Abstracts

Rationale: Mitochondrial diseases comprise a phenotypically heterogeneous group of conditions with shared defect in the respiratory chain. Epilepsy is one of the most common symptoms of mitochondrial disorders but seizure type, onset and severity are variable. Methods: We performed a retrospective review of patients from the Mayo Clinic Mitochondrial Disease Database. Inclusion criteria were: diagnosis of mitochondrial disorder based on clinical, laboratory, and/or genetic evaluations, history of seizures, availability of electroencephalogram (EEG) and magnetic resonance imaging (MRI). Mitochondrial disease diagnosis was classified as definite (detected disease causing mutation) or probable/possible (based on clinical features, biochemical and/or genetic testing). Patients with low level heteroplasmy (less than 30% in blood or 50% in affected tissue) or insufficient clinical information were excluded. Results: Ninety-five patients were enrolled in our Mitochondrial Disease Database between 2011-2015. Seventy-six patients were excluded (42 limited/missing clinical information, 10 low level heteroplasmy, 24 with definite mitochondrial disease but no seizures).  Of the 19 patients who fulfilled inclusion criteria, 15 were classified as definite (8 MELAS, 4 POLG1, 1 MERFF, 1 Complex I deficiency, 1 Leigh disease), and 4 probable. Eighteen patients (95%) were initiated on a “mitochondrial cocktail” of which, at last follow-up, 16 patients (84%) were maintained.Initial EEGs showed: mild generalized slowing in 2 (11%), moderate epileptiform abnormalities in 7 (37%) (6 generalized, 1 focal), and severe epileptiform abnormalities in 7 (37%) (3 generalized, 4 focal and multifocal) and normal in 3 (16%). Additional features included delta slowing in 3 patients (16%) and background asymmetry in 4 (21%). Fourteen (74%) showed epileptiform abnormalities, which were predominant over the posterior head regions in 6 (32%) (3 MELAS, 1 POLG, 1 Leigh, and 1 Complex 1 deficiency).  An increase in epileptiform activation and background abnormalities were present on those undergoing subsequent EEGs. The prevalence of posterior/occipital discharges increased over time and was seen in up to 47% of patients and generalized or focal delta slowing was present in 71% of patients. Six patients (32%) were considered to have refractory epilepsy (failing 2 or more antiseizure medications and continuing seizures). At last follow-up, 4 patients (21%) were deceased (2 MELAS patients (1 toxic megacolon, 1 cancer), 1 POLG (refractory epilepsy), 1 Leigh (respiratory arrest)), 6 (32%) could not perform any activities of daily living (ADLs), 6 (32%) could perform ADLs with assistance, and 3 patients (16%) were living independently and able to perform all ADLs. Conclusions: This retrospective review provides evidence of the progressive course of epilepsy in the mitochondrial population.  It also suggests a propensity for posterior brain localization. While the retrospective nature of this study is a limitation, these data suggest seizures can be intractable in this population, and that the mitochondrial cocktail does not prevent epilepsy from worsening with disease progression. Funding: No funding.