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Phenytoin-related ataxia in patients with epilepsy: clinical and radiological characteristics

Shanmugarajah, Priya D., Hoggard, Nigel, Aeschlimann, Daniel, Aeschlimann, Pascale, Dennis, Gary J., Howell, Stephen J., Reuber, Markus, Grünewald, Richard A. and Hadjivassiliou, Marios 2018. Phenytoin-related ataxia in patients with epilepsy: clinical and radiological characteristics. Seizure - European Journal of Epilepsy 56 , pp. 26-30. 10.1016/j.seizure.2018.01.019

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Purpose Phenytoin is an effective anticonvulsant for focal epilepsy. Its use can be associated with long-term adverse effects including cerebellar ataxia. Whilst phenytoin is toxic to Purkinje cells in vitro; the clinical and radiological phenotype and mechanism of cerebellar degeneration in vivo remain unclear. We describe the prevalence, clinical and radiological characteristics of phenytoin-related ataxia. Methods Patients with epilepsy receiving treatment with phenytoin were recruited from the Epilepsy clinics at Royal Hallamshire Hospital, Sheffield, UK. Neurological examination was performed on all patients after recruitment. Patients were categorised into those with and without ataxia. We determined the severity of ataxia clinically (SARA score) and the pattern of cerebellar involvement by neuroimaging (MRI volumetry and MR spectroscopy). Results Forty-seven patients were recruited. Median duration of epilepsy was 24 years, median duration of phenytoin treatment was 15 years and current median phenytoin daily dose was 325 mg. Fifty-five percent of patients complained of poor balance. Clinical evidence of ataxia was seen in 40% patients. Gait, stance and heel-shin slide were the predominant features of cerebellar dysfunction. MRI demonstrated structural, volumetric and functional deficits of the cerebellum. Only one patient with ataxia had phenytoin levels above the normal range. Conclusions Cerebellar ataxia is present in 40% of patients with epilepsy and chronic exposure to phenytoin. Patients on long-term phenytoin have reduced cerebellar volume even if they have no clinical evidence of ataxia. Evidence of structural deficits on imaging suggests a predilection for vermian involvement.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Dentistry
Publisher: Elsevier
ISSN: 1059-1311
Date of First Compliant Deposit: 21 February 2018
Date of Acceptance: 29 January 2018
Last Modified: 02 Jul 2019 04:45

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