Complementing the therapeutic armamentarium for Miller Fisher Syndrome and related immune neuropathies

Abstract

In 1956 Miller Fisher described in his seminal paper three patients with an unusual variant of acute onset polyneuritis characterized by the clinical triad of ophthalmoplegia, ataxia and areflexia (Fisher, 1956). Although there was only minor limb involvement in his cases, Miller Fisher recognized that the syndrome he delineated has a significant overlap with other inflammatory neuropathies such as Guillain–Barre syndrome (GBS). Nowadays Miller Fisher syndrome (MFS) is widely regarded a part of the GBS spectrum (Hughes and Cornblath, 2005; Lo, 2007). MFS is commonly preceded by an infectious illness such as Campylobacter jejuni enteritis (Koga et al. , 2005). Specific C. jejuni strains associated with MFS contain in their lipooligosaccharides ganglioside mimics that elicit an antibody response to shared neural epitopes (Yuki, 2007). In the vast majority of MFS patients, serum antibodies to the tetrasialoganglioside GQ1b can be detected (Chiba et al. , 1993; Willison and Yuki, 2002). These antibodies are usually IgG antibodies of complement fixing isotypes. Furthermore, anti-GQ1b antibodies can bind to the nodes of Ranvier and to the presynaptic terminal of neuromuscular junctions in extraocular and somatic muscles. Immunolocalization studies demonstrated that GQ1b is much more widely expressed in the oculomotor cranial nerves than in other cranial and peripheral nerves. It is also expressed on sensory neurons. This differential distribution may account for part of the clinical spectrum typically seen in Miller Fisher syndrome (Chiba et al. , 1997). It is worth noticing that antibodies of other related specificities, such as for gangliosides GT1a, GD1b and GD3, and more recently for ganglioside complexes containing GQ1b have also been identified in MFS, and for that matter, GBS (Kaida et al. , 2006; Nagashima et al. , 2007; Yuki, 2007; Kanzaki et al. , 2008). Insight into the molecular targets of an aberrant …