A composite clinical motor score as a comprehensive and sensitive outcome measure for Parkinson's disease.

BACKGROUND: An unmet need remains for sensitive outcome measures in neuroprotective trials. The study aims to determine whether a composite clinical motor score, combining the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III motor examination score, Purdue Pegboard Test, and Timed Up and Go, provides greater sensitivity in detecting motor change in early disease than the MDS-UPDRS III alone. METHODS: The Oxford Discovery longitudinal cohort study involves individuals with isolated rapid eye movement sleep behaviour disorder (iRBD) (n=272, confirmed polysomnographically, median follow-up: 1.6 years), idiopathic Parkinson's disease (PD) (n=909, median follow-up: 3.5 years, baseline: <3.5 years disease duration) and controls (n=316, age-matched and sex-matched, without a first-degree family history of PD). Motor and non-motor assessments were performed at each in-person visit. RESULTS: Compared with the MDS-UPDRS III, the composite clinical motor score demonstrated a wider score distribution in iRBD and controls, lower coefficient of variation (37% vs 67%), and higher correlation coefficients with self-reported measures of motor severity (0.65 vs 0.61) and overall health status (-0.40 vs -0.33). Greater score range in mild to moderate PD, higher magnitude of longitudinal change in iRBD and longitudinal score linearity suggest better sensitivity in detecting subtle motor change. The composite clinical motor score was more accurate than the MDS-UPDRS III in predicting clinical outcomes, requiring 64% fewer participants with PD and 51% fewer participants with iRBD in sample size estimations for a hypothetical 18-month placebo-controlled clinical trial. CONCLUSION: The composite clinical motor score may offer greater consistency and sensitivity in detecting change than the MDS-UPDRS III.

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

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.