Seizure Semiology, EEG, and Imaging Findings in Epilepsy Secondary to Mitochondrial Disease

Abstract

Background: Identification of an underlying mitochondrial disorder can be challenging due to the significant phenotypic variability between and within specific disorders. Epilepsy can be a presenting symptom with several mitochondrial disorders. In this study, we evaluated clinical, electrophysiologic, and imaging features in patients with epilepsy and mitochondrial disorders to identify common features, which could aid in earlier identification of a mitochondrial etiology.Methods: This is a retrospective case series from January 2011 to December 2019 at a tertiary referral center of patients with epilepsy and a genetically confirmed diagnosis of a mitochondrial disorder. A total of 164 patients were reviewed with 20 patients fulfilling inclusion criteria.Results: A total of 20 patients (14 females, 6 males) aged 0.5–61 years with epilepsy and genetically confirmed mitochondrial disorders were identified. Status epilepticus occurred in 15 patients, with focal status epilepticus in 13 patients, including 9 patients with visual features. Abnormalities over the posterior cerebral regions were seen in 66% of ictal recordings and 44% of imaging studies. All the patients were on nutraceutical supplementation with no significant change in disease progression seen. At last follow-up, eight patients were deceased and the remainder had moderate-to-severe disability.Discussion: In this series of patients with epilepsy and mitochondrial disorders, we found increased propensity for seizures arising from the posterior cerebral regions. Over time, electroencephalogram (EEG) and imaging abnormalities increasingly occurred over the posterior cerebral regions. Focal seizures and focal status epilepticus with visual symptoms were common. Additional study is needed on nutraceutical supplementation in mitochondrial disorders.

Focal epilepsies: Update on diagnosis and classification

“…Occipital lobe seizures have been noted and, in certain cases, seizures may progress to status epilepticus. 38 MELAS is caused by mutations in the mitochondrial DNA in the MT-TL1 (mitochondrially encoded tRNA leucine 1) gene. Status epilepticus can occur in the context of stroke-like symptoms.…”

“…POLG ‐related phenotypes with adult‐onset typically feature multiple mitochondrial DNA deletions. Occipital lobe seizures have been noted and, in certain cases, seizures may progress to status epilepticus 38 . MELAS is caused by mutations in the mitochondrial DNA in the MT‐TL1 (mitochondrially encoded tRNA leucine 1) gene.…”

Mitochondrial Epilepsy, a Challenge for Neurologists

“…Ictal EEG typically presents focal spikes or multifocal spikes and, sometimes, generalized spike-wave activity or hypsarrhythmia [ 5 , 7 , 8 ]. Epileptiform abnormalities most commonly localize to the posterior temporal, parietal and occipital regions [ 8 , 11 ]. Interestingly, brain MRI abnormalities, mostly T2 hyperintensities and abnormal diffusion restriction, frequently involve the parieto-occipital lobes, often in concordance with EEG findings [ 11 ].…”

“…This can explain why not all complexes’ defects provoke epilepsy with the same frequency and degree, and why some genetic defects are more prone to causing epilepsy ( Table 1 ). An astrocyte–neuron metabolic interplay through the action of a lactate shuttle is supposed to primarily sustain the energetic requirement of neurons, especially during high synaptic activity [ 11 ].…”

“…EEG is not pathognomonic, but its alterations, commonly in the form of abnormal background activity, typically present occipital predilection [ 5 , 8 , 11 ]. Mitochondrial patients with a history of seizures have higher rates of brain MRI abnormalities (cortical/subcortical atrophy, stroke-like lesions, basal ganglia and white matter signal alterations) and increased serum lactic acid [ 5 , 7 , 8 ].…”