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Until recently, multiple sclerosis (MS) was considered an inflammatory demyelinating disorder of the central nervous system, characterized by axonal sparing. The origin of this misconception is nebulous, and its existence astonishing. Jean Martin Charcot was among the first to recognize the presence of axonopathies in MS. He observed that MS lesions are sometimes located adjacent to cerebral gray matter and that they may infiltrate gray matter, deep nuclei, and the cerebral cortex.1 These observations, along with their confirmation by other investigators, took place 140 years ago. Knowledge of gray matter disease in MS has advanced little since then.
Richert ND, Kraft E, Stüve O. Visualizing the Cause of Gray Matter Atrophy in Multiple Sclerosis. Arch Neurol. 2009;66(2):159–160. doi:10.1001/archneurol.2008.563