Myoclonus epilepsy associated with ragged-red fibres (mitochondrial abnormalities): Disease entity or a syndrome?

Fukuhara, Nobuyoshi; Tokiguchi, S.; Shirakawa, K; Tsubaki, Tadao

doi:10.1016/0022-510x(80)90031-3

Cited by 390 publications

(136 citation statements)

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“…In the following decade, additional cases with similar presentations were included in the literature, and on this basis, Fukuhara et al gave the best characterization of the disease, which they referred to as MERRF (Myoclonus Epilepsy associated with Ragged-Red Fibers) 2 . The disease was so named because the patients all had myoclonus epilepsy and mitochondrial dysfunction was found upon muscle biopsy 2 . The MERRF diagnostic criteria described in 1980 by Fukuhara et al included as typical manifestations of the disease the following: myoclonus, generalized epilepsy, cerebellar ataxia and ragged-red fibers (RRF) on muscle biopsy 2 .…”

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When should MERRF (myoclonus epilepsy associated with ragged-red fibers) be the diagnosis?

Lorenzoni

Scola

Kay

et al. 2014

Arq. Neuro-Psiquiatr.

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Myoclonic epilepsy associated with ragged red fibers (MERRF) is a rare mitochondrial disorder. Diagnostic criteria for MERRF include typical manifestations of the disease: myoclonus, generalized epilepsy, cerebellar ataxia and ragged red fibers (RRF) on muscle biopsy. Clinical features of MERRF are not necessarily uniform in the early stages of the disease, and correlations between clinical manifestations and physiopathology have not been fully elucidated. It is estimated that point mutations in the tRNA Lys gene of the DNAmt, mainly A8344G, are responsible for almost 90% of MERRF cases. Morphological changes seen upon muscle biopsy in MERRF include a substantive proportion of RRF, muscle fibers showing a deficient activity of cytochrome c oxidase (COX) and the presence of vessels with a strong reaction for succinate dehydrogenase and COX deficiency. In this review, we discuss mainly clinical and laboratory manifestations, brain images, electrophysiological patterns, histology and molecular findings as well as some differential diagnoses and treatments.Keywords: MERRF, mitochondrial, epilepsy, myoclonus, myopathy. RESUMOEpilepsia mioclônica associada com fibras vermelhas rasgadas (MERRF) é uma rara doença mitocondrial. O critério diagnóstico para MERRF inclui as manifestações típicas da doença: mioclonia, epilepsia generalizada, ataxia cerebelar e fibras vermelhas rasgadas (RRF) na biópsia de músculo. Na fase inicial da doença, as manifestações clínicas podem não ser uniformes, e correlação entre as manifestações clínicas e fisiopatologia não estão completamente elucidadas. Estima-se que as mutações de ponto no gene tRNA Lys do DNAmt, principalmente a A8344G, sejam responsáveis por quase 90% dos casos de MERRF. As alterações morfológicas na biópsia muscular incluem uma grande proporção de RRF, fibras musculares com deficiência de atividade da citocromo c oxidase (COX) e presença de vasos com forte reação para succinato desidrogenase e deficiência da COX. Nesta revisão, são discutidas as principais manifestações clínicas e laboratoriais, imagens cerebrais, padrões eletrofisiológicos, histológicos e alterações moleculares, bem como, alguns dos diagnósticos diferenciais e tratamentos.

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When should MERRF (myoclonus epilepsy associated with ragged-red fibers) be the diagnosis?

Lorenzoni

Scola

Kay

et al. 2014

Arq. Neuro-Psiquiatr.

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“…Vale ressaltar que desde a descrição inicial por Fukuhara 10 , vários estudos têm demonstrado a variabilidade clínico-genotípica desta afecção.…”

Section: Fig 1 Rm De Crânio Corte Axial T 1 (A) E Flair (B) Revelanunclassified

Síndrome psicótica evoluindo com demência como manifestação clinica de deleção do DNA mitocondrial

Vasconcellos

Leite

Cavalcanti

et al. 2007

Arq. Neuro-Psiquiatr.

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RESUMO -As manifestações das doenças mitocondriais são variadas, acometendo, mais freqüentemente, órgãos com alto metabolismo aeróbico em que são mais abundantes, como, por exemplo, o sistema nervoso. O início dos sintomas em geral é observado na infância havendo relatos de início na idade adulta. Apresentamos caso atípico de doença mitocondrial associada à deleção do DNA mitocondrial em um homem de 39 anos com sintomas psiquiátricos configuraram quadro clínico inicial e somente 12 anos após o início dos sintomas surgiram alterações neurológicas. O diagnóstico da doença mitocondrial foi confirmado por biópsia de músculo sendo documentada deleção do DNA mitocondrial. PALAVRAS-CHAVE: demência, síndrome psicótica, mitocondriopatia, genética.Psycothic syndrome developing into dementia as a clinical manifestation of mitochondrial DNA deletion ABSTRACT -The manifestations of mitochondrial disease are variable, affecting more frequently the organs with high aerobic metabolism in which they are more abundant, for example the nervous system. The beginning of symptoms in general is observed at chilhood, but some patients presented on adult age. We present an atypical case associated with mitochondrial DNA deletion. A 39-years-old man with psychiatric symptoms that configured initial clinical picture and only after 12 years of the beginning of symptoms neurological alterations became noticeable. The diagnosis of mitochondrial illness was confirmed by muscle biopsy being documented mitochondrial DNA deletion.KEY WORDS: dementia, psychotic syndrome, mitochondriopathy, genetic.As mitocôndrias são estruturas citoplasmáticas que desempenham funções vitais na produção aeró-bica de energia, sendo a única organela das células eucarióticas a possuir DNA próprio, designado DNA mitocondrial (mtDNA). As mitocondriopatias são doenças que ao nível celular se caracterizam por disfunção na produção de energia em forma de adenosina trifosfato (ATP), resultado final da fosforilação oxidativa de glicose, ácidos graxos e aminoácidos pela mitocôndria 1 . A grande variabilidade na expressão clínica desse grupo de doenças se deve não só às importantes funções metabólicas que a mitocôndria desempenha na vida celular, mas também ao número variável de mitocôndrias nos diferentes tecidos e à sua característica particular de conter seu próprio DNA. Os órgãos preferencialmente acometidos nas doenças mitocondriais são aqueles que dependem de metabolismo aeróbico intenso, ou seja, sistema nervoso central e periférico, muscular, ocular, cardía-co, hepático, renal, endócrino, hematopoiético e gastrointestinal 1 . Costuma-se dividir as desordens mitocondriais de acordo com as alterações do DNA em três categorias: deleção única, deleção múltipla, duplicação e mutação de ponto 2 . O diagnóstico das doenças mitocondriais implica uma investigação multidisciplinar que envolve, além da análise molecular, avaliação clínica, o estudo morfológico e o estudo bioquí-mico (estudo das enzimas da cadeia respiratória mitocondrial), preferencialmente realizado em material...

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“…Focal and generalized status epilepticus can occur in association with these stroke‐like episodes. In other syndromes, for example, M yoclonic E pilepsy with R agged R ed F ibers, usually as a result of the m.8344A>G point mutation, epilepsy is one of the defining clinical features and typically manifests as generalized myoclonus with photosensitivity 11, 12, 13, 14. As with other clinical features, the type of epilepsy found only partially reflects the underlying genotype, with a large degree of overlap found between syndromes 15, 16…”

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Epilepsy in adults with mitochondrial disease: A cohort study

Whittaker

Devine

Gorman

et al. 2015

Annals of Neurology

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ObjectiveThe aim of this work was to determine the prevalence and progression of epilepsy in adult patients with mitochondrial disease.MethodsWe prospectively recruited a cohort of 182 consecutive adult patients attending a specialized mitochondrial disease clinic in Newcastle upon Tyne between January 1, 2005 and January 1, 2008. We then followed this cohort over a 7‐year period, recording primary outcome measures of occurrence of first seizure, status epilepticus, stroke‐like episode, and death.ResultsOverall prevalence of epilepsy in the cohort was 23.1%. Mean age of epilepsy onset was 29.4 years. Prevalence varied widely between genotypes, with several genotypes having no cases of epilepsy, a prevalence of 34.9% in the most common genotype (m.3243A>G mutation), and 92.3% in the m.8344A>G mutation. Among the cohort as a whole, focal seizures, with or without progression to bilateral convulsive seizures, was the most common seizure type. Conversely, all of the patients with the m.8344A>G mutation and epilepsy experienced myoclonic seizures. Patients with the m.3243A>G mutation remain at high risk of developing stroke‐like episodes (1.16% per year). However, although the standardized mortality ratio for the entire cohort was high (2.86), this ratio did not differ significantly between patients with epilepsy (2.96) and those without (2.83).InterpretationEpilepsy is a common manifestation of mitochondrial disease. It develops early in the disease and, in the case of the m.3243A>G mutation, often presents in the context of a stroke‐like episode or status epilepticus. However, epilepsy does not itself appear to contribute to the increased mortality in mitochondrial disease. Ann Neurol 2015;78:949–957

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Myoclonus epilepsy associated with ragged-red fibres (mitochondrial abnormalities): Disease entity or a syndrome?

Cited by 390 publications

References 49 publications

When should MERRF (myoclonus epilepsy associated with ragged-red fibers) be the diagnosis?

When should MERRF (myoclonus epilepsy associated with ragged-red fibers) be the diagnosis?

Síndrome psicótica evoluindo com demência como manifestação clinica de deleção do DNA mitocondrial

Epilepsy in adults with mitochondrial disease: A cohort study

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