Multiple System Atrophy

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MSA refers to a neurodegenerative disease characterized by parkinsonism, cerebellar ataxia, and orthostatic hypotension (31). There is no known genetic risk factor or genetic locus in MSA. The MSA brain shows varying degrees of atrophy of the cerebellum, cerebellar peduncles, pons and medulla, as well as atrophy and discoloration of the posterolateral putamen and pigment loss in the substantia nigra. The histopathological findings include neuronal loss, gliosis, and microvacuolation, involving the putamen, substantia nigra, cerebellum, olivary nucleus, pontine base, and intermediolateral cell column of the spinal cord. White matter inevitably shows demyelination, with the brunt of the changes affecting white matter tracts in the cerebellum and pons (Fig. 3).

Lantos et al. (32) first described oligodendroglial inclusions in MSA and named them glial cytoplasmic inclusions (GCIs). GCIs can be detected with silver stains, such as the Gallyas silver stain, but are best seen with antibodies to synuclein, where they appear as flame- or sickle-shaped inclusions in oligodendrocytes (Fig. 3). Like Lewy bodies, GCIs are also immunostained with antibodies to ubiquitin (32). At the ultrastructural level, they are nonmembrane-bound cytoplasmic inclusions composed of filaments (7 to 10 nm) and granular material that often coats the filaments making precise measurements difficult (33). GCIs are specific for MSA and have not been found in other neurodegenerative diseases. In addition to GCIs, synuclein immunoreactive lesions are also detected in some neurons in MSA. Biochemical studies of synuclein in MSA have shown changes in its solubility (34).

FIGURE 3 Multiple system atrophy (MSA): Substantia nigra neuronal loss in MSA is obvious in the cluster of pigment-laden macrophages (arrow in A), but neuronal inclusions are not present. Synuclein immunostaining of the substantia nigra shows many small inclusions in oligodendroglial cells

(B). The white matter in the cerebellum shows marked myelin loss (Luxol fast blue stain for myelin)

(C) and in the affected areas there are many synuclein-immunoreactive glial inclusions (arrows) (D).

FIGURE 3 Multiple system atrophy (MSA): Substantia nigra neuronal loss in MSA is obvious in the cluster of pigment-laden macrophages (arrow in A), but neuronal inclusions are not present. Synuclein immunostaining of the substantia nigra shows many small inclusions in oligodendroglial cells

(B). The white matter in the cerebellum shows marked myelin loss (Luxol fast blue stain for myelin)

(C) and in the affected areas there are many synuclein-immunoreactive glial inclusions (arrows) (D).

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