We report 2 patients with a treatable, immune-mediated motor polyneuropathy associated with antibodies to defined neural antigens. In these patients asymmetrical weakness developed in one arm and progressed over 2 to 3 years to involve the other arm, legs, and trunk. Both patients were initially diagnosed as having lower motor neuron forms of amyotrophic lateral sclerosis. However, repeated electrophysiological testing eventually showed multifocal conduction blocks in motor but not sensory fibers compatible with patchy selective demyelination. Serum testing by thin-layer chromatography and enzyme-linked immunosorbent assay revealed that both patients had high titers of antibody directed against GM1 and other gangliosides. Initial therapeutic trials of prednisone (100 mg daily for 4 to 6 months) and plasmapheresis were unsuccessful. Treatment with cyclophosphamide, however, was followed by marked improvement in strength in both patients.

A significant number of patients with progressive leukodystrophy do not have a definitive diagnosis. This report describes the clinical, morphological, and biochemical characteristics of 4 unrelated girls with progressive ataxic diplegia of unknown etiology. These patients had normal development until the ages of 1.5 to 5 years. A diffuse confluent abnormality of the white matter of the central nervous system was present on computed tomography and magnetic resonance scans obtained early in the course of the illness. Dementia was not present and peripheral nerves were normal. All patients were evaluated for known metabolic and degenerative diseases and no abnormalities were observed. Light and electron microscopy of open-brain biopsy specimens from 2 girls showed selective white matter abnormalities including hypomyelination, demyelination, and gliosis. Myelin-specific proteins in the subcortical white matter were examined immunocytochemically and by Western blot analysis. They were of normal molecular size but were markedly reduced in quantity in both patients compared to control subjects. Lipid analysis revealed decreased levels of characteristic myelin lipids. When examined by magnetic resonance spectroscopic imaging, all patients showed a marked decrease of N-acetylaspartic acid, choline, and creatine in white matter only. The magnetic resonance spectroscopic imaging profile is a unique diagnostic feature of this clinicopathological syndrome.

The myelin-associated glycoprotein (MAG) is a type I transmembrane glycoprotein localized in periaxonal Schwann cell and oligodendroglial membranes of myelin sheaths where it functions in glia-axon interactions. It contains five immunoglobulin (Ig)-like domains and is in the sialic acid-binding subgroup of the Ig superfamily. It appears to function both as a ligand for an axonal receptor that is needed for the maintenance of myelinated axons and as a receptor for an axonal signal that promotes the differentiation, maintenance and survival of oligodendrocytes. Its function in the maintenance of myelinated axons may be related to its role as one of the white matter inhibitors of neurite outgrowth acting through a receptor complex involving the Nogo receptor and/or gangliosides containing 2,3-linked sialic acid. MAG is expressed as two developmentally regulated isoforms with different cytoplasmic domains that may activate different signal transduction pathways in myelin-forming cells. MAG contains a carbohydrate epitope shared with other glycoconjugates that is a target antigen in autoimmune peripheral neuropathy associated with IgM gammopathy and has been implicated in a dying back oligodendrogliopathy in multiple sclerosis. Keywords: multiple sclerosis, myelin, myelin-associated glycoprotein, neuropathy, oligodendrocyte, Schwann cell. The myelin-associated glycoprotein (MAG) is a 100 kDa transmembrane glycoprotein that is selectively localized in periaxonal Schwann cell and oligodendroglial membranes of myelin sheaths, suggesting that it functions in glia-axon interactions in both the PNS and CNS. It is important for the normal formation and maintenance of myelinated axons, although it is currently well known as one of several white matter inhibitors of axonal regeneration and as an antigen for IgM monoclonal antibodies that cause demyelinating peripheral neuropathy. The latter are negative characteristics with regard to neurological well-being, and a principal objective of this review will be to revitalize the concept that MAG has important positive functions in glia-axon interactions and myelination. In addition, it is proposed that aberrations or disruption of these normal physiological functions have negative consequences and contribute to neurological disabilities. In recent years, a substantial amount has been learned about a neuronal receptor complex for MAG from investigation of its capacity to inhibit neurite outgrowth, and this new information will be considered in the context of MAG's function in the formation and maintenance of myelinated axons. In addition, the roles of MAG in the pathology of peripheral neuropathy and multiple sclerosis (MS) will be reviewed. Finally, the implications of our current knowledge of MAG will be discussed with regard to directions for future research on its roles in myelination and neurological disorders. Although this review will cite some of the most important original references on MAG and others dealing with issues that are not yet fully resolved, description...