-
Annals of Clinical and Translational... Jun 2022To examine the correlation between verbal and visual memory function and correlation with brain metabolites (lactate and N-Acetylaspartate, NAA) in individuals with...
OBJECTIVE
To examine the correlation between verbal and visual memory function and correlation with brain metabolites (lactate and N-Acetylaspartate, NAA) in individuals with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).
METHODS
Memory performance and brain metabolites (ventricular lactate, occipital lactate, and occipital NAA) were examined in 18 MELAS, 58 m.3243A > G carriers, and 20 familial controls. Measures included the Selective Reminding Test (verbal memory), Benton Visuospatial Retention Test (visual memory), and MR Spectroscopy (NAA, Lactate). ANOVA, chi-squared/Fisher's exact tests, paired t-tests, Pearson correlations, and Spearman correlations were used.
RESULTS
When compared to carriers and controls, MELAS patients had the: (1) most impaired memory functions (Visual: p = 0.0003; Verbal: p = 0.02), (2) greatest visual than verbal memory impairment, (3) highest brain lactate levels (p < 0.0001), and (4) lowest brain NAA levels (p = 0.0003). Occipital and ventricular lactate to NAA ratios correlated significantly with visual memory performance (p ≤ 0.001). Higher lactate levels (p ≤ 0.01) and lower NAA levels (p = 0.0009) correlated specifically with greater visual memory dysfunction in MELAS. There was little or no correlation with verbal memory.
INTERPRETATION
Individuals with MELAS are at increased risk for impaired memory. Although verbal and visual memory are both affected, visual memory is preferentially affected and more clearly associated with brain metabolite levels. Preferential involvement of posterior brain regions is a distinctive clinical signature of MELAS. We now report a distinctive cognitive phenotype that targets visual memory more prominently and earlier than verbal memory. We speculate that this finding in carriers presages a conversion to the MELAS phenotype.
Topics: Brain; Humans; Lactic Acid; MELAS Syndrome; Phenotype; Stroke
PubMed: 35522125
DOI: 10.1002/acn3.51564 -
Pharmacological Research Jun 2022A mitochondrial stroke-like event is an evolving subacute neurological syndrome linked to seizure activity and focal metabolic brain derangement in a genetically...
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. Unfortunately, there are no etiopathogenetic therapies for stroke-like episodes to date, and the treatment is mainly based on anti-epileptic drugs and supportive therapies. This perspective opinion article discusses the current care standards for MELAS patients and revises current and innovative emerging therapies for mitochondrial stroke-like episodes.
Topics: Acidosis, Lactic; DNA, Mitochondrial; Humans; MELAS Syndrome; Mitochondrial Diseases; Mutation; Stroke
PubMed: 35462010
DOI: 10.1016/j.phrs.2022.106228 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2023Patients with epilepsy who have also hearing loss represent a distinct group of patients, often with aggravated medical history, comorbidities and high potential for...
Patients with epilepsy who have also hearing loss represent a distinct group of patients, often with aggravated medical history, comorbidities and high potential for disability. The etiopathogenetic factors of epilepsy and hearing loss may be common to these conditions (neuroinfections, craniocerebral injuries, cerebral circulatory disorders, perinatal pathology, etc.). In addition, these two syndromes may occur as part of hereditary diseases, so their timely recognition and genetic diagnosis are important for determining further medical and genetic prognosis. This article provides an overview of orphan genetic diseases associated with epilepsy and hearing loss - MERRF syndrome, MELAS syndrome, EAST syndrome, Ayme-Grippsyndrome, epilepsy, hearing loss and mental retardation syndromes, associated with mutations in SPATA5 gene, DOOR syndrome, Gustavson syndrome.
Topics: Humans; Deafness; Epilepsy; Epileptic Syndromes; Hearing Loss; Hearing Loss, Sensorineural; Mutation
PubMed: 36719116
DOI: 10.17116/jnevro202312301128 -
Iranian Journal of Child Neurology 2020Autism spectrum disorder (ASD) is a category of neurodevelopmental disorders characterized by social and communication impairment and restricted or repetitive behaviors.... (Review)
Review
Autism spectrum disorder (ASD) is a category of neurodevelopmental disorders characterized by social and communication impairment and restricted or repetitive behaviors. The pathogenesis of ASD is not well understood and it's proved that genetic is strongly associated with ASD in 5 to 25% of cases. Inborn errors of metabolism(IEMs), defined by a vast array of disorders that are caused by specific enzyme deficiencies or transport protein defects, is as frequent as in 1 in 800 births. IEMs can manifest several psychiatric or behavioral manifestations such as self-injuriesincreased activity and aggression, personality changes, paranoia, depression, catatonia, and psychosis. IEMs underlie autistic symptoms in less than 5% of cases. The literature on the association between ASD and respiratory chain abnormalities is growing, including complex III/IV deficiency and MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) syndrome, as well as glucose-6-phosphate dehydrogenase deficiency. Google Scholar, Pubmed, and SCOPUS databases were searched using a combination of the following keywords: "autism spectrum disorder", "autism spectrum", "autistic feature" and "inborn error of metabolism", " IEM", "congenital error of metabolism". Initially, 655 articles were found and our expert and methodologist altogether selected 187 articles based on the titles, relevance, and text language. After reading full texts, 37 studies were selected for review. We think it's best to consider IEMs in children with syndromic ASD and/or if there is a strong familial history of autism or parental consanguineous marriage.
PubMed: 33193781
DOI: No ID Found -
Journal of Neurology Jun 2022Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous disorder caused by mitochondrial DNA (mtDNA)... (Observational Study)
Observational Study
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. Given the relevance of neuron-astrocyte metabolic coupling and astrocyte function regulating energetic metabolism, we aimed to assess glutamate and glutamine CSF levels in MELAS patients.
METHODS
This prospective observational case-control study determined glutamate and glutamine CSF levels in patients with MELAS syndrome and compared them with controls. The plasma and CSF levels of the remaining amino acids and lactate were also determined.
RESULTS
Nine adult patients with MELAS syndrome (66.7% females mean age 35.8 ± 3.2 years) and 19 controls (63.2% females mean age 42.7 ± 3.8 years) were included. The CSF glutamate levels were significantly higher in patients with MELAS than in controls (18.48 ± 1.34 vs. 5.31 ± 1.09 μmol/L, p < 0.001). Significantly lower glutamine concentrations in patients with MELAS than controls were shown in CSF (336.31 ± 12.92 vs. 407.06 ± 15.74 μmol/L, p = 0.017). Moreover, the CSF levels of alanine, the branched-chain amino acids (BCAAs) and lactate were significantly higher in patients with MELAS.
CONCLUSIONS
Our results suggest the glutamate-glutamine cycle is altered probably due to metabolic imbalance, and as a result, the lactate-alanine and BCAA-glutamate cycles are upregulated. These findings might have therapeutic implications in MELAS syndrome.
Topics: Adult; Alanine; Case-Control Studies; DNA, Mitochondrial; Female; Glutamic Acid; Glutamine; Humans; Lactic Acid; MELAS Syndrome; Male; Middle Aged; Stroke
PubMed: 35088140
DOI: 10.1007/s00415-021-10942-7 -
American Journal of Ophthalmology Case... Jun 2024To describe examination and findings in a case of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) with particular focus on the ocular...
PURPOSE
To describe examination and findings in a case of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) with particular focus on the ocular sequelae from diabetes.
OBSERVATIONS
Neovascular glaucoma is not a common manifestation of MELAS.
CONCLUSIONS AND IMPORTANCE
We present a rare case of neovascular glaucoma in a patient with MELAS with a history of diabetes, hearing loss, and macular dystrophy. MELAS should be suspected in patients with this constellation of symptoms.
PubMed: 38707951
DOI: 10.1016/j.ajoc.2024.102064 -
Practical Neurology Aug 2019
Topics: Diagnosis, Differential; Epilepsies, Myoclonic; Genetic Diseases, Inborn; Humans; Leukoencephalitis, Acute Hemorrhagic; MELAS Syndrome; Optic Atrophy, Hereditary, Leber; Recurrence
PubMed: 30948557
DOI: 10.1136/practneurol-2018-002181 -
Nefrologia Dec 2023Mitochondrial diseases are a phenotype and genotype heterogeneous group of disorders that typically have a multisystemic involvement. The m.3243A>G pathogenic variant is... (Review)
Review
Mitochondrial diseases are a phenotype and genotype heterogeneous group of disorders that typically have a multisystemic involvement. The m.3243A>G pathogenic variant is the most frequent mitochondrial DNA defect, and it causes several different clinical syndromes, such as mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS), and the maternally inherited diabetes and deafness (MIDD) syndromes. Not frequently reported, renal involvement in these diseases is probably underestimated, yet it increases morbidity. It generally manifests as subnephrotic proteinuria and progressive deterioration of kidney function. Adult presentation of mitochondrial diseases is hard to recognize, especially in oligosymptomatic patients or those with exclusive kidney involvement. However, suspicion should always arise when family history, particularly on the maternal side, and multisystemic symptoms, most often of the central nervous system and skeletal muscles, are present. In this review we discuss the clinical diagnosis and approach of patients with renal manifestations in the context of the mtDNA m.3243A>G pathogenic variant.
Topics: Adult; Humans; DNA, Mitochondrial; MELAS Syndrome; Mitochondrial Diseases; Diabetes Mellitus, Type 2; Kidney; Hearing Loss, Sensorineural; Deafness
PubMed: 38355238
DOI: 10.1016/j.nefroe.2024.01.017 -
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