Elevated Serum Homocysteine Levels Research Articles

Serum levels of homocysteine at admission are associated with post-stroke depression in acute ischemic stroke.

The primary purpose of this study was to assess the serum levels of homocysteine (HCY) at admission to the presence of post-stroke depression (PSD). From September 2014 to December 2015, first-ever acute ischemic stroke patients within the first 24h after stroke onset were consecutively recruited and followed-up for 3months. Based on the symptoms, diagnoses of depression were made in accordance with DSM-IV criteria for depression. By the time of 3month after stroke, 238 had finished the follow-up and included in our study. Totally, 65 out of the 238 patients were diagnosed as depression (27.3%; 95% CI 19.6-35.4%). The results showed significantly higher HCY levels in patients with depression [21.4 (IQR 16.5-23.4) mmol/L vs. 14.1 (IQR 11.2-18.5) mmol/L, P<0.0001) at admission than patients without depression. In multivariate logistic regression analysis, HCY was an independent predictor of PSD with an adjusted OR of 1.07 (95% CI 1.01-1.22; P=0.013). Based on the ROC curve, the optimal cut-off value of serum HCY levels as an indicator for prediction of PSD was projected to be 16.5mmol/L, which yielded a sensitivity of 82.5% and a specificity of 63.6%, with the area under the curve at 0.745 (95% CI 0.672-0.818; P<0.0001). An increased risk of PSD was associated with serum HCY levels ≥16.5mmol/L (adjusted OR 6.13, 95% CI 3.32-14.16; P<0.001) after adjusting for above-recorded confounders. Elevated serum levels of HCY at admission were associated with depression 3-month after stroke, suggesting that these alterations might participate in the pathophysiology of depression symptoms in stroke patients.

HYPERHOMOCYSTEINEMIA IN MEN WITH METABOLIC SYNDROME AND EARLY STAGES OF CHRONIC KIDNEY DISEASE

Objective. We investigated homocysteine metabolism in men with early stages of chronic kidney disease (CKD) and metabolic syndrome (MS). Design and methods. A total of 79 men were selected and divided into two groups, i. e. CKD C1–C2 degree and MS with abnormal carbohydrate metabolism (main group, n = 44) and CKD C1‑C2 degree and MS with normal carbohydrate metabolism (control group, n = 35). We assessed serum levels of fasting and postprandial glucose, HbA1c, insulin, C‑peptide, homocysteine. We also studied polymorphisms of the genes encoding homocysteine metabolism-related enzymes. Results. 82,3% patients had elevated serum levels of homocysteine with no significant differences between the groups. 90,0% cases of hyperhomocysteinemia (HHC) in men with CKD C1–C2 degree and MS were associated with polymorphism of the genes encoding homocysteine metabolism-related enzymes. In men with CKD C1–C2 degree and MS with normal carbohydrate metabolism we found positive correlations between creatinine and homocysteine (rs = 0,4; p &lt; 0,05). Conclusions. The majority of men with MS and CKD C1–C2 degree have hyperhomocysteinemia that is usually determined by genetic factors. Serum level of homocysteine at the initial stages of renal dysfunction does not depend on the state of carbohydrate metabolism in MS.

Vein graft disease in a knockout mouse model of hyperhomocysteinaemia.

A major reason for vein graft failure after coronary artery bypass grafting is neointimal hyperplasia and thrombosis. Elevated serum levels of homocysteine (Hcy) are associated with higher incidence of cardiovascular disease, but homocysteine levels also tend to increase during the first weeks or months after cardiac surgery. To investigate this further, C57BL/6J mice (WT) and cystathionine-beta-synthase heterozygous knockout mice (CBS+/-), a mouse model for hyperhomocysteinaemia, underwent interposition of the vena cava of donor mice into the carotid artery of recipient mice. Two experimental groups were examined: 20 mice of each group underwent bypass surgery (group 1: WT donor and WT recipient; group 2: CBS+/- donor and CBS+/- recipient). After 4weeks, the veins were harvested, dehydrated, paraffin-embedded, stained and analysed by histomorphology and immunohistochemistry. Additionally, serum Hcy levels in CBS knockout animals and in WT animals before and after bypass surgery were measured. At 4weeks postoperatively, group 2 mice showed a higher percentage of thrombosis compared to controls, a threefold increase in neointima formation, higher general vascularization, a lower percentage of elastic fibres with shortage and fragmentation in the neointima, a lower percentage of acid mucopolysaccharides in the neointima and a more intense fibrosis in the neointima and media. In conclusion, hyperhomocysteinaemic cystathionine-beta-synthase knockout mice can play an important role in the study of mechanisms of vein graft failure. But further invitro and invivo studies are necessary to answer the question whether or not homocysteine itself or a related metabolic factor is the key aetiologic agent for accelerated vein graft disease.

Relation of serum homocysteine levels to cerebral artery calcification and atherosclerosis

Background and aimsElevated serum homocysteine level is known to be associated with increased risk of vascular event due to endothelial senescence. We investigated the association between serum homocysteine level and cerebral arteriosclerosis status including intracranial vascular calcification and atherosclerosis burden. MethodsWe identified 1193 consecutive patients (mean age = 68.6 ± 12.7, 537 female patients) who were admitted with acute cerebral infarction or transient ischemic attack from a single university medical center. The patients were categorized into three groups according to their serum homocysteine level. Cerebral artery calcification was assessed from the cavernous portion of both internal carotid arteries, and cerebral atherosclerosis burden was derived as the sum of stenosis degree of major intracranial arteries from brain computed tomography angiography. ResultsThe mean homocysteine level was 14.1 ± 6.2 μmol/L, and intracranial cerebral artery calcification was present in 974 patients (81.6%), with 339 cases of advanced calcification (28.4%). The prevalence of cerebral artery calcification, advanced cerebral artery calcification and cerebral atherosclerosis burden showed increasing tendency throughout the homocysteine tertiles. Multivariable logistic regression analysis including age, sex, vascular risk factors, serum C-reactive protein, estimated glomerular filtration rate and homocysteine tertile disclosed that the highest serum homocysteine tertile was an independent predictor of advanced cerebral artery calcification (odds ratio = 1.45, confidence interval = 1.02–2.05) and advanced cerebral atherosclerosis (odds ratio = 1.42, confidence interval = 1.01–1.99) compared to the lowest group. ConclusionsAn elevated serum homocysteine level was independently associated with intracranial arterial calcification and atherosclerosis burden. Future studies are warranted to test whether lowering serum homocysteine can delay cerebral arteriosclerotic changes.

Elevated serum homocysteine level as an independent risk factor for erectile dysfunction: a prospective pilot case-control study.

Homocysteine is an amino acid that is produced from the metabolic demethylation of dietary methionine. It has gained arising attention for its association with increased risk of myocardial infarction, stroke and venous thromboembolism. Erectile dysfunction (ED), especially for vasculogenic ED, is a vascular disorder of cavernosal vascular bed. In this prospective pilot case-control study, we investigated plasma homocysteine levels in 32 ED patients and 20 healthy control men. Related patients characteristics including age, weight, height, marital status, smoking and drinking status, level of education were collected and analysed as well as penile colour Doppler ultrasound parameters. ED patients were further categorised into mild, moderate and severe ED based on 5-item of the International Index of Erectile Function. Higher homocysteine levels were observed in ED patients as compared with controls (p<.05). A multivariate logistic regression with likelihood ratio test revealed that homocysteine and penile peak systolic blood flow velocity (PSV) levels posed significant indicators for ED (chi-square of likelihood ratio=20.42, df=2, p<.005) as well as moderate and severe ED occurrence (chi-square of likelihood ratio=28.50, df=2, p<.005). The threshold value of homocysteine concentration to discriminate ED and control subjects was 12.65μmol/L by performing receiver operating characteristic curve analyses. These data suggested that elevation of homocysteine levels was associated with an increased risk of ED.

Serum homocysteine levels and the risk of Osteoporosis

Introduction: Osteoporosis is a major health problem which has devastating health consequences through its association with osteoporotic fractures. Prevention of osteoporosis by identifying the risk factors is a major challenge in the field of medicine. Elevated homocysteine level in blood can be a potential risk factor for the development of osteoporosis. We aim to study if a person with high circulating level of homocysteine has a decreased Bone Mineral Density (BMD), thus establishing an association between homocysteine and the risk of developing osteoporosis. Method: Patients between the age group of 40-70 years attending BMD camps between July 2015 and December 2015 were included in the study. All of them underwent BMD test and blood samples were sent to the laboratory for estimation of serum homocysteine levels. The results were collected and analyzed to see if there was any association between serum homocysteine levels and osteoporosis. Results: Out of the 58 males and 20 females with normal BMD, none had elevated serum homocysteine. 21 out of the 58 males and 47 out of the 82 females with osteopenia had elevated serum homocysteine. Of the 27 males with osteoporosis, 25 had elevated serum homocysteine while among the 125 females with osteoporosis, all 125 had elevated serum homocysteine levels. Conclusion: From our study we concluded that people with high circulating level of homocysteine had a decreased Bone Mineral Density (BMD), thus establishing an association between homocysteine and the risk of developing osteoporosis.

Impact of Folic‐acid Intervention and MTHFRC677T Gene Polymorphism on All‐cause Mortality Associated with Elevated Serum Homocysteine Levels in Chinese Adults with Hypertension

BackgroundMortality is one of the most fundamental metrics of population health. The role of nutrition in reducing mortality is of great public health interest. High levels of homocysteine (HHcy, in part, due to low folate intake) are known to increase the risk of cardiovascular diseases. However, data are limited on the longitudinal association of HHcy levels with all‐cause mortality in low folate regions such as China.ObjectiveIn a population with relatively low folate intake and high rate of HHcy, we aimed to test the hypothesis that HHcy is associated with increased mortality and folic acid therapy can reduce the risk of all‐cause mortality associated with HHcy. We also examined whether the effect may be affected by individual MTHFR (a key enzyme involved in Hcy metabolism) gene C677T polymorphism.MethodsWe analyzed the data of 20,702 hypertensive adults (age: 59.6 ± 7.5 years) enrolled in the China Stroke Primary Prevention Trial (CSPPT), with measurements for individual baseline serum total Hcy (tHcy) levels and MTHFR C677T genotypes. These participants were randomized to receive 5‐year, double‐blind daily treatment with 10mg enalapril and 0.8mg folic acid (n=10,348) or 10mg enalapril alone (n=10,354). Kaplan‐Meier survival analysis and Cox proportionate hazard model were used to estimate the effect of tHcy levels on all‐cause mortality and to test effect modification by folic acid intervention and MTHFR C677T genotype.ResultsThere were 622 (3%) all‐cause deaths during a mean treatment period of 4.5 years. There was a dose‐response relationship between tHcy quartiles and all‐cause mortality (P for trend&lt;0.001) after adjusting for pertinent covariables. This relationship was stronger among participants with CC or CT genotypes than among those with TT genotype. Compared to the enalapril alone group, enalapril plus folic acid therapy further lowered the risk of all‐cause mortality associated with increased tHcy levels. The risk reduction was more pronounced in participants with CC or CT genotypes.ConclusionsIn this large‐scale study of population residing in a low folate region, we found that baseline tHcy levels were associated with all‐cause mortality in a dose‐response fashion; and folic acid therapy can lower the all‐cause mortality risk associated with HHcy. Our data suggest that tHcy and MTHFR genotypes may serve as biomarkers for risk stratification and folic acid therapy may offer a simple, inexpensive and safe intervention strategy to reduce mortality among population characterized by low folate intake and high rate of HHcy.

Abstract WP159: The Association Between Cerebral Artery Calcification and Homocysteine Among Stroke Patients

Introduction: Elevated serum homocysteine level is known to be associated with increased risk of atherosclerosis and cardiovascular event possibly through endothelial senescence. Also, homocysteine was reported to be a potential regulator of vascular calcification in animal study. Hypothesis: We hypothesized that elevated homocysteine level is associated with cerebral artery calcification. Methods: We identified 708 consecutive patients (mean age 66.3+/-12.9, 297 female patients) who were admitted with acute ischemic stroke or transient ischemic attack. Cerebral artery calcification was assessed from brain CT angiography, and advanced calcification was determined when calcification involved long (more than 1 cm) or thick (50% or more of vessel diameter) segment of distal cavernous internal carotid artery. Hyperhomocyseinemia was defined as serum homocysteine level exceeding 15 umol/L on admission. Results: Cerebral artery calcification from brain CT angiography was present in 546 patients (77.2%). Advanced cerebral artery calcification was detected in 156 patients (22.1%), and hyperhomocysteienemia was detected in 171 patients (24.2%). On bivariate analysis, advanced cerebral artery calcification was associated with hypertension, diabetes mellitus, smoking, atrial fibrillation, previous stroke history, high-sensitivity C-reactive protein (hs-CRP) and elevated homocysteine level. Multivariate logistic regression analysis including hyperhomocysteinemia, vascular risk factors, age&gt;70 years and hsCRP&gt;2.0mg/dL showed that hyperhomocysteinemia is independently associated with advanced cerebral artery calcification (odds ratio 1.8, confidence interval 1.1-2.8, p=0.011). Conclusion: Hyperhomocysteinemia was associated with advanced cerebral artery calcification. Our study suggests that homocysteine may be used as a biomarker for cerebral artery calcification.

EARLY MARKERS OF PROGRESSION OF HEART FAILURE AND APOPTOSIS: THEIR ROLE IN PREDICTING THE RISK OF ADVERSE CARDIOVASCULAR EVENTS IN PATIENTS WITH PRIOR MYOCARDIAL INFARCTION

Aim . To study the interrelation between hyperhomocysteinemia, the expression of endothelin-1, Fas-ligand (Fas-L), atrial natriuretic peptide (NT-proBNP) and the severity and course of chronic heart failure (CHF) in patients with coronary heart disease (CHD) during the 12-month prospective study to develop forecasting models of the probability of adverse cardiovascular events depending on gender. Materials and methods. The study included 94 patients with CHF. The control group included 32 people who did not have cardiovascular disorders. At baseline and after 12 months of observation in the blood serum levels of sFas-L, homocysteine, endothelin-1 and NT-proBNP were measured by enzyme-linked immunosorbent solid phase assay. Results . It is established that predictors of adverse cardiovascular events in men with coronary artery disease are elevated serum levels of homocysteine, the increased expression of NT-proBNP, platelet-derived growth factor AB (PDGF-AB) associated with the size of the left atrium and hypertriglyceridemia when in women are hyperhomocysteinemia with increased expression of NTproBNP, and TNF-α, as well as the enlarged size of the left atrium and hypercreatininemia. The most informative indicators of prognosis of cardiovascular complications in patients with CHF are homocysteinemia and the level of NT-proBNP. Conclusion . It is established that there is the interrelation between hyperhomocysteinemia, elevated levels of endothelin-1, Fas-L and NT-proBNP in the blood serum with the severity and course of CHF in patients with coronary artery disease. Proposed individual values of the integral index of the probability of occurrence of adverse cardiovascular events for men and women that provides the innovative approach to personalize preventive treatment of these patients.

Homocysteine as a biomarker for predicting alcohol withdrawal syndromes: Insight from a retrospective cohort study

BackgroundThe alcohol withdrawal syndrome is a group of symptoms and signs that usually arise within 24 -48 hours of abrupt alcohol cessation or significant reduction in consumption in alcohol dependent individuals. The most severe complication of alcohol withdrawal syndrome is alcohol withdrawal delirium (delirium tremens), which may be preceded or complicated by seizures. In recent years there is a growing interest in the role of serum homocysteine levels in chronic alcohol dependent patients undergoing withdrawal. A number of studies have shown that alcohol dependent patients have elevated serum homocysteine levels and that it can be considered to be a risk factor for severe withdrawal states. The purpose of this study was to evaluate the serum homocysteine levels in alcohol withdrawal syndromes.MethodolgyIt was a retrospective cohort study of alcohol dependent patients (N=49) admitted with a diagnosis of delirium tremens (DT) (n=28) and simple alcohol withdrawal (SW) (n=21) as per the ICD-10 classification. A semi-structured pro-forma was used to gather information from the file records covering both socio-demographic, clinical and biochemical variables. The historical variables included proposed risk factors like amount of daily consumption of alcohol, duration of abstinence and past history of complicated withdrawal. The serum homocysteine, vitamin B12 and folate levels of all patients sent within 24 hours of admission were also collected. Comparisons between clinical and biochemical variables were made between the two groups using Chi-square test and Student’s T test.ResultsThe mean age of patients of DT was 33.07 ± 8.24 years while that of patients with SW was 37.19 ±7.60 years. The mean duration of alcohol use in dependent pattern was 10.00 ±3.00 years in DT compared to 8.66 ±4.76 years in SW. The laboratory investigations revealed a mean serum homocysteine level of 21.09 ± 12.81 in patients presenting with DT as compared with 15.06 ± 6.17 in patients having SW and this difference was statistically significant (p<0.05). The serum folate levels differed significantly in the two groups with patients in DT having a lower mean value of 6.30 ± 3.67 as compared to patients with SW 10.23 ± 7.04. Patients with DT with withdrawal seizures (n=18) had statistically non significant rise in their mean homocysteine levels as compared to patients with DT without withdrawal seizures (n=10) [21.72±13.26 vs 19.96±12.58].ConclusionThe results of this study highlight the potential role of homocysteine as a new biomarker to predict the severity of alcohol withdrawal syndromes. However there is need for further research to prove whether targeting homocysteine levels will be of benefit with respect to alcohol related disorders.

Sex Difference in the Association between Serum Homocysteine Level and Non-Alcoholic Fatty Liver Disease.

BackgroundThe relationship between serum homocysteine levels and non-alcoholic fatty liver disease is poorly understood. This study aims to investigate the sex-specific relationship between serum homocysteine level and non-alcoholic fatty liver disease in the Korean population.MethodsThis cross-sectional study included 150 men and 132 women who participated in medical examination programs in Korea from January 2014 to December 2014. Patients were screened for fatty liver by abdominal ultrasound and patient blood samples were collected to measure homocysteine levels. Patients that consumed more than 20 grams of alcohol per day were excluded from this study.ResultsThe homocysteine level (11.56 vs. 8.05 nmol/L) and the proportion of non-alcoholic fatty liver disease (60.7% vs. 19.7%) were significantly higher in men than in women. In men, elevated serum homocysteine levels were associated with a greater prevalence of non-alcoholic fatty liver disease (quartile 1, 43.6%; quartile 4, 80.6%; P=0.01); however, in females, there was no significant association between serum homocysteine levels and the prevalence of non-alcoholic fatty liver disease. In the logistic regression model adjusted for age and potential confounding parameters, the odds ratio for men was significantly higher in the uppermost quartile (model 3, quartile 4: odds ratio, 6.78; 95% confidential interval, 1.67 to 27.56); however, serum homocysteine levels in women were not associated with non-alcoholic fatty liver disease in the crude model or in models adjusted for confounders.ConclusionSerum homocysteine levels were associated with the prevalence of non-alcoholic fatty liver disease in men.

Evaluation of cardiovascular risk in patients with Parkinson disease under levodopa treatment.

BackgroundLevodopa is the indispensable choice of medial therapy in patients with Parkinson disease (PD). Since L-dopa treatment was shown to increase serum homocysteine levels, a well-known risk factor for cardiovascular disorders, the patients with PD under L-dopa treatment will be at increased risk for future cardiovascular events. The objective of this study is to evaluate cardiovascular risk in patients with PD under levodopa treatment.MethodsThe study population consisted of 65 patients with idiopathic PD under L-dopa treatment. The control group included 32 age and gender matched individuals who had no cognitive decline. Echocardiographic measurements, serum homocysteine levels and elastic parameters of the aorta were compared between the patients with PD and controls.ResultsAs an expected feature of L-dopa therapy, the Parkinson group had significantly higher homocystein levels (15.1 ± 3.9 µmol/L vs. 11.5 ± 3.2 µmol/L, P = 0.02). Aortic distensibility was significantly lower in the patients with PD when compared to controls (4.8 ± 1.5 dyn/cm2 vs. 6.2 ± 1.9 dyn/cm2, P = 0.016). Additionally, the patients with PD had higher aortic strain and aortic stiffness index (13.4% ± 6.4% vs. 7.4% ± 3.6%, P < 0.001 and 7.3 ± 1.5 vs. 4.9 ± 1.9, P < 0.001 respectively). Furthermore, serum homocysteine levels were found to be positively correlated with aortic stiffness index and there was a negative correlation between aortic distensibility and levels of serum homocysteine (r = 0.674, P < 0.001; r = −0.602, P < 0.001, respectively).ConclusionsThe patients with PD under L-dopa treatment have increased aortic stiffness and impaired diastolic function compared to healthy individuals. Elevated serum homocysteine levels may be a possible pathophysiological mechanism.

Clinical Relevance of MTHFR, eNOS, ACE, and ApoE Gene Polymorphisms and Serum Vitamin Profile among Malay Patients with Ischemic Stroke

The purpose of this study was threefold. First, it was to determine the relationship between serum vitamin profiles and ischemic stroke. The second purpose was to investigate the association of methylenetetrahydrofolate reductase (MTHFR), endothelial nitric oxide synthase (eNOS), angiotensin converting enzyme (ACE), and apolipoprotein-E (ApoE) gene polymorphisms with ischemic stroke and further correlate with serum vitamin profiles among ischemic stroke patients. The third purpose of the study was to highlight the interaction of MTHFR and eNOS haplotypes with serum vitamin profiles and ischemic stroke risks. Polymorphisms of these genes were analyzed in age-, sex-, and ethnicity-matched case-controls (n=594); serum vitamin profiles were determined using immunoassays. The MTHFR 677C>T, 1298A>C, eNOS intron 4a/b, and ApoE polymorphisms were significantly associated with the increased risk of ischemic stroke. Elevated serum homocysteine and vitamin B12 levels were associated with MTHFR 677C>T and eNOS intron 4a/b polymorphisms. The ApoE and eNOS -786T>C polymorphisms were associated with increased serum vitamin B12 levels. However, none of the polymorphisms influenced serum folate levels except for the MTHFR 1298A>C. Different patterns of MTHFR and eNOS haplotypes tend to affect serum vitamin profiles to different degrees, which contribute to either different susceptibility risk or protective effect on ischemic stroke. Overall, increased levels of serum homocysteine and vitamin B12 levels were associated with higher risk of ischemic stroke in the investigated population. The present study suggests that the genotypes and haplotypes of MTHFR 677C>T and eNOS intron 4a/b polymorphisms are potential serum biomarkers in the pathophysiological processes of ischemic stroke, by modulating homocysteine and vitamin B12 levels.

Vitamin B12 deficiency in the elderly: is it worth screening?

Vitamin B12 deficiency is common among the elderly. Elderly people are particularly at risk of vitamin B12 deficiency because of the high prevalence of atrophic gastritis-associated food-cobalamin (vitamin B12) malabsorption, and the increasing prevalence of pernicious anaemia with advancing age. The deficiency most often goes unrecognised because the clinical manifestations are highly variable, often subtle and non-specific, but if left undiagnosed the consequences can be serious. Diagnosis of vitamin B12 deficiency, however, is not straightforward as laboratory tests have certain limitations. Setting a cut-off level to define serum vitamin B12 deficiency is difficult; though homocysteine and methylmalonic acid are more sensitive for vitamin B12 deficiency, it may give false result in some conditions and the reference intervals are not standardised. At present, there is no consensus or guideline for diagnosis of this deficiency. It is most often based on the clinical symptoms together with laboratory assessment (low serum vitamin B12 level and elevated serum homocysteine or methylmalonic acid level) and the response to treatment to make definitive diagnosis. Treatment and replacement with oral vitamin B12 can be as effective as parenteral administration even in patients with pernicious anaemia. The suggested oral vitamin B12 dose is 1 mg daily for a month, and then maintenance dose of 125 to 250 µg for patients with dietary insufficiency and 1 mg daily for those with pernicious anaemia. Vitamin B12 replacement is safe and without side-effects, but prompt treatment is required to reverse the damage before it becomes extensive or irreversible. At present, there is no recommendation for mass screening for vitamin B12 in the elderly. Nevertheless, the higher prevalence with age, increasing risk of vitamin B12 deficiency in the elderly, symptoms being difficult to recognise, and availability of safe treatment options make screening a favourable option. However, the unavailability of reliable diagnostic tool or gold standard test makes screening difficult to carry out.

Elevated Serum Homocysteine (Hcy) Levels May Contribute to the Pathogenesis of Cerebral Infarction.

The purpose of this meta-analysis was to investigate the correlation between serum homocysteine (Hcy) levels and the pathogenesis of cerebral infarction (CI). Relevant studies involving serum Hcy levels and the pathogenesis of CI were identified using electronic database search supplemented with manual search. The search result studies were screened in accordance with our strict inclusion and exclusion criteria. Statistical analyses were conducted with Comprehensive Meta Analysis 2.0 (CMA 2.0) software. A total of 13 studies were eligible for our meta-analysis and included 1206 patients with CI and 1202 healthy controls. Our meta-analysis revealed that the serum Hcy levels in CI patients were significantly higher than those in healthy controls. Subgroup analysis based on ethnicity showed that Caucasians and Asians had significantly higher serum Hcy levels in CI patients compared to healthy controls and Africans showed no significant differences in serum Hcy levels between CI patients and controls. In conclusion, our meta-analysis reveals a strong correlation between elevated serum Hcy levels and the pathogenesis of CI, suggesting that serum Hcy levels may be an important biomarker for the early diagnosis and treatment assessment of CI.

Elevated serum homocysteine level in the development of diabetic peripheral neuropathy

The development of diabetic peripheral neuropathy (DPN) is always followed by changes in vascular endothelial cells that are related to the reactivity of the homocysteine (Hcy) sulfhydryl group. In this meta-analysis, we investigated the association of Hcy with the pathogenesis and progression of DPN. We screened the Embase, Ovid, PubMed, Web of Science, Wangfang, and China National Knowledge Infrastructure databases. All analyses were performed by using the STATA software, version 12.0 (StataCorp, College Station, TX, USA) and the Comprehensive Meta-analysis 2.0 software (Biostatic Inc., Englewood, NJ, USA). The standardized mean difference (SMD) and 95% confidence interval (95%CI) were further calculated. The electronic literature search identified six articles that included 603 patients with DPN and 687 healthy controls. The pooled SMD of those six studies revealed that increased serum levels of Hcy may be correlated with DPN (SMD = 1.23, 95%CI: 1.09-1.36, P < 0.001). Subgroup analysis according to ethnicity indicated that high serum Hcy levels might be an important risk factor for DPN in both Asian and Caucasian populations (Asians: SMD = 0.62, 95%CI: 0.45-0.79, P < 0.001; Caucasians: SMD = 2.32, 95%CI: 2.10-2.55, P < 0.001; respectively). Elevated serum levels of Hcy indicate the risk of development of DPN in patients, suggesting that Hcy levels could be used as a marker for new therapeutic approaches to DPN.

"Inverted V sign" in Sub-Acute Combined Degeneration of Cord.

A 54-year-old male patient presented to the outpatient department of neurology with complaints of tingling and numbness of hands since two months. Neurological examination revealed reduced power and decreased proprioception and vibration sense of hands. Laboratory investigations done showed normal Hb-13.7g/dl (normal range, 13.5-17.5 g/dl).Other routine blood, urine parameters were within normal limits. MRI of cervical spine was advised and performed which showed symmetric T2W hyperintense signals in dorsal columns of cervical spinal cord from C2 to C5 [Table/Fig-1a&b,​,2]2] levels (Characteristic Inverted V sign). A provisional diagnosis of Sub-Acute Combined Degeneration of Cord (SACD) was considered. Retrospective investigations of blood showed reduced serum VITAMIN B12 levels of 78.6pg/mL (Normal-200 to 900pg/mL), mild increased mean corpuscular volume 120fl (normal range, 80-100 fl),elevated serum homocysteine levels. Patient was started on vitamin B12 therapy and showed progressive resolution of clinical symptoms. [Table/Fig-1a&b]: Axial T2W MRI at C3 (A) and C4 (B) vertebral level of the spinal cord showing characteristic “inverted v pattern” hyperintene signal (arrow) in the posterior compartment of the spinal cord [Table/Fig-2]: Sagittal T2W MRI showing linear hyperintense signal (arrows) predominantly in the posterior compartment of the cervical spinal cord extending from C2-C5 vertebral levels of the cord Causes of vitamin B12 deficiency include malabsorption syndromes such as pernicious anaemia, crohns disease, celiac disease, bacterial overgrowth in intestinal blind loops, postgastrectomy and ileal resection. Deficiency of vitamin B12 results in failure of conversion of methyl malonyl coenzyme A to succinyl co A resulting in accumulation of methylmalonic acid which causes myelin toxicity of preferential dorsal/posterior columns of the cord [1]. Pathologically multifocal vacuolated and demyelinating lesions involving the dorsal columns, predominately in the lower cervical and upper thoracic region [1] are seen. Demyelination of posterior columns of thoracic spinal cord appears to be the earliest manifestation of vitamin B12 deficiency.It is also considered as the most reversible pathological stage in a case of SACD. MRI findings in SACD of cord are minimal spinal cord enlargement with dorsal spinal cord hypointensity on T1WI, hyperintensity on T2W images. On sagittal images longitudinal signal changes are noted along the dorsal columns of spinal cord.T2WI – axial images show typically characteristic pattern of symmetric bilateral hyperintense signals in the dorsal columns. This specific MRI appearance has been described as the “Inverted V sign” or “Inverted Rabbit Ears appearance”. Some cases may show T2 hyperintense signal in lateral columns of cord and cerebral white matter. Differential diagnsosis for bilateral posterior column involvement [2] include infectious myelitis, infarction of spinal cord, inflammatory demyelination including multiple sclerosis, acute disseminated encephalomyelitis, acute transverse myelitis, and copper deficiency myelopathy. Once the diagnosis of SACD is suspected, treatment with vitamin B12 injection should be started as early as possible to avoid irreversible neurologic damage [3]. Recognition of the specific MRI pattern of cord involvement together with clinical and laboratory analysis helps in early detection and treatment of the Subacute combined degeneration of the spinal cord.

Elevated serum homocysteine is a predictor of accelerated decline in renal function and chronic kidney disease: A historical prospective study

ObjectiveTo estimate the effect of elevated serum homocysteine level on renal function decline and on the incidence of chronic kidney disease (CKD) in the general population. MethodsA historical prospective study on 3602 subjects attending a screening center in Israel between the years 2000 and 2012. Only subjects with normal estimated glomerular filtration rate (eGFR) and without proteinuria were included. Subjects were divided to two groups according to mean total serum homocysteine level (≤15, >15μmol/l). Linear mixed effect model was used to estimate the annual eGRF decline in respect to homocysteine group. Cox proportional hazards models were used to estimate hazard ratios for CKD in the normal compared to the elevated homocysteine group. ResultsAnnual eGFR decline was 25% higher in subjects with elevated versus normal mean homocysteine level (0.90±0.16ml/min/1.37m2 vs. 0.72±0.14ml/min/1.37m2, p<0.001). In a median follow up of 7.75years, 38 subjects developed CKD (1.05%). Elevated mean homocysteine level was highly associated with developing CKD (HR 4.85, 95% CI 2.48–9.49, p<0.001). In a multivariate analysis which adjusted for age, baseline kidney function, HDL cholesterol, BMI, vitamin B12 and folic acid levels, these relationships remained substantially unchanged. ConclusionsElevated mean serum homocysteine level is associated with an accelerated decline in renal function in both men and women, and is an independent risk factor for the development of CKD in the general population. Further prospective randomized clinical trials are needed to clarify whether the reduction in serum homocysteine concentrations will result in an improved renal prognosis.

Homocysteine-Lowering Therapy and Risk of Recurrent Stroke, Myocardial Infarction and Death: The Impact of Age in the VISP Trial

Background: Clinical trials have failed to show a benefit of B vitamin therapy in reducing composite outcomes of cardiovascular death, myocardial infarction, and stroke among stroke survivors with elevated total serum homocysteine (tHcy) levels. Recent post hoc analyses have shown that numerous factors including age, baseline tHcy levels, folic acid fortification of grains, B₁₂ status, renal function, comorbidities, and medications may modify the effect of B vitamin therapy on vascular risk in individuals with high tHcy. It remains possible that tHcy-lowering therapy may reduce cardiovascular risk in certain subgroups of stroke survivors. Post hoc subgroup analysis of the Heart Outcomes Prevention Evaluation-2 randomized controlled trial, which randomized participants with known cardiovascular disease to tHcy-lowering therapy or placebo, revealed larger treatment benefit for patients aged younger than 69 years; however, that analysis did not control for other factors. The aim of this study was to determine the effect of age on the impact of tHcy-lowering therapy for reducing vascular risk after stroke while controlling for other factors known to modify the effect of tHcy and tHcy-lowering therapy on vascular risk. Methods: In this post hoc analysis of the Vitamin Intervention for Stroke Prevention (VISP) trial, a randomized controlled trial of tHcy lowering for secondary stroke prevention, we excluded individuals who had poor renal function (glomerular filtration rate <47; the 10th percentile) or were treated with vitamin B₁₂ injections. We assessed the effects of high-dose vitamin replacement on primary (stroke, myocardial infarction, or death) and secondary (stroke) outcomes, after stratifying by age (< vs. ≥ median age, 67 years) and adjusting for demographic and clinical factors. Results: This subgroup consisted of 2,993 individuals. Among individuals older than 67 years, high-dose vitamin therapy was associated with reduced risk of stroke, myocardial infarction or death (adjusted HR 0.76, 95% CI 0.58-0.99) and a trend towards reduced likelihood of stroke (adjusted HR 0.86, 95% CI 0.59-1.25). High-dose vitamin therapy did not impact outcomes among individuals younger than 67 years. Conclusions: In this post hoc subgroup analysis of the VISP trial, age modified the association between B vitamin therapy and recurrent vascular risk among stroke survivors with elevated serum tHcy levels. Older individuals with stroke were more likely to benefit from B vitamin therapy than younger individuals. These findings can help inform the future design of clinical trials of tHcy-lowering therapy for cardiovascular risk reduction after stroke.

Homocysteine as a Predictor of Early Neurological Deterioration in Acute Ischemic Stroke

Hyperhomocysteinemia is a well-known risk factor for vascular disease. However, its action, mechanism, and role in the acute phase of stroke have not been determined. We tried to determine whether an association existed between elevated serum homocysteine levels and early neurological deterioration (END) in patients with acute ischemic stroke. We performed a secondary analysis from the Cilostazol in Acute Ischemic Stroke Treatment (CAIST) trial, which was a double-blinded, randomized, multicenter trial, assessing the noninferiority of cilostazol over aspirin within 48 hours of an acute ischemic stroke. END was defined as an increase of ≥1 point in motor power or an increase of ≥2 points in the total National Institute of Health Stroke Scale score within 7 days. The mean (±SD) serum homocysteine level was 11.4±4.7 μmol/L. Of the 396 patients studied, 57 (14.4%) patients worsened during the 7 days after inclusion. Most (68%) of the END cases occurred within the first 24 hours after treatment. High levels (>10.3 μmol/L) of serum homocysteine were independent predictors for END (third quartile odds ratio, 3.45; 95% confidence intervals, 1.25-9.50; P=0.016; fourth quartile odds ratio, 3.36; 95% confidence intervals 1.18-9.52; P=0.023) in multivariate analysis. Patients with acute stroke with elevated serum homocysteine levels are at an increased risk for END.