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Query: UMLS:C0162671 (MELAS)
 587 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four patients with clinically and genetically defined MELAS were examined using quantitative localized proton magnetic resonance spectroscopy of the brain. Acute and chronic lesions were located in the occipital lobe and mostly characterized by strongly elevated concentrations of lactate (Lac) and glucose (GIc) as well as severely reduced concentrations of total N-acetylaspartyl compounds (tNAA, neuroaxonal markers), glutamate (Glu), and total creatine. These findings indicate a high degree of nonoxidative glycolysis reflecting either impaired oxidative energy metabolism or the use of anaerobic metabolism by infiltrating macrophages as well as damage or loss of viable neuroaxonal tissue. In contrast, glial cell populations, in particular astrocytes, seem to remain unaffected as evidenced by unchanged concentrations of myo-inositol (glial marker). In addition, all patients including one who never experienced a stroke-like episode showed elevated Lac and Glc as well as reduced tNAA and Glu in tissues appearing normal on MRI. These disturbances were stronger in cortical gray matter and cerebellum than in white matter and indicate that neuroaxonal damage is not restricted to structural lesions. The steady presence of Lac is consistent with a reduced capacity of the mitochondrial oxidative energy metabolism resulting from impaired respiratory chain function.
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PMID:Quantitative proton magnetic resonance spectroscopy of cerebral metabolic disturbances in patients with MELAS. 1059 37

We herein report a rare case of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and diabetes mellitus with ketoacidosis. An 18-year-old female patient was diagnosed to have diabetes mellitus and insulin therapy was thereafter initiated. At 26 years of age, she was hospitalized for diabetic ketoacidosis, soon followed by a loss of consciousness, left-sided dysmetria, and ataxic speech. MELAS was diagnosed because of the presence of ragged red fibers in a muscle biopsy. At 33 years of age, she was admitted to our hospital because of ketoacidosis and partial status epilepticus. A blood gas examination revealed as follows; arterial pH, 6.88; bicarbonate, 2.1 mmol/l; base excess - 29.8 mmol/l. The serum level of glucose had also increased to 30 mmol/l. The serum levels of lactate and B-hydroxybutyrate were elevated to 11.4 mmol/l and 1,990 micromol/l, respectively. Ketoacidosis improved by fluid replacement and continuous intravenous insulin infusion. A brain MRI demonstrated hyperintensity areas on FLAIR images in the bilateral temporal lobes and the cerebellum. A proton MRS demonstrated the abnormal lactate accumulation in the bilateral temporal and occipital lobes. Since epileptic seizures are rare in patients with diabetic ketoacidosis, such seizures may indicate the existence of MELAS syndrome.
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PMID:Ketoacidosis accompanied by epileptic seizures in a patient with diabetes mellitus and mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). 1111 21

We report a patient with MELAS treated for 24 months with idebenone and riboflavin, during which no stroke-like episodes occurred. Moreover neurological symptoms clearly improved, and a recovery of brain MRI and EEG abnormalities was observed. We conclude that the combined treatment with idebenone and riboflavin may restore the metabolic impairment in MELAS, possibly improving the long-term prognosis in these patients.
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PMID:Long-term treatment with idebenone and riboflavin in a patient with MELAS. 1138 1

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

Leigh syndrome is a subacute necrotising encephalomyopathy frequently ascribed to mitochondrial respiratory chain deficiency. This condition is genetically heterogeneous, as mutations in both mitochondrial (mt) and nuclear genes have been reported. Here, we report the G13513A transition in the ND5 mtDNA gene in three unrelated children with complex I deficiency and a peculiar MRI aspect distinct from typical Leigh syndrome. Brain MRI consistently showed a specific involvement of the substantia nigra and medulla oblongata sparing the basal ganglia. Variable degrees of heteroplasmy were found in all tissues tested and a high percentage of mutant mtDNA was observed in muscle. The asymptomatic mothers presented low levels of mutant mtDNA in blood leucocytes. This mutation, which affects an evolutionary conserved amino acid (D393N), has been previously reported in adult patients with MELAS or LHON/MELAS syndromes, emphasising the clinical heterogeneity of mitochondrial DNA mutations. Since the G13513A mutation was found in 21% of our patients with Leigh syndrome and complex I deficiency (3/14), it appears that this mutation represents a frequent cause of Leigh-like syndrome, which should be systematically tested for molecular diagnosis in affected children and for genetic counselling in their maternal relatives.
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PMID:The mitochondrial DNA G13513A MELAS mutation in the NADH dehydrogenase 5 gene is a frequent cause of Leigh-like syndrome with isolated complex I deficiency. 1262 37

The male proband reported here was born with appropriate anthropometric parameters at term as the second child of healthy nonconsanguineous parents. His only clinical symptom was bilateral congenital cataracts with strabismus at birth, and both lenses were removed surgically at the age of 8 months. The perinatal and infantile period thereafter was clinically uneventful and his psychomotor development appeared almost normal. At the age of 6 years he was hospitalized for slight muscle weakness, minor ptosis, nystagmus and decreased physical activity. Soon after, his general condition worsened, gait ataxia presented, dysphagia and difficulty of speech followed by rapidly progressive generalized ataxia, and myopathy developed. Typical progressive gray matter degeneration with focal necrosis in the basal ganglia characteristic of the Leigh type of neuropathology could be detected by cranial MRI, the muscle histology showed ragged-red fibers. At the age of 7.5 years, unexpected left side hemiparesis with speech disability resembling that seen in MELAS syndrome developed, from which he recovered within 1.5 days. The mtDNA of the patient showed single 6.7 kb large-scale deletion harboring between 7817 and 14 536 bp. This case represents the first report of a verified mtDNA mutation associated with congenital cataracts as the first clinical sign of a later developing progressive neuromuscular disease presented with a combination of Leigh neuropathology, ragged-red fiber histopathology and stroke-like attack.
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PMID:Congenital cataract as the first symptom of a neuromuscular disease caused by a novel single large-scale mitochondrial DNA deletion. 1273 42

A 30-year-old man was hospitalized with dysarthria and weakness of his right arm and leg. Three months previously, he had noticed numbness and weakness of his right shoulder, which spread to involve his left leg but which improved after 8 months. On admission, neurological examination revealed limb kinetic apraxia and constructive apraxia of the right hand, motor aphasia, dysarthria, and spastic quadriplegia. Sensory examination revealed hyperalgesia and dysesthesia in the right arm and left leg. Deep tendon reflexes were hyperactive in all four extremities. And he had bilateral Babinski signs. Laboratory examination revealed pH 7.38, PCO2 46.1 Torr, PO2 93.4 Torr, BE 1.7, and blood lactate, 9.0 mg/dl (normal 5-20 mg/dl). Cerebrospinal fluid lactate level was 20.0 mg/dl. pyruvate 1.34 mg/dl. and protein 83 mg/dl. Blood lactate and pyruvate values were markedly elevated after aerobic exercise. T2WI brain MRI showed scattered high signal lesions in the left precentral and postcentral gyrus, right paracentral lobes, both superior frontal gyri, and right superior temporal gyrus. Right biceps brachi biopsy showed almost complete cytochrome c oxidase (COX) deficiency. There were no ragged-red fibers. There was marked decrease of COX activity: 2.7 nmol/min/mg-mitochondrial protein (normal range: 33.0 +/- 16.1, n = 7) in the biopsied muscle. Open brain biopsy (after permission from the patient and his family) revealed gliosis and perivascular infiltration of lymphocytes and macrophages without vascular proliferation. There was no mitochondrial DNA mutations, deletion or duplication, including tRNA-Leu 3243, 8993, 3271, 9176, 3291, and tRNA-Lys 8344, 8356, and 8363. From these findings, a diagnosis of COX deficiency presenting as MELAS-like episodes was done. His mother also showed abnormality on aerobic exercise test, but she had no episode of stroke or neurological dysfunction. Six months later, his aphasia and apraxia of the right hand had resolved, and at discharge he was able to ambulate with a cane. Ten months later, he returned to his work. There has been no recurrence of neurologic symptoms over the next 3 years and 10 months. This patient appears to represent a rare case of adult onset COX deficiency presenting as MELAS-like episodes.
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PMID:[MELAS-like episodes in an adult case with cytochrome c oxidase deficiency]. 1523 72

A thirty-two-year-old woman who had been diagnosed MELAS with 3243A > G mutation presented headache, nausea, decreased bilateral visual acuity, and topographical disturbance on January 1 in 2002. Although brain CT showed no fresh lesion, recurrence of stroke-like episode was considered. Immediately, she was treated with ubiquinone (210 mg/day, p.o.) and tocopherol nicotinate (300 mg/day, p.o.). She became confused on the fifth day. Diffusion weighted- and T2 weighted-MRI revealed appearance of hyperintense lesion at the right occipital lobe. We started edaravone infusion (30 mg, twice a day, div.) for two weeks with informed consent from her family. On 13th day her consciousness was improved. Edema and signal intensity of the lesion were decreased on MRI with minimal spread to the parietal lobe. She discharged on the 30th day with marked visual field loss, hemispatial neglect, and topographical amnesia. MRI after four months showed remarkable atrophy of the right occipital region. In our department, five stroke-like episodes including this case were treated with ubuiquinone and tocopherol nicotinate. This regimen was effective in prevention of progressive spread of lesions only in two episodes. Edaravone is radical scavenger used in acute cerebral infarction. Progressive spread into the neighboring regions is one of characteristics of MELAS, although its precise mechanisms are not well known. Oxidative stress induced by released free radicals through mitochondrial dysfunction might be one of factors and edaravone would make an effect through blockage of the free radicals. Edaravone could not rescue neurons in the initial lesion. Although more numbers of cases are needed to establish the effect of edaravone on MELAS, it could minimize the neurological deficits after stroke-like episode of MELAS.
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PMID:[A case of stroke-like episode of MELAS of which progressive spread would be prevented by edaravone]. 1602 65

We report a case of MELAS in which lesions were detected by perfusion-weighted MR imaging. Perfusion-weighted MRI using contrast media (PWI) and FAIR (flow-sensitive alternating inversion recovery), an arterial spin labeling method, clearly showed these lesions as hyperperfused areas. One of these lesions, diminished after steroid therapy, could also be detected by FAIR.
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PMID:A case of MELAS: hyperperfused lesions detected by non-invasive perfusion-weighted MR imaging. 1603 68

Mitochondrial encephalopathy, lactic acidosis with stroke-like episodes (MELAS) is a rare mitochondrial disorder that affects adults. MELAS syndrome can mimic cerebrovascular disease, encephalitis or toxic-metabolic encephalopathy. The authors reported two patients who presented with auditory symptoms before the onset of encephalopathy and stroke-like episodes. The first patient was a 28 year-old man, who presented with acute sensorineural hearing loss (SNHL) followed by headache, left hemiparesis and generalized tonic-clonic seizure. CT scan of the brain showed hypodensity lesion at the tip of right temporooccipital region. Audiogram and brainstem auditory evoked potential (BAEP) showed abnormal conduction of left brainstem auditory pathway. MRI of the brain showed a lesion involving gray and white matters of the right occipital, parietal and temporal lobes. The distribution of the lesions was not compatible with distribution of arterial supply. MRA was normal. The second patient was a 56 year-old woman with a one-year history of hearing loss. The audiogram revealed bilateral SNHL. A few days before admission, her hearing was acutely deteriorated She could not understand a conversation while she could communicate by writing. CT scan of the brain showed hypodensity in both temporal lobes and MRI revealed lesions in the same area. Pure tone audiogram showed moderate SNHL but BAEP was normal. One week later, she developed global dysphasia and generalized tonic-clonic seizure. Both patients had elevated cerebrospinal fluid and serum lactate: pyruvate ratio. Polymerase chain reaction-restriction fragment length polymorphism disclosed A3243G mtDNA mutation in the blood in the first patient and in muscle biopsy in the second patient. Ubiquinone supplement was prescribed The auditory symptoms in combination with stroke-like episode in supratentorium are important clues to diagnose MELAS syndrome.
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PMID:Auditory symptoms: a critical clue for diagnosis of MELAS. 1647 Nov 25


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