The Molecular Basis for Selective Involvement of the Extraocular Muscles in Miller Fisher Syndrome

Abstract

Purpose:: To investigate the distribution of gangliosides GQ1b, GT1a, GD3, GD1a, GD1b and GM1 in human extraocular (EOM), axial and limb muscles.

Methods:: Samples from five EOMs and eight limb and axial muscles were processed for immunocytochemistry with highly specific monoclonal antibodies (Abs) against gangliosides GQ1b+GT1a+GD3, GD1a, GD1b and GM1.

Results:: Abs against gangliosides GQ1b+GT1a+GQ1b strongly labelled the neuromuscular junctions (NMJs) in the human EOMs, particularly in regions rich in multiply innervated, slow tonic fibers in the orbital layer. In limb and axial muscles, staining was also observed inside muscle spindles but no corresponding massive labeling of NMJs was apparent. The Ab against ganglioside GD1b also labeled NMJs in EOMs, especially those of slow tonic fibers, but it did not label the muscle spindles in other muscles.

Conclusions:: Ophthalmoplegia, ataxia and arreflexia, along with the presence of autoantibodies against ganglioside GQ1b (and in 50% of cases also against GD1b) are typical of Miller Fisher syndrome. The autoantibodies against gangliosides arise through molecular mimicry with microbial oligosaccharides and Miller Fisher syndrome is regarded as a variant of Guillan-Barré syndrome. The differential distribution of gangliosides GQ1b and GD1b in the different human muscles investigated here provides a molecular basis for the selective involvement of the EOMs in Miller Fisher syndrome. Our data further suggest that the slow tonic fibers in the orbital layer may be the preferential target. Further studies are underway to correlate fiber types in the EOMs and in the muscle spindles with the presence of the different gangliosides at their neuromuscular junctions.

Keywords: extraocular muscles: structure • eye movements • pathology: human