Guillain–Barré and Fisher syndromes : current topics

Abstract

Guillain–Barré syndrome (GBS) is currently classified into the two major categories ; classical demyelinating form, and axonal form termed acute motor axonal neuropathy (AMAN). AMAN is a pure motor axonal subtype of GBS that was identified in the late 1990s. In Asia and Central and South America, it is the major subtype of GBS, seen in 30–65% of patients. One of the main causes is molecular mimicry of human gangliosides by Campylobacter jejuni lipo–oligosaccharides. In addition to axonal degeneration, electrophysiology shows rapidly reversible nerve conduction blockade or slowing, presumably due to pathological changes at the nodes or paranodes. Autoantibodies that bind to GM1 or GD1a gangliosides at the nodes of Ranvier activate complement and disrupt sodium–channel clusters and axoglial junctions, which leads to nerve conduction failure. Improved understanding of the disease mechanism and pathophysiology might lead to new treatment options. Currently eculizumab (anti–complement C5 monocloncal antibody) is a promising agent, and the phase 2 trial has been finished in Japan.

Fisher syndrome has been regarded peculiar inflammatory neuropathy with ophthalmoplegia, ataxia, and areflexia, whereas Bickerstaff brainstem encephalitis has been considered pure central nervous system disease characterized with ophthalmoplegia, ataxia, and consciousness disturbance. Both disorder share common features including preceding infection, albumin–cytological dissociation, and association with Guillain–Barré syndrome. The discovery of anti–GQ1b IgG antibodies further supports the view that the two disorder represent a single disease spectrum. The lesions in Fisher syndrome and Bickerstaff brainstem encephalitis are presumably determined by expression of ganglioside GQ1b in the human nervous system, either peripheral or central. Bickerstaff brainstem encephalitis is likely to represent a variant of Fisher syndrome with central nervous system involvement.