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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical features of a patient in a Chinese family with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) are reported. The study revealed that hearing and visual impairments and miscarriages may be early clinical presentations in MELAS. A heteroplasmic A to G transition in the tRNA(Leu(UUR)) gene was noted at the nucleotide pair 3243 in the mitochondrial DNA of muscle, blood, and hair follicles of the proband and his maternal relatives. Quantitative analysis of the mutated mitochondrial DNA revealed variable proportions in different tissues and subjects of maternal lineage in the family. Muscle tissue contained a higher proportion of the mutant mitochondria than other tissues examined. The function of the reproductive system of the proband seems to be impaired. In one clinically healthy sibling, the 3243rd point mutation was found in sperm mitochondrial DNA, although sperm motility was not affected. It seems that biochemical defects in mitochondrial respiration and oxidative phosphorylation are tissue specific expressions of the 3243rd point mutation in the mitochondrial DNA of the affected target tissues.
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PMID:MELAS syndrome with mitochondrial tRNA(Leu(UUR)) gene mutation in a Chinese family. 820 29

Localized brain proton MR spectra were acquired from patients with different mitochondrial encephalomyopathies (myoclonus epilepsy with ragged-red fibers [MERRF], Kearns-Sayre syndrome [KSS], and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes [MELAS]). The regional brain metabolic abnormalities in patients with these syndromes showed different features consistent with the distinct phenotypes. In MERRF, only one of four patients showed an increase in the lactate/creatine resonance intensity ratio (an index of impairment of oxidative metabolism) in spectra from central (supraventricular) or occipital brain volumes, and this was small. There were significant decreases in N-acetylaspartate/creatine (a measure of neuronal loss or dysfunction) in central cerebral volumes of demented patients and, more prominently, in occipital volumes. In the one patient in whom it was studied, the cerebellum also showed a decreased N-acetylaspartate/creatine. Spectra from two patients with KSS both showed large (four- to sevenfold) increases in lactate/creatine and large decreases in N-acetylaspartate/creatine in central brain volumes. Yet another pattern of regional metabolic abnormality was present in the MELAS syndrome, where proton spectroscopic imaging demonstrated focal localization of abnormally increased lactate/creatine and decreased N-acetylaspartate/creatine to the regions of the stroke-like lesions on conventional MR images. Serial studies emphasized that the regional metabolic abnormalities in MELAS are highly variable as the stroke-like lesions appear and evolve.
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PMID:Proton MR spectroscopic characterization of differences in regional brain metabolic abnormalities in mitochondrial encephalomyopathies. 825 44

A new mitochondrial DNA (mtDNA) mutation of tRNA(Leu)(UUR) at nucleotide position 3271 (MELAS3271) was determined to be involved in the pathogenic process of mitochondrial diseases MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) using intercellular transfer of patient-derived mtDNA to mtDNA-less HeLa cells (rho 0 HeLa cells). Cybrid clones containing imported mtDNA exclusively from a MELAS patient with MELAS3271 mtDNA were isolated, and the influence of MELAS3271 mtDNA on mitochondrial translation activity and mitochondrial respiratory complex I enzyme activity were examined. Accumulation of more than 87% MELAS3271 mutant mtDNA in the cybrid clones induced both low complex I activity and abnormal mtDNA-encoded polypeptide synthesis including at least complex I subunit ND6. suggesting involvement of the new MELAS-associated mutation in the pathogenesis.
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PMID:Accumulation of mtDNA with a mutation at position 3271 in tRNA(Leu)(UUR) gene introduced from a MELAS patient to HeLa cells lacking mtDNA results in progressive inhibition of mitochondrial respiratory function. 828 Jan 19

MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) is a clinically devastating disease of children and young adults. The cause of the stroke-like episodes is not known. We have sequenced the mitochondrial DNA (mtDNA) in archival paraffin-embedded material from two cases. In only one of these did the mitochondrial tRNA(Leu(UUR) gene contain the nucleotide 3243 A-to-G mutation that is most commonly responsible for MELAS. In this case, we determined the relative proportion of mutant:wild-type mtDNA in sections of the central nervous system and other tissues by PCR amplification, PalI digestion, DNA electrophoresis, and scanning densitometry of the ethidium bromide-stained gels. The technique allowed the proportion of mitochondria that contain the mutant genome to be compared with the histological findings in immediately adjacent sections of tissue. The mutant mtDNA was detectable in most tissues, the percentage of mtDNA ranging from barely detectable levels to 78 per cent. The relative amount of mutant mtDNA correlated poorly with the distribution of histological lesions, both within the central nervous system and in other tissues examined. The proportion was high in tissues such as liver, kidney, adrenal, and pancreas that appeared histologically normal. Relatively low levels were present in some regions of the central nervous system, such as the occipital lobe, which contained many of the characteristic infarct-like lesions. These observations do not support previous speculation that the distribution of these lesions reflects that of the defective mitochondria. The results emphasize the usefulness of the polymerase chain reaction in correlative histogenetic studies.
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PMID:Sequencing and quantitative assessment of mutant and wild-type mitochondrial DNA in paraffin sections from cases of MELAS. 832 63

The mitochondrion is the only extranuclear organelle containing DNA (mtDNA). As such, genetically determined mitochondrial diseases may result from a molecular defect involving the mitochondrial or the nuclear genome. The first is characterized by maternal inheritance and the second by Mendelian inheritance. Ragged-red fibers (RRF) are commonly seen with primary lesions of mtDNA, but this association is not invariant. Conversely, RRF are seldom associated with primary lesions of nuclear DNA. Large-scale rearrangements (deletions and insertions) and point mutations of mtDNA are commonly associated with RRF and lactic acidosis, e.g. Kearns-Sayre syndrome (KSS) (major large-scale rearrangements), Pearson syndrome (large-scale rearrangements), myoclonus epilepsy with RRF (MERRF) (point mutation affecting tRNA(lys) gene), mitochondrial myopathy, lactic acidosis, and stroke-like episodes (MELAS) (two point mutations affecting tRNA(leu)(UUR) gene) and a maternally-inherited myopathy with cardiac involvement (MIMyCa) (point mutation affecting tRNA(leu)(UUR) gene). However, RRF and lactic acidosis are absent in Leber hereditary optic neuropathy (LHON) (one point mutation affecting ND4 gene, two point mutations affecting ND1 gene, and one point mutation affecting the apocytochrome b subunit of complex III), and the condition associated with maternally inherited sensory neuropathy (N), ataxia (A), retinitis pigmentosa (RP), developmental delay, dementia, seizures, and limb weakness (NARP) (point mutation affecting ATPase subunit 6 gene). The point mutations in MELAS, MIMyCa, and MERRF, and the large-scale mtDNA rearrangements in KSS and Pearson syndrome have a broader biochemical impact since these molecular defects involve the translational sequence of mitochondrial protein synthesis. The nuclear defects involving mitochondrial function generally are not associated with RRF. The biochemical classification of mitochondrial diseases principally catalogues these nuclear defects. This classification divides mitochondrial diseases into five categories. Primary and secondary deficiencies of carnitine are examples of a substrate transport defect. A lipid storage myopathy is often present. Disturbances of pyruvate or fatty acid metabolism are examples of substrate utilization defects. Only four defects of the Krebs cycle are known: fumarase deficiency, dihydrolipoyl dehydrogenase deficiency, alpha-ketoglutarate dehydrogenase deficiency, and combined defects of muscle succinate dehydrogenase and aconitase. Luft disease is the singular example of a defect in oxidation-phosphorylation coupling. Defects of respiratory chain function are manifold. Two clinical syndromes predominate, one involving limb weakness, and the other primarily affecting brain function. Leigh syndrome may result from different enzyme defects, most notably pyruvate dehydrogenase complex deficiency, cytochrome c oxidase deficiency, complex I deficiency, and complex V deficiency associated with the recently described NARP point mutation. A new group of mitochondrial diseases has emerged.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The expanding clinical spectrum of mitochondrial diseases. 833 7

We studied multiple different postmortem tissue samples from a woman and two of her daughters with the MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) tRNA(Leu(UUR)) mutation at nucleotide 3243 in mitochondrial DNA (mtDNA). All tissues examined were heteroplasmic for the mutation. The mean proportion of mutant mtDNAs in the mother's tissues (0.30 +/- 0.10) was significantly lower than that of each of her daughters' (0.76 +/- 0.11, p < 0.03, and 0.72 +/- 0.13, p < 0.001); there was no difference in the fraction of mutant mtDNAs between the daughters (p < 0.71). This difference in the mean proportion of mtDNA mutants between family members correlates with their clinical profiles; the mother had the latest onset of disease and lived longest, while the two daughters had a strikingly similar clinical course. In individual patients, the mean proportion of mutant mtDNAs was not different in tissues deriving from ectodermal, mesodermal, and endodermal germ layers. Variance in the mutant:wild-type mtDNA ratio was normally distributed about the mean, both when all tissues were considered together and when different regions of the CNS were considered separately. Thus, the proportion of mtDNAs carrying the tRNA(Leu(3243)) mutation was not uniform in members of this pedigree and did not undergo rapid mitotic segregation along germ-layer divisions. These findings are consistent with the hypothesis that the overall proportion of mtDNAs carrying this mutation is primarily determined by segregation during oogenesis or early embryologic development and that random replicative (mitotic) segregation, subsequent to the establishment of primary germ layers, is responsible for the variation between tissues.
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PMID:Variable distribution of mutant mitochondrial DNAs (tRNA(Leu[3243])) in tissues of symptomatic relatives with MELAS: the role of mitotic segregation. 835 Oct 17

We describe a 42-year-old woman with overlapping syndrome of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and MERRF (myoclonus epilepsy and ragged-red fibers). Clinically, she had episodic headache, stroke-like episode with left hemiparesis and lactic acidosis commonly found in MELAS syndrome. However, myoclonus seizure, and ataxia with dyssynergic gait characteristic of MERRF were also noted. Computed tomographic scans showed a right temporo-parietal hypodense lesion. The lesion disappeared 20 months later, even magnetic resonance images also failed to reveal this abnormality. A molecular analysis of mitochondrial DNA was conducted by using restriction endonucleases ApaI and NaeI. A transition from A to G was found at the nucleotide position 3243, but not found at the 8344th nucleotide pair. In this report, we document the fluctuating CT changes and emphasize the importance of molecular analysis in patients with overlapping syndrome of mitochondrial encephalomyopathies.
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PMID:Overlapping syndrome of MERRF and MELAS: molecular and neuroradiological studies. 835 81

Recent advances in molecular genetics have led to a better understanding of mitochondrially inherited diseases. Mitochondrial encephalomyopathy overlap syndrome is one such group of diseases in which ocular abnormalities are frequently manifest. The authors describe the clinical, molecular genetic, and pathologic findings of two patients with the mitochondrial encephalomyopathy overlap syndrome. The patients shared a similar clinical course with features overlapping the three traditionally distinct clinical phenotypes (the Kearns-Sayre syndrome; the syndrome of mitochondrial encephalopathy, lactic acidosis, and stroke [MELAS], and the syndrome of myoclonus, epilepsy, and ragged red fibers [MERRF]). The patients had identical mitochondrial DNA mutations (at nucleotide position 3243) and had similar ultrastructural abnormalities, including abundant enlarged mitochondria with "whorled" and "tubular" cristae. These abnormal mitochondria appeared to be preferentially distributed in cells with high metabolic activity (retinal pigment epithelium, corneal endothelium, and extraocular muscles).
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PMID:Ocular clinicopathologic study of the mitochondrial encephalomyopathy overlap syndromes. 836 69

Single-photon emission computed tomography (SPECT) of the brain has been used to define functional abnormalities in two groups of childhood behavior disorders: (1) a "primary" category in which there is exclusive or predominant presentation with cognitive and/or behavioral dysfunction and (2) encephalopathies, often defined etiologically at the biochemical or molecular level, in which clinical expression includes, but is not confined to, neural dysfunction. Radiopharmaceuticals available for such studies are manifold, but those used to date have been predominantly perfusion agents, eg, Xenon-133 (133Xe) and technetium-99m (99mTc) hexamethylpropylene amine oxime, and studies with [99mTc]bicisate are eagerly awaited. Xenon-133 studies require that the patient be in the field of view of the detector while the tracer is administered. This renders it difficult for a subject to perform cognitive and other exercises while being imaged, because the environment is quite foreign. On the other hand, the 99mTc-labeled perfusion agents permit a scintigraphic "snapshot" of regional cerebral blood flow during a behavioral event without having to have the patient under the imaging instrument. Thus, one can separate the administration of the radiotracer, which can be done under more controlled and physiological conditions, from the actual imaging. In addition, greater spatial resolution is achieved with the technetium-based agents. Currently, multidetector or dedicated annular crystal-type cameras are the preferred brain SPECT devices, and they are essential to applications such as cortical "activation mapping" or tomographic detection of receptor systems. Close attention to technical detail and standardization of the child's behavioral environment during the investigation are critical to a successful study. The relative advantages and disadvantages of qualitative versus semiquantitative analysis of imaging date are reviewed. Among primary behavioral disorders, 133Xe SPECT studies in attention deficit disorder-hyperactivity (ADHD) have suggested a pattern of hypoperfusion of striatal and periventricular structures with sensorimotor cortical hyperperfusion. This pattern is consistent with some neurophysiological models of the disorder. In cerebral palsy, perfusional abnormalities have paralleled clinical deficits and may offer information to help predict outcome. The important field of childhood affective disorders (schizophrenia, juvenile autism, depression, etc) remains largely unstudied with SPECT. Finally, representative examples of the use of SPECT to study perfusion in encephalopathies with behavioral expression (phenylketonuria, MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) syndrome, Wilson's disease, etc) are given.
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PMID:Brain single-photon emission computed tomography for behavior disorders in children. 837 98

MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) is one of the clinically-defined mitochondrial diseases, characterized by early onset and stroke-like symptoms. A point mutation at nucleotide pair 3243 within the tRNA-Leu (UUR) gene is found in 80% of MELAS patients and another mutation at nucleotide pair 3271 in 10%. In vitro and in vivo expression studies on 3243 mutant genome show that it affects both the transfer RNA and transcription termination functionally. By virtue of further analyses on relationship between the mutations and phenotypes, a new approach to deal with the disease could be obtainable.
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PMID:[MELAS (mitochondrial myopathy, encephalopathy lactic acidosis, and stroke-like episodes): clinical features and mitochondrial DNA mutations]. 841 15


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