Overview of Guillain-Barré Syndrome
Guillain-Barré syndrome (GBS) is an acute polyneuropathy characterized by muscle weakness that is thought to be autoimmune in nature. In its classic form, GBS is an acute inflammatory demyelinating polyneuropathy characterized by progressive, symmetric, ascending muscle weakness; paralysis; and hyporeflexia with or without sensory or autonomic symptoms. It comprises a group of conditions defined by varying clinical, electrophysical, and pathological features, characterized by motor, sensory, and autonomic dysfunction. Guillain-Barré syndrome variants involving the cranial nerves or pure motor involvement also exist. In severe cases, muscle weakness may lead to respiratory failure, and labile autonomic dysfunction may complicate the use of vasoactive and sedative drugs. Often GBS occurs a few days or weeks after the patient has had symptoms of a respiratory or gastrointestinal viral infection. Infections of Campylobacter jejuni, Cytomegalovirus, and Epstein-Barr virus have been linked with GBS.11329, 11330, 11331 A cluster of cases were also reported in the United States in 1976-1977, following a vaccination program for the swine flu.11332
The most commonly identified clinical subtype in the United States is acute inflammatory demyelinating polyneuropathy (AIDP). It is generally preceded by an antecedent bacterial or viral infection. Lymphocytic infiltration and macrophage-mediated demyelination of peripheral nerves is present in patients with AIDP. Symptoms generally resolve with remyelination. The acute motor axonal neuropathy (AMAN) subtype is a purely motor subtype that is more prevalent in pediatric age groups. Miller-Fisher Syndrome (MFS) is a rare variant that particularly affects the cranial nerves to the eye muscles and generally presents with the classic triad of ataxia, areflexia, and ophthalmoplegia.11330, 11329
Pathological Criteria of Guillain-Barré Syndrome
Guillain-Barré syndrome is manifested by primary demyelination, and less commonly axonal degeneration.12002 In cases following a C jejuni infection, the cause of GBS has been associated with cross-reactivity between epitopes in the lipo-oligosaccharide in the bacterial wall and the ganglioside.12003 Four pathological subtypes of GBS exist and each one may begin with infection, but axonal degeneration is most likely. The most common subtype is AIDP. In Europe and the United States, 90%-95% of GBS cases are the AIDP subtype. In Central and South America, China, and Japan, AIDP makes up 53%-70% of cases.12003 AIDP is caused by multifocal mononuclear cell infiltration throughout the peripheral nervous system (PNS), followed by macrophage invasion of myelin sheaths which denudes axons. The initial invasion into the basement membrane of Schwann cells is caused by a matrix of metalloproteinases, toxic nitric oxide radicals, and other mediators released by active macrophages. Acute motor axonal neuropathy is the subtype in which the neurological deficit is purely motor.12003 The motor axons are targeted by the Fc-receptor-mediated binding of antibodies directed against ganglioside antigens on the plasma membrane, or axolemma. Macrophages then invade the nodes of Ranvier, inserting between the axon and Schwann cell axolemma, leaving the myelin sheath intact. In more severe cases, the axons are damaged in the ventral root, causing degeneration of the entire axon. Patients with this subtype typically reach a nadir more quickly, but typically recover at the same rate as those with AIDP. In another subtype, the dorsal, as well as ventral, roots are affected, causing sensory fibers to be affected as well. This subtype is acute motor and sensory axonal neuropathy (AMSAN).12003 The pathology resembles that of AMAN, with the same pattern of macrophage invasion of perinodal space. A rare variant is Miller-Fisher syndrome. This subtype particularly affects the cranial nerves to eye muscles and typically presents with a combination of areflexia, ataxia, and ophthalmoplegia.12003
Clinical Manifestations of Guillain-Barré Syndrome
The classic presenting feature of GBS is rapidly progressive symmetric ascending muscle weakness.12002 It can vary greatly in severity but often has a proximal emphasis and begins in the legs, frequently spreading to the arms and 1 or both sides of the face. Maximum weakness is reached between 2 and 4 weeks after onset.11975 This is followed by a plateau phase that can last from days to months, and a much slower recovery phase.11975 Other symptoms are paraesthesias, numbness (in affected extremities and spreads proximally) paralysis, hyporeflexia, and possibly sensory or autonomic symptoms.11975, 12003 Autonomic disturbances may cause abnormal sweating, cardiac irregularities, impaired sphincter control, facial flushing, hypotension or hypertension, pulmonary dysfunction, or tachycardia.12003 Neuropathic pain may be the presenting feature, especially in children. Respiratory failure requiring the use of artificial ventilation occurs in 25% of severe cases, and labile autonomic dysfunction may complicate the use of vasoactive and sedative drugs.12003 In 80% of cases, prognosis is good, but recovery may take months, and some patients, especially the elderly, may remain disabled or severely fatigued for 3-6 years after onset.11975, 12002 Prognosis is also worse for patients with previous diarrheal illness, or C jejuni infection, and those with a rapid onset phase. Recovery is generally much quicker and more complete in children.12003
Diagnosis of Guillain-Barré Syndrome
A lumbar puncture should be used to examine the CSF since patients with GBS will have CSF that contains a high protein concentration and normal cell content; however, CSF protein levels may be normal during the first days of the syndrome.12003 Electromyography is another helpful test in confirming diagnosis in clinically difficult cases and is needed to determine the subtype of GBS and amount of axon loss.11975 Neurophysiologic studies can confirm that the disease is a peripheral neuropathy and its subtype. Sufficient information from these studies requires data from at least 3 sensory nerves, 3 motor nerves with multisite stimulation and F waves, and bilateral tibial H-reflexes.12003 Studies should be conducted soon after presentation and repeated after 1 or 2 weeks if initial studies are nondiagnostic.
Differential diagnosis can be complicated and initially depends on recognizing the problem as an acute peripheral neuropathy rather than a spinal cord, brain stem, or conus lesion. Some additional causes of acute peripheral neuropathy should be considered, including diphtheria, porphyria, tick paralysis, toxic neuropathy, and vasculitis.12003
Epidemiology and Etiology of Guillain-Barré Syndrome
Temporary increases of GBS incidences are rarely reported, but a few have occurred.11975 On the Caribbean island of Curaçao between 1987 and 1999, the annual occurrence increased from 1.6 to 3.1 cases per 100,000 but returned to normal by 2006. A Chinese study showed an increase in the amount of AMAN cases during the summer of 1991 and 1992 in a rural area.11975 The precise causes are unclear but probably have an immunologic basis. GBS also tends to follow infective illness, inoculations, and surgical procedures.12002 A cluster of cases were reported in the United States in 1976-1977 following a vaccination program for the swine flu. Twenty-five percent of patients have had a recent C jejuni infection. Small clusters of cases have been associated with outbreaks of bacterial enteritis caused by contaminated water. A range of bacteria and viruses are possible triggers since the infection they cause may elicit an immune response that cross-reacts with axolemma or Schwann cell antigens.12003
Immunology of Guillain-Barré Syndrome
The axonal subtypes AMAN and AMSAN are caused by antibodies to gangliosides on the axolemma, especially those to GM1, GM1b, and GD1a.12002 Following a C jejuni infection, lipo-oligosaccharides (LOS) which mimic carbohydrates of gangliosides are synthesized by bacterial isolates. These LOS trigger an immune response. The antibodies triggered are cross-reactive and recognize LOS as well as nerve gangliosides. The 4 factors that control the process of infection-induced abnormal immune responses that damage peripheral nerves are shown in Fig.3222. Bacterial factors depend on the specific gene variants within the C jejuni bacterium that are essential for the expression of gangliosidelike LOS. Host factors depend on single-nucleotide genetic polymorphisms that may play a part as disease-modifying factors, and immune status influences susceptibility. The extent of nerve damage depends on the ganglioside distribution in the nerves and the specificity and affinity of antibodies along with complement activation. Prognostic factors depend on age, severity at onset, and diarrhea.11975
Figure 3222 – Immunobiology of GBS
Figure 2 Page 942, Lancet Neurol, 2008;7(10) is used with permission of Elsevier Inc. All rights reserved.
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Content on this page was last reviewed on January 01, 2009.
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