Recommendations for the Management of Strokelike Episodes in Patients With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Strokelike Episodes

Koenig, Mary Kay; Emrick, Lisa; Karaa, Amel; Korson, Mark S.; Scaglia, Fernando; Parikh, Sumit; Goldstein, Amy

doi:10.1001/jamaneurol.2015.5072

Cited by 99 publications

(83 citation statements)

References 23 publications

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“…Open-label studies suggest that treatment of acute mitochondrial stroke-like episodes with intravenous (IV) arginine hydrochloride, a precursor of nitric oxide, is beneficial for patient with the m.3243A>G mutation in MTTL1 (11). Open-label studies also suggest that daily oral arginine to prevent strokes should be considered in patients with mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS) due to the m.3243A>G mutation (5).…”

Section: Existing Therapeutic Optionsmentioning

confidence: 99%

Emerging therapies for mitochondrial diseases

Hirano

Emmanuele

Quinzii

2018

Essays in Biochemistry

114

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For the vast majority of patients with mitochondrial diseases, only supportive and symptomatic therapies are available. However, in the last decade, due to extraordinary advances in defining the causes and pathomechanisms of these diverse disorders, new therapies are being developed in the laboratory and are entering human clinical trials. In this review, we highlight the current use of dietary supplement and exercise therapies as well as emerging therapies that may be broadly applicable across multiple mitochondrial diseases or tailored for specific disorders. Examples of non-tailored therapeutic targets include: activation of mitochondrial biogenesis, regulation of mitophagy and mitochondrial dynamics, bypass of biochemical defects, mitochondrial replacement therapy, and hypoxia. In contrast, tailored therapies are: scavenging of toxic compounds, deoxynucleoside and deoxynucleotide treatments, cell replacement therapies, gene therapy, shifting mitochondrial DNA mutation heteroplasmy, and stabilization of mutant mitochondrial transfer RNAs.

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Section: Existing Therapeutic Optionsmentioning

confidence: 99%

Emerging therapies for mitochondrial diseases

Hirano

Emmanuele

Quinzii

2018

Essays in Biochemistry

114

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“…There is growing evidence for the use of arginine therapy in MELAS syndrome for both acute treatment and prevention of stroke-like episodes 12. Arginine is required for nitric oxide synthesis, and the observation of low arginine and citrulline levels in patients, particularly during acute stroke episodes, supports the hypothesis that vasodysregulation contributes to the aetiology of the stroke-like episodes.…”

Section: Management Of Mitochondrial Disordersmentioning

confidence: 96%

“…MELAS syndrome is the combination of m itochondrial e ncephalomyopathy, l actic a cidosis and s troke-like episodes, with the majority of cases being caused by a common mtDNA mutation (m.3243A>G) in the mtDNA gene encoding a mitochondrial leucine transfer RNA (tRNA) 12. Stroke-like episodes are typically heralded by migraine headache, vomiting and seizures.…”

Section: Recognition Of Mitochondrial Diseasementioning

confidence: 99%

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Recognition, investigation and management of mitochondrial disease

Davison

Rahman

2017

Arch Dis Child

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Mitochondria are dynamic organelles present in virtually all human cells that are needed for a multitude of cellular functions, including energy production, control of cell apoptosis and numerous biochemical catabolic and synthetic pathways that are critical for cellular health. Primary mitochondrial disorders are a group of greater than 200 single gene defects arising from two genomes (nuclear and mitochondrial) leading to mitochondrial dysfunction, and are associated with extremely heterogeneous phenotypes. Neuromuscular features predominate, but often with multisystem involvement. Clinical suspicion of a mitochondrial disorder should prompt multipronged investigation with biochemical and molecular genetic studies. Recent wide-scale adoption of next-generation sequencing approaches has led to a rapid increase in the number of disease genes. The advances in unravelling the genetic landscape of mitochondrial diseases have not yet been matched by progress in developing effective therapies, and the mainstay of care remains supportive therapies in a multidisciplinary team setting.

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“…После первоначального болюса продолжают непрерывную инфузию в течение 24 ч в анало-гичной дозе 3-5 дней. Переход в дальнейшем на перораль-ный прием препарата в дозе 0,15-0,3 г/кг/сут уменьшает ча-стоту и тяжесть инсультоподобных эпизодов [11,12]. Одна-ко нужно учитывать, что передозировка L-аргинина может вызвать гипотензию и тяжелую гипонатриемию (возможно, вследствие натрийуреза, обусловленного повышением про-дукции оксида азота), а также развитие центрального пон-тинного/экстрапонтинного миелинолиза при быстрой кор- [13].…”

Section: рис 6 мрт головного мозга в режимах т2 ви и Flair (ок-тябрunclassified