Distribution of cerebello‐olivary degeneration in idiopathic late cortical cerebellar atrophy: Clinicopathological study of four autopsy cases

Abstract

Late cortical cerebellar atrophy (LCCA) is a neurodegenerative disease which presents with slowly progressive cerebellar ataxia as a prominent symptom and is characterized neuropathologically by a limited main lesion to the cerebellar cortex and inferior olivary nucleus. To elucidate the features of lesions in the cerebellar cortex and inferior olivary nucleus, four autopsy cases suffering from idiopathic LCCA without other cortical cerebellar atrophies, such as alcoholic cerebellar degeneration, phenytoin intoxication, or hereditary cerebellar atrophy including spinocerebellar ataxia type 6, were examined. All affected patients had identical distinct features of cerebellar cortical lesions. In all four cases, the most obvious pathological finding throughout the cerebellum was loss of Purkinje cells, but the rarefaction of granular cell layers was observed only where loss of Purkinje cells was very severe, and thinning of the molecular layer was seen only where the rarefaction of granular cell layers was moderate to severe. Two patients presented with vermis dominant cerebellar cortical lesions, but the other two patients showed hemispheric dominant pathological changes. Neuronal loss of the inferior olivary nucleus was observed in the three autopsy cases. Two of the three cases had a prominent lesion in the dorsal part of the inferior olive and the cerebellar cortical lesion disclosed the vermis dominance, but the other patient, showing prominent neuronal loss in the ventral olivary nucleus, had a cerebellar hemisphere dominant lesion. The patient without neuronal loss in the inferior olivary nucleus had suffered from a shorter period of disease than the others and the rarefaction of granular cell layers and narrowing of the molecular layer of the cerebellar cortex were mild. Therefore, it is obvious that there are two types of cerebellar cortex lesions in idiopathic LCCA; one is vermis dominant and the other is cerebellar hemispheric dominant. The lesion of the inferior olivary nucleus occurs as a secondary degeneration after rarefaction of the granular cell layer and thinning of the molecular layer of the cerebellar cortex progresses. Furthermore, the distribution of the degeneration in the inferior olivary nucleus depends on the distribution of the cerebellar cortex lesions.

Torpedoes in the Cerebellar Vermis in Essential Tremor Cases vs. Controls

“…The cerebellum is neither anatomically nor functionally homogeneous, and there are a number of examples of toxic or disease processes that do not affect the cerebellum in a uniform manner. For example, the cerebellar hemispheres are relatively less involved than the vermis in chronic alcoholics [26][27][28]; conversely, some forms of cerebellar olivary degeneration are manifest by relative preservation of the vermis in contrast to the cerebellar hemispheres [29]. The sine qua non of ET is the presence of hand tremor [30] and, on that basis, one would expect that the postmortem changes would involve the cerebellar hemispheres, which are physiologically responsible with limb coordination.…”

Update on degenerative ataxias

“…Neuropathological examination of autopsied brains of four SAOA patients showed cerebellar cortical degeneration variably affecting the vermis and hemispheres with secondary involvement of the inferior olives [37].…”

Hypocupremia: A Possible Association with Late Cortical Cerebellar Atrophy

“…The Purkinje layer sends inhibitory output to the deep cerebellar nuclei and is an important modulating force on the deep cerebellar nuclei 20. Purkinje cell lesions have been observed in autopsy study of LCCA patients 4,21. Perinatal copper deficient rats demonstrated irregularities in the Purkinje cell monolayer in the cerebellum cortex compared to rats with adequate copper 22…”