Epilepsy in adults with mitochondrial disease: A cohort study

Abstract

ObjectiveThe aim of this work was to determine the prevalence and progression of epilepsy in adult patients with mitochondrial disease.MethodsWe prospectively recruited a cohort of 182 consecutive adult patients attending a specialized mitochondrial disease clinic in Newcastle upon Tyne between January 1, 2005 and January 1, 2008. We then followed this cohort over a 7‐year period, recording primary outcome measures of occurrence of first seizure, status epilepticus, stroke‐like episode, and death.ResultsOverall prevalence of epilepsy in the cohort was 23.1%. Mean age of epilepsy onset was 29.4 years. Prevalence varied widely between genotypes, with several genotypes having no cases of epilepsy, a prevalence of 34.9% in the most common genotype (m.3243A>G mutation), and 92.3% in the m.8344A>G mutation. Among the cohort as a whole, focal seizures, with or without progression to bilateral convulsive seizures, was the most common seizure type. Conversely, all of the patients with the m.8344A>G mutation and epilepsy experienced myoclonic seizures. Patients with the m.3243A>G mutation remain at high risk of developing stroke‐like episodes (1.16% per year). However, although the standardized mortality ratio for the entire cohort was high (2.86), this ratio did not differ significantly between patients with epilepsy (2.96) and those without (2.83).InterpretationEpilepsy is a common manifestation of mitochondrial disease. It develops early in the disease and, in the case of the m.3243A>G mutation, often presents in the context of a stroke‐like episode or status epilepticus. However, epilepsy does not itself appear to contribute to the increased mortality in mitochondrial disease. Ann Neurol 2015;78:949–957

Review: Central nervous system involvement in mitochondrial disease

“…In these patients, epilepsy may be classified as focal motor seizures with or without a loss of consciousness. While in patients harbouring MT‐TK , epilepsy affects 92% of patients and is usually progressive myoclonus and generalized tonic clonic seizures . Epilepsy occurring in infancy is associated with a particularly poor prognosis with a 50% fatality rate in children 9 months after a diagnosis of epilepsy being made .…”

Epileptic phenotypes in children with early‐onset mitochondrial diseases

“…[2][3][4][5][6][7][8][9] Epilepsy resulting from MDs may manifest at any age and may be the presenting or prominent symptom in both syndromic (eg, Alpers-Huttenlocher syndrome (AHS), Leigh syndrome) and non-syndromic MDs. Epileptic seizures are one of the most frequent symptoms of CNS involvement due to mitochondrial dysfunction 1 with a prevalence rate ranging from 35% to 60%.…”

“…[2][3][4][5][6][7][8][9] Epilepsy resulting from MDs may manifest at any age and may be the presenting or prominent symptom in both syndromic (eg, Alpers-Huttenlocher syndrome (AHS), Leigh syndrome) and non-syndromic MDs. 2,8,9 Only a few series are focused on epilepsy in children affected by MDs 3,5,6,10 and even rarer reports are available for infants aged less than 1 year. 12,13 Details on epileptic phenotypes in MDs are mainly based on case reports and case series with mixed population of pediatric and adult patients.…”

“…Epileptic seizures are one of the most frequent symptoms of CNS involvement due to mitochondrial dysfunction 1 with a prevalence rate ranging from 35% to 60%. [2][3][4][5][6][7][8][9] Epilepsy resulting from MDs may manifest at any age and may be the presenting or prominent symptom in both syndromic (eg, Alpers-Huttenlocher syndrome (AHS), Leigh syndrome) and non-syndromic MDs. 10,11 The term "non-syndromic" MDs apply to cases whose clinical, pathological, and imaging findings do not fit any defined mitochondrial syndrome.…”

“…12,13 Details on epileptic phenotypes in MDs are mainly based on case reports and case series with mixed population of pediatric and adult patients. 2,8,9 Only a few series are focused on epilepsy in children affected by MDs 3,5,6,10 and even rarer reports are available for infants aged less than 1 year.…”