Which pathologic findings indicate multiple system atrophy (MSA)?

Updated: Sep 24, 2018
  • Author: Stephen M Bloomfield, MD; Chief Editor: Selim R Benbadis, MD  more...
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Answer

MSA syndromes have common pathologic findings such as cell loss and gliosis in the striatum, substantia nigra, locus ceruleus, inferior olive, pontine nuclei, dorsal vagal nuclei, cerebellar Purkinje cells, and intermedio-lateral cell columns of the spinal cord. The specific histologic hallmark is glial cytoplasmic inclusions (GCI), which are found mainly in oligodendrocytes. [13]

Macroscopic findings in patients with MSA correlate with neuroimaging and clinical findings. Each MSA subtype demonstrates various degrees of atrophy in the extrapyramidal, spinocerebellar, pyramidal, and autonomic nervous systems. Some depigmentation of the substantia nigra and locus ceruleus is noted in all MSA subtypes. Atrophy of the motor and premotor cortices has also been noted. The intermediolateral cell column of the spinal cord is preferentially involved.

Patients with MSA-P primarily develop extrapyramidal system atrophy such that the posterolateral putamen and ventrolateral substantia nigra appear atrophic and discolored. Patients with MSA-C primarily have shrinkage of the cerebellum, middle cerebellar peduncles, inferior olives, and basis pontis. [14]

Histopathologic findings include neuronal loss, gliosis, and microvacuolation in the involved neuronal systems. These findings are present in varying degrees proportional to the volume loss on gross inspection. Even in regions where atrophy is not noted, these changes are present to some extent.

Demyelination eventually ensues in the white matter in the involved regions. An epitope of myelin basic protein was discovered only in degenerating myelin. Monoclonal antibody probes for this aberrant myelin demonstrate that these white matter lesions are more widespread than previously demonstrated with routine myelin stains.

Autonomic and endocrine manifestations of MSA may be related to neuronal loss in the hypothalamus, spinal cord, and medulla. Cell loss has been found in histaminergic neurons in the tuberomammillary nucleus, arginine-vasopressin neurons in the suprachiasmatic nucleus, and tyrosine hydrolase neurons in the medulla, arcuate nucleus, and spinal cord lateral horns and intermediate zone of the anterior horns. Abnormalities in peripheral nerves and muscles that are absent in patients with idiopathic PD have been found in patients with MSA. Sural nerve biopsy demonstrates a 23% reduction in unmyelinated nerve fibers. Nerve conduction studies are abnormal in 40% of patients with MSA. Abnormal electromyography findings suggesting partial denervation have been found in 22.5% of patients with MSA. [15]


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