Patterns of cerebellar atrophy in patients with chronic epilepsy: a quantitative neuropathological study

Cerebellar atrophy occurring in patients with chronic epilepsy is considered either to be a sequel of cumulative seizure-mediated cell loss or a side effect of phenytoin treatment but there is little neuropathological data regarding the distribution of this cerebellar damage. We aimed to address if there is any relationship between the localisation of the cortical pathology in symptomatic epilepsy and the pattern of neocerebellar atrophy. A quantitative neuropathological post mortem analysis of the lobular distribution of hemispheric cerebellar atrophy in 16 patients with chronic epilepsy and four controls was carried out. Cerebellar atrophy, as measured by significant reductions in hemispheric linear Purkinje cell densities was confirmed in the epilepsy patients (P = 0.015) and even where the cerebellum appeared macroscopically normal, Purkinje cell loss was evident (P = 0.062). Two distinct patterns of atrophy were observed, predominantly involving either the anterior or posterior cerebellar lobes. Posterior lobe atrophy was more often associated with old fronto-temporal contusions and may be post traumatic in aetiology rather than a result of excitotoxic damage mediated via cerebro cerebellar pathways. As the majority of patients showing either pattern of atrophy had received phenytoin treatment, we concluded that it is unlikely that this drug acts alone in inducing the Purkinje cell loss.