Spinocerebellar ataxia type 1 with multiple system degeneration and glial cytoplasmic inclusions

Abstract

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited progressive neurological disorder characterized by neuronal degeneration and reactive gliosis in the cerebellum, brainstem, spinocerebellar tracts, and dorsal columns. Multiple system atrophy is a sporadic progressive neurological disorder with degeneration and gliosis in the basal ganglia, cerebellum, brainstem, and spinal autonomic nuclei, and with argyrophilic glial cytoplasmic inclusions. We describe 4 members of a family with the SCA1 mutation and a dominantly inherited progressive ataxia in which autopsy examination of 1 member showed neuropathological changes typical of multiple system atrophy, including glial cytoplasmic inclusions. In this patient, magnetic resonance imaging revealed marked brainstem and cerebellar volume loss and mild supratentorial generalized volume loss. Positron emission tomography with [18F]fluorodeoxyglucose revealed widespread hypometabolism in a pattern found in sporadic multiple system atrophy and not in dominantly inherited olivopontocerebellar atrophy. Positron emission tomography with [11C]flumazenil revealed normal benzodiazepine receptor distribution volumes, similar to those seen in sporadic multiple system atrophy. Two other family members still living had similar changes in the imaging studies. The findings in this family suggest that the SCA1 gene mutation can result in a disorder similar to multiple system atrophy, both clinically and neuropathologically.

Executive Dysfunction in Spinocerebellar Ataxia Type 1

“…Such impairment is commonly ascribed to lesions of the frontal cortex. Since the cerebral cortex is mostly preserved in SCA1 [27], a prefrontal degeneration is yet not likely to represent the primary origin of cognitive dysfunction in SCA1. In basal ganglia disorders with normal frontal lobe morphology, ‘subcortical dementia’ with executive dysfunction is explained by degeneration of subcortical structures at the level of the striatum or thalamus [28].…”

Clinical and molecular advances in autosomal dominant cerebellar ataxias: from genotype to phenotype and physiopathology

“…115 Cell loss is mild in the substantia nigra, the locus coeruleus and the Clarke's column. 52,116 The SCA2 profile is considered typical of OPCA since the inferior olive, substantia nigra, cerebellum (severe Purkinje cells loss) and pontine nuclei are affected. 117 It can be distinguished from SCA1, however, since the superior cerebellum peduncles are spared and the substantia nigra severely lesioned.…”

Lateral cerebellar hemispheres actively support sensory acquisition and discrimination rather than motor control.

“…The most conspicuous and therefore best-studied effects of cerebellar lesions are on movement coordination (Holmes 1939;Thach et al 1992;Subramony 1994;Gilman et al 1996). Classic theory has emphasized that the output of the deep cerebellar nuclei in mammals is to primarily influence motor structures (Asanuma et al 1983;Aumann et al 1994;Keifer and Houk 1994).…”