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Query: UMLS:C0038454 (stroke)
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Two patients are reported with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes in whom CT documented massive focal brain swelling with midline shift concurrent with exacerbations of their conditions. Brain swelling producing mass effect should be recognized as a feature of MELAS.
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PMID:Massive focal brain swelling as a feature of MELAS. 324 75

MELAS is a distinctive syndrome manifested by mitochondrial myopathy, encephalopathy, lactic acidosis, and recurrent stroke-like episodes such as seizures, alternating hemiparesis, hemianopsia, or cortical blindness. Pathologically the disorder is characterized by multiple, solitary or continuous foci of necrosis (infarct or softening), varying in size and stage, predominantly involving the bilateral cerebral cortices and to a lesser degree cerebral white matter, basal ganglia, brainstem and cereblum. The distribution of the lesions does not correspond to vascular territories, suggesting that they are not due to usual thrombotic or embolic process. The exact nature and pathogenesis of these lesions with characteristic distribution pattern remain to be elucidated. We studied systematically cerebral blood vessels from two autopsied patients with MELAS by electron microscopy. All the main cerebral arteries including anterior, middle and posterior cerebral, basilar and vertebral arteries were examined at their proximal portions at the cerebral base and at their peripheral portions at the cortical surface as well as within brain parenchyma. We found marked accumulation of mitochondria in the cell bodies of smooth muscle cells and endothelial cells and numerous smooth muscle cells showing degeneration or necrosis, sporadically or in clusters in the tunica media. These abnormalities were most prominent in the walls of pial arterioles and small arteries up to 250 mu in diameter, and less frequent and severe in the larger pial arteries and intracerebral arterioles and small arteries. These vascular changes are different from any of those described in various disorders known to involve the cerebral blood vessels and are thus characteristic to the cerebral blood vessels of MELAS. We think that these peculiar vascular changes called mitochondrial angiopathy are caused by primary mitochondrial dysfunction in the vascular smooth muscle cells and endothelial cells themselves, as is the same in the skeletal and cardiac muscles in this disease, and that they constitute the pathogenic base of the brain lesions with unusual distribution pattern and nature in MELAS.
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PMID:[Mitochondrial angiopathy in the cerebral blood vessels of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes)]. 337 Jan 63

Three familial cases of MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke) have been reported. We describe a family with four normal sons and an affected mother, son, and daughter. Although mitochondrial inheritance has been proposed, autosomal and X-linked dominant patterns are also possible. This family also illustrates the variability of expression of MELAS. The proband has the full syndrome, while the mother and daughter manifested less severe findings. All three did not develop symptoms until adulthood.
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PMID:MELAS syndrome involving a mother and two children. 361 16

Among mitochondrial encephalomyopathies, MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes, Pavlakis et al. 1983) is recognized as a distinct syndrome characterized by generalized convulsions and recurrent stroke-like episodes. The neuroradiological findings of three patients with MELAS are reported here. Retrospective review shows that MELAS should be included in the differential diagnosis of infarct-like lesions of the cerebrum.
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PMID:Computed tomography and angiography in MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes); report of 3 cases. 362 23

In a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes [MELAS] who had normal mitochondrial enzyme activity, high doses of coenzyme Q10 (CoQ) were administered. Clinical improvement with decreased serum lactate and pyruvate levels was observed. Though the mechanism of action of CoQ is not known, a trial is worthwhile in patients with MELAS.
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PMID:Clinical improvement after administration of coenzyme Q10 in a patient with mitochondrial encephalomyopathy. 381 89

We have devised a novel method for quantitative analysis of the MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) tRNA(Leu(UUR)) mutation of mitochondrial DNA using a PCR-SSCP (polymerase chain reaction-single-strand conformation polymorphism) method, and compared the results obtained using the PCR-SSCP method with those obtained using other methods including Southern blotting, last one cycle hot PCR, and conventional PCR-RFLP (restriction fragment length polymorphism). The standard curve obtained using the PCR-SSCP method is linear, with a correlation coefficient of 0.999; it was determined that this method is more accurate than other methods for quantitative analysis. The PCR-SSCP method does not require restriction digestions, thereby avoiding potential problems of partial digestions or heteroduplex formation during PCR. The method is quite simple and should have a broad range of application for quantitation of mutant mtDNAs in various mitochondrial encephalomyopathies. We applied the method for quantitation of mutant mitochondrial DNA carrying a single base substitution in the tRNA(Leu(UUR)) gene in two autopsied cases of MELAS. In both cases, the mutant mtDNA is abundantly present (82-95%) withd little variation among tissues.
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PMID:Quantitation of heteroplasmy of mitochondrial tRNA(Leu(UUR)) gene using PCR-SSCP. 747 61

An A to G transition at nucleotide 3,243 in the tRNA(Leu(UUR)) gene of mitochondrial DNA (mtDNA) has been suggested to be the disease-related mutation for MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes). Recently, the same mutation has also been found in several pedigrees with maternally inherited diabetes mellitus and sensorineural deafness. We report here a family showing the association of deafness and diabetes mellitus, as the predominant clinical features, with this mutation. The mutation was detected by restriction-enzyme analysis of the relevant PCR-amplified segment of the mtDNA, in two generations. In this family, it is noteworthy that two members with the mutation had some symptoms of MELAS such as short stature, seizures and mental retardation and that one had no clinical symptoms though the mtDNA mutation was identified in his blood. The findings in this family demonstrate the diversity of clinical expression of the mtDNA mutation and suggest that a combination of sensorineural deafness and diabetes mellitus is only one typical presentation of the various phenotypic features caused by the 3,243 mutation.
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PMID:[Detection of a mutation in mitochondrial DNA in a family with sensorineural deafness and diabetes mellitus as the predominant clinical features]. 756 31

We screened 214 Japanese NIDDM (non-insulin-dependent) diabetic patients with a family history of diabetes for mutations in the mitochondrial tRNA(Leu(UUR)) gene using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Six patients were identified as having an A to G transition at position 3243 (3243 mutation), but no patients were detected with a T to C transition at position 3271, in the mitochondrial tRNA(Leu(UUR)) gene. These two mutations were not present in 85 healthy control subjects. It was disclosed that the patients' mothers were also affected by diabetes mellitus in five of the six cases. In these six affected patients, the 3243 mutation shows variable phenotypes, such as the degree of multiple organ involvement, intrafamilial and interfamilial differences in disease characteristics, and the degree of the involvement of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) phenotype. Endocrinological examinations revealed that those diabetic patients with the 3243 mutation show not only beta-cell dysfunction, but also a defect in alpha-cell function, which is considered characteristic of diabetes with the 3243 mutation. When compared with 50 selected diabetic control subjects without the 3243 mutation, whose mothers, but not fathers, were found to have diabetes, it was established statistically that those with the 3243 mutation possess the following clinical characteristics; 1) the age of diabetes onset is lower, 2) they have lean body constitutions, and 3) they are more likely to be treated with insulin than control subjects. We suggest that diabetes with the 3243 mutation possesses phenotypes distinct from those in common forms of diabetes.
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PMID:Diabetes mellitus carrying a mutation in the mitochondrial tRNA(Leu(UUR)) gene. 926 98

We examined the clinical and biochemical features of 27 cases with acute myoglobinuria who had been suspected of having metabolic myopathies. The systematic biochemical studies included the measurements of 13 glycolytic enzymes, mitochondrial respiratory chain enzymes, carnitine palmitoyltransferase (CPT) and 5 enzymes of fatty acid beta-oxidation. Enzyme defects were found in 9 patients using muscle biopsy specimens: phosphorylase deficiency in 3, CPT deficiency in 4 and phosphoglycerate kinase deficiency in 2. One patient was diagnosed as MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) with the histopathological examination and clinical data. A suspicion of beta-oxidation disorder was entertained in some patients of which the activities were about 50% of control means. However, no evidence to substantiate its significance as the enzyme defects was obtained from our data. Sixteen of 17 undiagnosed cases could be divided into two groups according to precipitating factors as follows: one had exercise as the factors and the other had infection. These groups also showed some differences in clinical features. In the infection group, myoglobinuria tended to progress more rapidly and was occasionally followed by acute renal failure. And some cases had additional associated conditions such as mental retardation or epilepsy. On the other hand, the exercise group had only myopathic symptoms. The difference in these clinical features between the two groups suggested that they had the different pathogenic mechanisms respectively.
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PMID:[Clinical and biochemical analysis of 27 patients with myoglobinuria of unknown causes]. 778 Dec 10

Patients with several inherited human encephalomyopathies exhibit systemic and neurological symptoms in association with specific mitochondrial mutations. The mechanisms by which these mitochondrial mutations result in cellular injury have not been elucidated. One potential cause of neuronal vulnerability is an inability to effectively buffer intracellular calcium. We report that fibroblasts from patients with one specific inherited encephalomyopathy, MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) syndrome, have elevated levels of ionized calcium and cannot normally sequester calcium influxes. Quantitative fluorescence imaging demonstrated that this abnormality was associated with a relative decrease in mitochondrial membrane potential compared to control fibroblasts. This documentation of pathological calcium homeostasis in a genetic neurological disease extends the calcium hypothesis of toxic cell injury to human mitochondrial encephalomyopathies.
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PMID:Abnormal calcium homeostasis and mitochondrial polarization in a human encephalomyopathy. 784 43


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