Facts and fallacies on anti-GM1 antibodies: physiology of motor neuropathies

Antibodies to ganglioside GM1 (anti-GM1 antibodies) have been implicated in the pathogenesis of Guillain–Barre syndrome (GBS), multifocal motor neuropathy (MMN) and motor neuron disease. Although the elevated titres of these antibodies have been amply documented in multifocal motor neuropathy and a motor axonal variant of GBS, or acute motor axonal neuropathy (AMAN), their exact role in the pathogenesis remains elusive. The GM1 epitope is present not only in motor neurons and their axons but also in the dorsal root ganglion cells and sensory axons. If anti-GM1 antibodies are pathogenic, what dictates the predilection for the motor system, and how do these antibodies affect the nervous system?In an in vitro study, Takigawa and colleagues (Takigawa et al ., 1995) showed an acute increase in the potassium current and, in the presence of complement, irreversible loss of the sodium current after topical application of the antibody to a mixed nerve, providing a rationale for the hypothesis that anti-GM1 antibodies block sodium channels, causing conduction block (Waxman, 1995). This finding also led to the contention that sodium channels may play a role in the pathophysiology of motor neuron disease (Gutmann et al ., 1996).In this issue of Brain , Paparounas and colleagues (Paparounas …