Inflammatory Demyelinating Polyradiculoneuropathy
• Emergent Management of Myasthenia Gravis
• Heavy Metal Toxicity
• Lyme Disease
• Metabolic Myopathies
• Multiple Sclerosis
• Nutritional Neuropathy
• Vasculitic Neuropathy
 Variants
• 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.
• 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.
• 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 [
• 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].
• chronic inflammatory demyelinating polyneuropathy (CIDP) is a
neurological disorder characterized by progressive weakness and
impaired sensory function in the legs and arms. The disorder, which is
sometimes called chronic relapsing polyneuropathy, is caused by
damage to the myelin sheath (the fatty covering that wraps around
and protects nerve fibers) of the peripheral nerves. Although it can
occur at any age and in both genders, CIDP is more common in young
adults, and in men more so than women. It often presents with
symptoms that include tingling or numbness (beginning in the toes
and fingers), weakness of the arms and legs, loss of deep tendon
reflexes (areflexia), fatigue, and abnormal sensations. CIDP is closely
related to Guillain-Barre syndrome and it is considered the chronic
counterpart of that acute disease.
• The term chronic inflammatory demyelinating polyradiculoneuropathy
(CIDP) has been used to identify patients with a chronically progressive or
relapsing symmetric sensorimotor disorder with cytoalbuminologic
dissociation and interstitial and perivascular endoneurial infiltration by
lymphocytes and macrophages. It can be considered the chronic equivalent
of acute inflammatory demyelinating polyradiculoneuropathy, the most
common form of Guillain-Barré syndrome.
• Signs and symptoms
• CIDP typically starts insidiously and evolves slowly, in either a slowly
progressive or a relapsing manner, with partial or complete recovery
between recurrences; periods of worsening and improvement usually last
weeks or months. Most experts consider the necessary duration of
symptoms to be greater than 8 weeks for the diagnosis of CIDP to be made.
 Diagnostic Investigations
• History and physical examination- The diagnosis of GBS is mainly made on
clinical grounds of progressive ascending weakness or paralysis and absent or
depressed deep tendon reflexes.

The clinical diagnosis of GBS is supported if cerebrospinal fluid (CSF) and

electrodiagnostic studies show typical abnormalities

• Lumbar puncture:  an elevated cerebrospinal fluid (CSF) protein (> 400 mg/dl)
with a normal white blood cell count. This finding is called albuminocytologic
dissociation, and is present in up to 66 percent of patients with GBS at one
week after onset of symptoms.

Elevated or rising protein levels on serial lumbar punctures and 10 or fewer

mononuclear cells/mm3 strongly support the diagnosis.
 Diagnostic Investigations
• Additional studies can be done: EMG and
Nerve conduction studies, biochemical
studies.
 Treatment
• Treatment with plasma exchange or
intravenous immune globulin (IVIG) is
indicated for most patients with GBS because
these treatments accelerate recovery.
• Treatment with plasma exchange or IVIG for
nonambulatory adult patients with GBS, is
usually recommended for patients who are
within four weeks of symptom onset.
 Treatment (Continued)
• In addition, treatment with plasma exchange
or IVIG for ambulatory adult patients with GBS
who are not yet recovering within four weeks
of symptom onset should also be considered.
• The choice between plasma exchange and
IVIG is dependent on local availability and on
patient preference, risk factors, and
contraindications. 
 Treatment (Continued)
• 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. 
 IVIG
•  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) hyper-
viscosity leading to stroke.
• It is contraindicated in IgA deficiency as it can
lead to anaphylaxis.
 Mechanism of action of IVIG
• Possible mechanisms for beneficial effects include
blockade of Fc receptors on macrophages preventing
antibody targeted attachment on Schwann cell
membrane and myelin or on axolemma in axonal
variants of GBS; regulation of autoantibodies or
cytokines by anti-idiotypic or anti-cytokine antibodies in
the pooled immunoglobulin; and interference with the
complement cascade or regulatory effects on T cells. 
• An alternative hypothesis may be that high
concentrations of circulat
 Management
• According to the BMJ, the management of the
acute phase of GBS should involve a
multidisciplinary approach.
• This should involve a combination of
supportive and disease-modifying therapy (
• Using a multidisciplinary approach, has been
shown to improve disability and quality of life
as well as reduce fatigue.
 Supportive therapy (Respiratory
management)
• Supportive care- this is very important due to the associated risk of respiratory failure
and autonomic dysfunction
• Up to 30% of patients develop neuromuscular respiratory failure requiring mechanical
ventilation.
• Risk factors for progression to mechanical ventilation include rapid disease
progression, bulbar dysfunction, bilateral facial nerve weakness, and dysautonomia.
Pulse oximetry and ABGs should not be relied on, as hypoxia or hypercarbia is a late
sign and patients will decompensate very quickly. There is insufficient evidence to
recommend specific methods for monitoring respiratory function, but respiratory
status should be monitored in all patients. 
• Bedside spirometry should be performed every 6 hours initially. Early spirometry will
also help triage the patient between the ICU and regular ward. Patients with bulbar
dysfunction, high risk of aspiration (i.e., infiltrates on CXR), and new atelectasis on CXR
should be intubated early for airway protection and impending respiratory failure. In
patients with no bulbar dysfunction or with mild bulbar dysfunction without aspiration
risk, the 20/30/40 rule should be used as detailed below.
• The patient should be monitored in the ICU and elective intubation
considered if:
• Vital capacity is <20 mL/kg
• Maximal inspiratory pressure is worse than -30 cmH2O (negative
inspiratory force)
• Maximal expiratory pressure is <40 cmH2O
• Vital capacity, maximal inspiratory pressure, or maximal expiratory
pressure is reduced by 30% from baseline initial measurement. 
• The mean duration of ventilation is 15 to 43 days, and weaning should be
guided by serial PFTs and assessment of strength.  The need for
tracheostomy should be addressed from week 2 onwards, especially if PFTs
do not show improvement. If there is improvement of PFTs above baseline,
tracheostomy may be delayed by an additional week before reassessment
 Supportive therapy (Cardiovascular
management)
• Haemodynamic monitoring of pulse and BP should be started on admission.
Telemetry would be prudent here, especially if there is evidence of
dysautonomia. If dysautonomia is present, continuous cardiac monitoring and
placement of a Foley catheter should be initiated on admission. There are
insufficient data for methods and setting of monitors, but all patients with severe
disease should have their pulse and BP monitored until they are off ventilator
support and have begun to recover. 
•  Fluid balance should be monitored carefully, especially because the autonomic
dysfunction renders clinical determination of hydration status very difficult.
Hypotensive episodes can be managed with fluid boluses. If BP is very labile, then
intra-arterial BP monitoring should be initiated. Hypertensive episodes should be
treated with short-acting agents (e.g., labetalol, esmolol, and nitroprusside) to
prevent abrupt hypotension. Other factors that may potentiate dysautonomia
include manoeuvres such as suctioning, changing position (i.e., lying to sitting),
and medicines (antihypertensive drugs, succinylcholine). 
 Supportive therapy (DVT prophylaxis)

• Immobility and hypercoagulability from

treatments such as intravenous
immunglobulin (IVIG) can increase the risk of
DVT in these patients. 
• Subcutaneous heparin or enoxaparin and
support stockings are recommended for non-
ambulatory patients until they are able to
walk independently.
Supportive therapy (pain management)
• Gabapentin or carbamazepine are generally
recommended in the ICU in the acute phase
• However, further studies are required to investigate the
safety and efficacy of potential interventions in patients
with pain.  
• Adjuvant therapy with tricyclic antidepressants, tramadol,
gabapentin, carbamazepine, or mexiletine may be helpful
for long-term management of neuropathic pain. 
• Although opioids may be effective, they may aggravate
autonomic gut dysmotility and bladder distension. 
 Rehabilitation
• This is recommended in the acute phase. It comprises
gentle strengthening involving isometric, isotonic,
isokinetic, and manual resistive and progressive
resistive exercises. It should be focused on proper
limb positioning, posture, orthotics, and nutrition.
•  Occupational therapy professionals should be
involved early in the rehabilitation program to
promote positioning, posture, upper body
strengthening, range of motion (ROM), and activities
that aid functional self care.
 Rehabilitation (continued)
• Speech therapy is aimed at promoting speech
and safe swallowing skills for patients who
have significant oropharyngeal weakness with
resultant dysphagia and dysarthria.
 Prognosis
• The proportion of patients with GBS who walk independently at
six months and 12 months after diagnosis is approximately 80
and 84 percent, respectively .
• 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 .
• Within one year of diagnosis, approximately 3 to 7 percent of
patients with GBS die despite intensive care. Of patients who
become ventilator dependent, about 20 percent will die.
 Prognosis
Poor prognostic factors:
– ● 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
 Prognosis (continued)
• Causes of GBS-related death include acute
respiratory distress syndrome (ARDS), sepsis,
pneumonia, venous thromboembolic disease
(including pulmonary embolism) , and unexplained
sudden cardiac arrest.
• Most cases of mortality are due to severe autonomic
instability or from the complications of prolonged
intubation and paralysis.
• The leading cause of death in elderly patients with
GBS is arrhythmia.
 References
• https://www-uptodate-
com.ezproxy.sastudents.uwi.tt/contents/guillai
n-barre-syndrome-in-adults-clinical-features-
anddiagnosis?
source=search_result&search=guillain
%20barre%20syndrome
%20adult&selectedTitle=1~150
• http://emedicine.medscape.com/article/3156
32-overview