vitamin-b-12 and Brain-Ischemia

To analyze the effect of mecobalamin on the early-functional outcomes of patients with ischemic stroke and H-type hypertension.. From October of 2014 to October of 2016, 224 cases of ischemic stroke and H-type hypertension were selected. The patients were randomly divided into treatment control groups, with 112 patients in each group. The control group was treated with the conventional therapy. The observation group was treated with 500 µg of mecobalamin three times a day in addition to the conventional therapy. We compared serum homocysteine (Hcy), hs-CRP levels, carotid plaques, and NIHSS scores between the two groups on the 2nd day and at 4 weeks, 8 weeks, 3 months, and 6 months.. After 4 weeks, 8 weeks, 3 months and 6 months, the difference of serum Hcy level between the two groups was statistically significant (t = 4.049, 3.896, 6.052, 6.159, respectively. All P <0.05). After the treatment, at 4 weeks, 8 weeks, 3 months and 6 months, the levels of hs-CRP in the treatment group were significantly lower than those in the control group (t = 37.249, 28.376, 26.454, 20.522, respectively. All P <0.01). After 3 months and 6 months, the carotid artery plaques were significantly reduced in the treatment group compared to those in the control group (t = 2.309 and 2.434. All P <0.05). After 3 months and 6 months, the NIHSS score was significantly higher in the treatment group compared to those in the control group (t = 2.455 and 2.193. All P <0.05).. Mecobalamin can reduce the level of plasma homocysteine, then lead to reductions of levels of plasma inflammatory factors and volume of carotid artery plaques, resulting in more significant functional recovery.

Topics: Aged; Aged, 80 and over; Brain Ischemia; Female; Homocysteine; Humans; Hypertension; Male; Middle Aged; Prognosis; Stroke; Treatment Outcome; Vitamin B 12

Epidemiological studies suggest that elevated homocysteine is linked to stroke and heart disease. However, the results of lowering homocysteine levels in reducing the risk of stroke recurrence are controversial.. The study aims to evaluate whether homocysteine-lowering therapy with folic acid and vitamins B6 and B12 reduces recurrent stroke events and other combined incidence of recurrent vascular events and vascular death in ischemic stroke patients of low folate regions.. This is a multicenter, randomized, double-blinded, placebo-controlled trial. Patients (n = 8000, α = 0.05, β = 0.10) within one-month of ischemic stroke (large-artery atherosclerosis or small-vessel occlusion) or hypertensive intracerebral haemorrhage with plasma homocysteine level ≥ 15 μmol/l will be enrolled. Eligible patients will be randomized by a web-based, random allocation system to receive multivitamins (folic acid 0.8 mg, vitamin B6 10 mg, and vitamin B12 500 μg) or matching placebo daily with a median follow-up of three-years.. Patients will be evaluated at six monthly intervals. The primary outcome event is the composite event 'stroke, myocardial infarction, or death from any vascular cause', whichever occurs first. Secondary outcome measures include nonvascular death, transient ischemic attack, depression, dementia, unstable angina, revascularization procedures of the coronary, and cerebral and peripheral circulations.. This is the first multicenter randomized trial of secondary prevention for ischemic stroke in a Chinese population with a higher homocysteine level but without folate food fortification.

Topics: Adult; Aged; Brain Ischemia; China; Double-Blind Method; Folic Acid; Homocysteine; Humans; Intracranial Hemorrhage, Hypertensive; Middle Aged; Myocardial Infarction; Protective Agents; Research Design; Secondary Prevention; Stroke; Vitamin B 12; Vitamin B 6

Increased levels of asymmetric dimethylarginine (ADMA) have been observed in patients with acute ischemic stroke. We aimed to investigate the correlation between ADMA and ischemic stroke, and evaluate the effect of supplementation of folic acid and vitamin B12 on concentrations of ADMA. Patients were randomized into intervention and non-intervention groups within 3 days after symptom onset. Intervention group patients were treated with folic acid (5mg daily) and vitamin B12 (500 μg twice daily) for 12 weeks. ADMA and homocysteine (Hcy) concentrations were measured before treatment (baseline) and 2 and 12 weeks after treatment. The laboratory measures were also collected from healthy controls. Eighty five subjects were enrolled in this study, from whom 72 with complete baseline and follow-up laboratory data were included in the present analysis. Thirty four patients were assigned to the intervention group and 38 patients to the non-intervention group. Sixty people were enrolled as healthy controls. Levels of ADMA and Hcy were raised (p<0.05) in patients with acute ischemic stroke. With supplementation of both folic acid and vitamin B12, the levels of ADMA and Hcy decreased significantly at 2 and 12 weeks (p<0.05). The present study reconfirmed that ADMA can be regarded as a risk biomarker for acute ischemic stroke. We observed that with supplementation of folic acid and vitamin B12, levels of ADMA were decreased in patients with acute ischemic stroke.

Topics: Aged; Arginine; Blood Chemical Analysis; Brain Ischemia; Dietary Supplements; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Male; Nitric Oxide; Nitric Oxide Synthase Type III; Stroke; Time Factors; Treatment Outcome; Vitamin B 12

Elevated concentrations of homocysteine are associated with cerebral small vessel disease (CSVD). B-vitamin supplementation with folate and vitamins B12 and B6 reduces homocysteine concentrations. In a substudy of the VITAmins TO Prevent Stroke (VITATOPS) trial, we assessed the hypothesis that the addition of once-daily supplements of B vitamins would reduce the progression of CSVD-related brain lesions.. A total of 359 patients with recent stroke or transient ischemic attack, who were randomly allocated to double-blind treatment with placebo or b vitamins, underwent brain MRI at randomization and after 2 years of B-vitamin supplementation. MR images were analyzed blinded to treatment allocation. Outcomes related to the prespecified hypothesis were progression of white matter hyperintensities and incident lacunes. We also explored the effect of B-vitamin supplementation on the incidence of other ischemic abnormalities.. After 2 years of treatment with b vitamins or placebo, there was no significant difference in white matter hyperintensities volume change (0.08 vs 0.13 cm3; P=0.419) and incidence of lacunes (8.0% vs 5.9%, P=0.434; odds ratio=1.38). In a subanalysis of patients with MRI evidence of severe CSVD at baseline, b-vitamin supplementation was associated with a significant reduction in white matter hyperintensities volume change (0.3 vs 1.7 cm3; P=0.039).. Daily B-vitamin supplementation for 2 years did not significantly reduce the progression of brain lesions resulting from presumed CSVD in all patients with recent stroke or transient ischemic attack but may do so in the subgroup of patients with recent stroke or transient ischemic attack and severe CSVD.. http://vitatops.highway1.com.au/. Unique identifier: NCT00097669 and ISRCTN74743444.

Topics: Aged; Brain Ischemia; Cerebrovascular Circulation; Disease Progression; Double-Blind Method; Female; Folic Acid; Humans; Ischemic Attack, Transient; Leukoencephalopathies; Magnetic Resonance Imaging; Male; Middle Aged; Placebos; Stroke, Lacunar; Treatment Failure; Vitamin B 12; Vitamin B 6; Vitamin B Complex

No data are currently available on the prevalence and control of cardiovascular (CV) risk factors in secondary prevention depending on the cardiac or cerebral localization of the ischemic disease. We investigated the prevalence and control of modifiable CV risk factors, as well as the determinants of CV risk factors' control and adequate treatment in a secondary prevention cohort, the SU-FOL-OM3 study cohort, to determine the role of the localization of the ischemic disease including events.. A total of 2491 patients were included in the study. The prevalence of all modifiable risk factors was high in both coronary heart disease and cerebrovascular disease (CVD) groups. Control of all risk factors and the presence of antiplatelet medication were noted in 29.6% of patients with coronary heart disease and 11% of patients with CVD. The cardiac localization of the including event was independently associated with the control of each of the risk factors studied (hypertension, low-density lipoprotein-cholesterol, smoking) and to the control of all risk factors present and prescription of antiplatelet therapy with an odds ratio (95% confidence interval) of 2.72 (1.97-3.75).. There is a need to improve the control of CV risk factors in secondary prevention patients. This is particularly crucial for patients with CVD.

Topics: Aged; Anticholesteremic Agents; Antihypertensive Agents; Biomarkers; Brain Ischemia; Chi-Square Distribution; Cholesterol, LDL; Cohort Studies; Diabetes Mellitus; Dietary Supplements; Double-Blind Method; Fatty Acids, Omega-3; Female; Folic Acid; France; Humans; Hypercholesterolemia; Hypertension; Hypoglycemic Agents; Logistic Models; Male; Middle Aged; Myocardial Ischemia; Odds Ratio; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Secondary Prevention; Smoking Cessation; Treatment Outcome; Vitamin B 12; Vitamin B 6

Circulating homocysteine is a risk factor of cardiovascular and cerebrovascular events. Hyperhomocysteinemia may be an early indicator for vitamin B12 disorders because cobalamin is a cofactor in the remethylation process of homocysteine. Serum holotranscobalamin (holoTC II) becomes decreased before the development of metabolic dysfunction. In this study, we assessed circulating holoTC II to estimate the diagnosis of vitamin B12 deficiency in the first ischemic cerebrovascular attack. We also compared the efficacy of the measurement of plasma holoTC II with the other standard biochemical and hematological markers used to reach the diagnosis of cobalamin deficiency. Forty-five patients (age 71 years (range 35-90), 16 men/29 women) within the first ischemic cerebrovascular event were included in this prospective study. All the enrolled patients have been administered vitamin B12 1 mg intramuscular injection once a day for 10 days. At the baseline and on the tenth day of treatment, plasma levels of holoTC II and the proper biochemical and hematological markers in diagnosing cobalamin deficiency were measured. After admission, anemia and diminished serum vitamin B12 levels were determined to be only 20% (9/45) and 44% (20/45), respectively; 78% (35/45) of the patients had low serum holoTC II (<37 pmol/l). Serum homocysteine was higher in patients (49% of them) who had previously suffered a stroke. Thrombocytopenia, hypersegmentated neutrophils, and indirect hyperbilirubinemia were observed in 20% of the patients. Leukopenia and macrocytosis were not evident in any of them. In 18 of 27 patients (67%) that had low holoTC II levels after joining the study and who remained in the study until the end of cobalamin treatment, serum holoTC II levels returned to normal values. Cobalamin deficiency should be considered in patients with cerebrovascular diseases, even if anemia, elevated mean cell volume, depression of the serum cobalamin, or other classic hematological and/or biochemical abnormalities are lacking. Furthermore, measurement of serum holoTC II looks promising as a first-line of tests for diagnosing early vitamin B12 deficiency.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Brain Ischemia; Female; Humans; Hyperhomocysteinemia; Male; Middle Aged; Prospective Studies; Radioimmunoassay; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

Hyperhomocysteinemia is associated with atherosclerotic risk. Although vitamins can lower homocysteine (Hcy), information about effects on atherosclerosis is scarce.. We used carotid intima-media thickness (IMT) as an accepted marker of atherosclerotic changes. Fifty patients (60 +/- 8 years) with IMT> or =1 mm were included. In a double blind, randomized trial they received daily 2.5 mg folic acid, 25 mg Vitamin B6, and 0.5mg Vitamin B12 or placebo for 1 year.. In the treatment group, Hcy decreased from 10.50 +/- 3.93 to 6.56 +/- 1.53 micromol/l (P < 0.0001), whereas it remained unchanged in the placebo group (10.76 +/- 2.36 versus 10.45+/-3.30 micromol/l). IMT decreased from 1.50 +/- 0.44 to 1.42 +/- 0.48 mm (P = 0.034) in the treatment group, whereas it increased from 1.47 +/- 0.57 to 1.54 +/- 0.71 mm in the placebo group. The mean individual changes of IMT between both groups differed significantly (-0.08 +/- 0.17 versus 0.07 +/- 0.25 mm, P = 0.019). Multiple regression analysis revealed that the observed effect on IMT depended only on medication.. Vitamin supplementation significantly reduces IMT in patients at risk. This effect is independent of Hcy concentration.

Topics: Aged; Brain Ischemia; Carotid Arteries; Double-Blind Method; Female; Folic Acid; Homocysteine; Humans; Intracranial Arteriosclerosis; Male; Middle Aged; Risk Factors; Tunica Intima; Tunica Media; Ultrasonography; Vitamin B 12; Vitamin B 6

Severely elevated serum homocysteine is a rare cause of ischaemic stroke and extra-cranial arterial and venous thrombosis. Several factors can lead to mild elevation of homocysteine including dietary folate and B12 deficiency, and genetic variants of the methylenetetrahydrofolate reductase (MTHFR) enzyme. The use of Anabolic androgenic steroid (AAS) is under-reported, but increasingly linked to ischaemic stroke and can raise homocysteine levels.. We present a case of a man in his 40s with a large left middle cerebral artery (MCA) territory ischaemic stroke and combined multifocal, extracranial venous, and arterial thrombosis. His past medical history was significant for Crohn's disease and covert use of AAS. A young stroke screen was negative except for a severely elevated total homocysteine concentration, folate and B12 deficiencies. Further tests revealed he was homozygous for the methylenetetrahydrofolate reductase enzyme thermolabile variant (MTHFR c.667 C > T). The etiology of this stroke was a hypercoagulable state induced by raised plasma homocysteine. Raised homocysteine in this case was likely multifactorial and related to chronic AAS use in combination with the homozygous MTHFR c.677 C > T thermolabile variant, folate deficiency and, vitamin B12 deficiency.. In summary, hyperhomocysteinemia is an important potential cause of ischaemic stroke and may result from genetic, dietary, and social factors. Anabolic androgenic steroid use is an important risk factor for clinicians to consider, particularly in cases of young stroke with elevated serum homocysteine. Testing for MFTHR variants in stroke patients with raised homocysteine may be useful to guide secondary stroke prevention through adequate vitamin supplementation. Further studies looking into primary and secondary stroke prevention in the high-risk MTHFR variant cohort are necessary.

Topics: Anabolic Androgenic Steroids; Brain Ischemia; Folic Acid; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Ischemic Stroke; Male; Methylenetetrahydrofolate Reductase (NADPH2); Risk Factors; Stroke; Thrombosis; Vitamin B 12

Cerebral ischemia-reperfusion injury (CIRI) is often accompanied by upregulation of homocysteine (Hcy). Excessive Hcy damages cerebral vascular endothelial cells and neurons, inducing neurotoxicity and even neurodegeneration. Normally, supplementation of vitamin B

Topics: Animals; Brain Ischemia; Endothelial Cells; Homocysteine; Lysosomes; Malondialdehyde; Mice; Reperfusion Injury; Vitamin B 12; Vitamins

Cobalamin (Cbl) and folate are common supplements clinicians prescribe as an adjuvant therapy for dementia patients, on the presumption of their neurotrophic and/or homocysteine (Hcy) lowering effect. However, the treatment efficacy has been found mixed and the effects of Cbl/folate/Hcy on the human brain remain to be elucidated.. To explore the neurovascular correlates of Cbl/folate/Hcy in Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SIVD).. Sixty-seven AD patients and 57 SIVD patients were prospectively and consecutively recruited from an outpatient clinic. Multimodal 3-Tesla magnetic resonance imaging was performed to quantitatively evaluate cerebral blood flow (CBF) and white matter integrity. The relationship between neuroimaging metrics and the serum levels of Cbl/folate/Hcy was examined by using the Kruskal-Wallis test, partial correlation analysis, and moderation analysis, at a significance level of 0.05.. As a whole, CBF mainly associated with Cbl/folate while white matter hyperintensities exclusively associated with Hcy. As compared with AD, SIVD exhibited more noticeable CBF correlates (spatially widespread with Cbl and focal with folate). In SIVD, a bilateral Cbl-moderated CBF coupling was found between medial prefrontal cortex and ipsilateral basal ganglia, while in the fronto-subcortical white matter tracts, elevated Hcy was associated with imaging metrics indicative of increased injury in both axon and myelin sheath.. We identified the neurovascular correlates of previously reported neurotrophic effect of Cbl/folate and neurotoxic effect of Hcy in dementia. The correlates exhibited distinct patterns in AD and SIVD. The findings may help improving the formulation of supplemental Cbl/folate treatment for dementia.

Topics: Alzheimer Disease; Brain; Brain Ischemia; Dementia, Vascular; Folic Acid; Homocysteine; Humans; Vitamin B 12

Despite advances in the understanding of the pathophysiology of ischemic stroke, therapeutic options remain limited. Methylcobalamin is an endogenous vitamin B12 that exhibits anti-inflammatory and antiapoptotic activities in a variety of diseases. In this study, we aimed to explore the neuroprotective effects and mechanism of action of methylcobalamin on cerebral ischemic injury in vitro and in vivo. The oxygen and glucose deprivation/reperfusion model and middle cerebral artery occlusion model were used to simulate cerebral ischemic injury in vitro and in vivo. Cell viability, inflammatory factors, cell apoptosis, and protein expression levels were determined. Further, autophagy flux and the cerebral infarction volume were measured. The modified neurological severity score, Longa score, Rotarod assay, and foot-fault test were used to evaluate behavioral changes and neurological deficits in rats. In vitro, methylcobalamin significantly increased cell viability, decreased lactate dehydrogenase release, attenuated inflammatory cytokine expression, reduced the apoptotic proportion, and enhanced autophagy flux after OGD treatment. In addition, Bcl-2 and Beclin1 expression levels and the LC3 II/I ratio were increased, whereas levels of Bax and cleaved caspase-3 were decreased. In vivo, methylcobalamin significantly reduced the cerebral infarction volume and neurological deficits in the rats. Furthermore, methylcobalamin activated the ERK1/2 pathway, whereas ERK1/2 inhibitors diminished its effects in the in vitro and in vivo models. In conclusion, methylcobalamin may exert a neuroprotective effect on cerebral ischemia and is a promising drug candidate for developing novel neuroprotective therapies.

Topics: Animals; Apoptosis; Autophagy; Brain Ischemia; Cell Line; Cell Survival; Cytokines; Disease Models, Animal; Infarction, Middle Cerebral Artery; Male; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Neuroprotective Agents; Protein Kinase Inhibitors; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Vitamin B 12

Topics: Brain Ischemia; Folic Acid; Homocysteine; Humans; Ischemic Stroke; Stroke; Vitamin B 12

Trials of B vitamin therapy to lower blood total homocysteine (tHcy) levels for prevention of stroke are inconclusive. Secondary analyses of trial data and epidemiological studies suggest that tHcy levels may be particularly associated with small vessel stroke (SVS). We assessed whether circulating tHcy and B vitamin levels are selectively associated with SVS, but not other stroke subtypes, using Mendelian randomization.. We used summary statistics data for single-nucleotide polymorphisms (SNPs) associated with tHcy (n = 18), folate (n = 3), vitamin B. Genetically predicted tHcy was associated with SVS, with an odds ratio of 1.34 (95% confidence interval [CI], 1.13-1.58; p = 6.7 × 10. These findings suggest that any effect of homocysteine-lowering treatment in preventing stroke will be confined to the SVS subtype. Whether genetic variants at or near the MTHFR and MUT genes influence SVS risk through pathways other than homocysteine levels and downstream effects require further investigation. Ann Neurol 2019;85:495-501.

Topics: Brain Ischemia; Homocysteine; Humans; Mendelian Randomization Analysis; Microvessels; Polymorphism, Single Nucleotide; Stroke; Vitamin B 12

We explored the relationship between acute ischaemic stroke (IS) early functional outcome and serum levels of homocysteine, vitamin B12, and D in a noninterventional prospective clinical study. We enrolled 50 patients with first-ever IS and performed laboratory tests and functional assessment at three time points: on admission and three and six months after stroke. Modified Rankin Scale (mRS), NIHSS scale, and Barthel index (BI) scores were assessed in all participants by trained examiner blinded to laboratory data. Patients did not receive treatment that might alter laboratory data. Admission NIHSS correlated with homocysteine levels (

Topics: Aged; Aged, 80 and over; Brain Ischemia; Female; Homocysteine; Humans; Male; Middle Aged; Recovery of Function; Stroke; Vitamin B 12; Vitamin D

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Stroke; Vitamin B 12; Vitamin B 12 Deficiency; Warfarin

Recent studies have focussed on the association between elevated homocysteine levels with megaloblastic changes and thromboembolic events, but the relationship between occult megaloblastosis (with normal haemoglobin levels) and ischaemic stroke has not been widely explored. The objective of this study is to establish a simple and economical marker for the detection of occult megaloblastosis at the community health care level in developing countries. A hundred patients who met the inclusion criteria were studied. At the 5% level of significance, the levels of cobalamin and folate were significantly lower, while the number of hypersegmented neutrophils on the peripheral smear was higher in patients from Group A (70 patients with high homocysteine) compared with the patients in Group B (30 patients with normal homocysteine). Forty-five (64.2%) of the 70 patients in Group A showed hypersegmentation of neutrophils in the peripheral smear. The high cost and difficulty in performing the vitamin assays limit their use as early markers of megaloblastosis. Hence, we conclude that in developing countries, the detection of hypersegmented neutrophils can be used at the primary healthcare level for early diagnosis of occult megaloblastosis, so that early therapeutic interventions with vitamins can prevent attacks of hyperhomocysteinemia-induced ischaemic stroke.

Topics: Anemia, Megaloblastic; Biomarkers; Brain Ischemia; Early Diagnosis; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Neutrophils; Primary Health Care; Stroke; Vitamin B 12

A 38-year-old woman with a 2-year history of chronic neck pain radiating down her right arm underwent radiological and neurological evaluations, which revealed no anatomical cause for her pain. She sought alternative therapies including intramuscular heparin injections. Following a right occipital injection of heparin, cyanocobalamin, and lidocaine, she had a sudden cardiorespiratory arrest and was successfully resuscitated, but did not regain consciousness.Computed tomography of the head and neck and subsequent autopsy revealed a right vertebral artery dissection, but at autopsy, no significant subarachnoid hemorrhage was noted at the base of the brain. This is the first case report where heparin (a potent anticoagulant) used in an occipital injection was documented to cause a vertebral artery dissection. It is also the first reported case where radiographically and histologically documented vertebral artery dissection did not present with overwhelming subarachnoid hemorrhage at the base of the brain. The subtle gross anatomical findings in this case highlight the importance of evaluating the cervical spinal cord in any case of sudden cardiorespiratory arrest following even apparently minor neck injury.

Topics: Adult; Anesthetics, Local; Anticoagulants; Brain; Brain Ischemia; Female; Forensic Pathology; Heart Arrest; Heparin; Humans; Infarction; Injections; Lidocaine; Subarachnoid Hemorrhage; Thoracic Outlet Syndrome; Vertebral Artery Dissection; Vitamin B 12; Vitamin B Complex

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme, plays an important role in glycolysis. It was reported that GAPDH undergoes S-nitrosylation, which facilitated its binding to Siah1 and resulted in nuclear translocation and cell apoptosis. The results of this study show that GAPDH S-nitrosylation, Siah1 binding, translocation to nucleus, and concomitant neuron death occur during the early stages of reperfusion in the rat four-vessel occlusion ischemic model. N-Methyl-D-aspartate receptor antagonist MK801, neuronal nitric oxide synthase inhibitor 7-nitroindazole, or monoamine oxidase-B inhibitor (R)-(-)-deprenyl hydrochloride could inhibit GAPDH S-nitrosylation and translocation and exert neuroprotective effects.

Topics: Active Transport, Cell Nucleus; Analysis of Variance; Animals; Apoptosis; Brain Ischemia; CA1 Region, Hippocampal; Cell Nucleus; Dizocilpine Maleate; Enzyme Inhibitors; Glyceraldehyde-3-Phosphate Dehydrogenases; Humans; Indazoles; Male; Monoamine Oxidase; Neuroprotective Agents; Nitric Oxide; Nitric Oxide Synthase Type I; Nitroso Compounds; Nuclear Proteins; Pyramidal Cells; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Reperfusion Injury; Selegiline; Ubiquitin-Protein Ligases; Vitamin B 12

The aim of this study was to investigate blood folic acid and vitamin B12 levels in patients with ischemic and hemorrhagic stroke patients and correlate these levels with prognosis.. Patients presenting within 3 hours of onset of ischemic or hemorrhagic strokes were approached for participation in the study. Diagnosis was made by clinical examination and head computed tomography scan. Venous blood samples were taken for determination of blood folic acid and vitamin B12 levels. Parameters were evaluated with respect to stroke type and according to Glasgow coma scale (< or =8 or > or =9).. Eighty-seven patients with ischemic stroke (mean age: 65 +/- 10 years, 53% male) and 27 patients with hemorrhagic stroke (mean age: 60 +/- 10 years, 56% male) were included in the study. A significant direct correlation was found between Glasgow coma scale and mean plasma B12 levels in ischemic, but not hemorrhagic, stroke (r=112.75 and p=0.007, respectively). A significant direct correlation was found between Glasgow coma scale and mean plasma folic acid levels in hemorrhagic, but not ischemic, stroke (r=1.03 and p=0.017, respectively). In patients with Glasgow coma scale < or =8 (either hemorrhagic or ischemic stroke), a significant direct correlation was found between Glasgow coma scale and blood vitamin B12 levels. Vitamin B12 levels were significantly lower in patients with Glasgow coma scale < or =8 than in patients with Glasgow coma score > or =9 (p=0.04).. In patients with ischemic stroke, low vitamin B12 levels, and in patients with hemorrhagic stroke, low blood folic acid levels, are associated with lower Glasgow coma scale values and higher hospital mortality.

Topics: Acute Disease; Aged; Biomarkers; Brain Ischemia; Female; Folic Acid; Glasgow Coma Scale; Humans; Intracranial Hemorrhages; Male; Middle Aged; Prognosis; Stroke; Time Factors; Vitamin B 12

We sought to evaluate the magnetic resonance (MR) angiography (MRA) findings in patients with ischemic stroke (IS) from North India and correlate the changes with various conventional and nonconventional risk factors.. The study took place at a tertiary care teaching hospital. The patients with IS were clinically evaluated including body mass index, dietary habits, and family history of stroke. MR imaging, MRA, and testing for blood sugar, lipid profile, B12, folic acid, and homocysteine were carried out. The MRA abnormalities were considered significant if stenosis was 50% or greater and these were categorized into extracranial (EC), intracranial (IC), or combined lesions. The location of infarct on MR imaging was also noted.. There were 151 patients whose median age was 60 (22-85) years. The EC MRA was abnormal in 56.3% and the IC MRA in 63.3% of patients, the internal carotid artery being the most common site. Corresponding infarct was present in 64.7% and noncorresponding in 45.3% of patients. The MRA abnormality positively correlated with hypertension and diabetes, and negatively with alcohol consumption. The EC MRA abnormality was more common in upper caste Hindus and Muslims and in the city dwellers.. In North Indian patients with IS, the frequency of EC and IC MRA abnormality lies between Whites and the Orientals.

Topics: Adult; Aged; Aged, 80 and over; Alcohol Drinking; Biomarkers; Blood Glucose; Body Mass Index; Brain Ischemia; Carotid Artery, External; Carotid Artery, Internal; Diabetes Mellitus; Feeding Behavior; Female; Folic Acid; Homocysteine; Humans; Hypertension; India; Lipids; Magnetic Resonance Angiography; Male; Middle Aged; Racial Groups; Risk Factors; Socioeconomic Factors; Stroke; Vitamin B 12; Young Adult

Hyperhomocysteinemia (HH) is an emerging risk factor for ischemic stroke but its role in outcome is controversial. We compare the risk factors, nature of stroke and outcome of patients with and without hyperhomocysteinemia.. CT proven ischemic stroke patients were included. The conventional risk factors such as diabetes, hypertension, hyperlipidemia, obesity, smoking, and family history of stroke were recorded. Dietary history was noted. Fasting serum homocysteine (Hcy), B12 and folic acid were estimated after 1 month of stroke. Severity of stroke was assessed by Canadian Neurological Scale (CNS) and outcome at 3 months by Barthel Index (BI) score into good (BI > or = 12) and poor (BI < 12). Serum Hcy, B12 and folic acid were also estimated in 200 normal healthy volunteers.. There were 198 patients with ischemic stroke whose median age was 56 years and 36 were females. In the study group, 41.4% patients were vegetarian, 55.1% hypertensive, 24.7% diabetic, 30.8% smoker, 61.1% sedentary and 28.8% obese. 23.2% had past history of stroke and 21.7% had stroke in their first degree relative. Serum cholesterol was elevated in 11.7% and LDL in 10.8% patients. Serum Hcy was elevated in 60.6% and serum B12 low in 25.7% and folic acid in 42.1%. Hcy levels correlated with serum B12 and LDL. Patients with hyperhomocysteinemia had significantly better outcome at 3 months. Hcy levels in stroke patients did not significantly differ from controls.. Hyperhomocysteinemia is found in 60.6% stroke patients, which is related to low serum B12 level. Patients with hyperhomocysteinemia had a better 3-month outcome.

Topics: Adult; Aged; Brain Ischemia; Comorbidity; Diabetes Mellitus; Diet, Vegetarian; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Hyperlipidemias; Hypertension; India; Male; Middle Aged; Obesity; Risk Factors; Severity of Illness Index; Smoking; Stroke; Tomography, X-Ray Computed; Vitamin B 12

Vitamin B-12 and folate deficiency are common, especially in people aged 55 or over, and accompanied by elevated methylmalonic acid (MMA) and homocysteine concentrations. The aims of the study were to investigate the relationship between serum vitamin B-12, homocysteine, folate, erythrocyte folate and urinary MMA in patients with ischemic stroke, and to develop a simple screening HPLC method for the measurement of urinary MMA.. Twenty-eight patients aged 55 years and over with ischemic stroke and 23 age- and sex- matched healthy controls were included in the study. Serum vitamin B-12 and folate were measured by immunoassay; serum total homocysteine and urinary MMA concentrations by HPLC.. There was no significant difference in vitamin B-12, folate and homocysteine concentrations between the patient and control groups. Urinary MMA concentrations and erythrocyte folate levels were significantly higher in patients than controls. There was a significantly negative correlation between vitamin B-12 and MMA.. Increased urinary MMA excretion is associated with ischemic stroke and it may more robustly reflect vitamin B-12 deficiency in patients with ischemic stroke. The method used in this study is eligible for routine urinary MMA measurements.

Topics: Aged; Aged, 80 and over; Brain Ischemia; Creatinine; Female; Folic Acid; Homocysteine; Humans; Male; Methylmalonic Acid; Middle Aged; Stroke; Vitamin B 12

Homocysteine is known risk factor for the development of atherosclerosis, but its contribution to the different etiologies of ischaemic stroke remains unclear.. Comparison of homocysteine, folic acid and vitamin 812 plasma concentrations in patients with ischaemic stroke due to large vessel disease (LVD), small vessel disease (SVD) and in controls.. We studied 71 patients with ischaemic stroke (including 30 patients with LVD and 41 patients with SVD) as well as 30 control subjects. Aetiology of ischaemic stroke was established according to the TOAST criteria using computed tomography of the head, EKG, carotid ultrasound and echocardiography. In patients being 3-12 months after stroke we registered age, sex and the presence of common risk factors for stroke. The serum concentrations of homocysteine, folic acid, and vitamin 812 were measured in venous blood samples drawn after the overnight fasting.. Serum homocysteine concentrations were similar in patients with LVD, SVD, and in controls (19.5 +/- 8.9, 18.6 +/- 6.6, and 16.8 +/- 6.4 micromol/l, respectively) (p = 0.36, ANOVA). Vitamin 812 concentrations did not differ significantly among patients with LVD, SVD, and in controls (377 +/- 143, 414 +/- 179, and 412 +/- 173 pg/ml, respectively) (p = 0.66, ANOVA). Patients with LVD, SVD, and controls were also similar regarding the concentrations of folic acid (7.1 +/- 4.0, 6.4 +/- 2.7, and 7.6 +/- 4.0 ng/ml, respectively) (p = 0.38, ANOVA).. Serum concentrations of homocysteine, vitamin 812, and folic acid are similar in patients with stroke due to LVD, SVD, and in control subjects.

Topics: Brain Ischemia; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Vitamin B 12

Blood levels of total homocysteine (tHcy), cysteine (Cys), total and reduced glutathione (tGSH and rGSH), folic acid (FA), and vitamin B12 (B12) change during ischemic stroke as accompaniment of the tissue damage. The relationship between these changes remains scantly investigated. We evaluated the variation of these molecules in the 48 h after acute large artery atherothrombotic stroke (LAAS) and searched for the presence of matched variation of them. The study involved 50 subjects affected by acute LAAS and 49 healthy controls. Plasma levels of tHcy and Cys were significantly higher and serum levels of FA and B12 and plasma levels of rGSH were significantly lower in the patients than in the control group. Acute LAAS was associated with increased Hcy-decreased tGSH and decreased FA/tGSH. Pathways involved in cellular stress and in tissue repair are activated during acute LAAS.

Topics: Acute Disease; Aged; Aged, 80 and over; Brain Ischemia; Cysteine; Female; Folic Acid; Glutathione; Homocysteine; Humans; Hyperhomocysteinemia; Intracranial Thrombosis; Male; Middle Aged; Risk Factors; Stroke; Vitamin B 12; Vitamins

To study the relationship between smoking and hyperhomocysteinemia (HHe) in ischemic stroke patients.. The clinical data of 329 ischemic stroke patients with HHe and 306 age-matched ischemic stroke patients without HHe, including sex, symptoms, signs, history of smoking, and plasma homocysteine (Hcy), folate, and vitamin B(12) concentrations were compared. The ischemic stroke lesions were divided into 2 subtypes: large vessel disease group and small vessel disease group according to the TOAST system.. The number of cigarettes smoked per day, cumulative year of smoking, and smoking index (number of cigarettes smoked per day X cumulative year of smoking), and ratio of males of the HHe group were all significantly higher than those of the non-HHe group, and the plasma homocysteine, folate, and vitamin B(12) concentrations of the HHe group were all significantly lower than those of the non-HHe group (all P < 0.01). Smoking index was positively correlated with the Hcy concentrations and negatively correlated with the folate and vitamin B(12) concentrations (all P < 0.01). The smoking proportion and Hcy concentration of the male patients were significantly higher than those of the female patients (both P < 0.01), and the plasma folate and vitamin B(12) concentrations of the male patients were all significantly lower than those of the female patients (P < 0.01 and P < 0.05). The number of cigarettes smoked per day, cumulative year of smoking, smoking index, and Hcy concentration of the large vessel disease group were all significantly higher than those of the small vessel disease group (all P < 0.01).. Smoking and being male may be the risk factors of HHe in ischemic stroke patients. Smoking and HHe are prone to cause lesion in large vessel.

Topics: Aged; Brain Ischemia; Case-Control Studies; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Risk Factors; Sex Factors; Smoking; Stroke; Vitamin B 12

To investigate the effects of folic acid, vitamin B(6) and B(12) on plasma homocysteine and on learning and memory functions in focal cerebral ischemia rats.. Sprague-Dawley rats were randomly divided into four groups. They were sham operation group (Sham OP), middle cerebral artery occlusion model group (MCAO), MCAO + folic acid group (MCAO + FA) and MCAO + compound vitamin (folate, vitamin B(6) and B(12)) group (MCAO + CV). Plasma homocysteine was measured before and after supplementation and after ischemia.. The level of plasma homocysteine in MCAO + FA and MCAO + CV groups were significantly lower than those in Sham OP and MCAO groups after supplementation and ischemia (6.92 +/- 1.04) micromol/L and (5.49 +/- 1.00) micromol/L vs (9.33 +/- 1.11) micromol/L, (10.90 +/- 2.03 micromol/L), P < 0.05. While in MCAO + CV group was lower than that in MCAO + FA group (5.49 +/- 1.00) micromol/L vs (6.92 +/- 1.04) micromol/L, P < 0.05. The neurological deficit scores and shock times in Y-type maze of MCAO + FA and MCAO + CV groups were lower than those in MCAO group (1.75 +/- 0.46 and 1.38 +/- 0.52 vs 2.62 +/- 0.52; 123.50 +/- 39.77 and 86.25 +/- 21.39 vs 173.25 +/- 46.32, P < 0.05). The correct times of MCAO + CV group in Y-type maze was higher than that in MCAO group (3.75 +/- 0.42 vs 2.12 +/- 0.45, P < 0.05).. Folic acid intake could not only reduce plasma homocysteine concentration but also promote the recovery of the learning and memory functions of rats with cerebral ischemia. The effects of folic acid combined with vitamin B(6) and vitamin B(12) on cerebral ischemia rats was better than that of single folate.

Topics: Animals; Brain Ischemia; Disease Models, Animal; Female; Folic Acid; Homocysteine; Infarction, Middle Cerebral Artery; Learning; Male; Memory; Rats; Rats, Sprague-Dawley; Vitamin B 12; Vitamin B 6; Vitamin B Complex

National cholesterol guidelines have defined high vascular risk individuals as those who could potentially benefit most from statin therapy. The authors aimed to determine the rate of statin use, its predictors, and the achievement of national guideline target lipid goals among ischemic stroke survivors.. The authors abstracted data from the Vitamin Intervention for Stroke Prevention (VISP) study database from the United States and Canada to incorporate into algorithms for initiating statin therapy according to the National Cholesterol Education Program (NCEP) guidelines for high-risk individuals. The authors applied these algorithms to all study subjects. Univariate as well as multivariate associations for target lipid levels and statin implementation were then evaluated utilizing pertinent demographic, clinical, and laboratory data.. Of 2,894 subjects in the analysis dataset, 38% were women; 71% were recruited in the United States and 29% in Canada. Of 769 high-risk subjects, 262 (34%) had a low-density lipoprotein (LDL) level > or =130 mg/dL and 124 of these (47%) were not on statin. Among those high-risk persons on statin treatment, only 42% had an LDL < or =100 mg/dL. Subjects in the overall cohort were more likely to be on a statin if they were treated in the United States or had a history of hypertension or coronary artery disease.. Approximately one out of three guideline-eligible high vascular risk ischemic stroke patients in this study had low-density lipoprotein cholesterol concentrations above qualifying levels for pharmacologic therapy, but half of these patients were not taking a statin, and of those receiving statin treatment, less than half were within recommended lipid goals.

Topics: Adult; Aged; Brain Ischemia; Canada; Cholesterol, LDL; Double-Blind Method; Female; Folic Acid; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Multicenter Studies as Topic; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Risk Factors; Severity of Illness Index; United States; Vitamin B 12; Vitamin B 6

Folate metabolism has been implicated in stroke. However, the possibility of a role for folate and vitamin B12, independent of their effects on homocysteine status, remains to be explored. The aim of this prospective, nested case-referent study was to relate plasma and dietary intake levels of folate and vitamin B12 to risk of stroke, taking into consideration plasma homocysteine concentrations and methylenetetrahydrofolate reductase polymorphisms.. Subjects were 334 ischemic and 62 hemorrhagic stroke cases and matched double referents from the population-based Northern Sweden Health and Disease Cohort.. Plasma folate was statistically significantly associated with risk of hemorrhagic stroke in an inverse linear manner, both in univariate analysis and after adjustment for conventional risk factors including hypertension (odds ratio [OR] for highest versus lowest quartile 0.21 (95% confidence interval [CI], 0.06 to 0.71; P for trend=0.008)). Risk estimates were attenuated by inclusion of homocysteine in the model (OR, 0.34; 95% CI, 0.08 to 1.40; P for trend=0.088). A similar pattern was observed for increasing folate intake (multivariate OR, 0.07; 95% CI, 0.01 to 0.55; P for trend=0.031 without homocysteine, and OR, 0.16, 95% CI, 0.02 to 1.23; P for trend=0.118 with homocysteine in the analysis). We found little evidence of an association between plasma or dietary folate and risk of ischemic stroke. Neither plasma nor dietary vitamin B12 was associated with risk of either stroke subtype.. The results of this study suggest a protective role for folate, possibly in addition to its effects on homocysteine status, in hemorrhagic but not ischemic stroke.

Topics: Adult; Aged; Brain Ischemia; Case-Control Studies; Cohort Studies; Diet; Female; Folic Acid; Hemorrhage; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Multivariate Analysis; Nutritional Status; Odds Ratio; Polymorphism, Genetic; Prospective Studies; Registries; Risk; Stroke; Sweden; Vitamin B 12

Elevated fasting plasma total homocysteine concentration (tHcy) and lower vitamin status are associated with atherosclerotic states. Silent brain ischemic lesions and brain atrophy, prevailing in the elderly, are affected by tHcy and vitamin status. The study was performed on 56 outpatients who had undergone brain computed tomography (CT) before the onset of the study. According to brain CT evaluation, three groups were set: minor brain ischemia, brain atrophy and control. Brain CT, tHcy, plasma pyridoxal phosphate (PLP), vitamin B(12), folic acid and cognitive and functional capacities were measured or evaluated in all of the subjects. Plasma vitamin score for three vitamins was calculated. In subjects with minor brain ischemic lesions (n = 21), tHcy was higher by 5.6 microM, whereas vitamin score and cognitive function were lower than in controls (n = 24). In subjects with brain atrophy (n = 11), plasma PLP and cognitive function were lower. Particular attention should be paid to tHcy monitoring, vitamin status assessment and brain impairment evaluation.

Topics: Aged; Aged, 80 and over; Atrophy; Brain; Brain Ischemia; Cognition Disorders; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Vitamin B 12; Vitamin B 6; Vitamins

It has been suggested that patients with giant cell arteritis (GCA) may share a common pathway with atherosclerosis. Furthermore, patients with GCA and polymyalgia rheumatica (PMR), in addition to advanced age, are treated for prolonged periods of time with corticosteroids, a factor that can also accelerate atherosclerosis. Hyperhomocysteinaemia is considered an independent risk factor for atherosclerosis, and might play a role in ischaemic manifestations that occur with a variable frequency during the course of GCA. The purposes of the present study were: (i). to analyse the plasma levels of homocysteine in patients with GCA and PMR, (ii). to determine the influence of corticosteroid therapy on the homocysteine levels and (iii). to analyse if the levels of homocysteine may predict the development of ischaemic complications in patients with GCA.. Plasma homocysteine concentration was measured in 56 patients with active PMR/GCA (17 GCA and 39 isolated PMR) before steroid treatment and 23 healthy age-matched volunteers were used as controls. The total plasma homocysteine level was quantified using a fluorescent polarization immunoassay.. Homocysteine concentrations were higher in PMR and GCA patients than age-matched controls (P < 0.05). Patients with GCA had slightly higher levels of plasma homocysteine than those with isolated PMR (13.6+/-4.3 vs 12.7+/-3.1 micromol/l, P=0.6). In 30 of these patients (12 GCA and 18 PMR) a second measurement of homocysteine concentration was done when they were in clinical remission with steroid treatment. The post-treatment levels of homocysteine were significantly increased in GCA rather than in PMR patients. In 13 patients with homocysteine levels above the normal upper limit of our laboratory, therapy with folic acid and/or vitamin B12 was started. After 3 months of vitamin supplements, the homocysteine concentration significantly decreased from 19.2+/-3.1 to 13.6+/-3.2 micromol/l (P=0.001). Such decrease was less marked in the PMR than in GCA patients. Ten out of the 17 patients with GCA had ischaemic manifestations of the disease. The levels of homocysteine were slightly higher in GCA patients with ischaemia than in those without ischaemic manifestations, although the difference did not reach statistical significance (15+/-4.9 vs 11.6+/-1.9 micromol/l, P=0.46).. Patients with active PMR and GCA had elevated plasma concentrations of homocysteine. Corticosteroid therapy significantly increased such levels, especially in GCA patients. Treatment with supplements of folic acid and/or vitamin B12 reduced the homocysteine concentrations. These data support the hypothesis that patients with GCA (and to a lesser extend PMR patients) may share a common pathway with atherosclerosis and suggest a new atherogenic mechanism of corticosteroids.

Topics: Aged; Brain Ischemia; Drug Therapy, Combination; Female; Folic Acid; Giant Cell Arteritis; Glucocorticoids; Homocystine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Polymyalgia Rheumatica; Vitamin B 12

Moderate hyperhomocysteinemia is an independent risk factor for stroke. The relationship between homocysteinemia and stroke and its related factors are unknown in Spain.. We determined plasma homocysteine concentrations in 80 stroke patients and in 48 control subjects without vascular risk factors. Folate, vitamin B12 and creatinine concentrations were also measured in stroke patients.. Total plasma homocysteine concentrations were higher in stroke patients compared to controls (11.2 [SD 3.2] mumol/l versus 8.1 [2.6] mumol/l; p < 0.001). Hyperhomocysteinemia was present in 20% of patients and in 2.2% of controls (odds ratio [OR] = 5.75; 95% CI = 1.24-53.4; p < 0.01). Homocysteine values were related to vitamin B12 (r = 0.28; p < 0.05) and creatinine concentrations (r = 0.24; p < 0.05). Multiple regression analysis showed that about 15% of the variation in plasma homocysteine concentrations could be predicted by the values of vitamin B12 (p < 0.001) and creatinine (p < 0.05). Homocysteine values were unrelated to age, sex, folate concentrations, atherosclerotic subtype or to the presence of vascular risk factors.. Moderate hyperhomocysteinemia was present in about 20% of stroke patients in our series. Homocysteine plasma level was not related with other stroke risk factors or with the atherosclerotic subtype of stroke, but it was partially related with the renal function parameters and the serum levels of vitamin B12.

Topics: Brain Ischemia; Cerebral Infarction; Chromatography, High Pressure Liquid; Creatinine; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Regression Analysis; Risk Factors; Vitamin B 12

The effects of methylcobalamin, a vitamin B12 analogue, on the hypoxia/hypoglycemia- or glutamate-induced reduction in hippocampal CA1 presynaptic fiber spikes elicited by Schaffer collateral stimulation in rat brain slices were evaluated. Hippocampal slices were exposed to 15 min of hypoxia/hypoglycemia, and then these slices were returned to oxygenated and glucose-containing buffer for 3 h. Hypoxia/hypoglycemia reduced CA1 presynaptic potentials in vitro. Treatment with 10 microM methylcobalamin attenuated the impairment of CA1 presynaptic potentials induced by hypoxia/hypoglycemia or glutamate application (10 mM). Daily injection of methylcobalamin (0.5 mg/kg i.p./day) for 3 days in vivo also attenuated the hypoxia/hypoglycemia- or glutamate-induced reduction in presynaptic potentials in hippocampal slices. Pretreatment with cyanocobalamin at 10 microM failed to attenuate the impairment of CA1 presynaptic potentials. However, daily injection of cyanocobalamin (0.5 mg/kg i.p./day) for 3 days caused a protective action against the hypoxia/hypoglycemia- or glutamate-induced functional deficit. Furthermore, co-treatment of L-arginine (100 microM), a substrate for nitric oxide synthase, with methylcobalamin in vitro reversed the methylcobalamin-induced functional recovery. The present results demonstrate that methylcobalamin application in vivo or in vitro leads to functional recovery from hypoxia/hypoglycemia- or glutamate-induced impairment of CA1 presynaptic potentials. Neuroprotection was obtained by in vivo application of cyanocobalamin, but not by its in vitro application. It is reported that in vivo injected cyanocobalamin converted to methylcobalamin in the hepatic cells. Therefore, the results suggest that a transmethylation reaction in the hippocampal regions may be involved in the methylcobalamin-induced functional recovery from ischemic impairment.

Topics: Animals; Brain Ischemia; Glutamic Acid; Hippocampus; Hypoglycemia; Hypoxia; In Vitro Techniques; Male; Membrane Potentials; Rats; Rats, Wistar; Time Factors; Vitamin B 12

Topics: Brain Ischemia; Cerebral Infarction; Cerebrovascular Disorders; Diphenhydramine; Drug Therapy; Histamine H1 Antagonists; Humans; Ischemic Attack, Transient; Procaine; Thiamine; Toxicology; Vitamin B 12