Epilepsy in adults with mitochondrial disease: A cohort study

Abstract

Objective: The aim of this work was to determine the prevalence and progression of epilepsy in adult patients with mitochondrial disease.

Methods: We 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.

Results: Overall 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).

Interpretation: Epilepsy 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.

Figure 1

(A) Prevalence of epilepsy among a cohort of 182 adult patients with mitochondrial disease. Overall prevalence of epilepsy was 23.1%. The genotypes most commonly associated with epilepsy were m.3243A>G, m.8344A>G, and recessive POLG mutations and represented 11.8%, 6.4%, and 1.6% of the total cohort, respectively. One patient each with the m.12147A>G mutation, m.8993T>G mutation, single large‐scale deletion, multiple mtDNA deletions, and recessive TRIT1 mutations had epilepsy; together, this group represented 2.7% of the total cohort. (B) Seizure phenotypes for the eight genotypes in which epilepsy occurred. The total number of seizure types is greater than the number of patients with epilepsy because several patients had more than one seizure type. mtDNA = mitochondrial DNA.