Progressive myoclonic epilepsy due to rare mitochondrial ND6 mutation, m.14487T>C.

INTRODUCTION: Mitochondrial diseases exhibit wide phenotypic heterogeneity, and can present as progressive myoclonic epilepsy. SUMMARY: We report a case of adult-onset drug-resistant epilepsy, cortical myoclonus and bilateral optic neuropathies due to m.14487T>C, a rare mitochondrial gene mutation identified on whole-genome sequencing. This mutation, which affects the NADH dehydrogenase 6 (ND6) subunit of the mitochondrial respiratory chain, is most commonly implicated in cases of infantile-onset Leigh syndrome, although a broader phenotypic spectrum including migraine with aura and progressive myoclonic epilepsy have been described. Serial MRI scans over a 2-year period demonstrated the interval development of bihemispheric stroke-like lesions. Giant somatosensory evoked potentials and short-duration myoclonic jerks with craniocaudal spread on surface electromyography were consistent with cortical myoclonus. Optical coherence tomography showed bilateral symmetric thinning of the nerve fibre layer in the papillomacular bundles. CONCLUSION: Whole-genome sequencing can help to provide a definitive diagnosis for mitochondrial disease and should be considered in situations where clinical suspicion remains high despite normal genetic panels or muscle histopathology. Mitochondrial disease can present as adult-onset progressive myoclonic epilepsy, and bilateral optic neuropathies can be a striking feature of ND6 mitochondrial gene mutations. In our case, severe cortical myoclonus affecting speech and swallowing remained highly drug-resistant, however, symptomatic benefit was derived from targeted onabotulinum toxin A injections.

Neuroimaging in epilepsy.

PURPOSE OF REVIEW: Epilepsy neuroimaging is important for detecting the seizure onset zone, predicting and preventing deficits from surgery and illuminating mechanisms of epileptogenesis. An aspiration is to integrate imaging and genetic biomarkers to enable personalized epilepsy treatments. RECENT FINDINGS: The ability to detect lesions, particularly focal cortical dysplasia and hippocampal sclerosis, is increased using ultra high-field imaging and postprocessing techniques such as automated volumetry, T2 relaxometry, voxel-based morphometry and surface-based techniques. Statistical analysis of PET and single photon emission computer tomography (STATISCOM) are superior to qualitative analysis alone in identifying focal abnormalities in MRI-negative patients. These methods have also been used to study mechanisms of epileptogenesis and pharmacoresistance.Recent language fMRI studies aim to localize, and also lateralize language functions. Memory fMRI has been recommended to lateralize mnemonic function and predict outcome after surgery in temporal lobe epilepsy. SUMMARY: Combinations of structural, functional and post-processing methods have been used in multimodal and machine learning models to improve the identification of the seizure onset zone and increase understanding of mechanisms underlying structural and functional aberrations in epilepsy.