Mitochondrial epilepsy in pediatric and adult patients

Abstract

Few data are available about the difference between epilepsy in pediatric mitochondrial disorders (MIDs) and adult MIDs. This review focuses on the differences between pediatric and adult mitochondrial epilepsy with regard to seizure type, seizure frequency, and underlying MID. A literature search via Pubmed using the keywords 'mitochondrial', 'epilepsy', 'seizures', 'adult', 'pediatric', and all MID acronyms, was carried out. Frequency of mitochondrial epilepsy strongly depends on the type of MID included and is higher in pediatric compared to adult patients. In pediatric patients, mitochondrial epilepsy is more frequent due to mutations in nDNA-located than mtDNA-located genes and vice versa in adults. In pediatric patients, mitochondrial epilepsy is associated with a syndromic phenotype in half of the patients and in adults more frequently with a non-syndromic phenotype. In pediatric patients, focal seizures are more frequent than generalized seizures and vice versa in adults. Electro-clinical syndromes are more frequent in pediatric MIDs compared to adult MIDs. Differences between pediatric and adult mitochondrial epilepsy concern the onset of epilepsy, frequency of epilepsy, seizure type, type of electro-clinical syndrome, frequency of syndromic versus non-syndromic MIDs, and the outcome. To optimize management of mitochondrial epilepsy, it is essential to differentiate between early and late-onset forms.

Cerebral Manifestations of Mitochondrial Disorders

“…26 In adult MIDs, which are more frequently from mtDNA than nuclear DNA mutations, generalized seizures are more prevalent than focal seizures. 26 A common type of epilepsy in MIDs is myoclonic epilepsy. Among the specific MIDs, mitochondrial epilepsy with early onset occurs in MELAS, MERRF, KSS, Leigh syndrome, myoclonic epilepsy myopathy sensory ataxia, mitochondrial recessive ataxia syndrome (MIRAS), infantile onset spinocerebellar ataxia (IOSCA), leukoencephalopathy, brainstem and spinal cord lesions, and lactic acidosis, and Alpers-Huttenlocher syndrome.…”

“…26 Mitochondrial epilepsy with adult onset has been reported in MELAS, LHON, neuropathy ataxia and retinitis pigmentosa (NARP), and sensory ataxic neuropathy, dysarthria, and ophthalmoparesis. 26 In a study of seven MELAS patients, seizures usually occurred during the acute phase of an SLE and included epilepsia partialis continua, hemiclonic status epilepticus, nonconvulsive status, and occipital status epilepticus. 27 Among pediatric patients, infantile spasms, refractory or recurrent status epilepticus, epilepsia partialis continua, and myoclonic epilepsy were the most prevalent seizure types.…”

Mitochondrial Causes of Epilepsy: Evaluation, Diagnosis, and Treatment

“…The genetic basis of LS is complex, but approximately 50% of cases arise due to mutations in SURF1, a complex IV assembly gene. 9 A striking feature of LS is the characteristic bilateral, focal neuropathological change evident on magnetic resonance (MR) brain imaging. It is the most common manifestation of mitochondrial disease in children, and symptom onset usually occurs between 3 and 12 months.…”

“…[2][3][4][5][6][7] The heterogeneous patient populations used in many of the series describing seizures add a further challenge to seizure interpretation. 2,3,[8][9][10][11][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.…”

Phenotypic and genotypic features in pediatric and adult mitochondrial disorders

“…Another important factor for the outcome of MIDs is the involvement of the brain, particularly the presence of epilepsy. 4 The information about how many of the patients had cerebral involvement, particularly epilepsy, is incomplete. There is also no mention of how many patients experienced seizures associated with strokelike episodes.…”