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

Defects in mitochondrial DNA (mtDNA) are associated with several different human diseases, including the mitochondrial encephalomyopathies. The mutations include deletions but also duplications and point mutations. Individuals with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) carry a common A-to-G substitution in a highly conserved portion of the gene for transfer RNA(Leu(UUR)). Although the MELAS mutation may be comparable to the defect in the tRNA(Lys) gene associated with MERRF (myoclonus epilepsy associated with ragged-red fibres), it is also embedded in the middle of a tridecamer sequence necessary for the formation of the 3' ends of 16S ribosomal RNA in vitro. We found that the MELAS mutation results in severe impairment of 16S rRNA transcription termination, which correlates with a reduced affinity of the partially purified termination protein for the MELAS template. This suggests that the molecular defect in MELAS is the inability to produce the correct type and quantity of rRNA relative to other mitochondrial gene products.
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PMID:Impairment of mitochondrial transcription termination by a point mutation associated with the MELAS subgroup of mitochondrial encephalomyopathies. 175 69

EEG was studied in 25 children and adolescents with mitochondrial encephalomyopathies, defined on the basis of clinical, biochemical and morphological criteria. Twenty cases conformed to well-known mitochondrial syndromes: Alpers syndrome [6], Leigh syndrome [2], MERRF (myoclonus epilepsy and ragged red fibers) syndrome [3], MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) syndrome [5] and Kearns-Sayre syndrome [4]. Many patients were followed for several years with repeated EEG. In all, 112 EEG records were included in the study. A common feature of all the mitochondrial encephalomyopathic syndromes was slowing of the alpha rhythm. Epileptic discharges were seen in most syndromes. In spite of the small number of cases in each group, in Alpers, MERRF and MELAS syndromes we found sequential EEG patterns which seemed to be typical of the respective syndromes. In contrast, in Kearns-Sayre syndrome, a slow background rhythm was the only consistent finding. We conclude that EEG, especially repeated recordings, may be of help in the diagnostic evaluation of mitochondrial encephalomyopathies.
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PMID:EEG findings in children and adolescents with mitochondrial encephalomyopathies: a study of 25 cases. 192 9

Increasingly numerous studies are being devoted to mitochondrial diseases, notably those which involve the neuromuscular system. Our knowledge and understanding of these diseases is progressing rapidly. We owe to Luft et al. (1962) the first description of this type of diseases. Their patient, a woman, presented with clinical symptoms suggestive of mitochondrial dysfunction, major histological abnormalities of skeletal muscle mitochondria and defective oxidative phosphorylation coupling clearly demonstrated in mitochondria isolated from muscle. This clinical, histological and biochemical triad led to the definition of mitochondrial myopathies. Subsequently, the triad was seldom encountered, and most mitochondrial myopathies were primarily defined by the presence of morphological abnormalities of muscle mitochondria. This review deals with the morphological, clinical, biochemical and genetic aspects of mitochondrial encephalomyopathies. The various morphological abnormalities of mitochondria are described. These are not specific of any particular disease. They may be present in some non-mitochondrial diseases and may be lacking in diseases due to specific defects of mitochondrial enzymes (e.g. carnitine palmityl-transferase or pyruvate dehydrogenase). The clinical classification of mitochondrial encephalomyopathies is discussed. There are two main schools of thought: the "lumpers" do not recognize specific syndromes within the spectrum of mitochondrial "cytopathies", the "splitters" try to identify specific syndromes while recognizing the existence of borderline cases. The following syndromes are described: chronic progressive external ophthalmoplegia (CPEO), Kearns-Sayre syndrome (KSS), MERRF syndrome (myoclonic epilepsy with ragged-red fibers), MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) and Leigh and Alpers syndromes. The biochemical classification comprises five types of abnormalities: defects of transport through the mitochondrial membrane, of substrate utilization, of Krebs' cycle, of oxidative phosphorylation and of various complexes of the respiratory chain. The clinical pictures corresponding to these defects are briefly described. The genetic aspects of these diseases are especially interesting because mitochondria have their own genome coding for thirteen proteins, all of them belonging to the respiratory chain. Genetic mitochondrial diseases may result from alterations of the nuclear genome, which are transmitted by mendelian inheritance, but they may also be due to alterations of the mitochondrial genome and transmitted by non-mandelian "maternal" heredity. A few examples are discussed, including Leber's optic atrophy and MERRF syndrome. (ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mitochondrial encephalomyopathies. 268 27

Identical twins developed myoclonic epilepsy in their teens. One twin remained mildly affected but the other went on to develop sensorineural deafness and ataxia with lactic acidosis and ragged red fibres leading to a diagnosis of mitochondrial encephalopathy. Multiple stroke-like episodes with hemiparesis followed, indicating progression from a MERRF to a MELAS phenotype. Biochemical studies revealed a severe deficiency of mitochondrial NADH-ubiquinone reductase and a moderate deficiency of cytochrome aa3. Western immunoblotting experiments using polyclonal antibodies raised against human placental cytochrome oxidase identified a similar profile of bands to those seen in controls, supporting the view that cytochrome aa3 deficiency in this case may be a secondary consequence of a failure of assembly related to a severe proximal respiratory chain defect.
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PMID:Progression from MERRF to MELAS phenotype in a patient with combined respiratory complex I and IV deficiencies. 285 17

In the last 4 years much progress has been made in the understanding of mitochondrial disorders. Point-mutations, deletions and depletion of the mitochondrial genome are associated with disorders like Leber's disease, MERRF (Myoclonus Epilepsia with Ragged Red Fibers), MELAS (mitochondrial Myopathy, Encephalopathy, Lactic acidosis and Stroke-like episodes) and several others. Recently, mitochondrial dysfunctions have been also related to neurodegenerative disorders like Parkinson's disease and to aging. Since the brain depends mostly on mitochondrial energy supply, mitochondrial dysfunctions may affect the nervous system more severely than other tissues causing or worsening diseases and playing a role in the biological deterioration of aging. Furthermore, the mitochondrial energy supply is associated with the production of highly reactive oxygen species. Ninety-five percent of the molecular oxygen is metabolized within the mitochondria by the electron-transport chain so that mitochondria are highly exposed to oxidative stress which may damage selected neuronal populations. Oxygen radicals created during respiration induce mitochondrial dysfunction which accelerates the production of more deleterious species of oxygen. The latter step further increases mitochondrial malfunction, thus intensifying and perpetuating the cycle. These two mechanisms combined may lead to cell death in brain and other tissues with high metabolic rate. Therefore, in neurodegenerative disorders such as Parkinson's disease mitochondrial dysfunction and oxidative stress may cause or worsen the clinical features.
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PMID:Oxidative stress and mitochondrial dysfunction in neurodegeneration. 784 18

We studied free radical, lipid peroxide (LPO) and antioxidant levels of blood in three cases with mitochondrial encephalomyopathy. Case 1 was a 17-year-old man with MELAS. Serum vitamin E levels were decreased and LPO levels were increased after stroke-like episodes in case 1. Case 2 was a 68-year-old woman with MELAS and a maternal elder aunt of case 1. She showed an elevated serum LPO levels (6.58 nmol/ml) in the absence of stroke-like episode and serum CoQ10 level was 0.54 microgram/ml before therapy. By CoQ10, idebenone and tocopherol nicotinate therapy, serum LPO levels decreased gradually in parallel with the decrease of lactate and pyruvate levels. Free radicals were measured in case 2 and controls by spin trapping method. Hydroxyl radical and C center radical were increased and H radical was normal in blood. But these free radicals in serum were all normal. Her serum antioxidants revealed an elevated percent inhibition of SOD and a decreased transfferin level. Case 3 was a 52-year-old woman with MERRF. She showed an elevation of serum LPO (12.8 nmol/ml). Her serum antioxidants revealed an elevated vitamin E and ceruloplasmin levels and percent inhibition of SOD.
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PMID:[Free radical, lipid peroxide and antioxidant in mitochondrial encephalomyopathy]. 795 20

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

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

A number of human diseases are caused by inherited mitochondrial DNA mutations. Two of these diseases, MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and MERRF (myoclonic epilepsy and ragged-red fibres), are commonly caused by point mutations to tRNA genes encoded by mitochondrial DNA. Here we report on how these mutations affect mitochondrial function in primary fibroblast cultures established from a MELAS patient containing an A to G mutation at nucleotide 3243 in the tRNA(Leu(UUR) gene and a MERRF patient containing an A to G mutation at nucleotide 8344 in the tRNA(Lys) gene. Both mitochondrial membrane potential and respiration rate were significantly decreased in digitonin-permeabilized MELAS and MERRF fibroblasts respiring on glutamate/malate. A similar decrease in mitochondrial membrane potential was found in intact MELAS and MERRF fibroblasts. The mitochondrial content of these cells, estimated by stereological analysis of electron micrographs and from measurement of mitochondrial marker enzymes, was similar in control, MELAS and MERRF cells. Therefore, in cultured fibroblasts, mutation of mitochondrial tRNA genes leads to assembly of bioenergetically incompetent mitochondria, not to an alteration in their amount. However, the cell volume occupied by secondary lysosomes and residual bodies in the MELAS and MERRF cells was greater than in control cells, suggesting increased mitochondrial degradation in these cells. In addition, fibroblasts containing mitochondrial DNA mutations were 3-4-fold larger than control fibroblasts. The implications of these findings for the pathology of mitochondrial diseases are discussed.
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PMID:Altered mitochondrial function in fibroblasts containing MELAS or MERRF mitochondrial DNA mutations. 880 26


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