Phenytoin and damage to the cerebellum - a systematic review of published cases.
Day, Rachael Bradberry, Sally M
Day, Rachael
Bradberry, Sally M
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Affiliation
Sandwell and West Birmingham NHS Trust; University of Birmingham
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Publication date
2022-04-20
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Abstract
Introduction: The antiseizure medication phenytoin has been associated with changes in the cerebellum, cerebellar signs, and permanent cerebellar damage. We have systematically reviewed the clinical and radiological features, and their correlation. Areas covered: We identified sixty case reports and case series of the effects of phenytoin on the cerebellum by searching Medline and Embase and relevant reference lists. The reports described 92 [median 1, range 1-5] cases, documented median age 28 [2.7-78] years. Eighty-one cases described one or more clinical sign of ataxia (present in 96%), dysarthria (63%), and nystagmus (70%). The neurological outcome (in 76 cases): 10 (13%) recovered by 12 months; 55 (72%) suffered residual disability; and 11 (14%) died. Median serum phenytoin concentration (48 cases) was 50 (interquartile range 31-66) mg/L; only three values were below 20 mg/L. The radiological findings included cerebellar atrophy in 41 of 61 patients (67%) with at least one scan. Expert opinion: Evidence mainly comes from case reports, and is inevitably biased. Most patients with cerebellar dysfunction have phenytoin concentrations above the reference range. Clinical signs of ataxia can persist without radiological evidence of cerebellar atrophy, and cerebellar atrophy is seen without any clinical evidence of cerebellar dysfunction.
Citation
Ferner R, Day R, Bradberry SM. Phenytoin and damage to the cerebellum - a systematic review of published cases. Expert Opin Drug Saf. 2022 Jul;21(7):957-977. doi: 10.1080/14740338.2022.2058487
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Article