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Minerva Cardiology and Angiology Dec 2023
Topics: Humans; MELAS Syndrome; Stroke; Myocardial Infarction
PubMed: 37994634
DOI: 10.23736/S2724-5683.22.06194-4 -
American Journal of Medical Genetics.... Mar 2024The MT-TL2 m.12315G>A pathogenic variant has previously been reported in five individuals with mild clinical phenotypes. Herein we report the case of a 5-year-old child...
The MT-TL2 m.12315G>A pathogenic variant has previously been reported in five individuals with mild clinical phenotypes. Herein we report the case of a 5-year-old child with heteroplasmy for this variant who developed neurological regression and stroke-like episodes similar to those observed in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Biochemical evaluation revealed depletion of arginine on plasma amino acid analysis and low z-scores for citrulline on untargeted plasma metabolomics analysis. These findings suggested that decreased availability of nitric oxide may have contributed to the stroke-like episodes. The use of intravenous arginine during stroke-like episodes and daily enteral L-citrulline supplementation normalized her biochemical values of arginine and citrulline. Untargeted plasma metabolomics showed the absence of nicotinamide and 1-methylnicotinamide, and plasma total glutathione levels were low; thus, nicotinamide riboside and N-acetylcysteine therapies were initiated. This report expands the phenotype associated with the rare mitochondrial variant MT-TL2 m.12315G>A to include neurological regression and a MELAS-like phenotype. Individuals with this variant should undergo in-depth biochemical analysis to include untargeted plasma metabolomics, plasma amino acids, and glutathione levels to help guide a targeted approach to treatment.
Topics: Child, Preschool; Female; Humans; Acidosis, Lactic; Arginine; Citrulline; Glutathione; MELAS Syndrome; Mitochondrial Encephalomyopathies; Nitric Oxide Donors; Stroke
PubMed: 37953071
DOI: 10.1002/ajmg.a.63461 -
Schmerz (Berlin, Germany) Dec 2023Mitochondrial diseases are complex metabolic disorders caused by genetic mutations and lead to impaired energy production in the mitochondria of cells. The clinical...
Mitochondrial diseases are complex metabolic disorders caused by genetic mutations and lead to impaired energy production in the mitochondria of cells. The clinical spectrum ranges from severe multiorgan involvement in early childhood to mild monosymptomatic courses in adulthood. The brain, heart, and skeletal muscles are particularly affected due to their high energy demands. Headaches in general and migraine in particular, occur disproportionately more frequently in patients with mitochondrial diseases. In recent years similarities in the pathomechanism of mitochondrial diseases and migraine have been investigated in numerous biochemical, genetic, and therapeutic studies. The results suggest a dysfunctional energy metabolism with demonstrable mitochondrial damage as a central aspect in the pathogenesis of migraine. These findings are valuable for a better understanding of primary headache disorders and mitochondrial diseases as well as for the optimization of diagnostic and treatment procedures and should be applied in the clinical practice.
Topics: Child, Preschool; Humans; Migraine Disorders; Brain; Headache; Mitochondrial Diseases; Mitochondria
PubMed: 37921887
DOI: 10.1007/s00482-023-00764-z -
Cureus Oct 2023Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a complex and infrequently encountered mitochondrial cytopathy. Patients...
Anesthetic Management of a Patient With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes Syndrome During Extensive Spinal Surgery With Both Motor Evoked Potentials and Somatosensory Evoked Potentials: A Case Report.
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a complex and infrequently encountered mitochondrial cytopathy. Patients with MELAS often present with multi-systemic manifestations, making their anesthetic management particularly challenging. In this case report, we describe in detail our anesthetic approach for a 19-year-old male with confirmed MELAS linked to an m.3243A>G mutation. The patient had been diagnosed with MELAS at age 12 following a stroke-like episode and presented with progressive spinal deformities. He exhibited a 70° thoracic spine curvature and an 80° kyphosis, requiring a T1-L2 posterior spinal fusion. The surgical plan included neuromonitoring with both somatosensory and motor evoked potentials. Intravenous anesthetics such as propofol are typically preferred in this context due to their reduced interference with neuromonitoring compared to volatile anesthetics. Anticipating a surgical duration of six to seven hours, however, we hesitated to rely on propofol for this extended period due to its potential risks of lactic acidosis in the context of MELAS. Given that propofol infusion for extended periods (>48 hours) or at high doses (≥5 mg·kg·hour) is known to induce propofol-related infusion syndrome, and coupled with our concerns about the risk of lactic acidosis in this patient, we were compelled to design an anesthetic plan that avoided propofol altogether without excessive use of volatile anesthetics. This proactive approach ensured the maintenance of consistent neuromonitoring signals and the patient's safety, especially given his underlying mitochondrial dysfunction. Our primary rationale in presenting this case report is to highlight the challenges posed by MELAS in the setting of extended surgery, with a focus on anesthetic considerations during neuromonitoring. For prolonged surgeries that typically rely heavily on intravenous anesthetics, which interfere less with neuromonitoring than volatile anesthetics, the use of propofol should be approached with caution in MELAS contexts due to its associated risk of lactic acidosis. To our knowledge, this is the first case report that described the anesthetic management of a patient with MELAS undergoing a procedure of such duration, requiring both somatosensory and motor evoked potential neuromonitoring. We believe our experiences will serve as a reference for anesthesiologists and perioperative teams faced with similar challenging clinical situations.
PubMed: 37854475
DOI: 10.7759/cureus.47198 -
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 -
Journal of Neurology Feb 2024Mitochondrial myopathy without extraocular muscles involvement (MiMy) represents a distinct form of mitochondrial disorder predominantly affecting proximal/distal or...
OBJECTIVE
Mitochondrial myopathy without extraocular muscles involvement (MiMy) represents a distinct form of mitochondrial disorder predominantly affecting proximal/distal or axial muscles, with its phenotypic, genotypic features, and long-term prognosis poorly understood.
METHODS
A cross-sectional study conducted at a national diagnostic center for mitochondrial disease involved 47 MiMy patients, from a cohort of 643 mitochondrial disease cases followed up at Qilu Hospital from January 1, 2000, to January 1, 2021. We compared the clinical, pathological, and genetic features of MiMy to progressive external ophthalmoplegia (PEO) and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) patients.
RESULTS
MiMy patients demonstrated a more pronounced muscle involvement syndrome, with lower 6MWT scores, higher FSS, and lower BMI compared to PEO and MELAS patients. Serum levels of creatinine kinase (CK), lactate, and growth and differentiation factor 15 (GDF15) were substantially elevated in MiMy patients. Nearly a third (31.9%) displayed signs of subclinical peripheral neuropathy, mostly axonal neuropathy. Muscle biopsies revealed that cytochrome c oxidase strong (COX-s) ragged-red fibers (RRFs) were a typical pathological feature in MiMy patients. Genetic analysis predominantly revealed mtDNA point pathogenic variants (59.6%) and less frequently single (12.8%) or multiple (4.2%) mtDNA deletions. During the follow-up, a majority (76.1%) of MiMy patients experienced stabilization or improvement after therapeutic intervention.
CONCLUSIONS
This study provides a comprehensive profile of MiMy through a large patient cohort, elucidating its unique clinical, genetic, and pathological features. These findings offer significant insights into the diagnostic and therapeutic management of MiMy, ultimately aiming to ameliorate patient outcomes and enhance the quality of life.
Topics: Humans; MELAS Syndrome; Oculomotor Muscles; Cross-Sectional Studies; Quality of Life; Stroke; DNA, Mitochondrial; Acidosis, Lactic; Ophthalmoplegia, Chronic Progressive External
PubMed: 37847292
DOI: 10.1007/s00415-023-12005-5 -
Seizure Oct 2023
Topics: Humans; MELAS Syndrome; Seizures; Mutation
PubMed: 37827598
DOI: 10.1016/j.seizure.2023.03.001 -
Journal of Magnetic Resonance Imaging :... Jul 2024
Editorial for "Altered Neurovascular Coupling in Patients With Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS): A Combined Resting-State fMRI and Arterial Spin Labeling Study".
Topics: Humans; Magnetic Resonance Imaging; MELAS Syndrome; Spin Labels; Neurovascular Coupling; Brain
PubMed: 37800668
DOI: 10.1002/jmri.29043 -
Journal of Magnetic Resonance Imaging :... Jul 2024Coupling between neuronal activity and blood perfusion is termed neurovascular coupling (NVC), and it provides a potentially new mechanistic perspective into...
Altered Neurovascular Coupling in Patients With Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS): A Combined Resting-State fMRI and Arterial Spin Labeling Study.
BACKGROUND
Coupling between neuronal activity and blood perfusion is termed neurovascular coupling (NVC), and it provides a potentially new mechanistic perspective into understanding numerous brain diseases. Although abnormal brain activity and blood supply have been separately reported in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), whether anomalous NVC would be present is unclear.
PURPOSE
To investigate NVC changes and potential neural basis in MELAS by combining resting-state functional MRI (rs-fMRI) and arterial spin labeling (ASL).
STUDY TYPE
Prospective.
SUBJECTS
Twenty-four patients with MELAS (age: 29.8 ± 7.3 years) in the acute stage and 24 healthy controls (HCs, age: 26.4 ± 8.1 years). Additionally, 12 patients in the chronic stage were followed up.
FIELD STRENGTH/SEQUENCE
3.0 T, resting-state gradient-recalled echo-planar imaging and pseudo-continuous 3D ASL sequences.
ASSESSMENT
Amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and functional connectivity strength (FCS) were calculated from rs-fMRI, and cerebral blood flow (CBF) was computed from ASL. Global NVC was assessed by correlation coefficients of CBF-ALFF, CBF-fALFF, CBF-ReHo, and CBF-FCS. Regional NVC was also evaluated by voxel-wise and lesion-wise ratios of CBF/ALFF, CBF/fALFF, CBF/ReHo, and CBF/FCS.
STATISTICAL TESTS
Two-sample t-test, paired-sample t-test, Gaussian random fields correction. A P value <0.05 was considered statistically significant.
RESULTS
Compared with HC, MELAS patients in acute stage showed significantly reduced global CBF-ALFF, CBF-fALFF, CBF-ReHo, and CBF-FCS coupling (P < 0.001). Altered CBF/ALFF, CBF/fALFF, CBF/ReHo, and CBF/FCS ratios were found mainly distributed in the middle cerebral artery territory in MELAS patients. In addition, significantly increased NVC ratios were found in the acute stroke-like lesions in acute stage (P < 0.001), with a recovery trend in chronic stage.
DATA CONCLUSIONS
This study showed dynamic alterations in NVC in MELAS patients from acute to chronic stage, which may provide a novel insight for understanding the pathogenesis of MELAS.
EVIDENCE LEVEL
2 TECHNICAL EFFICACY: Stage 1.
Topics: Humans; MELAS Syndrome; Male; Female; Adult; Spin Labels; Magnetic Resonance Imaging; Prospective Studies; Brain; Young Adult; Neurovascular Coupling; Cerebrovascular Circulation; Adolescent
PubMed: 37795920
DOI: 10.1002/jmri.29035 -
Orphanet Journal of Rare Diseases Oct 2023Mitochondrial Diseases (MDs) are a diverse group of neurometabolic disorders characterized by impaired mitochondrial oxidative phosphorylation and caused by pathogenic...
BACKGROUND
Mitochondrial Diseases (MDs) are a diverse group of neurometabolic disorders characterized by impaired mitochondrial oxidative phosphorylation and caused by pathogenic variants in more than 400 genes. The implementation of next-generation sequencing (NGS) technologies helps to increase the understanding of molecular basis and diagnostic yield of these conditions. The purpose of the study was to investigate diagnostic and genotypic spectrum in patients with suspected MD. The comprehensive analysis of mtDNA variants using Sanger sequencing was performed in the group of 83 unrelated individuals with clinically suspected mitochondrial disease. Additionally, targeted next generation sequencing or whole exome sequencing (WES) was performed for 30 patients of the study group.
RESULTS
The overall diagnostic rate was 21.7% for the patients with suspected MD, increasing to 36.7% in the group of patients where NGS methods were applied. Mitochondrial disease was confirmed in 11 patients (13.3%), including few classical mitochondrial syndromes (MELAS, MERRF, Leigh and Kearns-Sayre syndrome) caused by pathogenic mtDNA variants (8.4%) and MDs caused by pathogenic variants in five nDNA genes. Other neuromuscular diseases caused by pathogenic variants in seven nDNA genes, were confirmed in seven patients (23.3%).
CONCLUSION
The wide spectrum of identified rare mitochondrial or neurodevelopmental diseases proves that MD suspected patients would mostly benefit from an extensive genetic profiling allowing rapid diagnostics and improving the care of these patients.
Topics: Humans; Mutation; Mitochondrial Diseases; DNA, Mitochondrial; Mitochondria; Genotype
PubMed: 37784170
DOI: 10.1186/s13023-023-02921-0