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Current Pain and Headache Reports Sep 2016Mitochondrial diseases are multisystem disorders that frequently involve the central nervous system. The clinical presentation of these disorders may be challenging to... (Review)
Review
Mitochondrial diseases are multisystem disorders that frequently involve the central nervous system. The clinical presentation of these disorders may be challenging to differentiate from cerebrovascular disorders. Various imaging techniques are now available that provide a wide range of imaging modalities during initial clinical evaluation and throughout the disease course. Recent technological advancements have introduced advanced neuroimaging modalities that provide detailed information of metabolic disorders at the tissue level. Imaging findings, though diverse, usually have characteristic features that support differentiating these disorders from vascular syndromes. This article provides an overview of various neuroimaging modalities available along with the advent of new imaging techniques being utilized in these disorders.
Topics: Humans; MELAS Syndrome; Neuroimaging
PubMed: 27477183
DOI: 10.1007/s11916-016-0583-7 -
International Journal of Molecular... Mar 2024MELAS syndrome, characterized by mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes, represents a devastating mitochondrial disease, with... (Review)
Review
MELAS syndrome, characterized by mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes, represents a devastating mitochondrial disease, with the stroke-like episodes being its primary manifestation. Arginine supplementation has been used and recommended as a treatment for these acute attacks; however, insufficient evidence exists to support this treatment for MELAS. The mechanisms underlying the effect of arginine on MELAS pathophysiology remain unclear, although it is hypothesized that arginine could increase nitric oxide availability and, consequently, enhance blood supply to the brain. A more comprehensive understanding of these mechanisms is necessary to improve treatment strategies, such as dose and regimen adjustments; identify which patients could benefit the most; and establish potential markers for follow-up. This review aims to analyze the existing evidence concerning the mechanisms through which arginine supplementation impacts MELAS pathophysiology and provide the current scenario and perspectives for future investigations.
Topics: Humans; MELAS Syndrome; Acidosis, Lactic; Arginine; Stroke; Dietary Supplements
PubMed: 38612442
DOI: 10.3390/ijms25073629 -
International Journal of Cardiology Feb 2019Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like (MELAS) syndrome is a rare condition with heterogeneous clinical presentation. Cardiac... (Observational Study)
Observational Study
BACKGROUND
Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like (MELAS) syndrome is a rare condition with heterogeneous clinical presentation. Cardiac involvement commonly develops during adulthood, comprising both structural and conduction/arrhythmic abnormalities; early paediatric onset has rarely been reported. We describe the clinical profile, outcome and clinical implication of MELAS-associated cardiomyopathy at a tertiary referral centre.
METHODS
From 2000 to 2016 we enrolled 21 patients affected by genetically-proven MELAS. Patients were followed-up at least annually over a mean of 8.5 years.
RESULTS
All patients carried the MT-TL1 3243A>G mutation. Cardiac involvement was documented in 8 (38%) patients (three <18 years; five ≥18 years), including 6 (75%) with hypertrophic cardiomyopathy, 1 (12.5%) with dilated cardiomyopathy, and 1 (12.5%) with persistent pulmonary hypertension. During follow-up, 3 patients died, all with cardiac onset <18 years. The cause of death, however, was non-cardiac (infections, respiratory failure, stroke). Neither events nor cardiac progression were recorded among patients with onset ≥18 years. Adult cardiologists were responsible for 5/8 of referrals, even in patients with long-standing extra-cardiac involvement.
CONCLUSIONS
Cardiac involvement was found in over 1/3 of patients with MELAS syndrome, and exhibited a bimodal age-related distribution with distinct final outcomes. Paediatric-onset cardiomyopathy represented a hallmark of systemic disease severity, without being the main determinant of outcome. Conversely, adult-onset cardiomyopathy appeared to represent a mild and non-progressive mid-term manifestation. Adult cardiologists played an important role in the diagnostic process, triggering suspicion of MELAS in most of patients diagnosis >18 years.
Topics: Adolescent; Adult; Age Factors; Cardiomyopathies; Child; Female; Follow-Up Studies; Humans; MELAS Syndrome; Male; Mitochondria; Mutation; Retrospective Studies
PubMed: 30482630
DOI: 10.1016/j.ijcard.2018.10.051 -
The European Journal of Neuroscience Jul 2022Mitochondria are an autonomous organelle that plays a crucial role in the metabolic aspects of a cell. Cortical spreading depression (CSD) and fluctuations in the... (Review)
Review
Mitochondria are an autonomous organelle that plays a crucial role in the metabolic aspects of a cell. Cortical spreading depression (CSD) and fluctuations in the cerebral blood flow have for long been mechanisms underlying migraine. It is a neurovascular disorder with a unilateral manifestation of disturbing, throbbing and pulsating head pain. Migraine affects 2.6% and 21.7% of the general population and is the major cause of partial disability in the age group 15-49. Higher mutation rates, imbalance in concentration of physiologically relevant molecules and oxidative stress biomarkers have been the main themes of discussion in determining the role of mitochondrial disability in migraine. The correlation of migraine with other disorders like hemiplegic migraine; mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes [MELAS]; tension-type headache (TTH); cyclic vomiting syndrome (CVS), ischaemic stroke; and hypertension has helped in the assessment of the physiological and morphogenetic basis of migraine. Here, we have reviewed the different nuances of mitochondrial dysfunction and migraine. The different mtDNA polymorphisms that can affect the generation and transmission of nerve impulse has been highlighted and supported with research findings. In addition to this, the genetic basis of migraine pathogenesis as a consequence of mutations in nuclear DNA that can, in turn, affect the synthesis of defective mitochondrial proteins is discussed along with a brief overview of epigenetic profile. This review gives an overview of the pathophysiology of migraine and explores mitochondrial dysfunction as a potential underlying mechanism. Also, therapeutic supplements for managing migraine have been discussed at different junctures in this paper.
Topics: Brain Ischemia; Humans; MELAS Syndrome; Migraine Disorders; Mitochondria; Mutation; Stroke
PubMed: 35478208
DOI: 10.1111/ejn.15676 -
Annals of Clinical and Laboratory... Mar 2018
Topics: Autoimmunity; DNA, Mitochondrial; Humans; MELAS Syndrome; Mutation; Phenotype
PubMed: 29678857
DOI: No ID Found -
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 -
European Journal of Paediatric... Nov 2016Stroke-like episodes (SLEs) are a hallmark of various mitochondrial disorders, in particular MELAS syndrome. SLEs manifest with vasogenic oedema (DWI and ADC... (Review)
Review
PURPOSE
Stroke-like episodes (SLEs) are a hallmark of various mitochondrial disorders, in particular MELAS syndrome. SLEs manifest with vasogenic oedema (DWI and ADC hyperintensity) or partial cytotoxic oedema (DWI hyperintensity, ADC hypointensity) in the acute and subacute stage, and with gyriform T1-hyperintensity (cortical necrosis) in the chronic stage.
PRINCIPAL RESULTS
SLEs must be clearly distinguished from ischaemic stroke, since management of these two entities is different. SLEs may go along with or without seizures or epileptiform discharges on EEG. However, in MELAS syndrome seizures may also occur in the absence of SLEs. Focal and generalised seizures have been reported but it is currently unknown if the one or the other prevail. SLEs with and without seizures may respond to NO-precursors l-arginine, succinate, or citrulline. As a supportive measure a ketogenic diet should be initiated. Seizures prior to or during a SLE or paroxysmal EEG-activity during a SLE should be initially treated with antiepileptic drugs (AEDs) with low mitochondrion-toxicity. Only in case these AEDs are ineffective, AEDs with higher mitochondrion-toxicity should be added.
MAJOR CONCLUSIONS
All patients with SLEs need to have an EEG recorded irrespective if they have manifesting seizures or not. There are no mtDNA or nDNA mutations which predispose for SLEs with seizures.
Topics: Aged; Anticonvulsants; Arginine; DNA, Mitochondrial; Diet, Ketogenic; Female; Humans; MELAS Syndrome; Male; Middle Aged; Mutation; Seizures; Stroke
PubMed: 27562097
DOI: 10.1016/j.ejpn.2016.08.002 -
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 -
Journal of Comparative Psychology... Nov 2018The question of personality in nonhuman animals has loomed large in the study of animal behavior. This issue's featured article assessed the possibility that different...
The question of personality in nonhuman animals has loomed large in the study of animal behavior. This issue's featured article assessed the possibility that different environments generate different patterns of personality. Roy and Bhat (2018) studied common measures of personality in two populations of wild zebrafish, . Roy and Bhat's studies support the hypothesis that personality will depend in part on the populations being studied and the environmental variation experienced by individuals in those populations. Populations differing in their exposure to predation should be expected to differ in their propensity to engage in risky behavior (like foraging or courtship) in the context of cues and signals of predators. Beyond this important finding, though, Roy and Bhat (2018) found that higher, as opposed to lower, predation pressure seems to be associated with lower levels of intra- and interindividual variability in boldness-related behavior. Key next steps proposed by the authors include experimental studies aimed at determining the individual effects of variation in predation, water-flow, and food resources on boldness and aggression in these populations, including multiple generations and replicates of each sampled population. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Topics: Aggression; Animals; Behavior, Animal; MELAS Syndrome; Personality; Predatory Behavior
PubMed: 30451522
DOI: 10.1037/com0000158