1/18. Quantitative proton magnetic resonance spectroscopy of cerebral metabolic disturbances in patients with MELAS.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.- - - - - - - - - - ranking = 1keywords = spectroscopy (Clic here for more details about this article) |
2/18. diffusion-weighted image and MR spectroscopic analysis of a case of MELAS with repeated attacks.We report the clinical and MR manifestations of an 18 year-old girl with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Recurrent status epilepticus caused reversible cytotoxic edema on diffusion-weighted images (DWI). Initial and one month follow-up MR spectroscopy, after seizure control, showed some discrepancies in the ratio of metabolites. N-acetylaspartate (NAA) partially recovered (NAA/creatine (Cr) ratio: 1.27-->1.84). This was because of a normalization of decreased NAA due to cellular dysfunction as a result of status epilepticus. A low ratio of NAA/Cr due to abnormal mitochondria remained in the decreased state. Reversible NAA/Cr ratios in the acute lesion suggested that NAA reflects the neuronal function as well as the level of neuronal structural damage. The altered NAA/Cr ratio better correlated with the abnormal signal intensity area of T2-weighted images (T2WI) and DWI than the lactate (Lac)/Cr ratio. With conservative treatment with anti-epileptics not accompanied by coenzyme Q or sodium dichloroacetate, lactate persistently increased (Lac/Cr ratio: 1.01-->1.21) because of the continued production of lactate in cells with respiratory deficiency, which is the main pathology of MELAS.- - - - - - - - - - ranking = 0.2keywords = spectroscopy (Clic here for more details about this article) |
3/18. Reversible brain dysfunction in MELAS: MEG, and (1)H MRS analysis.This case report describes a follow up investigation of a patient with impaired word discrimination due to mitochondrial encephalopathy with lactic acidosis and stroke-like syndrome (MELAS) using proton magnetic resonance spectroscopy ((1)H MRS) and auditory evoked magnetic fields (AEFs). The initial (1)H MRS showed no N-acetyl aspartate (NAA) and marked accumulation of lactate (Lac) in the stroke-like lesion of MELAS, which was silent in neural activity according to AEFs. The follow up investigations, however, demonstrated that NAA reappeared, that the formerly increased Lac signal was significantly reduced, and that the magnitude of AEFs of the lesion was markedly increased. Metabolic and functional changes in (1)H MRS and AEFs reflected the neurological recovery very well. The stroke-like lesion was shown, using AEFs and (1)H MRS, to be able to function properly, although brain tissue of the lesion initially had severe damage due to mitochondrial dysfunction.- - - - - - - - - - ranking = 0.2keywords = spectroscopy (Clic here for more details about this article) |
4/18. An 80-year-old mitochondrial disease patient with A3243G tRNA(Leu(UUR)) gene presenting cardiac dysfunction as the main symptom.MELAS is characterized by mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes, but cardiac involvement also frequently occurs. An 80-year-old female patient had been suffering from insulin-dependent diabetes mellitus and neurosensory hearing loss. At the age of 79 she suffered metabolic acidosis with persistent drowsiness and was subsequently found to have severe cardiac dysfunction. Muscle biopsy disclosed the presence of abnormal mitochondria, and the MELAS gene mutation (A3243G of the tRNA(Leu(UUR))) was demonstrated. It is noteworthy that this mitochondrial disease patient has survived until a great age, which shows the wide clinical spectrum of MELAS, especially in the age of onset.- - - - - - - - - - ranking = 7.2774751563271E-5keywords = spectrum (Clic here for more details about this article) |
5/18. Application of NMR spectroscopy to monitoring MELAS treatment: a case report.1H magnetic resonance spectroscopy (MRS) of the brain and (31)P MRS and saturation transfer of resting skeletal muscle were used to investigate intracellular metabolites and fluxes through the creatine kinase (CK) reaction in a patient with the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Acute cortical lesions were characterized by severely elevated lactate levels and reduced concentrations of N-acetylaspartyl compounds, glutamate, and myo-inositol. Similar but less extreme alterations were also observed in gray matter regions that appeared normal on magnetic resonance images. Investigation of the gastrocnemius muscle at rest demonstrated a reduced phosphocreatine level, elevated concentrations of inorganic phosphate and free adenosine 5'-diphosphate, and an abnormally low phosphorylation potential. Besides a moderately increased muscular phosphocreatine concentration, none of the metabolic disturbances detected on MRS improved with oral creatine supplementation. Forward and reverse fluxes through the CK reaction did not significantly change upon creatine treatment. Follow-up MRS investigations may thus provide objective markers of treatment response in vivo without the hazards or inconvenience of biopsy.- - - - - - - - - - ranking = 1keywords = spectroscopy (Clic here for more details about this article) |
6/18. Progressive cardiomyopathy as manifestation of mitochondrial disease.cardiomyopathies are a clinically and genetically heterogeneous group of cardiac diseases in which the myocardium is primarily involved. Mitochondrial dna point mutations have been identified in a broad spectrum of mitochondrial disorders, which are associated with neurological diseases. However, they also have been reported in patients with cardiomyopathy, either alone or as part of a multisystem disorder. A patient who presented with severe heart failure and was diagnosed as having a mitochondrial A3243G mutation is described.- - - - - - - - - - ranking = 7.2774751563271E-5keywords = spectrum (Clic here for more details about this article) |
7/18. Effects of oral creatine supplementation in a patient with MELAS phenotype and associated nephropathy.An 18-year-old male patient with MELAS phenotype and 2 previous episodes of cerebral stroke, recurrent seizures and nephropathy, was treated with creatine monohydrate after the acute onset of psychomental regression and changing states of somnolence and aggressive and agitated behaviour. These symptoms disappeared completely after 4 weeks of treatment with creatine after which the patient regained all his previous mental abilites. brain (white matter) proton magnetic resonance spectroscopy (chemical shift imaging) performed at 6 and 12 months of treatment showed lactic acid (Lac) accumulation and high creatine (Cr) levels in relation to choline-containing compounds (Cho). Urinary creatinine excretion as an indicator of the muscle and brain creatine pool increased upon short-term (12 days) high-dosage creatine supplementation (20 g per day) while plasma creatinine concentrations as possible indicators both of increasing creatine pool and of renal insufficiency increased during the course (28 months) of low-dosage creatine supplementation (5 g per day). Deterioration of renal function was finally indicated by urea retention and by impairment of renal creatinine clearance. These observations suggest that creatine supplementation may have a neuroprotective effect in patients with MELAS and episodes of acute mental deterioration. Adverse effects of creatine supplementation on renal function must be considered especially in patients with preexisting nephropathy.- - - - - - - - - - ranking = 0.2keywords = spectroscopy (Clic here for more details about this article) |
8/18. Late onset of stroke-like episode associated with a 3256C-->T point mutation of mitochondrial dna.Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) are usually associated with the common 3243A-->G mutation of mtDNA. Onset of stroke-like episodes usually occurs before age 30. We report a patient with late onset MELAS harboring a rare 3256C-->T mutation in the tRNA(Leu(UUR)) gene of mtDNA. The patient presented with a stroke-like episode at age 36. MRI showed a stroke-like lesion in the right parietooccipital brain region. Proton MR spectroscopy showed elevated lactate concentrations in the lesion (8.4 mmol/l), and in the mid-occipital region (2.3-3.2 mmol/l) that appeared normal on MRI. Further tests revealed evidence of a severe oxidative defect of muscle metabolism as well.- - - - - - - - - - ranking = 0.2keywords = spectroscopy (Clic here for more details about this article) |
9/18. melas syndrome with mitochondrial tRNA(Leu)(UUR) mutation: correlation of clinical state, nerve conduction, and muscle 31P magnetic resonance spectroscopy during treatment with nicotinamide and riboflavin.We report a patient with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes treated with riboflavin and nicotinamide for 18 months, during which time previously frequent encephalopathic spells ceased. To confirm clinical benefit, we withdrew treatment and monitored response with muscle 31P magnetic resonance spectroscopy (MRS) and sural nerve conduction studies. Of three prospectively chosen MRS variables, two changed coincidentally with clinical end points; phosphocreatine (PCr)/adenosine triphosphate recovery rates fell in parallel with sural nerve sensory amplitudes, and a drop in muscle bioenergetic efficiency (relationship of inorganic phosphate/PCr to the accelerating force of contracting muscle) coincided with development of encephalopathy. Investigations revealed a deficiency of respiratory complex I and mutation of the mitochondrial tRNA(Leu)(UUR). We suggest that a defective cellular energy state in mitochondrial disease may be partially treatable and that changes seen in appropriate muscle spectroscopy studies may parallel improvement in brain and peripheral nerve function.- - - - - - - - - - ranking = 1.2keywords = spectroscopy (Clic here for more details about this article) |
10/18. Beneficial effect of L-arginine for stroke-like episode in MELAS.We here reported the clinical course and therapeutic details of a 16-year-old girl with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) who had had five stroke-like episodes (two episodes were clinically mild, while the three subsequent episodes were severe). Among the three episodes, the symptoms improved earliest and magnetic resonance spectroscopy abnormality was minimal when given L-arginine in addition to prednisolone, glycerol and edalavone. L-arginine administration during the acute phase of MELAS might be a potential therapy to reduce brain damage due to mitochondrial dysfunction.- - - - - - - - - - ranking = 0.2keywords = spectroscopy (Clic here for more details about this article) |
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