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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

The pathophysiological significance of the mitochondrial microangiopathy in MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes) syndrome was evaluated in an autopsy study of a nearly 13-year-old girl who had suffered from multiple infarctlike lesions in the brain, a mitochondrial myopathy-cardiomyopathy, and a generalized mitochondrial microangiopathy. Cytochemically, defects of cytochrome c oxidase (complex IV) were visualized by light and electron microscopy in the skeletal and heart muscle and in the altered vessels, as well as in single bile duct cells, with the activity of the hepatocytes being diffusely reduced, whereas in the brain, the cytochemical activity was only slightly diminished. Biochemical studies revealed a 50% reduction of both NADH (the reduced from of nicotinamide-adenine dinucleotide) dehydrogenase (complex I) and complex IV in the skeletal muscle. In the brain, complex I was diminished to 20%, whereas complex IV was only slightly below the low-normal range. Immunohistochemical studies with the use of subunit-specific antiserum samples against cytochrome c oxidase showed a varying protein profile, with loss of both mitochondrially and nuclearly derived subunits being most pronounced in the heart muscle and lesser in the skeletal muscle. In the brain, liver, bile ducts, and especially the vessels, no loss of enzyme protein content was observed. The results illustrate heterogeneous tissue expression of respiratory chain defects in MELAS syndrome and indicate that vascular cytochrome c oxidase deficiency may be involved in the cerebral manifestation of the disease, whereas in other organs like the heart, a similar pathogenetic importance of the microangiopathy cannot be verified.
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PMID:Generalized mitochondrial microangiopathy and vascular cytochrome c oxidase deficiency. Occurrence in a case of MELAS syndrome with mitochondrial cardiomyopathy-myopathy and combined complex I/IV deficiency. 838 Dec 71

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

Two MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) patients with diabetes mellitus (DM), and their family members are described clinically and genetically. The probands have the following features in common; normal early development, short stature, deterioration of intellectual ability, convulsions, cardiac conduction defect, sensorineural hearing loss, cortical blindness, and hemiparesis. Biochemical tests showed high levels of lactate and pyruvate in the blood and cerebrospinal fluid. Muscle biopsy showed ragged-red fibers. Molecular genetic analysis of both patients revealed that they had an A-to-G substitution at nucleotide position 3243 of the mitochondrial DNA in a heteroplasmic fashion. From these clinical and molecular genetic data they were diagnosed as having MELAS. In addition, fasting blood glucose levels were also high and they were diagnosed as having insulin-dependent DM. Some of the maternal family members in both cases also had insulin-dependent DM and several clinical symptoms of MELAS. DM and clinical features of MELAS were transmitted exclusively in the maternal line. In these cases, DM and MELAS might be a clinical manifestation of the same metabolic defect.
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PMID:Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and diabetes mellitus: molecular genetic analysis and family study. 844 2

We report an autopsy case of a 19 year-old man with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) a subgroup of mitochondrial encephalomyopathy presenting cardiomyopathy. He had repeatedly suffered from transient unconsciousness, hemiplegia, hemianopsia and convulsion attacks since the age of 9, and he died of severe congestive heart failure. In laboratory findings, blood lactate and pyruvate were markedly increased. Skeletal muscle biopsy demonstrated numerously scattered ragged-red fibers with modified Gomori's trichrome staining. Enzymatic activities of the mitochondrial respiratory chain showed a marked decrease of NADH cytochrome c reductase (complex I). In postmortem examination, the heart was 310g in weight and had right ventricular dilatation. Microscopically, degenerated and scattered myocardial cells (ragged-red fibers), interstitial edema and microvascular hyperplasia were demonstrated in the myocardium. Under the electron microscope, abnormal mitochondria proliferated and myofibrils were unusually sparse. Immunohistochemical studies with specific antibodies against the mitochondrial electron transfer enzyme subunits revealed a reduction of immunoreactive materials for complex I in the myocardium. These results suggested the relationship of myocardial disorders and decreased activity of complex I in electron transfer enzymes in this patient.
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PMID:[A study of myocardial disorders in an autopsy case of mitochondrial encephalomyopathy]. 846 36

Mitochondrial DNA (mtDNA) mutation associated with sensorineural hearing loss (SNHL) has previously been described in MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and in aminoglycoside-induced deafness. The authors of this study report three cases of SNHL associated with mtDNA mutation (3243A-->G). They examined the clinical features of this type of SNHL by audiologic studies and examined the mtDNA mutation by the polymerase chain reaction technique. In the three cases described, the SNHL had an adult onset and was bilateral and symmetrical. All patients had adult-onset diabetes mellitus. Audiologic studies revealed that the SNHL in all patients derived from the cochlea rather than from retrocochlear sites. It is presumed that mtDNA mutation results in mitochondrial dysfunction in cochlear tissues (i.e., hair cells and stria vascularis) and in neurons of the auditory pathway. Genetic analysis of mtDNA offers new insight into the diagnosis and treatment of SNHL.
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PMID:Bilateral sensorineural hearing loss associated with the point mutation in mitochondrial genome. 854 26

N-Acetylaspartate (NAA), which constitutes the major proportion of the dominant resonance in proton MR spectra of brain, is localized in mature brain exclusively in neurons and neuronal processes. A decrease in NAA has been observed in many cerebral pathologies and has usually been interpreted as an index of irreversible neuronal loss. The authors report a follow-up study of six patients with acute brain damage (four from demyelinating lesion and two from mitochondrial encephalopathy with lactic acidosis and stroke-like episodes [MELAS]). All patients underwent serial MR spectroscopy examinations. The four patients with acute demyelinating lesions initially showed decreases in NAA in the centers of the lesions that ranged between 34-72% of values from homologous brain volumes in the other hemisphere. All four patients subsequently showed substantial recovery of NAA as their clinical status improved. The two patients with MELAS syndrome had large decreases of NAA signal (50% and 20% of normal values, respectively) from their occipital lobe lesions during the acute stroke-like episodes. After the acute phase of the illness a progressive increase of NAA in the same volumes was seen in both patients (to 76% and 60% of normal values, respectively). These results demonstrate that significant recovery of NAA can occur after acute brain damage. The potential contribution of reversible neuronal dysfunction (as well as neuronal loss) must be considered in the interpretation of decreases in the NAA resonance associated with acute brain pathology.
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PMID:Reversible decreases in N-acetylaspartate after acute brain injury. 854 93

MELAS, a syndrome characterized by Myopathy, Encephalopathy, Lactic Acidosis and Stroke-like episodes, is one of a group of diseases known as mitochondrial encephalopathies. These genetically-transmitted diseases result in metabolic abnormalities associated with mitochondrial dysfunction, which contribute to neuronal destruction. Clinical manifestations include dementia, seizures, muscle weakness and stroke-like episodes. Accurate diagnosis is difficult to make and effective treatment is nonexistent at this time. The focus of care is supportive and the nurse's role centers on identification of deficits and maintenance of existing function.
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PMID:MELAS: a mitochondrial encephalomyopathy syndrome. 856 43


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