As discussed elsewhere in this chapter, the expected latency between an antecedent event (when infection or administration of antigen occurs) and the first symptoms of GBS is mainly between 7 and 21 days. Occasional cases appear to have latencies of between 22 and 42 days. All evidence indicates that GBS is immune mediated via a delayed-type hypersensitivity mechanism. Taken together, these two observations allow a range of latencies to be stated for GBS, that is, 5 days to 6 weeks. Similarly, ADEM is widely believed to be the human counterpart of experimental allergic encephalomyelitis, and EAE has an observed latency of about 10 to 20 days. ADEM has a similar clinical latency, and its pathologic features also have all of the hallmarks of a delayed-type hypersensitivity response. On the basis of these observations and inferences, a conservative estimate of the limits of the latencies for both GBS and ADEM is considered to be from 5 days to 6 weeks throughout this report.

Pathology and Pathogenesis

A characteristic pathologic feature of GBS is the presence of mono-nuclear cell infiltrates in peripheral nerves and roots in both a diffuse and a perivenular distribution (Arnason and Soliven, 1992; Asbury et al., 1969). Lesions are patchy and variable, and some patients may show almost no cellular inflammation (Honavar et al., 1991). Lesions are most prominent in the proximal plexuses and roots, particularly the ventral root, but may be found scattered throughout the peripheral nervous system, including the autonomic trunks and intramuscular twigs. Demyelination often corresponds to the distribution of cellular infiltration, but demyelination is quite extensive even in those patients in whom cellular infiltration is minimal. Axonal degeneration occurs, presumably as a secondary event at sites where lesions are intense, but the extent and distribution of axonal degeneration vary widely from patient to patient. The extent of axonal degeneration has a strong effect on the rate and completeness of recovery.

Lymphocytes in the infiltrate are primarily T cells, with CD4-positive cells predominating in early lesions and CD8-positive cells being the most plentiful in mature lesions. Bone marrow-derived macrophages swarm into the lesions and constitute by far the most numerous pathologic cell types in nerves. Myelin destruction appears to be macrophage mediated, either by myelin lamellar stripping by macrophage processes or by vesicular disruption of myelin. The role of lymphocytes in myelin destruction is unclear. The pathologic appearance of GBS is characteristic of a delayed-type hypersensitivity response and closely resembles the lesions of experimental allergic neuritis (Waksman and Adams, 1955). In addition, there is abundant evidence of immune system activation in patients with GBS, including greatly increased levels of circulating soluble interleukin-2 receptor and



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