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Pediatric Neurology Oct 2017Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder often causing progressive brain injury that is...
BACKGROUND
Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder often causing progressive brain injury that is not confined to large arterial territories. Severe insults ultimately lead to gyral necrosis affecting the cortex and juxtacortical white matter; the neuroimaging correlate is partial gyral signal suppression on T2/FLAIR sequences that resemble black toenails. We aimed to characterize the imaging features and the natural history of MELAS-related gyral necrosis.
MATERIALS AND METHODS
Databases at two children's hospitals were searched for brain magnetic resonance imaging studies of individuals with MELAS. Examinations with motion artifact and those lacking T2/FLAIR sequences were excluded. The location, the cumulative number, and the maximum transverse diameter of necrotic gyral lesions were assessed using T2-weighted images and T2/FLAIR sequences. Wilcoxon signed-rank test was employed to evaluate the relationship between disease duration and the number of necrotic lesions.
RESULTS
One hundred twenty-four examinations from patients with 14 unique MELAS patients (16 ± 3 years) were evaluated. Six of the eight patients who developed brain lesions also developed gyral necroses (mean 13, range 0 to 44). Necrotic lesions varied in maximal diameter from 4 to 25 mm. Cumulative necrotic lesions correlated with disease duration (P < 0.001).
CONCLUSIONS
The black toenail sign signifying gyral necrosis is a common imaging feature in individuals with MELAS syndrome. The extent of gyral necrosis correlates with disease duration.
Topics: Acidosis, Lactic; Adolescent; Brain; Female; Follow-Up Studies; Genes, Mitochondrial; Humans; MELAS Syndrome; Magnetic Resonance Imaging; Male; Mutation; Nails; Necrosis; Retrospective Studies; White Matter; Young Adult
PubMed: 28818358
DOI: 10.1016/j.pediatrneurol.2017.06.017 -
Pediatric Neurology Feb 2017
Topics: DNA, Mitochondrial; Epilepsy; Humans; MELAS Syndrome
PubMed: 27867040
DOI: 10.1016/j.pediatrneurol.2016.10.015 -
Acta Neurologica Belgica Jun 2023Stroke-like episodes (SLEs) in patients with MELAS syndrome are often initially misdiagnosed as acute ischemic stroke (AIS), resulting in treatment delay. We aimed to...
BACKGROUND AND OBJECTIVES
Stroke-like episodes (SLEs) in patients with MELAS syndrome are often initially misdiagnosed as acute ischemic stroke (AIS), resulting in treatment delay. We aimed to determine clinical features that may distinguish SLEs from AISs and explore the benefit of early L-arginine treatment on patient outcomes.
METHODS
We looked retrospectively for MELAS patients admitted between January 2005 and January 2022 and compared them to an AIS cohort with similar lesion topography. MELAS patients who received L-arginine within 40 days of their first SLE were defined as the early treatment group and the remaining as late or no treatment group.
RESULTS
Twenty-three SLEs in 10 MELAS patients and 21 AISs were included. SLE patients had significantly different features: they were younger, more commonly reported hearing loss, lower body mass index, had more commonly a combination of headache and/or seizures at presentation, serum lactate was higher, and hemiparesis was less common. An SLE Early Clinical Score (SLEECS) was constructed by designating one point to each above features. SLEECS ≥ 4 had 80% sensitivity and 100% specificity for SLE diagnosis. Compared to late or no treatment, early treatment group patients (n = 5) had less recurrent SLEs (total 2 vs. 11), less seizures (14% vs. 25%, p = 0.048), lower degree of disability at first and last follow-up (modified ranking scale, mRS 2 ± 0.7 vs. 4.2 ± 1, p = 0.005; 2 ± 0.7 vs. 5.8 ± 0.5, p < 0.001, respectively), and a lower mortality (0% vs. 80% p = 0.048).
CONCLUSIONS
The SLEECS model may aid in the early diagnosis and treatment of SLEs and lead to improved clinical outcomes.
Topics: Humans; Arginine; Early Diagnosis; Ischemic Stroke; MELAS Syndrome; Retrospective Studies; Seizures; Stroke
PubMed: 36792807
DOI: 10.1007/s13760-023-02196-z -
The Journal of International Advanced... Aug 2019The mitochondrial DNA (mtDNA) point mutation m.3243A>G is known to express the following two syndromes among others: maternally inherited diabetes and deafness (MIDD)...
OBJECTIVES
The mitochondrial DNA (mtDNA) point mutation m.3243A>G is known to express the following two syndromes among others: maternally inherited diabetes and deafness (MIDD) and mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Sensorineural hearing loss (SNHL) is the most frequent symptom in individuals harboring the m.3243A>G mutation. However, dysfunction of the vestibular organs has been scarcely examined. Therefore, the present study aimed to study the impact of the m.3243A>G mutation on the inner ear.
MATERIALS AND METHODS
A total of 8 subjects harboring the blood-verified m.3243A>G mutation underwent thorough audiological and vestibular examinations, including tone and speech audiometry, video head impulse test (vHIT), ocular and cervical vestibular-evoked myogenic potential (oVEMP and cVEMP), and full otoneurological examination. The subjects also answered a Dizziness Handicap Inventory (DHI) questionnaire.
RESULTS
SNHL was identified in all the 8 subjects, with a mean pure-tone average-4 (PTA-4) of 59 dB. Speech discrimination score (n=7) ranged from 24% to 100% (mean 74%), and vHIT (n=42) detected pathology in nine lateral semicircular canals (SCCs), five posterior SCCs, and one anterior SCC, whereas three measurements were inconclusive. All oVEMPs (n=14 ears) were absent, nine cVEMPs were absent, and two were inconclusive. Based on the DHI scores, 6 subjects reported none to mild dizziness, 1 reported moderate, and 1 reported severe dizziness.
CONCLUSION
Our study population had pathological findings from every audiological and vestibular end organs. The results indicated that the pathological findings originated from within the end organs themselves and not within the superior and inferior vestibular or cochlear nerve.
Topics: Aged; Audiometry, Pure-Tone; Audiometry, Speech; Dizziness; Female; Head Impulse Test; Hearing Loss, Sensorineural; Humans; Labyrinth Diseases; MELAS Syndrome; Male; Middle Aged; Point Mutation; Saccades; Speech Perception; Vestibular Evoked Myogenic Potentials; Vestibule, Labyrinth
PubMed: 31347509
DOI: 10.5152/iao.2019.5913 -
Revista Espanola de Enfermedades... Feb 2021MELAS syndrome with chronic intestinal pseudo-obstruction and neurological symptoms in a patient with a fatal evolution despite medical and surgical treatment.
MELAS syndrome with chronic intestinal pseudo-obstruction and neurological symptoms in a patient with a fatal evolution despite medical and surgical treatment.
Topics: Chronic Disease; Humans; Intestinal Pseudo-Obstruction; MELAS Syndrome
PubMed: 33226257
DOI: 10.17235/reed.2020.7099/2020 -
Mitochondrion Jan 2019To examine clinical severity, cognitive impairment, and MRI changes in patients with MELAS syndrome.
OBJECTIVE
To examine clinical severity, cognitive impairment, and MRI changes in patients with MELAS syndrome.
METHODS
Cognitive-mnestic functions, brain MRI (lesion load, cella media index) and clinical severity of ten patients with MELAS syndrome were examined. All patients carried the m.3243A>G mutation.
RESULTS
The detailed neuropsychological assessment revealed cognitive deficits in attention, executive function, visuoperception, and -construction. There were significant correlations between these cognitive changes, lesion load in MRI, disturbances in everyday life (clinical scale), and high scores in NMDAS.
CONCLUSION
Patients with MELAS syndrome showed no global neuropsychological deficit, but rather distinct cognitive deficits.
Topics: Adult; Brain; Cognitive Dysfunction; Female; Humans; MELAS Syndrome; Magnetic Resonance Imaging; Male; Middle Aged; Young Adult
PubMed: 29289801
DOI: 10.1016/j.mito.2017.12.012 -
JCI Insight Jul 2023Variants within the high copy number mitochondrial genome (mtDNA) can disrupt organelle function and lead to severe multisystem disease. The wide range of manifestations...
Variants within the high copy number mitochondrial genome (mtDNA) can disrupt organelle function and lead to severe multisystem disease. The wide range of manifestations observed in patients with mitochondrial disease results from varying fractions of abnormal mtDNA molecules in different cells and tissues, a phenomenon termed heteroplasmy. However, the landscape of heteroplasmy across cell types within tissues and its influence on phenotype expression in affected patients remains largely unexplored. Here, we identify nonrandom distribution of a pathogenic mtDNA variant across a complex tissue using single-cell RNA-Seq, mitochondrial single-cell ATAC sequencing, and multimodal single-cell sequencing. We profiled the transcriptome, chromatin accessibility state, and heteroplasmy in cells from the eyes of a patient with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and from healthy control donors. Utilizing the retina as a model for complex multilineage tissues, we found that the proportion of the pathogenic m.3243A>G allele was neither evenly nor randomly distributed across diverse cell types. All neuroectoderm-derived neural cells exhibited a high percentage of the mutant variant. However, a subset of mesoderm-derived lineage, namely the vasculature of the choroid, was near homoplasmic for the WT allele. Gene expression and chromatin accessibility profiles of cell types with high and low proportions of m.3243A>G implicate mTOR signaling in the cellular response to heteroplasmy. We further found by multimodal single-cell sequencing of retinal pigment epithelial cells that a high proportion of the pathogenic mtDNA variant was associated with transcriptionally and morphologically abnormal cells. Together, these findings show the nonrandom nature of mitochondrial variant partitioning in human mitochondrial disease and underscore its implications for mitochondrial disease pathogenesis and treatment.
Topics: Humans; Heteroplasmy; MELAS Syndrome; Mitochondrial Diseases; DNA, Mitochondrial; Retina; Retinal Diseases; Chromatin
PubMed: 37289546
DOI: 10.1172/jci.insight.165937 -
ENeurologicalSci Sep 2016This paper reported an unusual manifestation of a 19-year-old Chinese male patient presented with a complex phenotype of mitochondrial encephalomyopathy, lactic acidosis...
This paper reported an unusual manifestation of a 19-year-old Chinese male patient presented with a complex phenotype of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome and Kearns-Sayre syndrome (KSS). He was admitted to our hospital with the chief complaint of "acute fever, headache and slow reaction for 21 days". He was initially misdiagnosed as "viral encephalitis". This Chinese man with significant past medical history of intolerating fatigue presented paroxysmal neurobehavioral attacks that started about 10 years ago. During this span, 3 or 4 attack clusters were described during which several attacks occurred over a few days. The further examination found that the hallmark signs of this patient included progressive myoclonus epilepsy, cerebellar ataxia, hearing loss, myopathic weakness, ophthalmoparesis, pigmentary retinopathy and bifascicular heart block (Wolff-Parkinson-White syndrome). By young age the disease progression is characterized by the addition of migraine, vomiting, and stroke-like episodes, symptoms of MELAS expression, which indicated completion of the MELAS/KSS overlap syndrome. The m. A3243G mitochondrial DNA mutation and single large-scale mtDNA deletions were found in this patient. This mutation has been reported with MELAS, KSS, myopathy, deafness and mental disorder with cognitive impairment. This is the first description with a MELAS/KSS syndrome in Chinese.
PubMed: 29430542
DOI: 10.1016/j.ensci.2016.04.006 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2018Differential diagnosis of migraine, can be difficult, especially of migraine with aura. On the one hand, some diseases can produce symptoms similar to migraine (cerebral... (Review)
Review
Differential diagnosis of migraine, can be difficult, especially of migraine with aura. On the one hand, some diseases can produce symptoms similar to migraine (cerebral aneurysm before rupture, reversible cerebral vasoconstriction syndrome). On the other hand, migraine with aura and some other disorders are conditions that have common pathophysiological mechanisms (e.g., CADASIL and MELAS syndrome, antiphospholipid syndrome). Thirdly, clinical presentations of migraine are often difficult to distinguish from features of other headache conditions (migraine with aura - transient ischemic attack, migraine with visual aura - occipital epilepsy). The author discusses the differential diagnosis of acute headache, especially thunderclap headache, and main strategies of effective treatment of migraine attacks.
Topics: Acute Pain; CADASIL; Diagnosis, Differential; Epilepsies, Partial; Female; Headache; Humans; Ischemic Attack, Transient; MELAS Syndrome; Male; Migraine Disorders; Migraine with Aura
PubMed: 29460913
DOI: 10.17116/jnevro20181181196-102 -
Seizure Jan 2023
Topics: Humans; MELAS Syndrome; Epilepsy; Brain; Stroke
PubMed: 36642493
DOI: 10.1016/j.seizure.2022.09.012