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

In the past few years several syndromes have been associated with lesions of the human mitochondrial DNA. MtDNA is a small, circular extra-nuclear chromosome encoding essential components of the respiratory chain. MtDNA-related syndromes can be divided into two groups: mitochondrial encephalomyopathies, characterized by the presence of ragged-red fibres (RRF) as the morphological hallmark, or "pure" encephalopathies with no gross morphological abnormalities in muscle. The first group includes myoclonic epilepsy with ragged-red fibres (MERRF), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO) and a new entity, maternally inherited myopathy and cardiomyopathy. The second group includes Leber's Hereditary Optic Neuroretinopathy (LHON) and the newly described ataxia-retinitis pigmentosa-dementia complex. Three kinds of molecular lesions have been identified: point mutations of protein encoding mtDNA-genes (similar to yeast mit- mutations); point mutations of mtDNA-tRNA genes (similar to yeast syn- mutations); and large-scale rearrangements of mtDNA (similar to yeast rho- mutations). In general, "mit-" mutations are responsible for non-RRF encephalopathies, while "syn-" and "rho-" mutations are associated with mitochondrial encephalomyopathies with RRF. Furthermore, point mutations (mit- and syn-) are usually maternally- inherited, while large-scale mtDNA rearrangements are either sporadic or inherited as mendelian traits. In most cases, the molecular detection of the known defects of mtDNA can be carried out by non-invasive techniques, thus making it an easy and relatively inexpensive procedure in the differential diagnosis of the mitochondrial disorders, a rapidly expanding area of clinical neurology.
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PMID:Defects of mitochondrial DNA. 134 53

We describe the full history and postmortem findings in one of the first identified cases of mitochondrial encephalomyopathy with stroke-like episodes (MELAS). To clarify diagnostic criteria, we analyzed 69 reported cases. The syndrome should be suspected by the following three invariant criteria: (1) stroke-like episode before age 40 yr; (2) encephalopathy characterized by seizures, dementia, or both; and (3) lactic acidosis, ragged-red fibers (RRF), or both. The diagnosis may be considered secure if there are also at least two of the following: normal early development, recurrent headache, or recurrent vomiting. There are incomplete syndromes in relatives of patients with the full syndrome and incomplete syndromes might also be encountered in sporadic cases. Some MELAS patients have features of the Kearns-Sayre syndrome (KSS) or myoclonic epilepsy with ragged-red fibers (MERRF), but none had the full KSS syndrome. In partial or confusing cases, analysis of mitochondrial DNA (mtDNA) may point to the correct diagnosis; however, not all patients with clinical MELAS have had the typical mtDNA point mutation and some patients with the mutation have clinical syndromes other than MELAS.
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PMID:Melas: an original case and clinical criteria for diagnosis. 142

Since the time of Liveing and Gowers in the nineteenth century, migraine has been thought to be inherited, although family history has been widely studied, nearly all the reports are not scientifically based and studies on twins have never shown 100% concordance in monozygotic (MZ) pairs, indicating that migraine cannot be inherited by a single gene. Furthermore, the criteria for a polygenic trait are not fulfilled by migraine patients. The only two syndromes with a strong genetic basis of inheritance are familial hemiplegic migraine and migraine occurring in Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes (MELAS). It is the predisposition to headache that is likely to be inherited; this is supported by the induction of migraine-like headaches with either m-chlorophenyl-piperazine (m-CPP) or nitroglycerin in normal subjects with a positive family history for migraine.
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PMID:Migraine and heredity. 149 12

A number of mitochondrial DNA (mtDNA) mutations have been identified which cause familial, late onset neuromuscular degenerative diseases. These include missense mutations in most of the mtDNA polypeptide genes as well as base substitutions in several tRNA genes. Missense mutations in the mitochondrial electron-transport genes cause Leber hereditary optic neuropathy. Ten mutations have been associated with this disease, but four at nps 11,178, 3460, 4160 and 15,257 appear sufficient in themselves to cause the disease. One missense mutation in the ATPase 6 gene at np 8993 causes a second phenotype, neurogenic muscle weakness, ataxia and retinitis pigmentosum. Transfer RNA mutations have been identified for myoclonic epilepsy and ragged-red fibre disease in the tRNA(Lys) gene at np 8344 and for the mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome and for maternal mitochondrial myopathy and cardiomyopathy syndrome in the tRNA(Leu)(UUR) gene at nps 3234 and 3260, respectively. Deficiencies in mitochondrial oxidative phosphorylation enzymes have been observed in several common neurodegenerative diseases such as Alzheimer and Parkinson diseases. Perhaps mtDNA mutations play a role in these as well.
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PMID:Diseases resulting from mitochondrial DNA point mutations. 152 7

An autopsy case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is reported. It presented with generalized muscle atrophy, stroke-like episodes, schizophrenia-like mental disorder and progressive dementia. Serum lactate and pyruvate levels were high. In the biopsied muscles, ragged-red fibers were observed by light microscopy and aggregation of abnormal mitochondria with paracrystaline formation by electron microscopy. The most characteristic neuropathological findings were infarct-like lesions widespread in the cerebral cortex. In addition, this case showed some unusual pathological features: (1) diffuse moderate fibrillary gliosis in the whole cerebral and cerebellar white matter, which might have been due to metabolic disturbances; (2) several focal lesions with demyelination and numerous spheroids in the pontocerebellar fibers; and (3) marked degeneration of the posterior columns and spinocerebellar tracts. Electron microscopic examination revealed that abnormal mitochondria were markedly aggregated in smooth muscle cells and endothelium of the cerebral and cerebellar blood vessels. These fine structural findings suggest a "mitochondrial angiopathy".
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PMID:Central nervous system changes in mitochondrial encephalomyopathy: light and electron microscopic study. 157 24

We studied 23 patients with clinically defined mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), 25 oligosymptomatic or asymptomatic maternal relatives, and 50 mitochondrial disease control subjects for the presence of a previously reported heteroplasmic point mutation at nt 3,243 in the transfer RNA(Leu(UUR)) gene of mitochondrial DNA. We found a high concordance between clinical diagnosis of MELAS and transfer RNA(Leu(UUR)) mutation, which was present in 21 of the 23 patients with MELAS, all 11 oligosymptomatic and 12 of 14 asymptomatic relatives, but in only five of 50 patients without MELAS. The proportion of mutant genomes in muscle ranged from 56 to 95% and was significantly higher in the patients with MELAS than in their oligosymptomatic or asymptomatic relatives. In subjects in whom both muscle and blood were studied, the percentage of mutations was significantly lower in blood and was not detected in three of 12 asymptomatic relatives. The activities of complexes I + III, II + III, and IV were decreased in muscle biopsies harboring the mutation, but there was no clear correlation between percentage of mutant mitochondrial DNAs and severity of the biochemical defect.
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PMID:MELAS: clinical features, biochemistry, and molecular genetics. 158 40

We describe a sporadic case of adult-onset, complex I deficiency mitochondrial encephalomyopathy (MEM), the clinical and pathological features of which failed to fit any of the known subgroups of MEM, such as Kearns-Sayre syndrome, mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes or myoclonus epilepsy with ragged-red fibers. Clinically, this patient had only progressive cerebellar ataxia, generalized muscle weakness and hearing loss. The principal finding at autopsy was degeneration of the olivo-ponto-cerebellar system. This case suggests that mitochondrial disease could underlie some cases of olivo-ponto-cerebellar atrophy.
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PMID:An autopsy case of mitochondrial encephalomyopathy with prominent degeneration in olivo-ponto-cerebellar system. 179 71

Several reports showed that abnormality of mitochondrial DNA (mt DNA) can be an etiology of cardiomyopathy in recent years. Cardiac involvement in mitochondrial disease other than Kearns-Sayre syndrome (KSS), however, has not been documented clearly. Therefore, cardiac involvement, abnormality of mt DNA and defects of the respiratory chain in mitochondrial disease were studied. Thirty-eight patients with mitochondrial disease were studied. The patients were consisted of 2 patients with KSS, 1 patient with probable KSS, 15 patients with ocular myopathy, 1 patient with myoclonus epilepsy with ragged-red fibers (MERRF), 6 patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), 5 patients with undefined mitochondrial encephalomyopathy and 8 patients with mitochondrial myopathy. Cardiac involvement was evaluated by electrocardiogram (ECG), chest roentgenogram and echocardiogram. Abnormality of mt DNA was examined using Southern blotting and polymerase chain reaction method in 25 patients. Defects of the respiratory chain were examined in 27 patients. All of the KSS and probable KSS showed heart block, and 2 of the 3 patients showed abnormalities on echocardiogram. Five of the 15 patients with ocular myopathy showed abnormalities on EGG. Four of the 6 patients with MELAS showed abnormalities on ECG, 1 showed cardiomegaly, and 3 showed left ventricular hypertrophy on echocardiogram. Three of the 5 patients with undefined mitochondrial encephalomyopathy showed abnormalities on ECG, 2 showed cardiomegaly and 2 showed asymmetric septal hypertrophy and wall motion abnormalities on echocardiogram. Large-scale deletions of mt DNA were detected in all of the KSS and probable KSS, and 7 patients with ocular myopathy. Deletions of mt DNA in the skeletal and cardiac muscles were proved to be identical in a case of KSS. A point mutation in mt DNA was detected in 5 patients with MELAS. Defects of the respiratory chain were detected in 22 patients. In conclusion, cardiac involvement is frequently seen in mitochondrial disease. Abnormality of ECG, especially heart block, is characteristic of KSS. Left ventricular hypertrophy is characteristic of mitochondrial encephalomyopathy.
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PMID:[Cardiac involvement in mitochondrial disease: a clinical study of 38 patients]. 182 6

A case of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes, in which a pituitary growth hormone (GH) secretion deficiency of hypothalamic origin was revealed through neuro-endocrinological examinations, was described. The case was a 10-year-old girl, who had been suffering from generalized tonic seizures since age 5, four episodes of alternating hemiplegia since age 6, stunted growth since age 7, and simple partial motor seizures as well as gelastic seizures since age 8. Marked elevation of lactate and pyruvate in both serum and CSF, abundant ragged red fibers in biopsied muscle, and low density areas in the left occipital lobe and bilateral globus pallidus in addition to diffuse brain atrophy on CT scan and MRI of the head were demonstrated, although the activities of muscle enzymes complex I-IV were within normal ranges. Pituitary GH secretion was deficient under the loadings with insulin, L-DOPA, sleep, and a single growth hormone releasing factor (GRF) administration, but normal GH response was registered under the repetitive stimulation with GRF. Activities of other hormonal axes were normal. It is likely that short stature commonly observed in MELAS patients is due to hypothalamic dysfunction, which might be brought out by chronic ischemia and energy deficiency of the diencephalon based upon mitochondrial abnormality of that region. It is likely that gelastic seizure in this case is due to hypothalamic dysfunction.
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PMID:[Hypothalamic GH Deficiency and gelastic seizures in a 10-year-old girl with MELAS]. 187 57

A 9-year-old girl and an 11-year-old boy had ptosis, progressive external ophthalmoplegia, pigmentary retinopathy, and sensorineural hearing loss. The girl had diabetes mellitus and the boy had hypoparathyroidism. Both children also developed recurrent vomiting and cerebral infarcts with lactic acidosis. Muscle biopsy specimens showed ragged-red fibers and Southern analysis demonstrated a distinct heteroplasmic deletion of muscle mitochondrial DNA in each patient but no evidence of the point mutation in the transfer RNALeu(UUR) gene recently identified in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). These 2 children had combined features of Kearns-Sayre syndrome and MELAS, suggesting that mitochondrial DNA deletions occasionally can have pleomorphic clinical expression.
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PMID:Deletion of mitochondrial DNA in patients with combined features of Kearns-Sayre and MELAS syndromes. 189 71


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