Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Diffusion-weighted image and MR spectroscopic analysis of a case of MELAS with repeated attacks. 1129 91

The neurotoxic effects of immunosuppressive agents used after transplantation are well known. In most cases a decrease in drug dosage results in resolution of the neurotoxicity. At early stages in the post-transplantation clinical course, neurotoxicity and other complications such as infectious disease, encephalopathy and seizures are sometimes difficult to diagnose with neuroimaging. Recently, diffusion weighted imaging (DWI) has been used in patients with ischemic disease, mitochondrial myopathy, encephalopathy and demyelinating disease. We examined the magnetic resonance images (MRI), including DWI and fluid attenuated inversion recovery image (FLAIR), in three cases of post-transplantation neurological complication: two cases of neurotoxicity and a case of acute disseminated encephalomyelitis (ADEM). Hyper-intense lesions representing neurotoxicity were seen on FLAIR but not on DWI in two cases with neurotoxicity induced by an immunosuppressive agent. In ADEM, hyper-intense lesions were seen on both FLAIR and DWI. Neurotoxicity due to the immunosuppressive agent showed a favorable outcome, although the hyper-intense lesions temporally presented on FLAIR. In the state after transplantation, hyper-intense lesions on FLAIR and DWI represented in the brain from the initial stage, we might be care of other severe complications but for neurotoxicity.
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PMID:Magnetic resonance imaging in cases with encephalopathy secondary to immunosuppressive agents. 1209 40

Mitochondrial encephalomyopathies are a multisystemic group of disorders that are characterised by a wide range of biochemical and genetic mitochondrial defects and variable modes of inheritance. Among this group of disorders, the mitochondrial myopathy, encephalopathy, lactic acidosis with stroke-like episodes (MELAS) syndrome is one of the most frequently occurring, maternally inherited mitochondrial disorders. As the name implies, stroke-like episodes are the defining feature of the MELAS syndrome, often occurring before the age of 15 years. The clinical course of this disorder is highly variable, ranging from asymptomatic, with normal early development, to progressive muscle weakness, lactic acidosis, cognitive dysfunction, seizures, stroke-like episodes, encephalopathy and premature death. This syndrome is associated with a number of point mutations in the mitochondrial DNA, with over 80% of the mutations occurring in the dihydrouridine loop of the mitochondrial transfer RNA(Leu(UUR)) [tRNA(Leu)((UUR))] gene. The pathophysiology of the disease is not completely understood; however, several different mechanisms are proposed to contribute to this disease. These include decreased aminoacylation of mitochondrial tRNA, resulting in decreased mitochondrial protein synthesis; changes in calcium homeostasis; and alterations in nitric oxide metabolism. Currently, no consensus criteria exist for treating the MELAS syndrome or mitochondrial dysfunction in other diseases. Many of the therapeutic strategies used have been adopted as the result of isolated case reports or limited clinical studies that have included a heterogeneous population of patients with the MELAS syndrome, other defects in oxidative phosphorylation or lactic acidosis due to disorders of pyruvate metabolism. Current approaches to the treatment of the MELAS syndrome are based on the use of antioxidants, respiratory chain substrates and cofactors in the form of vitamins; however, no consistent benefits have been observed with these treatments.
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PMID:The mitochondrial myopathy encephalopathy, lactic acidosis with stroke-like episodes (MELAS) syndrome: a review of treatment options. 1673 97

We have identified compound heterozygous missense mutations in POLG1, encoding the mitochondrial DNA polymerase gamma (Pol gamma), in 7 children with progressive encephalopathy from 5 unrelated families. The clinical features in 6 of the children included psychomotor regression, refractory seizures, stroke-like episodes, hepatopathy, and ataxia compatible with Alpers-Huttenlocher syndrome. Three families harbored a previously reported A467T substitution, which was found in compound with the earlier described G848S or the W748S substitution or a novel R574W substitution. Two families harbored the W748S change in compound with either of 2 novel mutations predicted to give an R232H or M1163R substitution. Muscle morphology showed mitochondrial myopathy with cytochrome c oxidase (COX)-deficient fibers in 4 patients. mtDNA analyses in muscle tissue revealed mtDNA depletion in 3 of the children and mtDNA deletions in the 2 sibling pairs. Neuropathologic investigation in 3 children revealed widespread cortical degeneration with gliosis and subcortical neuronal loss, especially in the thalamus, whereas there were only subcortical neurodegenerative findings in another child. The results support the concept that deletions as well as depletion of mtDNA are involved in the pathogenesis of Alpers-Huttenlocher syndrome and add 3 new POLG1 mutations associated with an early-onset neurodegenerative disease.
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PMID:POLG1 mutations associated with progressive encephalopathy in childhood. 1689 9

Epilepsy is one of the most common presentations of patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). MELAS is typically caused by an A-to-G substitution at nucleotide position 3243 of mitochondrial DNA. Valproic acid, a common anticonvulsant, can actually increase the frequency of seizures in individuals with MELAS. Here, we report a single case-study of a 38-year-old man who presented with focal seizures and had MELAS Syndrome due to the A3243G mitochondrial DNA mutation. Manifestation of epilepsia partialis continua was aggravated by use of valproic acid. Convulsions abated after discontinuation of valproic acid. Our experience suggests that valproic acid should be avoided for the treatment of epilepsy in individuals with mitochondrial disease.
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PMID:Valproic acid aggravates epilepsy due to MELAS in a patient with an A3243G mutation of mitochondrial DNA. 1722 98

We encountered an 11-year-old girl with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) who developed occipital lobe epilepsy at the age of 7 years and 4 months. Thereafter she had repeated status epilepticus associated with stroke-like episodes. Status epilepticus consisted of repetitive complex partial seizures with or without secondarily generalized tonic clonic seizures. The seizures did not respond to conventional anticonvulsive drugs, including diazepam, midazolam, phenytoin, lidocaine, chloral hydrate, and thiamylal sodium, and lasted for several hours (mean 9.5 hours). At the age of 11 years, intravenous infusion of L-arginine (0.5 g/kg body weight) was first given five hours after the onset of status epilepticus. The seizures and electroencephalographic abnormalities improved dramatically. After the introduction of L-arginine, in addition to shortened duration of status epilepticus (mean 3 hours), clinical recovery from the status epilepticus was prompt, and the average hospitalization periods could be shortened. There were no obvious adverse effects, including vomiting, hypotension, and urticaria. Our experience suggests that early intravenous administration of L-arginine may be useful in the treatment of status epilepticus associated with stroke-like episode in patients with MELAS.
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PMID:[Usefulness of L-arginine infusion for status epilepticus in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes]. 1722 17

We describe an unusual vasculopathy in two sisters of non-consanguineous parents. The first child developed an acute hemiparesis and focal seizures at the age of 6 months during a febrile illness. Magnetic resonance imaging (MRI) of the brain showed bilateral cortical-subcortical infarction not confined to a vascular territory. Subsequently, the child had a persistent stable neurological deficit. Her younger sister had a similar encephalitis-like episode at the age of 4 months, with left-sided cortical-subcortical ischaemic lesions. Two months later she had left-sided focal seizures. MRI showed a right-sided cortical enhancement, magnetic resonance angiography (MRA) was normal. The neurological deficit was stable and she was seizure free. These episodes were initially interpreted as metabolic strokes, but work-up was normal and mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) was excluded. In their teens both sisters were diagnosed with pulmonary and systemic hypertension and, due to the arterial hypertension, myocardial hypertrophy. Renal artery stenosis, pathological pulmonary arteries, and stenosis and rarefication of coronary arteries were found; the aorta and retinal vessels were normal. Repeat cranial MRI and MRA showed multiple collaterals, while the carotid and basilar arteries were extremely narrowed (moyamoya appearance). We suggest the diagnosis is a hereditary systemic vasculopathy of unknown origin.
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PMID:Siblings with infantile cerebral stroke and delayed multivessel involvement--a new hereditary vasculopathy? 1742 10

A 34-year-old man with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) showed chronic intestinal pseudo-obstruction (CIPO), which was improved by the administration of distigmine bromide. He exhibited generalized tonic clonic seizures at the age of 21, and mitochondrial DNA analysis showed the MELAS mutation. At the age of 34, he became akinetic mutism after nonconvulsive status epilepticus and needed enteral nutrition through a nasogasrtic tube. However, he developed abdominal distention and vomiting, and was diagnosed as CIPO, therefore tube feeding was stopped. Although the administration of domperidone, mosapride citrate, butyric acid bacteria, sodium picosulfate, prostaglandin F2 alpha, pantothenic acid, dioctyl sodium sulfosuccinate, and so on, was ineffective, the administration of distigmine bromide improved his bowel motion disturbance and abnormal distention. The present case is the first MELAS patient with CIPO to be ameliorated by distigmine bromide, which might work acetylcholine receptor on the interstitial cells of Cajal.
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PMID:[Distigmine bromide improves chronic intestinal pseudo-obstruction in a case of MELAS]. 1751 Dec 91

We report here the clinical course of a 31-year-old male who recovered from a fulminant form of mitochondrial myopathy with lactic acidosis. The patient was transferred to our hospital with acute dyspnea and a convulsive seizure. On admission, he was in a state of shock, and presented with severe high-output heart failure, acute renal failure, and rhabdomyolysis. Treatment with continuous venovenous hemodiafiltration (CVVHDF) resulted in an excellent response, with no signs of hemodynamic instability. This case suggests that CVVHDF with serial hemodynamic monitoring may be effective in treating hypotensive patients with a life-threatening mitochondrial disorder.
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PMID:Continuous venovenous hemodiafiltration for life-threatening mitochondrial myopathy with lactic acidosis and rhabdomyolysis. 1772 68

In single cases mitochondrial disorders may manifest as pancreatitis, but recurrent, chronic pancreatitis with exacerbations of at least 15 times without morphological alterations of the pancreas but concomitant diabetes mellitus has not been reported. In a 57-year-old Caucasian male mitochondrial disorder was diagnosed at the age of 49 years upon epilepsy with generalized and focal seizures, cognitive decline, migraine, mitochondrial myopathy, polyneuropathy, diabetes mellitus, hypokalie-mia, hyperlipidemia, atrial fibrillation, heart failure, sicca syndrome, recurrent pancreatitis, chronic diarrhea, polydipsia, hyperhidrosis, steatosis hepatis, anemia, thrombopenia, an abnormal lactate stress test, and a muscle biopsy showing ragged-red muscle fibers, single completely COX-negative fibers, target fibers, increased number of sarcoplasmatic lipid droplets, but normal mitochondrial morphology on electron microscopy. Between the age of 33 years and the age of 44 years, at least 15 episodes of pancreatitis, manifesting as severe abdominal pain, and elevated exocrine pancreatic enzymes, but without morphological alterations of the pancreas, responding well to H2-blockers and food restriction had occurred. Recurrent pancreatitis without morphological alterations of the pancreas may be a feature of multisystem mitochondrial disorder resulting in diabetes mellitus. Physicians should familiarize with pancreatitis as a manifestation of a mitochondrial disorder and mitochondrial disorder should be excluded in patients with pancreatitis.
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PMID:Recurrent pancreatitis as a manifestation of multisystem mitochondrial disorder. 1791 91


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