1/21. Mitochondrial maculopathy: geographic atrophy of the macula in the MELAS associated A to G 3243 mitochondrial dna point mutation.PURPOSE: To report ocular findings in the mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (melas syndrome) in a family with the A to G 3243 mitochondrial (mt) dna point mutation. methods: case reports. Ocular findings are described from four family members with the MELAS associated A to G 3243 mt dna point mutation. RESULTS: Findings included ophthalmoplegia, neurosensory deafness, reduction of photopic and scotopic electroretinogram b-wave amplitudes, and myopathy, as well as macular retinal pigment epithelial atrophy. No family members had nyctalopia, attenuation of retinal blood vessels, or retinal bone spicule pigmentation. CONCLUSION: The finding of slowly progressive macular retinal pigment epithelial atrophy expands the reported phenotypic diversity of patients with A3243G mt dna mutations.- - - - - - - - - - ranking = 1keywords = blood vessel, vessel (Clic here for more details about this article) |
2/21. Atypical MELAS associated with mitochondrial tRNA(Lys) gene A8296G mutation.We report on a unique patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) presenting optic atrophy, cardiomyopathy, and bilateral striatal necrosis before stoke-like episodes became apparent. Skeletal muscle total mitochondrial dna analysis identified a heteroplasmic A to G point mutation in the tRNA(Lys) gene at position 8296. Skeletal muscle pathology revealed typical MELAS findings, including ragged-red fibers cytochrome c oxidase positive strongly succinate dehydrogenase-reactive blood vessels. Recent reports describe the 8296 mutation identified in patients with diabetes mellitus or myoclonus epilepsy with ragged-red fibers, not MELAS. We conclude that the 8296 mutation is likely to be pathogenic and that it may be not only a mutation responsible for diabetes mellitus or myoclonus epilepsy with ragged-red fibers but also for MELAS.- - - - - - - - - - ranking = 1keywords = blood vessel, vessel (Clic here for more details about this article) |
3/21. MELAS: clinical phenotype and morphological brain abnormalities.We describe the clinical and neuropathological findings of three unrelated autopsy cases of MELAS harboring the A3243G transition in the mitochondrial dna (mtDNA). Using immunohistochemical techniques, we studied the expression of several subunits of the respiratory chain in various brain regions from the same cases. In all three cases there was a reduced immunocytochemical staining for mtDNA-encoded subunits of the respiratory chain, confirming the presence of a defective mitochondrial protein synthesis in this disease. Mitochondrial abnormalities were mostly confined to multiple areas of different size and shape, in agreement with the focal character of the brain pathology in MELAS, and were most prominent in the cerebral cortex, providing a morphological contribution to the explanation of the cognitive regression of the patients. Immunoreactivity for mtDNA-encoded subunits was reduced in the walls of many pial and intracerebral arterioles of different brain regions but there was no clear correlation between territories of affected vessels and distribution of the histological and immunohistochemical lesions. Cerebral focal lesions in MELAS might have a metabolic nature and several pathogenetic mechanisms might be involved in the genesis of stroke-like episodes when there is a local increased ATP demand.- - - - - - - - - - ranking = 0.02385740879938keywords = vessel (Clic here for more details about this article) |
4/21. Novel mitochondrial dna ND5 mutation in a patient with clinical features of MELAS and MERRF.BACKGROUND: The mitochondrial dna gene encoding subunit 5 of complex I (ND5) has turned out to be a hot spot for mutations associated with mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes (MELAS) and various overlap syndromes. OBJECTIVE: To describe a novel mutation in the ND5 gene in a young man man with an overlap syndrome of MELAS and myoclonus epilepsy with ragged-red fibers. DESIGN: Case report. PATIENT: A 25-year-old man had recurrent strokes, seizures, and myoclonus. His mother also had multiple strokes. A muscle biopsy specimen showed no ragged-red fibers but several strongly succinate dehydrogenase-reactive blood vessels. RESULTS: Biochemical analysis showed isolated complex I deficiency and molecular analysis revealed a novel heteroplasmic mutation (G13042A) in the ND5 gene. CONCLUSIONS: These data confirm that ND5 is a genetic hot spot for overlap syndromes, including MELAS and strokelike and myoclonus epilepsy with ragged-red fibers.- - - - - - - - - - ranking = 1keywords = blood vessel, vessel (Clic here for more details about this article) |
5/21. Vascular involvement in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes.A 26-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) was admitted to our hospital for further cardiovascular examination. A muscle biopsy demonstrated strongly succinate dehydrogenase-reactive blood vessels. pulse wave contour analysis revealed that both capacitive and oscillatory compliance were markedly reduced in this patient compared with 45 normal age-matched control subjects. hepatocyte growth factor was remarkably elevated in this patient over that of 10 normal control subjects. These findings suggest that a MELAS patient has not only pathologic but also functional vascular involvement. If so, patients with MELAS need systemic vascular assessment.- - - - - - - - - - ranking = 1keywords = blood vessel, vessel (Clic here for more details about this article) |
6/21. aortic rupture in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes.BACKGROUND: Microangiopathy has been well described in the brain and muscle of patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). OBJECTIVE: To describe a patient with the common A3243G/MELAS point mutation who had aortic rupture and whose mother also died of large vessel rupture. DESIGN: Case report. SETTING: Collaboration between a primary care hospital and 2 academic tertiary care hospitals. RESULTS: Histologically, there was marked disarray of the smooth muscle architecture of the aorta, and immunohistochemical staining with antibodies against the mitochondrial dna-encoded cytochrome-C oxidase I subunit showed uniformly decreased immunostaining of the endothelial and smooth muscle cells of the aorta and vasa vasorum. polymerase chain reaction and restriction fragment length polymorphism analysis showed that the mutation load was 40.5% in blood but 85.3% in the blood vessels. CONCLUSIONS: The severe vasculopathy in this patient is probably directly related to the high mutation load in the blood vessels. Although aortic rupture is an unusual manifestation of MELAS, it is an important potential complication in patients undergoing minor surgical procedures.- - - - - - - - - - ranking = 1.0477148175988keywords = blood vessel, vessel (Clic here for more details about this article) |
7/21. An infant with a mitochondrial A3243G mutation demonstrating the MELAS phenotype.Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a syndrome associated with mitochondrial dna mutations such as A3243G, the most common mutation. Ragged-red fibers and strongly succinate dehydrogenase-reactive blood vessels in the muscle are diagnostic pathologic features of MELAS. In general, the first typical attack of MELAS occurs in children at school age; it is rare for stroke-like episodes to occur in early infancy. This report describes a 4-month-old male harboring A3243G, whose phenotype at onset was consistent with that of MELAS in infancy. The patient was admitted because of disturbances of consciousness and ventilatory insufficiency. Remarkable lactic acidosis was observed. MRI revealed several bilateral lesions. Periodic lateralized epileptic discharges on the EEG suggested regional lesions. Biopsied muscle displayed scattered ragged-red fibers and succinate dehydrogenase-reactive blood vessels; over 90% of muscle mitochondrial dna had A3243G. This case suggests that MELAS can develop in early infancy with its typical clinical presentation. The high percentage of A3243G may contribute to the early onset of the MELAS phenotype in this patient.- - - - - - - - - - ranking = 2keywords = blood vessel, vessel (Clic here for more details about this article) |
8/21. Molecular neuropathology of MELAS: level of heteroplasmy in individual neurones and evidence of extensive vascular involvement.Mitochondrial dna (mtDNA) disease is an important genetic cause of neurological disability. A variety of different clinical features are observed and one of the most common phenotypes is MELAS (Mitochondrial Myopathy, Encephalopathy, Lactic acidosis and stroke-like episodes). The majority of patients with MELAS have the 3243A>G mtDNA mutation. The neuropathology is dominated by multifocal infarct-like lesions in the posterior cortex, thought to underlie the stroke-like episodes seen in patients. To investigate the relationship between mtDNA mutation load, mitochondrial dysfunction and neuropathological features in MELAS, we studied individual neurones from several brain regions of two individuals with the 3243A>G mutation using dual cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) histochemistry, and polymerase chain reaction Restriction Fragment Lenght Polymorphism (PCR-RFLP) analysis. We found a low number of COX-deficient neurones in all brain regions. There appeared to be no correlation between the threshold level for the 3243A>G mutation to cause COX deficiency within single neurones and the degree of pathology in affected brain regions. The most severe COX deficiency associated with the highest proportion of mutated mtDNA was present in the walls of the leptomeningeal and cortical blood vessels in all brain regions. We conclude that vascular mitochondrial dysfunction is important in the pathogenesis of the stroke-like episodes in MELAS patients. As migraine is a commonly encountered feature in MELAS, we propose that coupling of the vascular mitochondrial dysfunction with cortical spreading depression (CSD) might underlie the selective distribution of ischaemic lesions in the posterior cortex in these patients.- - - - - - - - - - ranking = 1keywords = blood vessel, vessel (Clic here for more details about this article) |
9/21. Heteroplasmic mitochondrial dna mutation in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes.A 16-year-old female presented with clinical, morphologic and molecular features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Her early development was normal. Starting from the age of 14 years, she experienced recurrent episodes of headaches, with vomiting, seizures, transient right hemiparesis and decreased visual acuity. Computed tomographic brain scans revealed calcification in the bilateral basal ganglia. Biopsied specimens from her left biceps brachii and rectus femoris muscles revealed ragged-red fibers and strong succinate dehydrogenase-reactive blood vessels. Electron microscopy revealed paracrystalline inclusions in muscle mitochondria. Analysis of mitochondrial dna (mtDNA) from blood, hair follicles and muscle specimens showed an A to G point mutation at nucleotide position 3,243 in the transfer rna(Leu(UUR)). The proportion of mutant mtDNA in the patient's blood was 43%, in hair follicles 62% and in muscle 82%. The patient was followed up for 4 years and had progressive mental deterioration and died of an episode of status epilepticus. This patient and 5 other MELAS patients reported in taiwan are compared.- - - - - - - - - - ranking = 1keywords = blood vessel, vessel (Clic here for more details about this article) |
10/21. A MERRF/MELAS overlap syndrome associated with a new point mutation in the mitochondrial dna tRNA(Lys) gene.Several members of a three-generation kindred from Sardinia were affected by a maternally inherited syndrome characterized by features of both myoclonus epilepsy with ragged-red fibers (MERRF) and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). Clinically, symptoms such as myoclonus epilepsy, neural deafness and ataxia were variably associated with stroke-like episodes and/or migrainous attacks. Morphologically, numerous MELAS-associated SDH-stained vessels were observed in muscle biopsies, either alone or in combination with ragged-red fibers, the morphological hallmark of MERRF. sequence analysis of the mtDNA tRNA genes revealed the presence of a single, heteroplasmic T-->C transition at nt 8356, in the region of the tRNA(Lys) gene corresponding to the T-psi-C stem. The T-->C(8356) transition was exclusively found in the maternal lineage of our family, and the relative amount of the mutant mtDNA species in muscle was correlated with the severity of the clinical presentation. Therefore, we propose that the T-->C(8356) transition is responsible for the mitochondrial encephalomyopathy found in our family, and must be added to the expanding list of the pathogenetically relevant mutations of human mtDNA.- - - - - - - - - - ranking = 0.02385740879938keywords = vessel (Clic here for more details about this article) |
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