Clinical Research

Significance of Cerebellar Atrophy in Intractable Temporal Lobe Epilepsy: A Quantitative MRI Study
*Evan K. Sandok, *Terence J. O'Brien, Clifford R. Jack, and *Elson L. So
Departments of *Neurology and Diagnostic Radiology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, U.S.A.

Summary: Purpose: To detennine the incidence of cerebellar atrophy (CA) in patients with intractable temporal lobe epilepsy, whether any clinical factors are significantly associated with CA, whether Cerebellar atrophy is unilateral or asymmetric and whether this feature has any relationship to the side of epileptogenicity, and whether the presence of CA is related to epilepsy surgery outcome.

Methods: We developed a magnetic resonance imaging method of measuring the presurgical volumes of the cerebellar hemispheres of 185 patients who underwent temporal lobec-tom y for intractable epilepsy and of 80 control subjects.

In addition, cerebellar volumes were normalized to the total brain volumes. CA was detennined as being present when the mea-sured volume was smaller than two standard deviations from the mean value found in control subjects.

Results: Both absolute and normalized cerebellar volumes were found to be significantly reduced in the epilepsy patients compared with the control subjects.

 

Cerebral Atrophy
Caused by Dilantin
Raise Risk Concerns

2000 Aug;41(1):63-73.

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

Abstract

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.



Epilepsia. 1977 Sep;18(3):375-86. Cerebellar atrophy in phenytoin-treated mentally retarded epileptics. Iivanainen M, Viukari M, Helle EP.

Abstract The relationship among the serum concentration of phenytoin, pneumoencephalographic measurements describing, in particular, cerebellar atrophy, and various other clinical variables was analyzed statistically in a series of 131 phenytoin-treated mentally retarded epileptics.

Phenytoin intoxication was diagnosed retrospectively in 73 patients (56%), of whom 18 had persistent loss of locomotion. The mean duration of phenytoin intoxication until locomotion was lost was 22.8 +/- 23.6 months. There was a temporal relationship between the high serum level of phenytoin and the loss of locomotion. The degree of brain atrophy in the posterior fossa was most severe in these 18 patients with severe phenytoin intoxication. The frequency of cerebellar and/or brain stem atrophy in the present series was 28%, the same as in mentally retarded epileptics without phenytoin treatment from the same institution. That phenytoin levels in serum correlated significantly with the heights of the fourth ventricle suggests that an overdosage of phenytoin or an underlying disease, or both, were the probable causes of cerebellar impairment and atrophy.

Thus brain-damaged mentally retarded epileptics appear to be unusually susceptible to the side effects of phenytoin. This antiepiliptic drug is therefore not recommended for patients with no locomotor ability or with marked cerebellar signs and symptoms. To prevent phenytoin intoxication in susceptible patients, careful observation of the patients and routine monitoring of phenytoin levels in blood are stressed.