Mitochondrial DNA Mutations and Mitochondrial Dysfunction in Epilepsy

Cock, Hannah R.; Schapira, Anthony H.V.

doi:10.1111/j.1528-1157.1999.tb00897.x

Cited by 26 publications

(10 citation statements)

References 75 publications

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“…In addition to participating in cellular calcium homeostasis, generation of reactive oxygen species, and oxidative phosphorylation, mitochondria are a primary source of neuronal ATP, and mitochondrial dysfunction significantly affects neuronal excitability and synaptic transmission. Mechanisms postulated in the literature as potential causes of epileptogenesis in primary mitochondrial disease include the following: alterations in calcium homeostasis, excitotoxicity, and overproduction of free radicals …”

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confidence: 99%

“…Mechanisms postulated in the literature as potential causes of epileptogenesis in primary mitochondrial disease include the following: alterations in calcium homeostasis, excitotoxicity, and overproduction of free radicals. 5 Syndromic mitochondrial disorders associated with epilepsy as a dominating phenotypic feature include Alpers-Huttenlocher syndrome (AHS), ataxia neuropathy spectrum (ANS), Leigh syndrome, myoclonic epilepsy myopathy sensory ataxia (MEMSA), and myoclonic epilepsy with ragged red fibers (MERRF). The most common type of seizures seen in these syndromic MDs is generalized tonic-clonic (GTC).…”

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Seizure semiology and EEG findings in mitochondrial diseases

2014

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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.

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Seizure semiology and EEG findings in mitochondrial diseases

2014

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“…It has been suggested that primary and secondary mitochondrial dysfunctions might contribute to the development of epilepsy (Kunz, 2002; Liang & Patel, 2004). Many types of clinically confirmed mitochondrial diseases have been identified as being associated with epileptic conditions resulting from mitochondrial dysfunction (Cock & Schapira, 1999; Canafoglia et al, 2001).…”

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“…Blackwell Publishing, Inc. C 2008 International League Against Epilepsy fied as being associated with epileptic conditions resulting from mitochondrial dysfunction (Cock & Schapira, 1999;Canafoglia et al, 2001).…”

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Mitochondrial respiratory chain defects: Underlying etiology in various epileptic conditions

et al. 2008

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SUMMARYPurpose: To determine if defects in mitochondrial respiratory chain enzyme complexes (MRCs) contribute to the etiology of childhood epilepsy. Methods: We reviewed the clinical and laboratory features of 48 epileptic patients (23 male, 25 female) with MRC defects that were confirmed by biochemical assays using muscle biopsies. Results: (1) Thirty-five cases (72.9%) were MRC I deficient, one case (2.1%) was MRC II deficient, 11 cases (22.9%) were MRC IV deficient, and one case (2.1%) had combined MRC I and IV deficiencies.

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“…Other potential mechanisms of dysfunction in mitochondrial disorders include free radical production with oxidative damage to multiple cellular components such as DNA and DNA repair mechanisms, lipids and proteins comprising ion channels, neurotransmitter receptors, and second messenger systems [Cock and Schapira, 1999]. Mitochondria play a critical role in calcium homeostasis, and ineffective calcium buffering could facilitate local energy failure and excitotoxicity [Schinder et al, 1996;Luo et al, 1997;Stout et al, 1998;Cock and Schapira, 1999]. At this point, we can only speculate as to the mechanisms by which mitochondrial dysfunction leads to paroxysmal neuronal firing characteristic of epilepsy.…”

Section: Mitochondrial Genome Mutation: Merrfmentioning

confidence: 99%

Epilepsy genes: The link between molecular dysfunction and pathophysiology

Stafstrom

Tempel

2000

Ment. Retard. Dev. Disabil. Res. Rev.

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Our understanding of the genetic basis of epilepsy is progressing at a rapid pace. Gene mutations causing several of the inherited epilepsies have been mapped, and several more are likely to be added in coming years. In this review, we summarize the available information on the genetic basis of human epilepsies and epilepsy syndromes, emphasizing how genetic defects may correlate with the pathophysiological mechanisms of brain hyperexcitability. Mutations leading to epilepsy have been identified in genes encoding voltage‐ and ligand‐gated ion channels (benign familial neonatal convulsions, autosomal dominant nocturnal frontal lobe epilepsy, generalized epilepsy with febrile seizures “plus”), neurotransmitter receptors (Angelman syndrome), the molecular cascade of cellular energy production (myoclonic epilepsy with ragged red fibers), and proteins without a known role in neuronal excitability (Unverricht‐Lundborg disease). Gene defects can lead to epilepsy by altering multiple and diverse aspects of neuronal function. MRDD Research Reviews 2000;6:281–292. © 2000 Wiley‐Liss, Inc.

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Mitochondrial DNA Mutations and Mitochondrial Dysfunction in Epilepsy

Cited by 26 publications

References 75 publications

Seizure semiology and EEG findings in mitochondrial diseases

Seizure semiology and EEG findings in mitochondrial diseases

Mitochondrial respiratory chain defects: Underlying etiology in various epileptic conditions

Epilepsy genes: The link between molecular dysfunction and pathophysiology

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