Mitochondrial Causes of Epilepsy: Evaluation, Diagnosis, and Treatment

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


Semin Neurol. 2015;35(3):300-309. 

In This Article


Epilepsy is a common feature of mitochondrial disorders, occurring in approximately one in three of all people with a confirmed respiratory chain defect.[2] Although seizures are highly heterogeneous in both manifestation and severity, there are often additional clinical indicators to suggest underlying mitochondrial dysfunction. Furthermore, although catastrophic (often) early-onset seizure disorders arise due to mitochondrial disease, for many individuals, seizures can be successfully managed with routine antiepileptic drugs.[2]

The investigation of suspected mitochondrial disease may be complex, particularly in nonsyndromic presentations. However, the increasing integration of next-generation sequencing technologies into clinical practice is likely to revolutionize the current diagnostic pathway. Far from removing clinicians from this diagnostic process, accurate interpretation of genetic variants requires skilled clinical phenotyping, and as such, physicians' clinical skills will continue to be needed at the "coal face."

Although approaches to prevent the transmission of mitochondrial disorders are being actively developed, these will not be appropriate in all circumstances.[82] As such, the need for disease-modifying treatments in mitochondrial disorders will remain a priority for both those working in the field, and those affected by the disorders. Identifying the clinical features and genetic basis of mitochondrial disorders is just the first step in this process. Multicenter international collaboration will be required to conduct natural history studies of genetically defined cohorts, and thereby ensure the scientific robustness of future clinical trials.[83]