Seizure semiology and EEG findings in mitochondrial diseases

Abstract

SUMMARYObjective: Seizures constitute a frequent yet under-described manifestation of mitochondrial disorders (MDs). The aim of this study was to describe electroencephalography (EEG) findings and clinical seizure types in a population of children and adults with mitochondrial disease. Methods: Retrospective chart review of 165 records of children and adults with mitochondrial disease seen in the University of Texas Houston Mitochondrial Center between 2007 and 2012 was performed; all subjects were diagnosed with confirmed mitochondrial disease. EEG findings and clinical data, including seizure semiology and response to antiepileptic drugs (AEDs), were analyzed and categorized. Results: Sixty-six percent (109/165) of subjects had a routine EEG performed. Sixtyone percent (67/109) of EEG studies were abnormal and 85% (56/67) had epileptiform discharges. The most common EEG finding was generalized slowing (40/67, 60%). The most frequent category of epileptiform activity seen was multifocal discharges (41%), followed by focal (39%) and generalized (39%) discharges. Clinical seizures were seen in 55% of subjects and the most common types of seizures observed were complex partial (37%) and generalized tonic-clonic (GTC; 37%). The most common seizure type in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) was GTC (33%), with generalized or focal discharges seen on EEG. In Leigh syndrome GTC (11%) and complex partial (11%) seizures were the most frequent types. Of 60 subjects with clinical seizures, 28% were intractable to medical treatment. Significance: Mitochondrial disorder should be included in the list of differential diagnosis in any child that presents with encephalopathy, seizures, and a fluctuating clinical course. Given the relatively high prevalence of EEG abnormalities in patients with MD, EEG should be performed during initial evaluation in all patients with MD, not only upon clinical suspicion of epilepsy.

Epileptic phenotypes in children with early‐onset mitochondrial diseases

“…[2][3][4][5][6][7][8][9] Epilepsy resulting from MDs may manifest at any age and may be the presenting or prominent symptom in both syndromic (eg, Alpers-Huttenlocher syndrome (AHS), Leigh syndrome) and non-syndromic MDs. Epileptic seizures are one of the most frequent symptoms of CNS involvement due to mitochondrial dysfunction 1 with a prevalence rate ranging from 35% to 60%.…”

Use of the Ketogenic Diet to Treat Intractable Epilepsy in Mitochondrial Disorders

“…Epilepsy is a common feature [3,10], although preceded by other clinical presentations in most cases [11]. In fact, mitochondrial dysfunction has been shown to both generate seizures as well as result in neuronal cell death [12]. Seizures can manifest at any age and be the presenting feature of an underlying biochemical defect.…”

“…Although there are no data on the exact prevalence of epilepsy in mitochondrial disorders, seizures are more common in some mitochondrial disorders than in others [10]. For example, in children with mitochondrial disorders the reported prevalence of seizures ranged between 35% and 61% [12]. Whittaker et al, found an overall prevalence of epilepsy of 23.1% in a prospective cohort of 182 adults with mitochondrial disease followed up for 7 years [14].…”

“…Moreover, the mitochondrial syndromes with epilepsy as a leading clinical feature include MERFF, Alpers-Huttenlocher syndrome, Leigh syndrome, myoclonic epilepsy myopathy sensory ataxia (MEMSA), MELAS and others [12]. The seizures most commonly encountered in these disorders are myoclonic and focal, with a predilection to occipital lobes (at least initially), but can be generalized tonic–clonic seizures and status epilepticus [2,12]. In MELAS specifically, the seizures encountered are often associated with migraine-like headache and affected individuals frequently present in status epilepticus.…”

Differential Mitochondrial Requirements for Radially and Non-radially Migrating Cortical Neurons: Implications for Mitochondrial Disorders

“…Although MDs consist of a spectrum of disorders that can involve single or multisystem presentations, neurological symptoms are common clinical characteristics. In recent years, clinical, genetic, and biochemical studies have revealed an emerging link between mitochondrial dysfunction and neurodevelopmental disorders, including intellectual disability (ID) (Valenti et al, 2014) childhood epilepsy (Chevallier et al, 2014) and autism spectrum disorder (ASD) (Rossignol and Frye, 2012). Interestingly, these conditions have also been associated with interneuron dysfunction (Marin, 2012).…”