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Stroke and Vascular Neurology Jun 2020Headache is a common accompanying symptom of cerebrovascular diseases. The most common patterns of headache for different cerebrovascular disorders, aetiology and... (Review)
Review
Headache is a common accompanying symptom of cerebrovascular diseases. The most common patterns of headache for different cerebrovascular disorders, aetiology and pathogenesis and diagnostic workup are reviewed with emphasis on distinguishing characteristics. It will be a clinical guide for physicians who treat patients with headache or cerebral vascular disease.
Topics: CADASIL; Cerebrovascular Circulation; Cerebrovascular Disorders; Headache; Hemodynamics; Humans; Intracranial Thrombosis; MELAS Syndrome; Prognosis; Risk Factors; Subarachnoid Hemorrhage; Vasculitis, Central Nervous System; Vasospasm, Intracranial; Vertebral Artery Dissection
PubMed: 32606088
DOI: 10.1136/svn-2020-000333 -
Pediatric Endocrinology, Diabetes, and... 2021With 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...
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]. The study is appealing but raises the following concerns.
Topics: Acidosis, Lactic; Child; Female; Humans; Leigh Disease; MELAS Syndrome; Mitochondrial Encephalomyopathies; Stroke
PubMed: 35114773
DOI: 10.5114/pedm.2022.112695 -
International Journal of Molecular... Dec 2023Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome, caused by a single base substitution in mitochondrial DNA (m.3243A>G), is one...
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome, caused by a single base substitution in mitochondrial DNA (m.3243A>G), is one of the most common maternally inherited mitochondrial diseases accompanied by neuronal damage due to defects in the oxidative phosphorylation system. There is no established treatment. Our previous study reported a superior restoration of mitochondrial function and bioenergetics in mitochondria-deficient cells using highly purified mesenchymal stem cells (RECs). However, whether such exogenous mitochondrial donation occurs in mitochondrial disease models and whether it plays a role in the recovery of pathological neuronal functions is unknown. Here, utilizing induced pluripotent stem cells (iPSC), we differentiated neurons with impaired mitochondrial function from patients with MELAS. MELAS neurons and RECs/mesenchymal stem cells (MSCs) were cultured under contact or non-contact conditions. Both RECs and MSCs can donate mitochondria to MELAS neurons, but RECs are more excellent than MSCs for mitochondrial transfer in both systems. In addition, REC-mediated mitochondrial transfer significantly restored mitochondrial function, including mitochondrial membrane potential, ATP/ROS production, intracellular calcium storage, and oxygen consumption rate. Moreover, mitochondrial function was maintained for at least three weeks. Thus, REC-donated exogenous mitochondria might offer a potential therapeutic strategy for treating neurological dysfunction in MELAS.
Topics: Humans; MELAS Syndrome; Mitochondria; Acidosis, Lactic; DNA, Mitochondrial; Mitochondrial Diseases; Neurons; Mesenchymal Stem Cells
PubMed: 38139018
DOI: 10.3390/ijms242417186 -
Life (Basel, Switzerland) Oct 2021Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, a maternally inherited mitochondrial disorder, is characterized by its... (Review)
Review
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, a maternally inherited mitochondrial disorder, is characterized by its genetic, biochemical and clinical complexity. The most common mutation associated with MELAS syndrome is the mtDNA A3243G mutation in the MT-TL1 gene encoding the mitochondrial tRNA-leu(UUR), which results in impaired mitochondrial translation and protein synthesis involving the mitochondrial electron transport chain complex subunits, leading to impaired mitochondrial energy production. Angiopathy, either alone or in combination with nitric oxide (NO) deficiency, further contributes to multi-organ involvement in MELAS syndrome. Management for MELAS syndrome is amostly symptomatic multidisciplinary approach. In this article, we review the clinical presentations, pathogenic mechanisms and options for management of MELAS syndrome.
PubMed: 34832987
DOI: 10.3390/life11111111 -
Genes Oct 2021Mitochondrial stroke-like episodes (SLEs) are a hallmark of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). They should be suspected...
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. The diagnosis of MELAS has important implications for those affected and their relatives, given it enables early initiation of appropriate treatment and genetic counselling. However, the diagnosis is frequently challenging, particularly during the acute phase of an event. We describe four cases of mitochondrial strokes to highlight the considerable overlap that exists with other neurological disorders, including viral and autoimmune encephalitis, ischemic stroke, and central nervous system (CNS) vasculitis, and discuss the clinical, laboratory, and imaging features that can help distinguish MELAS from these differential diagnoses.
Topics: Adult; Brain; Cardiomyopathies; Central Nervous System; Deafness; Diabetes Mellitus; Diagnosis, Differential; Female; Humans; MELAS Syndrome; Magnetic Resonance Imaging; Male; Middle Aged; Mitochondrial Encephalomyopathies; Vasculitis, Central Nervous System
PubMed: 34681037
DOI: 10.3390/genes12101643 -
AJNR. American Journal of Neuroradiology Jan 2020Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder affecting children and young adults....
BACKGROUND AND PURPOSE
Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder affecting children and young adults. Stroke-like episodes are often associated with acute cortical lesions in the posterior cerebral cortex and are classically described as asymmetric and transient. In this study we assessed the anatomic distribution of acute cortical lesions, the incidence of symmetry, and the temporal evolution of lesions.
MATERIALS AND METHODS
This was a retrospective cohort study of patients who had a confirmed genetic diagnosis of a pathogenic variant associated with MELAS and MR imaging performed at our center (2006-2018). Each MR imaging study was assessed for new lesions using T1, T2, FLAIR, DWI, ADC, and SWI. The anatomic location, symmetry, and temporal evolution of lesions were analyzed.
RESULTS
Eight patients with the same pathogenic variant of MELAS (MT-TL1 m.3243A>G) with 31 MR imaging studies were included. Forty-one new lesions were identified in 17 of the studies (5 deep, 36 cortical). Cortical lesions most commonly affected the primary visual cortex, the middle-third of the primary somatosensory cortex, and the primary auditory cortex. Thirty of 36 cortical lesions had acute cortical diffusion restriction, of which 21 developed cortical laminar necrosis on subacute imaging. Six of 11 studies with multiple lesions showed symmetric cortical involvement.
CONCLUSIONS
Acute cortical lesions in MELAS most commonly affect the primary visual, somatosensory, and auditory cortices, all regions of high neuronal density and metabolic demand. The most common pattern of temporal evolution is acute cortical diffusion restriction with subacute cortical laminar necrosis and chronic volume loss. Symmetric involvement is more common than previously described.
Topics: Adolescent; Adult; Cohort Studies; Female; Humans; MELAS Syndrome; Magnetic Resonance Imaging; Male; Middle Aged; Retrospective Studies; Stroke; Young Adult
PubMed: 31806591
DOI: 10.3174/ajnr.A6325 -
Frontiers in Neurology 2021Mitochondrial diseases are characterized by considerable clinical and genetic heterogeneity. Mitochondrial encephalomyopathy with lactate acidosis and stroke-like...
Mitochondrial diseases are characterized by considerable clinical and genetic heterogeneity. Mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS) and Leigh syndrome (LS) are both established mitochondrial syndromes; sometimes they can overlap. A retrospective observational cohort study was done to analyze the clinical manifestations, biochemical findings, neuroimaging and genetic data, and disease outcomes of 14 patients with identified MELAS/LS overlap syndrome. A total of 14 patients, 9 males and 5 females, were enrolled. The median age at onset was 14 years, while the average age was 12.6 years. As for clinical features in concordance with MELAS, the top three most common symptoms were seizures, cognitive impairment, and stroke-like episodes (SLE). Brain atrophy was present in seven patients. As for the clinical hallmarks of LS, the top three most common symptoms were ataxia, spastic paraplegia, and bulbar palsy. Patients presented with individual syndrome or overlap syndromes with similar frequency, and the prognosis did not seem to be related to the initial presentation. Thirteen patients were identified with mutations, among which m.13513G>A mutation in the gene was the most common. Only one patient with m.8344A>G mutation of gene was found. Our study demonstrated that genes are important mutation hot spots in MELAS/LS overlap syndrome. The follow-up is very important for the final diagnosis of overlap syndrome.
PubMed: 34025555
DOI: 10.3389/fneur.2021.648740 -
Acta Neurologica Taiwanica Mar 2024A 13-year and 4-month-old girl was brought to the emergency department due to fever, dizziness,vomiting, and blurred vision. Laboratory data revealed hyperglycemia with...
A 13-year and 4-month-old girl was brought to the emergency department due to fever, dizziness,vomiting, and blurred vision. Laboratory data revealed hyperglycemia with an HbA1C of 7.3 percent, ketonuria, and lactic acidosis. The initial impression was diabetic ketoacidosis. During admission, recurrent focal impaired awareness seizures were noted, and magnetic resonance imaging of the brain revealed multiple brain infarctions in the bilateral cerebrum. Mitochondrial gene report showed A3243 G with 64 percent heteroplasmy, and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes was diagnosed. At 16 years and 7 months old, recurrence of vomiting and onset of right hemianopia and mild right limb weakness were observed and follow-up T2 images showed massive edema in her left parieto-occipital region. At 16 years and 10 months old, she developed clonus in her left hand associated with an unsteady gait and blurred vision. MRI of the brain revealed recurrent brain infarction, and T2 images showed massive edema of the right parieto-occipital region. MELAS is a rare disease entity and occasionally comorbid with mitochondrial diabetes in childhood. Characteristic radiological features of MELAS include infarction-like lesions over the parieto-occipital or parieto-temporal areas, which help distinguish MELAS from childhood ischemic stroke.
Topics: Humans; Female; Infant; MELAS Syndrome; Diabetic Ketoacidosis; Stroke; Acidosis, Lactic; Ketosis; Edema; Vomiting; Diabetes Mellitus
PubMed: 37853548
DOI: No ID Found -
Nucleic Acids Research Aug 2023Mutations in mitochondrial (mt-)tRNAs frequently cause mitochondrial dysfunction. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes...
Mutations in mitochondrial (mt-)tRNAs frequently cause mitochondrial dysfunction. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and myoclonus epilepsy associated with ragged red fibers (MERRF) are major clinical subgroups of mitochondrial diseases caused by pathogenic point mutations in tRNA genes encoded in mtDNA. We previously reported a severe reduction in the frequency of 5-taurinomethyluridine (τm5U) and its 2-thiouridine derivative (τm5s2U) in the anticodons of mutant mt-tRNAs isolated from the cells of patients with MELAS and MERRF, respectively. The hypomodified tRNAs fail to decode cognate codons efficiently, resulting in defective translation of respiratory chain proteins in mitochondria. To restore the mitochondrial activity of MELAS patient cells, we overexpressed MTO1, a τm5U-modifying enzyme, in patient-derived myoblasts. We used a newly developed primer extension method and showed that MTO1 overexpression almost completely restored the τm5U modification of the MELAS mutant mt-tRNALeu(UUR). An increase in mitochondrial protein synthesis and oxygen consumption rate suggested that the mitochondrial function of MELAS patient cells can be activated by restoring the τm5U of the mutant tRNA. In addition, we confirmed that MTO1 expression restored the τm5s2U of the mutant mt-tRNALys in MERRF patient cells. These findings pave the way for epitranscriptomic therapies for mitochondrial diseases.
Topics: Humans; DNA, Mitochondrial; MELAS Syndrome; MERRF Syndrome; Mitochondria; Mutation; RNA, Transfer
PubMed: 36928678
DOI: 10.1093/nar/gkad139 -
Neurology. Genetics Aug 2023Stroke-like episodes (SLEs) in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome are often misdiagnosed as acute...
BACKGROUND AND OBJECTIVES
Stroke-like episodes (SLEs) in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome are often misdiagnosed as acute ischemic stroke (AIS). We aimed to determine unique clinical and neuroimaging features for SLEs and formulate diagnostic criteria.
METHODS
We retrospectively identified patients with MELAS admitted for SLEs between January 2012 and December 2021. Clinical features and imaging findings were compared with a cohort of patients who presented with AIS and similar lesion topography. A set of criteria was formulated and then tested by a blinded rater to evaluate diagnostic performance.
RESULTS
Eleven MELAS patients with 17 SLE and 21 AISs were included. Patients with SLEs were younger (median 45 [37-60] vs 77 [68-82] years, < 0.01) and had a lower body mass index (18 ± 2.6 vs 29 ± 4, < 0.01), more commonly reported hearing loss (91% vs 5%, < 0.01), and more commonly presented with headache and/or seizures (41% vs 0%, < 0.01). The earliest neuroimaging test performed at presentation was uniformly a noncontrast CT. Two main patterns of lesion topography with a stereotypical spatiotemporal evolution were identified-an anterior pattern (7/21, 41%) starting at the temporal operculum and spreading to the peripheral frontal cortex and a posterior pattern (10/21, 59%) starting at the cuneus/precuneus and spreading to the lateral occipital and parietal cortex. Other distinguishing features for SLEs vs AIS were cerebellar atrophy (91% vs 19%, < 0.01), previous cortical lesions with typical SLE distribution (46% vs 9%, = 0.03), acute lesion tissue hyperemia and venous engorgement on CT angiography (CTA) (45% vs 0%, < 0.01), and no large vessel occlusion on CTA (0% vs 100%, < 0.01). Based on these clinicoradiologic features, a set of diagnostic criteria were constructed for possible SLE (sensitivity 100%, specificity 81%, AUC 0.905) and probable SLE (sensitivity 88%, specificity 95%, AUC 0.917).
DISCUSSION
Clinicoradiologic criteria based on simple anamnesis and a CT scan at presentation can accurately diagnose SLE and lead to early administration of appropriate therapy.
CLASSIFICATION OF EVIDENCE
This study provides Class III evidence that an algorithm using clinical and imaging features can differentiate stroke-like episodes due to MELAS from acute ischemic strokes.
PubMed: 37426458
DOI: 10.1212/NXG.0000000000200082