MELAS Syndrome (Syndrome, MELAS)

A mitochondrial disorder characterized by focal or generalized seizures, episodes of transient or persistent neurologic dysfunction resembling strokes, and ragged-red fibers on muscle biopsy. Affected individuals tend to be normal at birth through early childhood, then experience growth failure, episodic vomiting, and recurrent cerebral insults resulting in visual loss and hemiparesis. The cortical lesions tend to occur in the parietal and occipital lobes and are not associated with vascular occlusion. VASCULAR HEADACHE is frequently associated and the disorder tends to be familial. (From Joynt, Clinical Neurology, 1992, Ch56, p117)

Also Known As:

Networked: 1119 relevant articles (45 outcomes, 105 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Stroke (Strokes)
2.	MELAS Syndrome (Syndrome, MELAS)
3.	Mitochondrial Diseases (Mitochondrial Disease)
4.	Lactic Acidosis
5.	Mitochondrial encephalopathy

Experts

1.	Koga, Yasutoshi: 16 articles (01/2020 - 03/2003)
2.	Goto, Yu-Ichi: 14 articles (01/2021 - 06/2002)
3.	Finsterer, Josef: 13 articles (06/2022 - 07/2009)
4.	Yuan, Yun: 13 articles (01/2020 - 07/2002)
5.	El-Hattab, Ayman W: 12 articles (01/2021 - 04/2012)
6.	Wang, Zhaoxia: 12 articles (01/2021 - 07/2002)
7.	DiMauro, Salvatore: 11 articles (01/2022 - 02/2002)
8.	Yoneda, Makoto: 10 articles (01/2021 - 02/2007)
9.	Wei, Yau-Huei: 10 articles (09/2017 - 01/2002)
10.	Scaglia, Fernando: 10 articles (01/2017 - 01/2006)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to MELAS Syndrome:

1.	Arginine (L-Arginine)FDA Link 01/01/2020 - "In our clinical trial followed by 7 years follow-up study, the systematic administration of L-arginine to patients with MELAS significantly improved the survival curve of patients compared with natural history. " 06/13/2006 - "Endothelial dysfunction in MELAS improved by l-arginine supplementation." 01/01/2015 - "We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine. " 05/01/2012 - "In vivo functional brain imaging and a therapeutic trial of L-arginine in MELAS patients." 11/01/2010 - "In the present study cardiac energetics and acute effects of L-arginine (Arg) were evaluated in MELAS patients. "
2.	Mitochondrial DNA (mtDNA)IBA 03/12/2021 - "Moreover, MELAS-iPSCs with a high proportion of G13513A mutant mtDNA showed unusual properties of spontaneous, embryoid body-mediated differentiation in vitro, which was relieved by decreasing the heteroplasmy level with G13513A-mpTALEN. " 01/01/2021 - "Furthermore, ATAD3B is little expressed in m.3243A > G mutated cells and MELAS patient fibroblasts showing endogenous oxidative stress, and ATAD3B re-expression promotes the clearance of m.3243A > G mutated mtDNA. " 01/01/2023 - "Thirty-five patients with a diagnosis of mitochondrial DNA-based MELAS (median age, 12 years; interquartile range, 7-24 years; 24 female) were eligible for this study. " 01/01/2023 - "This retrospective single-center study included individuals who had confirmed mitochondrial DNA pathogenic variants and a diagnosis of MELAS and whose data were reviewed from January 2000 through November 2021. " 04/06/2022 - "In the present study, we conducted a long-term hearing evaluation in patients with MELAS or MIDD who harbored the m.3243A>G mutation of mitochondrial DNA. "
3.	Biomarkers (Surrogate Marker)IBA 03/04/2014 - "(1)H MRSI assessment of cerebral metabolism in A3243G mutation carriers shows promise in identifying disease biomarkers as well as individuals at risk of developing the MELAS phenotype." 01/01/2021 - "The objective of this study was to investigate the serum neurofilament light chain (NfL) as a novel biomarker of neurological dysfunction in MELAS. " 07/28/2021 - "Author Correction: Neurofilament light is a novel biomarker for mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes." 01/01/2021 - "These circulating biomarkers have intriguing clinical potential that implicate disease pathophysiology and may prove important biomarkers for the future management of MELAS." 01/01/2021 - "Serum NfL may serve as a novel biomarker for the neurological dysfunction in MELAS patients."
4.	coenzyme Q10 (CoQ10)IBA 06/01/2023 - "Coenzyme Q10 was used for MELAS. " 06/01/2012 - "First, coenzyme Q10 may give some benefit to control MELAS. " 06/01/2012 - "Regain of visuospatial capacity after coenzyme Q10 in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes: a case report." 12/01/2000 - "Coenzyme Q10 improves psychiatric symptoms in adult-onset mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes: a case report." 01/01/1999 - "Noninvasive tissue oximetry may be useful to evaluate the effect of coenzyme Q10 supplementation to patients with mitochondrial encephalomyopathy including MELAS."
5.	CitrullineIBA 03/15/2005 - "We discuss the depressed citrulline levels in MELAS patients, who have an unusual and paradoxical pattern of vascular respiratory chain expression, in the context of NO homeostasis." 04/01/2016 - "This study, which is the first one to assess NO metabolism in children with mitochondrial diseases, adds more evidence to the notion that NO deficiency occurs in MELAS syndrome, suggests a better effect for citrulline because of its greater role as NO precursor, and indicates that impaired NO production occurs in children as well as adults with MELAS syndrome. " 11/01/2017 - "Clinical features combined with low level of plasma citrulline were highly suggestive of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, however, the common m.3243 A > G mutation was excluded. " 01/01/2017 - "Controlled studies are still needed to assess the clinical effects of L-arginine and L-citrulline on different aspects of MELAS syndrome." 03/01/2014 - "Controlled studies assessing the effects of arginine or citrulline supplementation on different clinical aspects of MELAS syndrome are needed. "
6.	Lactic Acid (Lactate)FDA LinkGeneric 07/01/2022 - "Laboratory features, such as elevated lactate, basal ganglia calcification, and gyriform restricted diffusion may be helpful in identifying patients with MELAS." 03/04/2014 - "Consistent with prior studies, the patients with MELAS had higher lactate (p < 0.001) and lower NAA levels (p = 0.01) than HVs. " 08/01/2007 - "In the present study, we have established a reliable method for lactate quantification in a phantom study and have shown a sample of clinical case of MELAS." 08/01/2007 - "In patients with MELAS, the lactate concentration measured by MRS was 6.2 mmol/kg wet weight, which is similar to the value obtained in previous studies. " 10/11/2022 - "Brain magnetic resonance imaging (MRI) revealed hyperintensities in the left temporal occipitoparietal lobe on DWI and correspondingly elevated lactate peak in the identified restricted diffusion area on magnetic resonance spectroscopy, mimicking the image of MELAS. "
7.	TaurineFDA Link 01/01/2021 - "We also analyzed the retinal pigment epithelium (RPE) differentiated from MELAS iPSCs by using a three-dimensional culture system and found that it showed epithelial mesenchymal transition (EMT), which was suppressed by taurine. " 01/01/2021 - "Taurine normalized these changes, suggesting that MELAS iPSCs were affected by the oxidative stress and taurine reduced its influence. " 01/01/2013 - "The present review tests this hypothesis by comparing the symptoms of MELAS and taurine deficiency." 01/01/2013 - "On the other hand, if the aminoacylation defect dominates, significant differences should exist between taurine deficiency and MELAS. " 01/01/2013 - "Hence, the wobble hypothesis predicts that the symptoms of MELAS mimic those of taurine deficiency, provided that the dominant defect in MELAS is wobble modification deficiency. "
8.	Nitric Oxide (Nitrogen Monoxide)FDA Link 10/20/2021 - "Angiopathy, either alone or in combination with nitric oxide (NO) deficiency, further contributes to multi-organ involvement in MELAS syndrome. " 01/01/2017 - "There is growing evidence that nitric oxide (NO) deficiency occurs in MELAS syndrome and results in impaired blood perfusion that contributes significantly to several complications in this disease. " 09/01/2015 - "In addition, nitric oxide deficiency occurs in MELAS syndrome and can contribute to its complications. " 01/01/2017 - "In addition to impaired energy production, nitric oxide (NO) deficiency occurs in MELAS syndrome and leads to impaired blood perfusion in microvasculature that can contribute to several complications including stroke-like episodes, myopathy, and lactic acidosis. " 03/01/2014 - "There is growing evidence that nitric oxide (NO) deficiency occurs in MELAS syndrome and results in impaired blood perfusion that contributes significantly to several complications including stroke-like episodes, myopathy, and lactic acidosis. "
9.	idebenoneIBA 08/01/1996 - "The results indicate that idebenone improves mitochondrial oxidative metabolism in the brain and suggest a therapeutic potential of idebenone for MELAS." 08/01/1996 - "Idebenone improves cerebral mitochondrial oxidative metabolism in a patient with MELAS." 11/01/2011 - "Our observation suggests long-term safety and potential benefit of oral L-arginine and idebenone in the prevention of recurrence of SLEs in adult MELAS patients." 11/01/2011 - "A 38-year-old patient with MELAS and SLEs was treated with oral L-arginine and idebenone for 27months. " 11/01/2011 - "There are very few reports on long-term prevention of SLEs with oral L-arginine and idebenone treatment in MELAS adult patients. "
10.	Therapeutic UsesIBA 01/01/2019 - "The specific aim of the study is to investigate whether WJMSCs exert therapeutic effect for mitochondrial dysfunction in cells of MELAS patient through donating healthy mitochondria. " 02/01/2007 - "We investigated the endothelial function in MELAS patients and also evaluated the therapeutic effects of L-arginine. " 08/01/1991 - "Therapeutic effect of sodium dichloroacetate on visual and auditory hallucinations in a patient with MELAS." 04/01/2012 - "The improvement in NO production with arginine or citrulline supplementation supports their use in MELAS and suggests that citrulline may have a better therapeutic effect than arginine. " 04/01/2016 - "Controlled clinical trials to assess the therapeutic effects of arginine and citrulline on clinical complications of MELAS syndrome are needed. "

Therapies and Procedures

1.	Therapeutics 11/01/2010 - "Many of the accepted therapies used in treating MELAS syndrome have been identified through a small number of clinical trials or isolated case reports. " 02/01/2022 - "There is currently no curative therapy for MELAS, and treatment focuses on managing complications that affect specific organs and functions. " 06/28/2021 - "There is currently no curative therapy for MELAS, and treatment focuses on managing complications that affect specific organs and functions. " 01/01/2019 - "Two patients with end-stage MELAS at baseline died during SP therapy. " 05/01/2012 - "In vivo functional brain imaging promotes a better understanding of the pathogenesis and potential therapies for MELAS patients. "
2.	Cochlear Implantation 04/01/2005 - "Two cases of MELAS patients who responded well to cochlear implantation are presented. " 01/01/2022 - "This article presents 2 cases of cochlear implantation in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome. " 01/01/2022 - "Cochlear Implantation in Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes Syndrome: Case Presentation." 04/01/2005 - "Cochlear implantation in patients with MELAS syndrome." 01/01/2003 - "Cochlear implantation can be recommended for patients with MELAS syndrome if they have residual retrocochlear function. "
3.	Intravenous Administration 01/01/2007 - "Our experience suggests that early intravenous administration of L-arginine may be useful in the treatment of status epilepticus associated with stroke-like episode in patients with MELAS." 12/01/2018 - "The primary endpoint in the clinical trial of oral L-arginine was the MELAS scale, while that for intravenous L-arginine was the improvement rates of headache and nausea/vomiting at 2 h after completion of the initial intravenous administration. "
4.	Artificial Respiration (Mechanical Ventilation) 11/01/1995 - "Despite the ill-defined nature of the disease and uncertain prognosis, we believe that long-term home mechanical ventilation of children with early onset MELAS syndrome is a viable option for both patients and their families and results in overall improvement in quality of life for the patient." 11/01/1995 - "There are no reports in the literature of long-term home mechanical ventilation of a child with mitochondrial encephalomyopathy (MELAS) syndrome despite the many descriptions of possible etiologies of the concomitant respiratory failure. "
5.	Intravenous Infusions 09/26/2022 - "The patients were diagnosed with MELAS syndrome and their symptoms improved with intravenous infusions of coenzyme Q10, coenzyme A, vitamin B, and vitamin C. "