Cerebellar Atrophy in Epileptic Patients

Abstract

High-resolution CT scans of the brain and posterior fossa were performed on 106 phenytoin (PHT)treated epileptics, 28 de novo epileptics and 43 control subjects. A higher incidence of cerebellar and brainstem (CBS) atrophy was observed in chronic PHT-or PHT+ phenobarbital-treated epileptics compared to the two other groups. Some control subjects and de novo epileptics presented mild CBS atrophy, whereas moderate to severe atrophy was noted exclusively in chronically-treated patients. In attempting to delineate the etiology of CBS atrophy, epileptic patients were divided in three groups: 55 subjects with normal CT scans, 30 with both cerebral and CBS atrophy, and 49 with pure CBS atrophy. Their ages, length of illness, number of generalized seizures, number of other seizures, and amount of PHT received during their lifetime were assessed. Statistical analysis revealed that posterior fossa atrophy in epileptics was significantly correlated with both the length of the illness and the amount of PHT ingested during the patient's lifetime. The number of seizures appears to not be related to CBS atrophy. RESUME: L'atrophie cerebelleuse chez les epileptiques. On a pratique la tomodensitometrie du cerveau avec haute resolution pour la fosse posterieure chez 106 epileptiques chroniques traites a la phenytoine (PHT), chez 28 Epileptiques chroniques traites a la PHT, chez 28 epileptiques de novo et chez 43 sujets-controles. Nous avons retrouve une fr6quence significativement elevee de l'atrophie cerebelleuse et du tronc cerebral (ACTC) chez les epileptiques chroniques par rapport aux deux autres groupes. Certains sujets controles et epileptiques de novo ont presente une atrophic ponto-c6r£belleuse legere tandis que les atrophies moderees ou severes ont ete observees en exclusivite chez les epileptiques. En essayant de preciser retiologie de l'ACTC, 134 patients traites sur base externe ont ete divises en trois groupes: 55 sujets avec une tomodensitometrie du cerveau normale, 30 patients avec ACTC et avec atrophies cerebrales et 49 epileptiques avec des ACTC pures. Les parametres etudies ont ete l'age, la duree de la maladie, le nombre de crises de grand-mal, le nombre d'autres crises et la quantite de PHT ingeree pendant la vie du malade. Les analyses statistiques ont demontre que l'ACTC est correlee avec la duree de la maladie et avec la quantite totale de PHT ingeree pendant la vie du malade. Le nombre de crises n'etait pas apparemment relie avec la frequence de l'atrophie des formations de la fosse posterieure.

Relação dose-dependente do uso crônico de fenitoína e atrofia cerebelar em pacientes com epilepsia

“…Embora haja relatos na literatura [1][2][3][4][5][6][7][8][9][10] de ataxia permanente associada ao uso de fenitoína em altas doses e por tempo prolongado, existem poucos estudos com casuística suficiente para definir a etiologia da atrofia cerebelar. O estabelecimento de correlação inequívoca entre o uso de fenitoína e a atrofia cerebelar é difícil pois, na maioria dos casos, além do uso da medicação anticonvulsivante, os pacientes também apresentam crises tônico-clônicas generalizadas e hipóxia decorrente destas crises.…”

“…Rapport & Shaw 4 estabeleceram com maior segurança a relação entre fenitoína e atrofia cerebelar ao relatar este achado em um paciente tratado profilaticamente com fenitoína e que nunca havia apresentado crise epiléptica. Entretanto, colaboram para a controvérsia dos estudos 3,8 que demonstram ser a hipóxia, devida às crises generalizadas frequentes, uma provável causa de lesão cerebelar.…”

“…Seu uso, entretanto, não é isento de efeitos adversos, sendo o mais comum a disfunção cerebelar após intoxicação aguda, levando a sintomas como diplopia e ataxia. Atrofia cerebelar irreversível pode ocorrer após intoxicação aguda 2 e também após o uso crônico da fenitoína [3][4][5][6][7] . Estudos anteriores indicam que a atrofia cerebelar devido ao efeito tóxico direto da droga sobre as células de Purkinje ou pela hipóxia causada pelas crises generalizadas tônico-clônicas [3][4][5][6][7] , ou por esses dois fatores atuando sinergicamente [8][9][10][11] .…”

Sudden death in a child with epilepsy: potential cerebellar mechanisms?

“…An additional important issue is evidence that phenytoin can exert toxic effects on the cerebellum in patients with epilepsy 32 ; the toxicity is associated with ataxia, tremor, nystagmus and diplopia 32,33 . Furthermore, cerebellar atrophy can occur in phenytoin-exposed patients with epilepsy in the absence of generalised tonicclonic seizures or pre-existent brain damage 32,34,35 . Since the child evaluated in our study did not use phenytoin in his antiepileptic drug therapy schedule, our research group did not consider this issue.…”

“…Specht and colleagues demonstrated in 1997 that cerebellar atrophy diagnosed by MRI was a frequent finding in surgically treated patients with temporal lobe epilepsy 44 , and concluded that increased age, presence of generalized seizures, and intellectual disability were the principal factors associated with cerebellar volume losses in their patients 44 . Botez and co-workers studied 134 adult patients with epilepsy using high-resolution CT scans, and found a higher incidence of cerebellar atrophy with longer duration of epilepsy and treatment with phenytoin 48 . Convincing evidence exists that prolonged phenytoin use, or a single episode of phenytoin intoxication can elicit severe and irreversible cerebellar atrophy 42,44,49,50 .…”