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Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality
questions as to the nature and regulation of this abnormal immune response, the nosologic limits of the disorder, and the identities of the specific antigens that were responsible for the syndrome are still not known.
Clinical and Laboratory Features
Guillain-Barré syndrome has recently been fully reviewed in several publications (Arnason and Soliven, 1992; Asbury and Gibbs, 1990; Hughes, 1990; Ropper, 1992; Ropper et al., 1991). The symptoms of GBS usually appear over the course of a single day and may continue to progress for from as few as 3 or 4 days up to 3 or 4 weeks. The symptoms in over 90 percent of the patients plateau by 4 weeks. The major symptom is weakness. generally symmetrical, usually ascending, and usually affecting the legs more than the arms. In a smaller proportion of patients, the symptoms begin in the arms or cranial nerves and descend. About 30 percent of all patients require respiratory support at some stage of the illness, and weakness of the tongue, swallowing, and facial muscles is common in up to 50 percent of all patients with GBS. Paresthesias and even painfulness are experienced in a majority of the patients, but major sensory deficits are not frequent. Ataxia of stance and gait may be an early sign. Reflexes disappear early and return only late in the recovery phase. Fever and constitutional symptoms are generally not present, although in children a degree of meningismus may be noted in a quarter to a third of the patients. The mortality rate is 5 percent or less. For survivors, recovery is the rule, requiring anywhere from a few weeks to well over a year. Some 15 to 20 percent of survivors manifest some residual findings, and 5 percent or more have serious residual disabilities.
Factors affecting prognosis are age (older people do more poorly), the fulminance and severity of the neuropathy, the severity of the electrodiagnostic findings early in the disease, and early treatment, either plasmapheresis or high-dose intravenous immunoglobulin (Cornblath et al., 1988; McKhann et al., 1988; van der Meché et al., 1992).
Cerebrospinal fluid is normal in the first few days of illness, but the protein content rises toward the end of the first week and remains elevated for several months in over 90 percent of patients. Spinal fluid cell counts are below 10 cells, mostly lymphocytes, per mm3, but in human immunodeficiency virus (HIV)-positive individuals, spinal fluid cell counts may be as high as 100 to 200/mm3.
The characteristic electrodiagnostic features are those of demyelination with variable degrees of admixed, presumably secondary, axonal degeneration. These abnormalities include prolongation of distal latencies and F-wave latencies, particularly as early features; slowing of nerve conduction velocity, frequently in a multifocal pattern; conduction block; and