Mitochondrial Causes of Epilepsy: Evaluation, Diagnosis, and Treatment

Hannah E. Steele, MBBS, MRCP; Patrick F. Chinnery, PhD, FRCP, FRCPath

Disclosures

Semin Neurol. 2015;35(3):300-309. 

In This Article

Abstract and Introduction

Abstract

Mitochondrial disorders are frequently associated with seizures. In this review, the authors discuss the seizure patterns and distinguishing features of mitochondrial epilepsy, alongside the indications for investigating, and how to investigate epilepsy from a mitochondrial perspective. Finally, they discuss management strategies for this complex group of patients.

Introduction

Seizures are a common and highly heterogeneous feature of mitochondrial disease. They can arise at any age, may be the presenting feature of the underlying biochemical defect, and can occur in the absence of a clear family history despite the genetic etiology. Furthermore, they are frequently a secondary feature in a complex phenotype; thus, detailed semiology is often lacking,[1] although increasingly this is being addressed.[2–7] The heterogeneous patient populations used in many of the series describing seizures add a further challenge to seizure interpretation.[2,3,8–12]

Ictal activity in mitochondrial disease may result from metabolic disturbance, encephalopathy, or an acquired structural lesion such as a stroke-like episode. However, seizures may occur without these factors. Furthermore, the mechanisms are not mutually exclusive. Accordingly, epilepsy in mitochondrial disease straddles the genetic and structural/metabolic categories in the 2010 International League Against Epilepsy (ILAE) classification of the epilepsies outlined in Table 1.[13]

A large driver for the restructuring of this classification is the ongoing advance in genetic medicine and diagnostic technologies,[13] exemplified by increasing descriptions of epilepsy causing gene variations[14] and mirrored in the field of mitochondrial disease.[15] As a combined consequence of the phenotypic diversity, the increasing genetic complexity and a historical paucity of detailed seizure semiology, the clinician is faced with a considerable challenge in identifying, classifying, and treating epilepsy arising due to mitochondrial disease.

The aim of this review is therefore to provide the nonspecialist reader with:

  • An introduction to the etiology and clinical features of mitochondrial disorders

  • An overview of epilepsy in the context of both syndromic and nonsyndromic mitochondrial disease

  • A practical approach of when to consider a mitochondrial disorder in a patient with epilepsy

  • A schema to investigate epilepsy with a suspected mitochondrial basis

  • An overview of mitochondrial seizure management

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