1,088 results match your criteria Metabolic Disease and Stroke - MELAS


Mitochondrial stroke-like episodes: The search for new therapies.

Pharmacol Res 2022 Apr 21;180:106228. Epub 2022 Apr 21.

Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Italy.

A mitochondrial stroke-like event is an evolving subacute neurological syndrome linked to seizure activity and focal metabolic brain derangement in a genetically determined mitochondrial disorder. The acronym "MELAS" (mitochondrial encephalopathy associated with lactic acidosis and stroke-like lesions) identifies subjects with molecular, biochemical and/or histological evidence of mitochondrial disorder who experience stroke-like lesions. MELAS is a rare inherited mitochondrial disease linked to severe multiorgan involvement and stress-induced episodes of metabolic decompensation and lactic acidosis. Read More

View Article and Full-Text PDF

Transient Postictal Hyperglycemia as a Diagnostic Clue of Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes.

Acta Neurol Taiwan 2022 Mar;31(2):79-83

Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Neurology, National Yang Ming Chiao Tung University, Taipei, Taiwan;Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Purpose: To propose that transient postictal hyperglycemia as a diagnostic clue of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).

Case Report: We reported two non-diabetic patients presenting with generalized seizure and transient postictal hyperglycemia. At the acute stage, both patients had hyperglycemia with serum glucose levels more than 400 mg/dl, normal glycated hemoglobin (HbA1C) levels, normal ketone body levels, and absence of infection signs. Read More

View Article and Full-Text PDF

Case Report: A Case of β-Ureidopropionase Deficiency Complicated With MELAS Syndrome Caused by Variant and Mitochondrial Gene Variant.

Front Pediatr 2022 21;10:838341. Epub 2022 Feb 21.

Tianjin Children's Hospital (Children's Hospital of Tianjin University), Tianjin, China.

Background: β-Ureidopropionase deficiency is a rare autosomal recessive disease affecting the last step of pyrimidine degradation. Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare inherited disorder caused by genetic defects in mitochondrial DNA.

Case Presentation: One 8-year-old boy presented with dizziness, vomiting, and convulsions. Read More

View Article and Full-Text PDF
February 2022

Immunonutrition for the acute treatment of MELAS syndrome.

Endocrinol Diabetes Nutr (Engl Ed) 2022 Feb;69(2):144-148

Internal Medicine, Hospital Juárez de México, Mexico City, Mexico.

MELAS syndrome (Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes) is one of the most frequent mitochondrial pathologies. Its diagnosis is based on the classic triad of symptoms its acronym stands for and the presence of ragged red fibres. There is currently no curative therapy for MELAS, and treatment focuses on managing complications that affect specific organs and functions. Read More

View Article and Full-Text PDF
February 2022

Cochlear Implantation in Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes Syndrome: Case Presentation.

J Int Adv Otol 2022 Jan;18(1):71-73

Emmeline Centre, Cambridge University Hospitals, Cambridge, UK; Department of Clinical Neurosciences, University of Cambridge Addenbrooke's Health Campus, Cambridge, UK.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome is a multisystem, progressive neurodegenerative condition, and the most common mitochondrial cytopathy. While not a primary characteristic, sensorineural hearing loss is a common additional symptom reported in up to 78% of cases. This article presents 2 cases of cochlear implantation in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome. Read More

View Article and Full-Text PDF
January 2022

A retrospective cohort study exploring the association between different mitochondrial diseases and hearing loss.

Mol Genet Metab 2022 04 15;135(4):333-341. Epub 2022 Feb 15.

Dept. Internal Medicine, Radboud Center for Mitochondrial Medicine, Radboudumc Nijmegen, the Netherlands.

Some pathogenic variants in mtDNA and nuclear DNA, affecting mitochondrial function, are associated with hearing loss. Behavioral and electrophysiological auditory performance are obtained from 62 patients, clinically diagnosed with different mitochondrial diseases (MD) using tone/speech audiometry and Auditory Brainstem Responses (ABR). Audiological variables (hearing loss type, pure tone average (PTA), interaural asymmetry, speech perception and brainstem neural conductivity) were analyzed and related to Newcastle Mitochondrial Disease Scale for Adults (NMDAS). Read More

View Article and Full-Text PDF

Neurological manifestations in m.3243A>G-related disease triggered by metformin.

J Diabetes Complications 2022 03 27;36(3):108111. Epub 2021 Dec 27.

Kowloon West Cluster Laboratory Genetic Service, Department of Pathology, Princess Margaret Hospital, Hong Kong. Electronic address:

Introduction: m.3243A>G-related disease has multi-systemic manifestations including diabetes mellitus. It is uncertain whether metformin would trigger neurological manifestations of this disease. Read More

View Article and Full-Text PDF

MELAS or Leigh syndrome, that's the question.

Authors:
Josef Finsterer

Pediatr Endocrinol Diabetes Metab 2021 ;27(4):311-312

Klinik Landstrasse, Messerli Institute, Vienna, Austria.

With interest we read the article by Baszyńska-Wilk et al. about a 12 years old female who was diagnosed with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome upon the clinical presentation, blood tests, and the cerebral magnetic resonance imaging (MRI) [1]. The diagnosis was neither confirmed by biochemical nor by genetic investigations [1]. Read More

View Article and Full-Text PDF
February 2022

Elevated glutamate and decreased glutamine levels in the cerebrospinal fluid of patients with MELAS syndrome.

J Neurol 2022 Jan 28. Epub 2022 Jan 28.

National Reference Center for Congenital Errors of Metabolism (CSUR) an European Reference Center for Inherited Metabolic Disease (MetabERN), University Hospital, 12 de Octubre, Madrid, Spain.

Background: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous disorder caused by mitochondrial DNA (mtDNA) mutations in the MT-TL1 gene. The pathophysiology of neurological manifestations is still unclear, but neuronal hyperexcitability and neuron-astrocyte uncoupling have been suggested. Glutamatergic neurotransmission is linked to glucose oxidation and mitochondrial metabolism in astrocytes and neurons. Read More

View Article and Full-Text PDF
January 2022

Stroke and stroke-like episodes in inborn errors of metabolism: Pathophysiological and clinical implications.

Mol Genet Metab 2022 01 23;135(1):3-14. Epub 2021 Dec 23.

Child Neurology and Psychiatry Unit - Department of Human Neuroscience-Sapienza, Università di Roma, Italy. Electronic address:

Inborn errors of metabolism causing stroke (ischemic or haemorrhagic) or stroke-like episodes (e.g., that are also called "metabolic strokes" and include acute brain lesions not related with alterations of blood flow) cover a wide range of diseases in which acute metabolic decompensations after trigger events (e. Read More

View Article and Full-Text PDF
January 2022

Integrated proteomic and metabolomic analyses of the mitochondrial neurodegenerative disease MELAS.

Mol Omics 2022 03 28;18(3):196-205. Epub 2022 Mar 28.

Department of Chemistry, The George Washington University, Science and Engineering Hall, 800 22nd St., NW, Washington, DC 20052, USA.

MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes) is a progressive neurodegenerative disease caused by pathogenic mitochondrial DNA variants. The pathogenic mechanism of MELAS remains enigmatic due to the exceptional clinical heterogeneity and the obscure genotype-phenotype correlation among MELAS patients. To gain insights into the pathogenic signature of MELAS, we designed a comprehensive strategy integrating proteomics and metabolomics in patient-derived dermal fibroblasts harboring the ultra-rare MELAS pathogenic variant m. Read More

View Article and Full-Text PDF

Reversal of Stroke-Like Episodes With L-Arginine and Meticulous Perioperative Management of Renal Transplantation in a Patient With Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS) Syndrome. Case Report.

Neurohospitalist 2022 Jan 15;12(1):67-73. Epub 2021 Mar 15.

Division of Neurology, The Hospital for Sick Children, Toronto, Canada.

Mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes (MELAS) syndrome is a maternally inherited mitochondrial disorder with recurrent non-arterial distribution stroke-like episodes (SLEs). A 17 yr old boy with MELAS (m.3243A>G tRNA) presented with SLEs at ages 8 and 10 yrs. Read More

View Article and Full-Text PDF
January 2022

Monogenic Causes of Strokes.

Genes (Basel) 2021 11 23;12(12). Epub 2021 Nov 23.

Department of Neurology, Wroclaw Medical University, 50-556 Wroclaw, Poland.

Strokes are the main cause of death and long-term disability worldwide. A stroke is a heterogeneous multi-factorial condition, caused by a combination of environmental and genetic factors. Monogenic disorders account for about 1% to 5% of all stroke cases. Read More

View Article and Full-Text PDF
November 2021

Forecasting stroke-like episodes and outcomes in mitochondrial disease.

Brain 2022 Apr;145(2):542-554

Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute; NIHR Newcastle Biomedical Research Centre and Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

In this retrospective, multicentre, observational cohort study, we sought to determine the clinical, radiological, EEG, genetics and neuropathological characteristics of mitochondrial stroke-like episodes and to identify associated risk predictors. Between January 1998 and June 2018, we identified 111 patients with genetically determined mitochondrial disease who developed stroke-like episodes. Post-mortem cases of mitochondrial disease (n = 26) were identified from Newcastle Brain Tissue Resource. Read More

View Article and Full-Text PDF

MELAS syndrome: an acute stroke-like episode complicated by renal tubular acidosis.

BMJ Case Rep 2021 Nov 2;14(11). Epub 2021 Nov 2.

Beaumont Hospital, Dublin, Ireland.

MELAS, a mitochondrially inherited multisystem disorder, can present with acute stroke-like episodes. The literature thus far supports the use of L-arginine therapy in acute MELAS flares to alleviate and shorten the duration of symptoms. This is the case of a patient who presented with ataxia and worsening confusion on a background of genetically confirmed MELAS syndrome. Read More

View Article and Full-Text PDF
November 2021

Mitochondrial Strokes: Diagnostic Challenges and Chameleons.

Genes (Basel) 2021 10 19;12(10). Epub 2021 Oct 19.

Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK.

Mitochondrial stroke-like episodes (SLEs) are a hallmark of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). They should be suspected in anyone with an acute/subacute onset of focal neurological symptoms at any age and are usually driven by seizures. Suggestive features of an underlying mitochondrial pathology include evolving MRI lesions, often originating within the posterior brain regions, the presence of multisystemic involvement, including diabetes, deafness, or cardiomyopathy, and a positive family history. Read More

View Article and Full-Text PDF
October 2021

First Case of MELAS Syndrome Presenting with Local Brain Edema Requiring Decompressive Craniectomy.

Turk Neurosurg 2022 ;32(1):155-159

Karadeniz Technical University, Faculty of Medicine, Department of Pediatrics, Division of Pediatric Critical Care Medicine, Trabzon, Turkey.

Mitochondrial encephalomyopathy, lactic acidosis, and recurrent stroke-like episodes (MELAS) syndrome is a rare but one of the most common maternally inherited multisystem disorder. Although patients with MELAS present a variable clinical profile, strokelike lesions have been detected in 90% of cases, with stroke being the first presenting symptom in 25% of cases. However, cases of local brain edema requiring decompressive craniectomy has not been reported. Read More

View Article and Full-Text PDF
January 2022

Endocrine disorders in a patient with a suspicion of a mitochondrial disease, MELAS syndrome - a case report and literature review.

Pediatr Endocrinol Diabetes Metab 2021 ;27(3):213-218

Department of Endocrinology and Diabetology, The Children's Memorial Health Institute, Poland.

MELAS syndrome (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) is a genetically determined disease caused by mutations in mitochondrial DNA. We present a girl who was suspected of MELAS syndrome during the diagnostic evaluation of short stature. The patient suffered from symptoms potentially indicating mitochondrial disease, such as muscular weakness, cranial nerve VI palsy, headaches, retinitis pigmentosa, sensory-neural hearing loss, and elevated lactic acid. Read More

View Article and Full-Text PDF
November 2021

Sensitive quantification of m.3243A>G mutational proportion in non-retinal tissues and its relationship with visual symptoms.

Hum Mol Genet 2022 03;31(5):775-782

Department of Ophthalmology and Visual Sciences, University of Iowa Institute for Vision Research, Iowa City, IA 52242, USA.

The m.3243A>G mutation in the mitochondrial genome commonly causes retinal degeneration in patients with maternally inherited diabetes and deafness and mitochondrial encephalopathy, lactic acidosis and stroke-like episodes. Like other mitochondrial mutations, m. Read More

View Article and Full-Text PDF

The m.3890G>A/MT-ND1 mtDNA rare pathogenic variant: Expanding clinical and MRI phenotypes.

Mitochondrion 2021 09 11;60:142-149. Epub 2021 Aug 11.

Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy. Electronic address:

Introduction: Isolated complex I deficiency causes several clinical syndromes, including Leigh syndrome (LS), Leber hereditary optic neuropathy (LHON) and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). Here we reported two new patients carrying the rare m.3890G>A/MT-ND1 (p. Read More

View Article and Full-Text PDF
September 2021

Pearls and Oy-sters: Symmetric Numbness and Paresthesia Due to Stroke-like Episode in an Adolescent Male With MELAS.

Neurology 2021 11 10;97(21):1006-1008. Epub 2021 Aug 10.

From the Child Neurology Residency Program, Department of Neurology, University of California San Francisco.

View Article and Full-Text PDF
November 2021

Sonlicromanol improves neuronal network dysfunction and transcriptome changes linked to m.3243A>G heteroplasmy in iPSC-derived neurons.

Stem Cell Reports 2021 09 29;16(9):2197-2212. Epub 2021 Jul 29.

Department of Human Genetics, Radboudumc, Donders Institute for Brain, Cognition, and Behaviour, Nijmegen, 6500 HB, the Netherlands. Electronic address:

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is often caused by an adenine to guanine variant at m.3243 (m.3243A>G) of the MT-TL1 gene. Read More

View Article and Full-Text PDF
September 2021

Mitochondrial Retinopathy.

Ophthalmol Retina 2022 01 10;6(1):65-79. Epub 2021 Jul 10.

Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom; Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom. Electronic address:

Purpose: To report the retinal phenotype and the associated genetic and systemic findings in patients with mitochondrial disease.

Design: Retrospective case series.

Participants: Twenty-three patients with retinopathy and mitochondrial disease, including chronic progressive external ophthalmoplegia (CPEO), maternally inherited diabetes and deafness (MIDD), mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), Kearns-Sayre syndrome, neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome, and other systemic manifestations. Read More

View Article and Full-Text PDF
January 2022

Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS) Syndrome: Frequency, Clinical Features, Imaging, Histopathologic, and Molecular Genetic Findings in a Third-level Health Care Center in Mexico.

Neurologist 2021 Jul 6;26(4):143-148. Epub 2021 Jul 6.

Neuromuscular Disease Clinic.

Introduction: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, is a multisystemic entity of mitochondrial inheritance. To date, there is no epidemiological information on MELAS syndrome in Mexico.

Case Series: A retrospective, cross-sectional design was employed to collect and analyze the data. Read More

View Article and Full-Text PDF

Metabolic abnormality in acute stroke-like lesion and its relationship with focal cerebral blood flow in patients with MELAS: Evidence from proton MR spectroscopy and arterial spin labeling.

Mitochondrion 2021 07 27;59:276-282. Epub 2021 Jun 27.

Department of Radiology, HuaShan Hospital, Fudan University, Shanghai 200040, China; Institute of Functional and Molecular Medical Imaging, Fudan University, Shanghai 200040, China. Electronic address:

Our purpose is to detect the metabolic alterations in acute stroke-like lesions (SLLs) and further investigate the correlations between metabolic concentrations and focal cerebral blood flow in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) using proton MR spectroscopy (H-MRS) and arterial spin labeling (ASL). A total of 23 patients with MELAS at acute stage of stroke-like episodes (SLEs) and 20 normal controls (NC) were recruited in this study, respectively. All subjects underwent conventional MRI andH-MRS. Read More

View Article and Full-Text PDF

Cortical cystic lesions - A typical endpoint of a stroke-like lesion.

Brain Dev 2021 10 24;43(9):972-973. Epub 2021 Jun 24.

University of Tunis ElManar, Pasteur Institute of Tunis, Tunis, Tunisia.

View Article and Full-Text PDF
October 2021

Clinical features, pathogenesis, and management of stroke-like episodes due to MELAS.

Metab Brain Dis 2021 12 12;36(8):2181-2193. Epub 2021 Jun 12.

Department of Neurology, International University of Health and Welfare Hospital, 537-3, Iguchi, Nasushiobara, Tochigi, 329-2763, Japan.

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a disease that should be considered as a differential diagnosis to acute ischemic stroke taking into account its onset pattern and neurological symptoms, which are similar to those of an ischemic stroke. Technological advancements in neuroimaging modalities have greatly facilitated differential diagnosis between stroke and MELAS on diagnostic imaging. Stroke-like episodes in MELAS have the following features: (1) symptoms are neurolocalized according to lesion site; (2) epileptic seizures are often present; (3) lesion distribution is inconsistent with vascular territory; (4) lesions are common in the posterior brain regions; (5) lesions continuously develop in adjacent sites over several weeks or months; (6) neurological symptoms and stroke-like lesions tend to be reversible, as presented on magnetic resonance imaging; (7) the rate of recurrence is high; and; (8) brain dysfunction and atrophy are slowly progressive. Read More

View Article and Full-Text PDF
December 2021

Effect of rapamycin on mitochondria and lysosomes in fibroblasts from patients with mtDNA mutations.

Am J Physiol Cell Physiol 2021 07 9;321(1):C176-C186. Epub 2021 Jun 9.

Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada.

Maintaining mitochondrial function and dynamics is crucial for cellular health. In muscle, defects in mitochondria result in severe myopathies where accumulation of damaged mitochondria causes deterioration and dysfunction. Importantly, understanding the role of mitochondria in disease is a necessity to determine future therapeutics. Read More

View Article and Full-Text PDF

Linear cortical cystic lesions: Characteristic MR findings in MELAS patients.

Brain Dev 2021 Oct 26;43(9):931-938. Epub 2021 May 26.

Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.

Background: Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a progressive neurodegenerative disorder with stroke-like lesions. The common MRI findings are gyral swelling and high signal intensity on T2WI/FLAIR images crossing the vascular territories. We have observed a linear cystic lesion and a laminar necrosis in the affected cortices of MELAS patients. Read More

View Article and Full-Text PDF
October 2021

Brain MRS correlates with mitochondrial dysfunction biomarkers in MELAS-associated mtDNA mutations.

Ann Clin Transl Neurol 2021 06 5;8(6):1200-1211. Epub 2021 May 5.

IRCCS Istituto delle Scienze Neurologiche di Bologna, Functional and Molecular Neuroimaging Unit, Bologna, Italy.

Objective: The purpose of this study was to investigate correlations between brain proton magnetic resonance spectroscopy ( H-MRS) findings with serum biomarkers and heteroplasmy of mitochondrial DNA (mtDNA) mutations. This study enrolled patients carrying mtDNA mutations associated with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS), and MELAS-Spectrum Syndrome (MSS).

Methods: Consecutive patients carrying mtDNA mutations associated with MELAS and MSS were recruited and their serum concentrations of lactate, alanine, and heteroplasmic mtDNA mutant load were evaluated. Read More

View Article and Full-Text PDF