Epilepsy and Mitochondrial Dysfunction

Saneto, Russell P.

doi:10.1177/2326409817733012

Cited by 14 publications

(3 citation statements)

References 38 publications

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“…Patient 1 developed profound cortical degeneration early in the disease course, which may explain the more severe epilepsy phenotype. It has been suggested that early-onset epilepsy portends more severe disease course among patients with mitochondrial disease [15]. The severe progression and poor outcome seen in patient 1 might be the result of severe metabolic decompensation triggered by systemic infections and a history of long-lasting episodes of decompensation with status epilepticus, rather than epilepsy per se.…”

Section: Discussionmentioning

confidence: 99%

The phenotypic variability and natural history of NARS2 associated disease

Sofou

Kollberg

Hedberg‐Oldfors

et al. 2021

European Journal of Paediatric Neurology

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Introduction:The phenotypic variability of NARS2 associated disease is vast, yet not thoroughly explored. We present the phenotypic and genetic features of 2 siblings with early-onset mitochondrial encephalopathy due to pathogenic variant in NARS2, along with the results from a systematic literature review. Aims: To better delineate the phenotypic variability and natural history of NARS2 associated disease. Methods: The clinical and radiological phenotype, along with the results from the morphological and biochemical investigations from the muscle biopsy as well as the postmortem investigations, where applicable, are presented. Genetic analysis was performed with next-generation sequencing.Results: Together with these 2 patients, we have diagnosed and followed 3 Scandinavian patients with the same homozygous p. Pro214Leu variant in NARS2 who presented with phenotypic features of earlyonset mitochondrial encephalopathy and variable disease course. Another 14 patients with pathogenic variants in NARS2 were identified in the literature. We found that sensorineural hearing impairment is a cardinal feature of early-onset NARS2 associated disease, either isolated or in combination with central nervous system disease. Early-onset mitochondrial encephalopathy due to NARS2 variants shared phenotypic features of Alpers or Leigh syndrome and was characterized by more severe disease course and poorer survival compared to the other NARS2 associated phenotypes. Conclusion: NARS2 variants present with a spectrum of clinical severity from a severe, infantile-onset, progressive disease to a mild, non-progressive disease, without strong association between the genotype and the disease outcome.

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Section: Discussionmentioning

confidence: 99%

The phenotypic variability and natural history of NARS2 associated disease

Sofou

Kollberg

Hedberg‐Oldfors

et al. 2021

European Journal of Paediatric Neurology

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“…Epilepsy is linked to mitochondrial alterations mainly because it is a common manifestation of mitochondrial diseases, with a high prevalence in patients with genetic mutations in mitochondrial DNA (mtDNA) [ 199 ]. The best accepted model suggests that, because neurons require high amounts of energy, they are especially vulnerable to mitochondrial ETC deficits, resulting in epilepsy.…”

Section: Mitophagy In Neuropsychiatric and Neurodegenerative Diseasesmentioning

confidence: 99%

Mitophagy in Human Diseases

Doblado

Lueck

Rey

et al. 2021

IJMS

120

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Mitophagy is a selective autophagic process, essential for cellular homeostasis, that eliminates dysfunctional mitochondria. Activated by inner membrane depolarization, it plays an important role during development and is fundamental in highly differentiated post-mitotic cells that are highly dependent on aerobic metabolism, such as neurons, muscle cells, and hepatocytes. Both defective and excessive mitophagy have been proposed to contribute to age-related neurodegenerative diseases, such as Parkinson’s and Alzheimer’s diseases, metabolic diseases, vascular complications of diabetes, myocardial injury, muscle dystrophy, and liver disease, among others. Pharmacological or dietary interventions that restore mitophagy homeostasis and facilitate the elimination of irreversibly damaged mitochondria, thus, could serve as potential therapies in several chronic diseases. However, despite extraordinary advances in this field, mainly derived from in vitro and preclinical animal models, human applications based on the regulation of mitochondrial quality in patients have not yet been approved. In this review, we summarize the key selective mitochondrial autophagy pathways and their role in prevalent chronic human diseases and highlight the potential use of specific interventions.

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“…As crises epiléticas podem ser classificadas de acordo com a manifestação clínica inicial (focais ou generalizadas) e segundo o estado de consciência durante a crise (perda ou manutenção da consciência) (FISHER et al, 2017). Segundo a etiologia, podem ser causadas por lesões corticais infecciosas, traumáticas, vasculares, inflamatórias, congênitas, doenças metabólicas e mitocondriais BRIGO, 2011;SANETO, 2017). A epilepsia refratária é definida pela manutenção das crises convulsivas, apesar do tratamento medicamentoso com no mínimo dois fármacos em dose máxima e adequados ao tipo de epilepsia, em associação.…”

Section: Introductionunclassified

Alternativas terapêuticas para a epilepsia refratária à farmacoterapia

Silva

Machado

2020

BJHR

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A epilepsia é definida como uma predisposição a crises epiléticas espontâneas. É associada a risco aumentado de mortalidade, de morbidade psiquiátrica e a problemas psicossociais. Pode ser classificada segundo sua manifestação clínica inicial em generalizada, focal ou desconhecida e segundo o estado de consciência durante a crise. Conceitua-se epilepsia refratária como a falha na farmacoterapia com no mínimo dois medicamentos adequadamente prescritos e em dose máxima. O objetivo do presente trabalho foi reconhecer as alternativas terapêuticas à epilepsia refratária à farmacoterapia. Se trata de uma revisão da literatura nas bases de dados SCIELO, Google Scholar e PubMed com os descritores "Epilepsia Refratária, Cirurgia de Epilepsia, Neuromodulação AND Epilepsia". Foram selecionados estudos publicados nos últimos 10 anos. Foram analisados 30 artigos. Os tratamentos identificados foram a Estimulação do Nervo Vago (ENV), a Estimulação Cerebral (EC), as Cirurgias Ressectivas e a Calostomia. Dentre as alternativas, a ressecção cirúrgica de focos epileptogênicos se mostrou uma medida segura e eficaz para controle das crises, tendo sucesso em até 90% dos pacientes. A ENV demonstrou redução na frequência das crises e melhora na qualidade de vida significativas. O efeito da calostomia e da EC sobre as crises ainda não é bem compreendido. Entretanto, alguns estudos relataram melhora das crises em pacientes operados. A calostomia foi associada a mais efeitos adversos, como a Síndrome da Desconexão Aguda. Desse modo, a adequada seleção e indicação de tais tratamentos pode resultar em melhoria significativa na ocorrência de crises e na qualidade de vida dos pacientes com epilepsia refratária.

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Epilepsy and Mitochondrial Dysfunction

Cited by 14 publications

References 38 publications

The phenotypic variability and natural history of NARS2 associated disease

The phenotypic variability and natural history of NARS2 associated disease

Mitophagy in Human Diseases

Alternativas terapêuticas para a epilepsia refratária à farmacoterapia

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