An autopsy case of an aged patient with spinocerebellar ataxia type 2

Abstract

We report the case of a woman who developed limb clumsiness in her fifties and gait disturbance in her sixties. She was bedridden after bone fractures at age 75 and showed disorientation, slow eye movement, gaze palsy, ataxic speech, muscle atrophy and weakness, and areflexia with pathological reflex. She died of respiratory failure at age 85. This patient was diagnosed genetically as having spinocerebellar ataxia type 2 (SCA2), and the number of expanded CAG repeats was 41. At autopsy, the brain weighed 965 g, and the brainstem, cerebellum, frontal convexity and spinal cord were atrophic. Neuronal loss and gliosis were severe in the pontine nucleus, inferior olivary nucleus, cerebellar cortex, gracile and cuneate nuclei and moderate in the substantia nigra, cerebellar dentate nucleus, anterior horns of the spinal cord and dorsal root ganglia. Axonal loss was observed in the middle and inferior cerebellar peduncles, pyramidal tract and posterior column of the spinal cord. Senile plaques and neurofibrillary tangles (NFTs) were diffusely found in the cerebrum (plaque stage C; NFT stage IV). Expanded polyglutamine-immunoreactive inclusions in the neuronal cytoplasm were widely distributed in the CNS, and neuronal intranuclear inclusions were observed in the pontine nucleus and cerebral cortex. This patient in this autopsy case is a late-onset and aged patient with SCA2, and this is the first report of SCA2 combined with Alzheimer's disease (AD) pathology. Neuropathological findings in this patient, except for AD pathology, were consistent with those of reported SCA2 cases. However, the olivo-ponto-cerebellar system of this patient was relatively preserved and the cerebellar dentate nucleus was more involved as compared with previously reported cases. These results suggest that age at onset or the number of CAG repeat expansions could correlate with the distribution pattern of SCA2 neurodegeneration.

Motor Dysfunctions and Neuropathology in Mouse Models of Spinocerebellar Ataxia Type 2: A Comprehensive Review

“…Also, recent studies have found degeneration in the striatum, pallidum , and even the neocortex (Estrada et al, 1999; Seidel et al, 2012). In addition to this, several groups have presented compelling evidence for the existence of nuclear and cytoplasmic inclusions, stained with anti-ataxin-2, anti-expanded PolyQ (1C2) and anti-ubiquitin antibodies, similarly to what happens in other polyQ diseases (Koyano et al, 1999; Pang et al, 2002; Ishida et al, 2011). All in all, this overall degeneration in the brains of SCA2 patients goes far beyond the purely cerebellar alterations that its name might imply and it ends up affecting the whole brain.…”

“…Other brain regions such as the cerebral frontal lobes, brainstem, cranial nerves, and spinal cord also show signs of degeneration (Estrada et al, 1999; Pang et al, 2002; Ishida et al, 2011). Interestingly, in vivo brain MRI of 24 SCA2 patients has also revealed a significant atrophy of regions like the pontine base, the middle cerebellar peduncles and the cerebellar hemispheres, when compared with either healthy controls or patients with SCA1 and Machado-Joseph disease (MJD/SCA3l; Bürk et al, 1996).…”

Neuromuscular electrical stimulation of the median nerve facilitates low motor cortex excitability in patients with spinocerebellar ataxia

“…Spinocerebellar ataxia (SCA) is one of several hereditary neurodegenerative disorders characterized by progressive loss of coordination of gait and poor coordination of speech or eye movements (Ishida et al, 2011;Jayadev and Bird, 2013;Liepert et al, 2000aLiepert et al, , 2004Rossi et al, 2014). To date, no existing treatment can cure this disease.…”

“…To date, no existing treatment can cure this disease. SCA is always observed in atrophy of the cerebellum, and the ataxia arises from damage to the different cerebellar regions Ishida et al, 2011;Jayadev and Bird, 2013;Rossi et al, 2014;Soong, 2002Soong, , 2004. The primary neurophysiological function of the cerebellum is to maintain the excitability of the motor cortex and its subsequent descending tract for movement control (Di Lazzaro et al, 2002;Klein et al, 2012;Liepert et al, 1998;Meyer et al, 1994;Wessel et al, 1996).…”

Multimodal evoked potentials in spinocerebellar ataxia types 1, 2, and 3

“…Pathologically these findings result due to degeneration of the olivopontocerebellar tracts[7] and involvement of other neural networks. [8910] The overlapping clinical features and imaging findings make it difficult to differentiate between each of these three types without resorting to genetic testing.…”