Cerebellar atrophy in patients with long-term phenytoin exposure and epilepsy

Arch Neurol. 1994 Aug;51(8):767-71. doi: 10.1001/archneur.1994.00540200043014.


Objective: Cerebellar atrophy has been noted in patients with phenytoin exposure. This finding has been attributed by some investigators to seizures, but by others to phenytoin. Previous studies included patients with mental retardation and convulsive seizures. We undertook a study in a group of nonretarded patients with partial epilepsy to better elucidate the cause of the cerebellar atrophy.

Design: Case control study.

Setting: Referral population from an epilepsy center.

Patients: Thirty-six patients with partial epilepsy and long-term phenytoin exposure were selected from a consecutive sample of admissions to an epilepsy center. Patients with histories of ethanol abuse, perinatal distress, anoxia, status epilepticus, or neurodegenerative disorders were excluded. Age- and sex-matched controls were selected from a pool of healthy volunteers and patients who had undergone magnetic resonance imaging for complaints of headache and dizziness.

Interventions: All patients and controls underwent magnetic resonance imaging.

Main outcome measure: Degree of cerebellar atrophy.

Results: The magnetic resonance imaging scans were reviewed in a blind fashion. A rating was assigned to each scan based on the degree of cerebellar atrophy. Cerebellar atrophy was significantly more pronounced in patients than in controls. No correlation was found between cerebellar atrophy and variables reflective of seizure severity or degree of phenytoin exposure.

Conclusions: Cerebellar atrophy may be seen in phenytoin-exposed patients with epilepsy in the absence of generalized tonic-clonic seizures or preexistent brain damage. Whether it is the phenytoin or the seizures that play the primary etiologic role remains unanswered. These factors may be synergistic.

MeSH terms

  • Adult
  • Atrophy
  • Cerebellum / pathology*
  • Epilepsy / complications*
  • Epilepsy / drug therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phenytoin / adverse effects*
  • Phenytoin / therapeutic use*


  • Phenytoin