Priya D Shanmugarajah1, Nigel Hoggard2, Daniel P Aeschlimann3, Pascale C Aeschlimann4, Gary J Dennis5, Stephen J Howell6, Markus Reuber7, Richard A Grünewald8, Marios Hadjivassiliou9. 1. Academic Department of Neurosciences, Royal Hallamshire Hospital and University of Sheffield, Sheffield, UK. Electronic address: p.d.shanmugarajah@sheffield.ac.uk. 2. Academic Unit of Radiology, University of Sheffield, Sheffield, UK. Electronic address: n.hoggard@sheffield.ac.uk. 3. Matrix Biology & Tissue Repair Research Unit, College of Biomedical and Life Sciences, School of Dentistry, Cardiff University, Cardiff, UK. Electronic address: AeschlimannDP@Cardiff.ac.uk. 4. Matrix Biology & Tissue Repair Research Unit, College of Biomedical and Life Sciences, School of Dentistry, Cardiff University, Cardiff, UK. Electronic address: aeschlimannpc@cardiff.ac.uk. 5. Academic Department of Neurosciences, Royal Hallamshire Hospital and University of Sheffield, Sheffield, UK. Electronic address: gary.dennis@sth.nhs.uk. 6. Academic Department of Neurosciences, Royal Hallamshire Hospital and University of Sheffield, Sheffield, UK. Electronic address: stephen.howell@sth.nhs.uk. 7. Academic Department of Neurosciences, Royal Hallamshire Hospital and University of Sheffield, Sheffield, UK. Electronic address: m.reuber@sheffield.ac.uk. 8. Academic Department of Neurosciences, Royal Hallamshire Hospital and University of Sheffield, Sheffield, UK. Electronic address: r.a.grunewald@sheffield.ac.uk. 9. Academic Department of Neurosciences, Royal Hallamshire Hospital and University of Sheffield, Sheffield, UK. Electronic address: m.hadjivassiliou@sheffield.ac.uk.
Abstract
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.
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.
Authors: Michel Sáenz-Farret; Marina A J Tijssen; Dawn Eliashiv; Robert S Fisher; Kapil Sethi; Alfonso Fasano Journal: CNS Drugs Date: 2022-07-21 Impact factor: 6.497
Authors: Manar Ibdali; Marios Hadjivassiliou; Richard A Grünewald; Priya D Shanmugarajah Journal: Int J Environ Res Public Health Date: 2021-01-08 Impact factor: 3.390