Treatment of epilepsy in mitochondrial disorders

Background: Due to lack of consensus on treatment of seizure in mitochondrial disorders and importance of seizure control in this group of patients, current study was conducted to review the literature and present the best possible treatments for epilepsy in setting of mitochondrial disorders. Methods: I have searched the Pubmed, Scopus and Embase databases between 1965 and 2017 with following keywords:mitochondrial disorders,seizure,epilepsy, antiepileptic and treatment. The inclusion criteria were: English articles in the form of case report, case series or clinical studies which considered treatment of mitochondrial epilepsy. Findings:Epilepsy commonly occurs during the course of most mitochondrial disorders and is a major feature in myoclonus epilepsy with ragged-red fibers (MERRF),mitochondrial encephalopathy,lactic acidosis, and stroke-like episodes (MELAS),and epileptic syndromes due to POLG gene mutation. MERRF can present with progressive myoclonus and generalized tonic-clonic seizures (GTCS) but also focal clonic and atonic seizures have been reported. The GTCS are frequently suppressed by antiepileptic drugs, but the myoclonus could be refractory. In MELAS, epilepsy occurs in patients with stroke-like lesions, leading to both focal and generalized seizures. In POLG-related syndromes, the seizures are often refractory with a possible presentation of status epilepticus (SE). When the myoclonic seizures are the main type, levetiracetam, topiramate and clonazepam should be considered, taking in mind to avoid sodium channel blockers such as lamotrigine, and gabapentin and also sodium valproate in patients with known POLG1 mutations. In setting of focal seizures with or without secondary generalization, carbamazepine, oxcarbazepine, and phenytoin are better options and could be combined with a benzodiazepine to provide better control of seizures. Due to higher risk of SE in MELAS and POLG1, aggressive treatment is indicated at the occurrence of seizures and if SE has been developed, prompt treatment with benzodiazepine infusion together with phosphenytoin following by phenobarbital, thiopental or propofol in refractory cases should be considered.Conclusion: Special consideration and new clinical trials are required for treatment of mitochondrial epilepsies.

Keywords:

Mitochondrial disorders , Seizure , Epilepsy , Treatment.