G u i l l a i n - B a r ré Syndrome

a, b
Vibhuti Ansar, MD *, Nojan Valadi, MD

KEYWORDS
 Guillain-Barré syndrome  Demyelinating syndrome
 Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)
 Acute motor axonal neuropathy  Miller Fisher syndrome

KEY POINTS
 Guillain-Barré syndrome (GBS) has several clinical variants, including acute inflammatory
demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy, acute
motor and sensory axonal neuropathy, acute pandysautonomia, sensory GBS, GBS
with ophthalmoplegia, and Miller Fisher syndrome.
 The incidence typically is 1 to 2 per 100,000, with a higher prevalence in men and the
elderly.
 GBS is often preceded by an acute viral infection and has been linked to vaccine
administration.
 Treatment may consist of several cycles of plasma exchange (PE) or intravenous
immunoglobulin (IVIG). Both treatments are effective. Corticosteroids have not been
shown to help in GBS.
 Approximately 80% to 90% of patients recover with no sequelae at 1 year.

INTRODUCTION

Acquired inflammatory demyelinating polyradiculoneuropathies are immunologically

mediated and can be classified by their clinical time course as acute or chronic or
by the constellation of symptoms and electrophysiologic pattern into one of several
GBS variants. In AIDP, the most common type of GBS, the maximal deficits appear
over days (at most 4 weeks), followed by a plateau phase and then gradual improve-
ment, whereas chronic inflammatory demyelinating polyradiculoneuropathy may be
more slowly progressive or relapsing. The axonal variants of GBS may be purely motor
or both sensory and motor neuropathies, both of which can be severe with poor recov-
ery. The clinical features of GBS as described by Guillan, Barré, and Strohl in 1916,
were motor weakness, areflexia, paresthesias with slight sensory loss, and cerebro-
spinal fluid (CSF) albuminocytologic dissociation. GBS has several clinical variants,

a
Department of Medical Education, Midtown Medical Center, Columbus Regional Healthcare,
1900 10th Avenue, Suite 100, Columbus, GA 31901, USA; b 2300-A Manchester Expressway,
Suite 201, Columbus, GA 31903, USA
* Corresponding author.
E-mail address: [email protected]

Prim Care Clin Office Pract 42 (2015) 189–193

http://dx.doi.org/10.1016/j.pop.2015.01.001 primarycare.theclinics.com
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190 Ansar & Valadi

including acute motor axonal neuropathy, acute motor and sensory axonal neuropa-
thy, and Miller Fisher syndrome.1 The subtypes differ in pathologic and electrodiag-
nostic features. Some clinical distinctions are also present, especially with Miller
Fisher variant.2

EPIDEMIOLOGY

With the decline of acute poliomyelitis, GBS has become the most common acute para-
lytic disease in Western countries. Incidence of GBS is approximately 1 to 2 per 100,000
and afflicts men and the elderly more commonly than women or younger patients.3

RISK FACTORS

GBS is typically preceded by an infection, most frequently from an upper respiratory

tract (58%) or gastrointestinal source (22%), but may also be caused by surgery or
being immunized 1 to 4 weeks prior to the onset of symptoms.4 Campylobacter jejuni
is the most commonly identified bacteria associated with the acute motor axonal neu-
ropathy and GBS variants. Immunizations that have been linked to the development of
GBS include swine flu, tetanus, diphtheria toxoids as well as rabies.3 Several viral in-
fections (cytomegalovirus, Epstein-Barr virus, HIV, varicella-zoster virus, and hepatitis
A and B); drugs, such as heroin, suramin, and streptokinase; and chronic conditions
(like systemic lupus erythematosus and HIV) have predisposed to GBS patients.

CLINICAL FEATURES

GBS and variants typically present with progressively ascending fairly symmetric
paralysis and areflexia over the course of hours to several days. Motor paralysis af-
fects the lower extremities more frequently than the upper extremeties.5 Sensory dis-
turbances may or may not occur. Respiratory failure due to neuromuscular
compromise is not uncommon, often requiring supportive ventilation.6 Autonomic
symptoms have been reported in as many as 65% of patients admitted to hospitals
for GBS and may include orthostatic hypotension, anhidrosis, urinary retention,
gastrointestinal atony, or iridoplegia.7 Miller Fisher syndrome, which accounts for
5% of GBS cases, is characterized by ophthalmoplegia, ataxia, and areflexia. Patients
present with diplopia followed by discoordination of the limbs and gait. Tables 1 and 2
indicate various physical signs and symptoms in patients with GBS.

DIAGNOSIS

Several consensus statements have been made about the required diagnostic criteria
for GBS and variants. Required criteria for the diagnosis include progressive weak-
ness of more than 2 limbs, areflexia, and progression for no more than 4 weeks.3 Sup-
portive criteria include mild sensory signs, relative symmetry of symptoms, absence of
fever, facial diplegia, and a cerebrospinal fluid (CSF) profile of albuminocytologic
dissociation with elevated protein concentration without CSF pleocytosis, with the
exception of the setting of HIV, where pleocytosis is the norm and not the exception.8
Laboratory testing could show an elevated erythrocyte sedimentation rate, mildly
abnormal renal and liver laboratory results, and electrolyte disturbances, such as
hyponatremia (from the syndrome of inappropriate secretion of antidiuretic hormone).
Nerve conduction studies may be abnormal and show slowed motor conduction
velocities, partial conduction block, and dispersed motor responses. Demyelination
at the nerve roots may cause absent or delayed F-wave responses or H-reflexes on
the studies. MRI of the lumbosacral spine typically shows enhancement of the nerve
 Guillain-Barré Syndrome 191

Table 1
Percentage of patients with these physical signs in GBS

Flaccid weakness 100%

Limb areflexia/hyporeflexia 100%
Distal weakness (predominant) 33.3%
Distal sensory loss 38.9%
Cranial nerve VII palsy 31.5%
Proximal weakness (predominant) 27.8%
Palate paralysis 14.8%
Respiratory failure requiring ICU 14.8%
Fluctuating arterial HTN 9.3%
Papilledema 7.4%
Ocular nerve palsy 5.6%
Weakness of jaw 3.7%

Data from Bahemuka M. Guillain-Barre syndrome in Kenya: a clinical review of 54 patients. J Neurol
1988;235:418–21.

roots.9 This inflammatory response at the nerve roots helps explain certain features,
including the CSF findings, some neurophysiologic findings, and autonomic dysfunc-
tion that may be seen in these patients. In Miller Fisher syndrome, serum IgG anti-
bodies to ganglioside GQ1b are found in most patients.

THERAPEUTIC OPTIONS

PE and IVIG are common treatments for GBS. Combination therapy is not superior to
either alone. Both are expensive but decrease the time to recovery.3 Both treatment
modalities are superior to supportive therapy alone. No significant differences have
been found between the two treatment options for disability scores at 4 weeks or
the time to wean ventilatory support or recover unassisted walking.10 Patients
receiving IVIG, however, have fewer side effects, have fewer complications, and are
less likely to quit therapy compared with those receiving PE.11
PE involves taking the autoantibodies out of the blood. It cannot be performed in
pregnant patients or hemodynamically unstable patients. Practice guidelines set by

Table 2
Presenting symptoms

Limb weakness 100%

Numbness/paresthesias 60%
Difficulty breathing 34%
Choking 20.4%
Sphincter disturbance 18.5%
Slurring speech 11.1%
Double vision 7.4%
Headache 5.6%
Difficulty chewing 3.7%

Data from Bahemuka M. Guillain-Barre syndrome in Kenya: a clinical review of 54 patients. J Neurol
1988;235:418–21.
192 Ansar & Valadi

the Quality Standards Subcommittee of the American Academy of Neurology (AAN) in

2003 endorse the use of PE within 4 weeks of symptom onset in nonambulatory pa-
tients and 2 weeks in ambulatory patients. Common side effects include hypotension,
hypocalcemia, and thrombocytopenia (typically improves within 24–48 hours). If pa-
tients need to undergo multiple exchanges, episodes should occur 24 hours apart
to help avoid the decrease in hemostatic factors: 2 to 6 treatments in a 1- to 2-
week period have been shown effective.2,12 Each session should exchange plasma
volume (50 mL/kg) with albumin (preferred over fresh frozen plasma). Long-term ben-
efits from PE therapy include recovered muscle strength, lower likelihood of motor
dysfunction, and fewer relapses at 1 year compared with supportive care.12
IVIG preparations differ depending on the manufacturer, with varying osmolality, salt
and sugar content, pH, and IgA content. Treatment with IVIG must be judiciously indi-
vidualized. The main component of IVIG is IgG. The usual dose is 2 g/kg divided over 2
to 5 days. High-dose IVIG has not been shown to be superior to low-dose IVIG. Vital
signs should be checked every 15 minutes during the first hour and then periodically
after. Acetaminophen or an antihistamine may be given prior to each dose. Renal func-
tion should be tested prior to each dose and periodically after. A repeat course may be
given if there is an inadequate response. People with renal dysfunction should have
the rate of infusion halved of the normal rate. Serious adverse side effects include
venous throembolism, anaphylaxis, acute renal failure, aseptic meningitis, and
stroke-like episodes.11 Due to the risk of anaphylaxis in patients with IgA deficiency
due to anti-IgA antibodies, IgA levels should be tested prior to administration of
IVIG.12 The Quality Standards Subcommittee of the AAN endorses starting IVIG ther-
apy within 2 to 4 weeks of disease onset in people unable to walk without assistance.
Corticosteroids are not beneficial in GBS. Corticosteroids in combination with IVIG
or alone have not shown benefit in a Cochrane review. Some studies showed steroids
delayed recovery. The time to recovery of unaided walking, time to discontinuation of
ventilation, and death rates were no better in the corticosteroid group compared with
placebo. Relapse rates did not differ. Diabetes developed in the steroid group more
frequently than with placebo. Hypertension (HTN) occurred less frequently in intrave-
nous steroid studies, however.13
Supportive care is essential in the treatment of GBS. Prophylaxis for deep vein
thrombosis using heparin, enoxaparin, or support stockings until patients can ambu-
late independently is vital. Respiratory function and pulse/blood pressure monitoring
should occur in GBS patients but not enough evidence exists to suggest specific
methods. Tracheostomy should be performed after 2 weeks in patients whose respi-
ratory status has not improved. Simple analgesics like acetaminophen and nonste-
roidal anti-inflammatory drugs may not be effective. Opioid analgesics improve pain
but must be monitored for side effects secondary to autonomic denervation (gut
dysmotility and bladder distention). Adjuvant therapy with tricyclic antidepressants,
tramadol, gabapentin, and carbamazepine may aid GBS. Monitoring bowel and
bladder function should occur daily and rehabilitation therapy should focus on proper
limb positioning, posture, orthotics, and nutrition. Immunizations should not be given
in the acute phase or for 1 year after a GBS episode. Thereafter, immunizations should
not be withheld unless there is a concern that one caused the disease. If so, only that
particular immunization should be withheld.6

CLINICAL OUTCOMES

Overall, patients afflicted with GBS have a good prognosis. Improvements in critical
care have vastly changed outcomes from GBS, decreasing mortality from 33% to
 Guillain-Barré Syndrome 193

5% to 10% with the introduction of positive pressure ventilation. A great majority of

patients recover with minimal deficits at 1 year.5 Some patients have persistent
disabilities.10

SUMMARY

In conclusion, GBS and its clinical variants are a group of rapidly progressing, poten-
tially debilitating neurologic disorders that may have significant morbidity/mortality if
left unrecognized or untreated. The most common symptoms include ascending
limb weakness and paralysis, which may progress to respiratory failure. Diagnosis is
made clinically with laboratory testing. Several treatment options exist, including PE
and IVIG administration. Most cases may resolve without sequelae, but those that
do not may leave behind significant persistent debility.

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