Guillain-Barré syndrome (GBS) is an acute demyelinating polyneuropathy. The eponym comes from a 1916 article by G. Guillain and J. A. Barré, who described a polyneuropathy in association with protein elevation in cerebrospinal fluid (CSF) but no inflammatory cells. Increasing evidence supports the long-standing supposition that GBS is an autoimmune disease triggered by an infectious or immunologic stimulus. Both plasma exchange and immunoglobulin therapy have proved to be effective. Acute inflammatory demyelinating polyneuropathy has been frequently reported as a complication of HIV disease.
The clinical features of GBS have been well described; however, the initial presentation may be variable. In general, patients first experience paresthesia and numbness in the extremities. A symmetric weakness develops over several days, usually in the lower extremities, making climbing stairs or walking difficult. Weakness characteristically ascends to the trunk and arms. Muscle pain and sciatica are frequent additional complaints. Weakness may progress for several weeks, affecting respiration, swallowing, eye movements, and autonomic nervous system function. On initial physical examination, symmetric limb weakness and absent deep-tendon reflexes are noted. Loss of sensation is usually mild despite complaints of paresthesia. Fever is absent.
Several variations in this clinical picture may be noted. The ascending nature of the process may not be striking. Miller-Fisher syndrome, which represents about 5% of all GBS, is characterized by ophthalmoplegia, ataxia, and areflexia. GBS may also present with isolated arm weakness or weakness of the oropharynx, severe ataxia, and sensory loss or with sudden, complete paralysis.
As noted, CSF findings confirm the diagnosis. The CSF will show few or no cells and a protein concentration greater than 0.55 g/L. Protein elevation occurs after about 1 week of illness. Abnormalities of nerve conduction reflect the demyelination process. Conduction block in motor nerves and spontaneous discharges in demyelinated sensory nerves make this study both sensitive and specific. Ropper emphasizes that several findings suggest alternate diagnoses: (a) reflexes that are normal for several days into the illness, (b) marked asymmetry of weakness, (c) fever in the initial disease presentation, and (d) a CSF protein level above 2.5 g/L. The differential diagnosis depends on the history and physical examination findings but may include spinal cord compression, transverse myelitis, myasthenia gravis, chronic meningitis, metabolic myopathies, paraneoplastic neuropathy, poliomyelitis, tick paralysis, botulism, and shellfish poisoning.
Recent studies suggest a lymphocytic T-cell mechanism for this inflammatory peripheral neuropathy. Inflammation is thought to be the result of an aberrant immune response to myelin antigens. Tumor necrosis factor-a is elevated in many GBS patients and may contribute to the inflammatory demyelination process. An antibody directed against myelin might lead to a macrophage response with tumor necrosis factor-a as the mediating factor in myelin destruction. Serum from patients with GBS causes demyelination and conduction block in some models. Antineural antibodies have also been demonstrated. IgM antibody to certain myelin antigens has been shown to correlate with clinical disease.
The list of infectious organisms that may trigger this process continues to grow. Viral agents such as herpes simplex virus, Epstein-Barr virus, cytomegalovirus, influenza virus, measles virus, mumps virus, respiratory syncytial virus, and hepatitis B virus have been implicated. GBS also occurred as a complication of swine flu vaccination in about 500 persons in 1977; however, no other cases of GBS have occurred in subsequent flu vaccination programs. Bacterial pathogens, particularly Campylobacter, Salmonella, and Yersinia species, appear to cause infections that precipitate GBS. In 1990, Yuki et al. reported that IgM antibody against ganglioside GM1 had been detected in the serum of two patients with GBS following Campylobacter infection. This antibody could well be cross-reactive with both the myelin components and the organism itself. In recent years, it has become apparent that Campylobacter jejuni is by far the most common agent to precipitate GBS. Thirty percent to 40% of cases are now felt to be caused by preceding Campylobacter infection.
The treatment of GBS is supportive and specific. Patients should be hospitalized, at least for observation. GBS is the most common neuromuscular disease requiring respiratory support. Paralysis of the respiratory muscles can occur suddenly without clinical warning. Patients with vital capacities that are declining or below 18 mL/kg should be observed in an ICU setting. Elective intubation for positive-pressure ventilation is recommended at about 15 mL/kg.
Specific treatment for GBS includes plasma exchange or infusion of gamma globulin. Corticosteroids have been used, but randomized controlled trials have not found them to be of benefit.
Plasma exchange has been shown to be beneficial in several randomized trials. The standard regimen appears to be five plasma exchanges (200 to 250 mL/kg in five sessions within 7 to 14 days). Plasma exchange decreased the time until patients could walk unassisted and decreased the need for mechanical ventilation. Benefit was less apparent if exchange was started after 2 weeks of illness. Because immune globulin has been used with beneficial effects in several autoimmune diseases, it was of interest to study its effects in GBS. The Dutch Guillain-Barré Study Group compared IV immune globulin with plasma exchange in 150 GBS patients who were unable to walk but had had the disease for less than 2 weeks. The incidence of improvement was higher in the immune globulin patients (53% vs. 34% in the exchange group) as measured by motor function grading. The median time to improvement by one grade was 41 days in the plasma exchange group and 27 days in the immune globulin group. The immune globulin patients had less need for artificial ventilation.
More recently, the Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group completed a randomized trial of plasma exchange versus IV immune globulin versus the combined treatments. The two treatments were equally efficacious, and the combination offered no advantage. Other studies have also concluded the two treatments to be equivalent. The optimal number of plasma exchanges has also been better defined. For mild disease, two plasma exchanges were better than none with respect to time to onset of motor recovery. For moderate disease, four exchanges were better than two. Six exchanges were no better than four, even in severe disease.
GBS has been associated with AIDS and HIV disease. GBS can occur in association with HIV seroconversion or may be a late manifestation of AIDS. As in other patients with GBS, patients with AIDS may report sudden or gradual onset of weakness. It may be particularly difficult in patients with AIDS to distinguish GBS from other causes of peripheral neuropathy. (S.L.B.)
Allos BM. Campylobacter jejuni infection as a cause of Guillain-Barré syndrome. Infect Dis Clin North Am 1998;12:173.
Molecular mimicry between lipopolysaccharide of some Campylobacter organisms and ganglioside antigens is the probable explanation for GBS as a sequela of Campylobacter infection. In 30% to 40% of cases, GBS is preceded by C. jejuni infection.
Appropriate number of plasma exchanges in Guillain-Barré syndrome. The French Cooperative Group on Plasma Exchange in Guillain-Barré syndrome. Ann Neurol 1997;41:298.
In moderate and severe disease, four plasma exchanges were better than two; six exchanges were no more beneficial than four.
Berlit P, Rakicky J. The Miller-Fisher syndrome. Review of the literature. J Clin Neuroophthalmol 1992;12:57.
An update on the GBS variant of the Miller-Fisher syndrome, which presents with ataxia, areflexia, and ophthalmoplegia. Prognosis is good, with a mean recovery of 10 weeks.
Brill V, et al. Pilot trial of immunoglobulin versus plasma exchange in patients with Guillain-Barré. Neurology 1996;46:100.
Results of the two treatments were similar, with no difference in relapse rate.
Dalakas MC, Pezeshkpour GH. Neuromuscular diseases associated with human immunodeficiency virus infection. Ann Neurol 1988;23:S38.
GBS is one of six subtypes of peripheral neuropathy commonly associated with AIDS. GBS may occur early or late in HIV disease.
Dyck PJ, Kurtzke JF. Plasmapheresis in Guillain-Barré syndrome. Neurology 1985; 35:1105.
The authors critique the plasmapheresis data of the GBS Study Group (see Guillain-Barré Syndrome Study Group. Plasmapheresis and acute Guillain-Barré syndrome. Neurology 1985;35:1096). The study was not blinded, and 12 patients randomized to plasmapheresis dropped out.
French Cooperative Study Group on Plasma Exchange in Guillain-Barré Syndrome. Efficiency of plasma exchange in Guillain-Barré syndrome: role of replacement fluids. Ann Neurol 1987;22:753.
The French Cooperative Study found improvement in GBS patients who received plasma exchange. There was no improvement in comparison with controls in an albumin or fresh-frozen plasma group.
Ginn DR. Guillain-Barré syndrome. An uncommon but severe illness. Postgrad Med J 1991;90:145.
A practical approach to GBS for the practicing physician.
Guillain-Barré Syndrome Study Group. Plasmapheresis and acute Guillain-Barré syndrome. Neurology 1985;35:1096.
Plasmapheresis was of benefit in GBS patients who received treatment within 7 days.
Harrison BM, et al. Demyelination induced by serum from patients with Guillain-Barré syndrome. Ann Neurol 1984;15:163.
Serum from 16 patients with GBS caused sciatic nerve conduction block in a rat model. Serum obtained in the recovery phase did not cause block.
Hartung HP. Immune-mediated demyelination. Ann Neurol 1993;33:563.
Describes the mechanism of the aberrant immune response responsible for GBS. Tumor necrosis factor may contribute to the inflammatory demyelinating process.
Hughes RA, Rees JH. Clinical and epidemiologic features of Guillain-Barré syndrome. J Infect Dis 1997;176(Suppl 2):S92.
Updates signs and symptoms of the disease and describes worldwide incidence and predisposing factors, emphasizing C. jejuni infection.
Hund EF, et al. Intensive management and treatment of severe Guillain-Barré syndrome. Crit Care Med 1993;21:433.
Describes the expected complications and treatment of GBS in the ICU. Prevention of thrombosis and pneumonia, psychologic support, and adequate nutrition are all important aspects of management.
Randomized trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barré syndrome. Plasma Exchange/Sandoglobulin Guillain-Barré syndrome Trial Group. Lancet 1997;349:225.
Plasma exchange and IV globulin were equally effective in the treatment of severe GBS when given during the first 2 weeks after onset of neuropathic symptoms.
Ropper AH. The Guillain-Barré syndrome. N Engl J Med 1992;326:1130.
Up-to-date comprehensive review that summarizes clinical features, pathophysiology, and results of treatment protocols.
Ropper AH, Wijdicks EFM, Shahani BT. Electrodiagnostic abnormalities in 113 consecutive patients with Guillain-Barré syndrome. Arch Neurol 1990;47:881.
Describes the types of electrodiagnostic abnormalities found in acute GBS. The types of abnormalities did not generally correlate with prognosis.
Ropper AH, Wijdicks EFM, Truax BT. Guillain-Barré syndrome. Philadelphia: FA Davis Co, 1991.
Includes detailed clinical descriptions of GBS and its variants.
Rostami AM. Pathogenesis of immune-mediated neuropathies. Pediatr Res 1993;33: S90–S94.
Review of the pathogenesis of GBS. An animal model of GBS has been induced by immunization with a myelin protein.
Shearn MA, Shearn L. A personal experience with Guillain-Barré syndrome: are the psychologic needs of patient and family being met? South Med J 1986;79:800.
Describes the personal and psychologic aspects of the disease by means of a patient and family diary.
Sovilla JY, Regli F, Francioli PB. Guillain-Barré syndrome following Campylobacter jejuni enteritis. Report of three cases and review of the literature. Arch Intern Med 1988;48:739.
Campylobacter jejuni is now recognized as a trigger of GBS. Eleven cases are reviewed.
Tabor E. Guillain-Barré syndrome and other neurologic syndromes in hepatitis A, B, and non-A, non-B. J Med Virol 1987;21:207.
Reviews the association of GBS and viral hepatitis.
van der Meche FGA, Schmitz PIM, Dutch Guillain-Barré Study Group. A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barré syndrome. N Engl J Med 1992;326:1123.
The Dutch Guillain-Barré Study Group found immune globulin superior to plasma exchange in the treatment of GBS. Patients improved faster on immune globulin and had fewer side effects.
Winer JB, Hughes RAC, Osmond C. A prospective study of acute idiopathic neuropathy. I. Clinical features and their prognostic value. J Neurol Neurosurg Psychiatry 1988;51:605.
Prospective study gives details of clinical features and prognosis in 100 patients. Age and action potential of abductor pollicis brevis were prognostic factors.
Yuki N, et al. Acute axonal polyneuropathy associated with anti-GM1 antibodies following Campylobacter enteritis. Neurology 1990;40:1900.
Describes two cases of GBS after Campylobacter enteritis. In both cases, high titers of IgF antibody against GM ganglioside were demonstrated.