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

Since the first identification in 1988 of pathogenic mitochondrial DNA (mtDNA) mutations, the mitochondrial diseases have emerged as a major clinical entity. The most striking feature of these disorders is their marked heterogeneity, which extends to their clinical, biochemical, and genetic characteristics. The major mitochondrial encephalomyopathies include MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes), MERRF (myoclonic epilepsy with ragged red fibers), KSS/CPEO (Kearns-Sayre syndrome/chronic progressive external ophthalmoplegia), and NARP/MILS (neuropathy, ataxia, and retinitis pigmentosum/maternally inherited Leigh syndrome) and they typically present highly variable multisystem defects that usually involve abnormalities of skeletal muscle and/or the CNS. The primary emphasis here is to review recent investigations of these mitochondrial diseases from the standpoint of how the complexities of mitochondrial genetics and biogenesis might determine their varied features. In addition, the mitochondrial encephalomyopathies are compared and contrasted to Leber hereditary optic neuropathy, a mitochondrial disease in which the pathogenic mtDNA mutations produce a more uniform and focal neuropathology. All of these disorders involve, at some level, a mitochondrial respiratory chain dysfunction. Because mitochondrial genetics differs so strikingly from the Mendelian inheritance of chromosomes, recent research on the origin and subsequent segregation and transmission of mtDNA mutations is reviewed.
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PMID:Human mitochondrial diseases: answering questions and questioning answers. 977 Feb 97

We review the mitochondrial diseases in which cerebrovascular changes are seen, such as the MERRF syndrome (myoclonic epilepsy and ragged red fibers) or the Kearns-Sayre syndrome (progressive external ophthalmoplegia, retinitis pigmentaria, cerebellar disorders and disorders of cardiac conduction), focusing on the syndrome involving mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). We consider the different clinical aspects, diagnostic methods, pathophysiological mechanisms of the cerebrovascular involvement as well as therapeutic approaches.
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PMID:[Mitochondrial diseases and stroke]. 981 May 97

The transcript levels of nuclear and mitochondrial genes involved in oxidative phosphorylation were quantified in human myoblasts and myotubes cultured from biopsies of patients harboring either heteroplasmic point mutation or deletion of mitochondrial DNA. The transcript patterns were determined by two different methodologies, competitive reverse-transcription polymerase chain reaction and classical Northern blot analysis, both referred to the mitochondrial to nuclear DNA ratio. In myoblasts from the patients with MELAS (myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) and KSS (Kearns-Sayre) syndromes, both methodologies revealed an increase of mtDNA transcript levels. A higher level of the nuclear ATP synthase beta transcript was observed in the MELAS patient cells and could be the consequence of a feedback effect of the mitochondrial DNA mutation. Moreover, the nuclear and mitochondrial transcript accumulation is more pronounced after myoblast differentiation. Thus, the OXPHOS expression is specifically altered in patients with mitochondrial diseases. The competitive RT-PCR, a rapid and sensitive technique, could be applied to investigation of mitochondrial myopathies.
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PMID:Quantification of OXPHOS gene transcripts during muscle cell differentiation in patients with mitochondrial myopathies. 988 18

We report an 8-year molecular study of mitochondrial DNA (mtDNA) mutations in patients with mitochondrial diseases in Taiwan. One hundred and seventy-seven patients met the diagnostic criteria of mitochondrial disease and were recruited into the study. The results showed that 32 patients, including 25 with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, one with Kearns-Sayre syndrome (KSS), one with diabetes mellitus and deafness, and five with chronic progressive external ophthalmoplegia (CPEO), harbored the A3243G mtDNA mutation. The A8344G mutation was found in nine patients, all of whom suffered from myoclonic epilepsy and ragged-red fibers (MERRF) syndrome. The G11778A mtDNA mutation was found in 18 of 22 patients with Leber's hereditary optic neuropathy. The T8993C and T8993G mutations were found, respectively, in one and two patients with Leigh syndrome. Large-scale deletions of mtDNA were found in 17 patients with CPEO, one with KSS, one with MELAS, and two with MERRF syndrome. The mtDNA mutations in patients with each of the mitochondrial diseases found in Taiwan were restricted mainly to a single site, while those reported for the same diseases in other ethnic groups occurred in many sites. Furthermore, significant levels of additional mtDNA mutations occurred in some patients with mitochondrial encephalomyopathies. We suggest that these additional (or secondary) mtDNA mutations are generated as a consequence of the preexisting primary mtDNA mutations and may contribute to the age-dependent progressive deterioration characteristic of mitochondrial diseases.
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PMID:Molecular epidemiologic study of mitochondrial DNA mutations in patients with mitochondrial diseases in Taiwan. 1042 Jul

Mitochondria are the principal site of generation of energy in form of adenosine triphosphate (ATP). They contain the enzymes of the Krebs and fatty acid cycles and the respiratory pathway. Ocular tissues with high energy consumption and dependence on oxidative energy production like the optic nerve, the retina, and the pigment epithelium are often involved in mitochondrial diseases. This article reviews the genetic mitochondrial diseases involving the visual system. Their most important ocular findings include: acute or slowly progressive bilateral visual loss and visual field loss due to an optic neuropathy or retinal degeneration, bilateral progressive decreased ocular motility, and bilateral upper lid ptosis. The following diseases are discussed: Leber's Hereditary Optic Neuropathy (LHON); Kearns-Sayre Syndrom (KSS); Chronic Progressive External Ophthalmoplegia (CPEO); Autosomal Recessive Cardiomyopathy, Ophthalmoplegia (ARCO); Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke-Like Episodes (MELAS); Neuropathy, Ataxia, Retinitis Pigmentosa (NARP); Mitochondrial Neuropathy, Gastro-Intestinal Encephalomyopathy (MNGIE); Myoclonus Epilepsy, Ragged-Red-Fibers (MERRF); Wilson's disease; Friedreich's ataxia. Diagnosis of mitochondrial encephalomyopathies is established by screening for mutations in blood or muscle biopsy samples. No specific therapies which influence the course of mitochondrial encephalomyopathies are known. Drugs interacting with the mitochondria function, alcohol consumption and smoking should be avoided.
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PMID:[Eye diseases in mitochondrial encephalomyopathies]. 1121 87

The mitochondrial cytopathies are genetically and phenotypically heterogeneous group of disorders caused by structural and functional abnormalities in mitochondria. To the best of our knowledge, there are very few studies published from India till date. Selected and confirmed fourteen cases of neurological mitochondrial cytopathies with different clinical syndromes admitted between 1997 and 2000 are being reported. There were 8 male and 6 female patients. The mean age was 24.42+/-11.18 years (range 4-40 years). Twelve patients could be categorized into well-defined syndromes, while two belonged to undefined group. In the defined syndrome categories, three patients had MELAS (mitochondrial encephalopathy, lactic acidosis and stroke like episodes), three had MERRF (myoclonic epilepsy and ragged red fibre myopathy), three cases had KSS (Kearns-Sayre Syndrome) and three were diagnosed to be suffering from mitochondrial myopathy. In the uncategorized group, one case presented with paroxysmal kinesogenic dystonia and the other manifested with generalized chorea alone. Serum lactic acid level was significantly increased in all the patients (fasting 28.96+/-4.59 mg%, post exercise 41.02+/-4.93 mg%). Muscle biopsy was done in all cases. Succinic dehydrogenase staining of muscle tissue showed subsarcolemmal accumulation of mitochondria in 12 cases. Mitochondrial DNA study could be performed in one case only and it did not reveal any mutation at nucleotides 3243 and 8344. MRI brain showed multiple infarcts in MELAS, hyperintensities in putaminal areas in chorea and bilateral cerebellar atrophy in MERRF.
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PMID:Neurological mitochondrial cytopathies. 1213 80

The mitochondrial encephalomyopathies are chronic progressive disorders affecting predominantly the neuromuscular system. Symptoms are induced by insufficient energy supply resulting from a deficiency of oxidative phosphorylation. We studied one male and four female patients with genetically proven mitochondrial encephalomyopathy. Their ages ranged from 7 to 19 years (two with Kearns-Sayre syndrome, one patient with neuronal muscle weakness, ataxia, and retinitis pigmentosa syndrome, and two patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), using a retrospective study method. We studied the effect of creatine supplementation (0.08 g-0.35 g/kg body weight/day; 9 months to 4 years, 10 months) and measured skeletal muscle power analysis (bicycle ergometer). After creatine supplementation all patients demonstrated an increase in their maximum performance (W) (+4% - +30%; mean: +12.1%). These results indicate an improved aerobic oxidative function of mitochondria after creatine administration in patients with mitochondrial encephalomyopathies. Continuous physical exercise was improved to a greater extent than instantaneous activity.
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PMID:Effectiveness of creatine monohydrate in mitochondrial encephalomyopathies. 1265 21

A case of Kearns-Sayre syndrome (KSS) diagnosed 18 years prior to death due to stroke and heart failure with postnatal onset was followed over 15 years and confirmed by postmortem examination. Within the brain, an old cystic infarction of the left hemisphere was found. Other features included white matter gliosis and cerebellar atrophy. Equal or similar features were observed in other conditions thought to be due to failure of mitochondrial metabolism, therefore, a common evolution of neuropathological changes must be discussed.
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PMID:Is there a final common pathway in mitochondrial encephalomyopathies? Considerations based on an autopsy case of Kearns-Sayre syndrome. 1453 49

Mitochondrial disorders are important causes of progressive ataxia in children. Clinical examination, metabolic studies, imaging studies, muscle biopsies, and mitochondrial DNA studies are required to arrive at a specific diagnosis. There is poor correlation between phenotype and genotype in mitochondrial disorders. Ataxia is a major clinical presentation in Kearns-Sayre syndrome; mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes; myoclonic epilepsy with ragged-red fibers; neurogenic muscle weakness, ataxia, and retinitis pigmentosa; Leigh's syndrome; and coenzyme Q10 deficiency.
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PMID:Mitochondrial disorders and ataxia. 1465 8

White matter involvement is recently being realized as a common finding in mitochondrial disorders. It is considered an inherent part of the classical mitochondrial syndromes which are usually associated with alterations in the mitochondrial DNA such as: Leigh disease, Kearns-Sayre syndrome, mitochondrial encephalomyopathy lactic acidosis, and stroke like episodes, mitochondrial neuro-gastro-intestinal encephalomyopathy and Leber's hereditary optic neuropathy. White matter involvement is also described in mitochondrial disorders due to mutations in the nuclear DNA which are transmitted in an autosomal pattern. MRI findings suggestive of a mitochondrial disease are: small cyst-like lesions in abnormal white matter, involvement of both cerebral and cerebellar white matter, and a combination of a leukoencephalopathy with bilateral basal ganglia lesions. The clinical manifestations may be disproportionate to the extent of white matter involvement. Other organs may frequently be involved. The onset is often in infancy with a neurodegenerative course. The finding of a leukoencephalopathy in a patient with a complex neurologic picture and multisystem involvement should prompt a thorough mitochondrial evaluation.
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PMID:White matter involvement in mitochondrial diseases. 1567 Jul 18


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