The relationship of multiple system atrophy to sporadic olivopontocerebellar atrophy and other forms of idiopathic late‐onset cerebellar atrophy

Multiple system atrophy (MSA) is a sporadic progressive neurodegenerative disease of undetermined cause characterized clinically by combinations of cerebellar, pyramidal, extrapyramidal, and autonomic disorders. ^1,2 Many patients with MSA initially develop extrapyramidal symptoms and later experience autonomic disturbance or cerebellar features, or both; others start with autonomic disturbance, and some first manifest cerebellar symptoms and later develop autonomic or extrapyramidal features. Many patients develop only extrapyramidal and autonomic symptoms, but in most of these cases, subsequent neuropathologic studies also demonstrate degenerative changes in the cerebellum and brainstem. ^3,4 The term MSA encompasses striatonigral degeneration (SND), the Shy-Drager syndrome (SDS), and many cases of sporadic olivopontocerebellar atrophy (sOPCA). Autopsy examination discloses neuronal loss and gliosis within some or all of the following structures: inferior olives, pons, cerebellum, substantia nigra, locus ceruleus, striatum (mainly putamen), and the intermediolateral columns and Onufs nucleus of the spinal cord. ⁵

Recently there have been descriptions of distinctive neuropathologic features of MSA consisting of oligodendroglial ^6–11 and neuronal ^12–14 intracytoplasmic and intranuclear argyrophilic inclusions containing accumulations of tubular structures. The glial cytoplasmic inclusions (GCIs) are present in all MSA brains, regardless of whether the patients were diagnosed in life as having SND, SDS, or sOPCA-type MSA. ^6,14,15 In contrast, GCIs were not initially ⁶ found in a large number of neurologic controls, including patients with Parkinson's disease, progressive supranuclear palsy (PSP), and Machado-Joseph disease. However, a recent report ¹⁶ indicates that, although characteristic of MSA, the presence of GCIs is not …