Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018991 (hemiplegia)
 3,997 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report an infant with molybdenum cofactor deficiency (MCD) and a unique clinical presentation of hemiplegia, hypotonia, dystonia, and bilateral basal ganglia changes. Biochemistry revealed absent serum homocysteine, low concentrations of plasma cystine, high levels of urinary S-sulfocysteine and sulfite, and high levels of oxypurines in serum and urine. The depletion of cysteine and cystine through reaction with sulfite suggests that other thiols and thiol-dependent proteins may be similarly depleted. Ahomocysteinemia may be a clue to the mechanism of cytotoxicity in MCD.
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PMID:Ahomocysteinemia in molybdenum cofactor deficiency. 974 7

Methotrexate-induced neurotoxicity (MTX-Ntox) is a frequent complication of methotrexate (MTX) therapy for patients with both malignant and inflammatory diseases. MTX-Ntox can occur after intrathecal MTX or after low-, intermediate-, or high-dose systemic administration. Symptoms can present in the acute, subacute, or late setting form, and can range from affective disorders, malaise, and headaches, to somnolence, focal neurologic deficits, and seizures. While the pathogenesis of MTX-Ntox is likely multifactorial, one potential biochemical pathway leading from MTX to neurotoxicity involves the folate dependent remethylation of homocysteine (Hcy). MTX therapy is known to cause elevations of both plasma and CSF Hcy. Hcy is directly toxic to vascular endothelium and it and its metabolites are excitatory agonists of the N-methyl-D-aspartate (NMDA) receptor. Competitive or noncompetitive antagonists might afford protection from or reversal of MTX-Ntox. Using high-performance liquid chromatography (HPLC) with coulometric electrochemical detection, the authors measured CSF Hcy in sequential patients with severe subacute MTX-Ntox. CSF Hcy was higher in these patients (n = 9, median = 0.93 microM) than in asymptomatic patients (n = 11, median 0.2 microM, p < .01). Five patients with severe subacute MTX-Ntox (most with dysarthria and/or hemiplegia) were treated with 1-2 mg/kg oral dextromethorphan (DM), a noncompetitive antagonist of the N-methyl-1-aspartate (NMDA) receptor. All five had resolution of symptoms. These data provide additional clinical support for elevated CSF Hcy in the induction of MTX-Ntox through activation of the NMDA-receptor. These data provide support for a placebo-controlled clinical trial to examine the ability of DM to prevent or alleviate MTX-Ntox.
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PMID:Dextromethorphan is effective in the treatment of subacute methotrexate neurotoxicity. 1207 63

Risk of hip fractures in stroke patients is higher than that in a reference population. Hyperhomocysteinemia is regarded as a risk factor for ischemic stroke. The high prevalence of osteoporosis among patients with homocystinuria suggests that hyperhomocysteine may also increase the risk of fractures. To determine the association between homocysteine concentration and the risk of hip fractures, we studied a cohort of stroke patients with hemiplegia. Age-adjusted incidence rates of a hip fracture were calculated for quartiles of homocysteine concentrations. Cox proportional-hazard regression was used to calculate hazard ratios for quartiles of homocysteine levels. The initial enrolment of 433 hemiplegic patients with ischemic stroke, older than 65 years old, were followed for up to 10 years. The mean plasma homocysteine concentration at the enrolment was 14.1 +/- 5.2 micromol/L. There were 33 hip fractures among men and 46 among women during the mean follow-up period of 9.0 years. The age-adjusted incidence rates per 1000 person-years for hip fractures increased almost linearly from 2.89 in the lowest to 27.87 in the highest quartiles of homocysteine levels. We conclude that hyperhomocysteinemia is one of the risk factors for hip fractures in stroke patients.
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PMID:Homocysteine as a predictive factor for hip fracture in stroke patients. 3071 Oct 56

The objective of this study is to report a new manifestation of acute stroke following antifibrinolytic agent administration in young women carrying heterozygosity for methylene-tetrahydrofolate reductase (MTHFR) C677T. The study included two young women who developed an acute ischaemic stroke following three days of tranexamic acid administration for bleeding gynaecological disorders. Case 1, a 44-year-old woman, presented left hemiplegia, mild dysarthria and anosognosia. Brain magnetic resonance imaging showed right ischaemic fronto-temporal lesion due to subocclusion of the right middle cerebral artery. Case 2, a 49-year-old woman, developed aphasia and right hemiplegia. Neuroimaging showed left capsular and periventricular infarcts due to near occlusion of the left internal carotid artery. Thrombophilia screening, coagulation parameters, homocysteine testing, 12-lead electrocardiography, and transthoracic and transoesophageal echocardiography were unremarkable. Genetic assay showed that both patients carried heterozygosity for MTHFR C677T, in which cytosine (C) is replaced by thymidine (T) at base position 677. To our knowledge, this is the first report describing the association between genetic factors and the onset of stroke following antifibrinolytic drugs intake. These data suggest a synergic effect of plasminogen activator inhibitor and heterozygosity for MTHFR C677T on the pathogenetic mechanisms leading to ischaemic stroke in young people.
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PMID:Ischaemic stroke following tranexamic acid in young patients carrying heterozygosity of MTHFR C677T. 2190 3