Peripheral nervous system and central nervous system pathology in rapidly progressive lower motor neuron syndrome with immunoglobulin M anti-GM1 ganglioside antibody

Abstract

Pathological studies, including novel teased peripheral nerve fiber studies, were performed in a patient who presented with a rapidly progressive, lower motor neuron syndrome and high titer of immunoglobulin M anti-GM1 ganglioside antibody. In the central nervous system, there was a severe loss of motor neurons and central chromatolysis with ubiquitin immunopositive cytoplasmic inclusions in residual motor neurons. In the peripheral nervous system, axonal degeneration of myelinated fibers in the anterior nerve roots was evident. Pathologic evidence of sensory nerve involvement was also found despite the absence of clinical or electrophysiological sensory abnormalities. Sectional studies of single myelinated nerve fibers from an antemortem sural nerve biopsy showed remyelination and globular paranodal swellings due to focal complex myelin folding and degeneration in 13% of fibers. Postmortem studies of the sural nerves 4 weeks later showed paranodal demyelination (90% of fibers), but no paranodal swellings and similar findings were present in samples of the ulnar, radial, median, tibial, and common peroneal nerves. Paranodal abnormalities of enlargement of the adaxonal space, myelin degeneration, and axonal compaction were found on cross-sectional studies of individual teased fibers, which on conventional light microscopic assessment appeared normal. These changes suggest a disturbance of paranodal axonal–myelin adhesion due to binding of the anti-GM1 ganglioside antibody to the common epitope known to be present on the myelin sheath and nodal axolemma in the paranodal region of both motor and sensory nerves.