vitamin-b-12 and Epilepsy

The prevalences of polyneuropathy and epilepsy are higher in people living with Parkinson's disease (PwPD) when compared to older adults. Vitamin B6 is widely available and affordable. PwPD are at higher risk of having abnormal serum levels of vitamin B6, which are associated with polyneuropathy and epilepsy that are potentially preventable and treatable. Potential contributors to abnormal B6 levels in PwPD include age, dietary habits, vitamin supplement misuse, gastrointestinal dysfunction and complex interactions with levodopa. The literature on the potential consequences of abnormal B6 levels in PwPD is limited by a small number of observational studies focused on polyneuropathy and epilepsy. Abnormal B6 levels have been reported in 60 of 145 PwPD (41.4% relative frequency). Low B6 levels were reported in 52 PwPD and high B6 levels were reported in 8 PwPD. There were 14 PwPD, polyneuropathy and low B6. There were 4 PwPD, polyneuropathy and high B6. There were 4 PwPD, epilepsy and low B6. Vitamin B6 level was low in 44.6% of PwPD receiving levodopa-carbidopa intestinal gel and in 30.1% of PwPD receiving oral levodopa-carbidopa. In almost all studies reporting low B6 in PwPD receiving oral levodopa-carbidopa, the dose of levodopa was ≥1000 mg/day. Rigorous epidemiological studies will clarify the prevalence, natural history and clinical relevance of abnormal serum levels of vitamin B6 in PwPD. These studies should account for diet, vitamin supplement use, gastrointestinal dysfunction, concurrent levels of vitamin B12, folate, homocysteine and methylmalonic acid, formulations and dosages of levodopa and other medications commonly used in PwPD.

Topics: Aged; Antiparkinson Agents; Carbidopa; Epilepsy; Humans; Levodopa; Parkinson Disease; Polyneuropathies; Vitamin B 12; Vitamin B 6; Vitamins

To determine the influence of phenytoin (PHT) monotherapy on the serum levels of homocysteine (Hcy), folate and vitamin B12 in patients with epilepsy.. Literature retrieval was performed through PubMed, Web of Science, Embase, Cochrane Library, Chinese Wanfang Data, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database databases as of the end of March 2018. Pooled weighted mean difference (WMD) and 95% CIs were calculated using a random effect model.. A total of ten eligible studies were identified. The result revealed that the serum level of homocysteine in PHT-treated patients with epilepsy was significantly higher than that in control group (WMD = 8.47, 95% CI: 6.74 to 10.20, P < .001). In addition, the serum levels of folate (WMD = -3.51, 95% CI: -4.20 to -2.83, P < .001) and vitamin B12 (WMD = -62.23, 95% CI: -83.27 to -41.19, P < .001) were decreased significantly compared with the control group.. Our meta-analysis indicates that PHT monotherapy is associated with the increase in the serum homocysteine levels and decreased levels of folate and vitamin B12, and hyperhomocysteinaemia may contribute to the acceleration of the atherosclerotic process. Therefore, the patients under these medications should be monitored plasma homocysteine.

Topics: Anticonvulsants; Epilepsy; Folic Acid; Homocysteine; Humans; Phenytoin; Research Design; Vitamin B 12

The objectives were to determine the influence of oxcarbazepine (OXC) monotherapy on the serum levels of total homocysteine (tHcy), vitamin B12 and folate in patient with epilepsy pooling together case-control or interventional studies. A comprehensive literature search was done through four databases including MEDLINE/PubMed, Scopus, Embase and Web of Science from January 2000 to February 2016. A random effects model (the DerSimonian-Laird estimator) was utilized to pool the effect sizes of the individual studies. The between-study variance was assessed using the Q2 test (significance level p<0.1) and quantified using the I

Topics: Anticonvulsants; Carbamazepine; Epilepsy; Folic Acid; Homocysteine; Humans; Oxcarbazepine; Vitamin B 12

Migraine is the most common form of headache disorder globally. The etiology of migraine is multifactorial, with genetic components and environmental interactions considered to be the main causal factors. Some researchers postulate that deficits in mitochondrial energy reserves can cause migraine or an increase in homocysteine levels can lead to migraine attacks; therefore, vitamins could play a vital role in migraine prevention. For instance, riboflavin influences mitochondrial dysfunction and prevents migraine. Genes such as flavoenzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), especially the C677T variant, have been associated with elevated plasma levels of homocysteine and migraine with aura. Homocysteine catalyzation requires the presence of vitamins B6, B12, and folic acid, which can decrease the severity of migraine with aura, making these vitamins potentially useful prophylactic agents for treating migraine with aura. Menstrual migraine, on the other hand, is associated with increased prostaglandin (PG) levels in the endometrium, indicating a role for vitamin E, which is an anti-PG. Vitamin C can also be used as a scavenger of reactive oxygen species for treating neurogenic inflammation in migraine patients. This paper reviews possible therapies based on vitamin supplementation for migraine prophylaxis, focusing on migraine with aura and menstrual migraine.

Topics: Adult; Ascorbic Acid; Epilepsy; Female; Folic Acid; Genotype; Homocysteine; Humans; Menstruation; Migraine Disorders; Migraine with Aura; Vitamin B 12; Vitamin B 6; Vitamin E

Over the last 10 years, there has been an explosion of interest in homocysteine, a sulfur-containing amino acid that occupies a central location in the metabolic pathways of thiol compounds. This interest is primarily because of the realization that hyperhomocysteinemia is an important risk factor for vascular disease, including stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. Since elevated homocysteine levels can often be normalized by supplementing the diet with folic acid (folate), pyridoxine hydrochloride (vitamin B(6)), and cyanocobalamin (vitamin B(12)), these observations raise the exciting possibility that this inexpensive and well-tolerated therapy may be effective in decreasing the incidence of vascular disease. In addition to its association with cerebrovascular disease, homocysteine may play a role in neurodegenerative disorders, even if only as a marker of functional vitamin B(12) deficiency. Homocysteine is also important to neurologists since most anticonvulsants raise homocysteine levels, an effect that may explain the teratogenic effects of these drugs. Practical knowledge concerning some details of homocysteine metabolism, the diagnosis of hyperhomocysteinemia, and the use of polyvitamin therapy to lower homocysteine levels will be increasingly important in the treatment of patients with neurologic disease. Arch Neurol. 2000;57:1422-1428

Topics: Brain Diseases; Epilepsy; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Neurodegenerative Diseases; Pyridoxine; Vascular Diseases; Vitamin B 12

Folic acid (FA) and vitamin B12 have been measured prospectively in 110 children that were under treatment with anticonvulsants. The control group consisted of 59 healthy children. A statistically significant difference in levels of serum FA and mean corpuscular volume (MCV) was observed between groups. Children under anticonvulsant treatment had lower serum FA levels and higher MCV. No significant difference was observed between the two groups in levels of serum vitamin B12. All children with serum FA levels lower than 3 ng/ml were given folate and no adverse side effects were observed due to treatment. Anticonvulsant drugs decrease serum FA levels; therefore, FA should be determined periodically in children under long-term anticonvulsant treatment.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Epilepsy; Female; Folic Acid; Folic Acid Deficiency; Humans; Infant; Long-Term Care; Male; Vitamin B 12

Topics: Adult; Aged; Anemia, Megaloblastic; Anticonvulsants; Blood-Brain Barrier; Brain; Brain Diseases; Child; Epilepsy; Erythrocytes; Female; Folic Acid; Folic Acid Deficiency; Formiminoglutamic Acid; Humans; Intellectual Disability; Male; Mental Disorders; Metabolism, Inborn Errors; Methotrexate; Middle Aged; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anticonvulsants; Blood-Brain Barrier; Clinical Trials as Topic; Epilepsy; Folic Acid; Folic Acid Deficiency; Humans; Phenobarbital; Phenytoin; Primidone; Seizures; Tetrahydrofolates; Vitamin B 12

Topics: Abnormalities, Drug-Induced; Anticonvulsants; Blood Coagulation; Epilepsy; Female; Fetal Death; Fetus; Folic Acid Deficiency; Humans; Infant, Newborn; Maternal-Fetal Exchange; Obstetric Labor Complications; Pregnancy; Pregnancy Complications; Vitamin B 12; Vitamin D; Vitamin D Deficiency; Vitamin K

Topics: Adult; Age Factors; Aged; Anemia, Hypochromic; Epilepsy; Female; Folic Acid; Humans; Male; Middle Aged; Psychotic Disorders; Schizophrenia; Vitamin B 12

Topics: Anemia, Macrocytic; Anticonvulsants; Electroconvulsive Therapy; Electroencephalography; Epilepsy; Folic Acid; Folic Acid Deficiency; Humans; Mental Disorders; Methionine; Phenethylamines; Phenothiazines; Schizophrenia; Vitamin B 12

To investigate the influence of vitamin B supplementation on the plasma total homocysteine (p-tHcy), serum folate (s-FA), serum B12 (s-B12), and clinical state of patients with chronic epilepsy.. Beck Depression Inventory (BDI) scores and p-tHcy, s-B12, and s-FA levels were assessed at baseline, after 1 year of supplementation (G1), and before and after 1 year of VPA or CBZ therapy (G2).. Eighty-one patients participated in the study: 51 patients with chronic epilepsy (G1) treated with carbamazepine (CBZ) or valproic acid (VPA), and 30 patients with newly diagnosed epilepsy (G2). At baseline, mean p-tHcy level was significantly higher in G1 than G2 (p=0.0001) with no significant differences in s-FA or s-B12 levels. p-tHcy level significantly decreased in CBZ-treated G1 patients (p=0.00002) after 1 year of supplementation and increased in G2 after 1 year of anti-epileptic drug (AED) therapy without supplementation. BDI scores in G1 decreased significantly after 1 year of supplementation (p=0.0001) and increased significantly in VPA-treated G2 patients after 1 year of AED therapy (p=0.02). The number of hyperhomocysteinemic patients significantly decreased in G1 after vitamin B supplementation (p=0.01) and increased in G2 (p=0.002). We also observed improved BDI scores and reduced seizure frequency in patients with chronic epilepsy.. These data support the hypothesis that AEDs play a major role in hyperhomocysteinemia development in patients with epilepsy. Adding folate and vitamin B12 to AED therapy is a safe and inexpensive way to reduce the risk of hyperhomocysteinemia.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Carbamazepine; Dietary Supplements; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Valproic Acid; Vitamin B 12; Vitamin B Complex; Young Adult

To assess the prevalence of hyperhomocysteinemia in pediatric patients treated with antiepileptic drugs (AEDs) and to evaluate the effect of folic acid supplementation on plasma total homocysteine (tHcy) concentrations in hyperhomocysteinemic patients.. 123 patients from three regional hospitals participated in the study. Patients with hyperhomocysteinemia were included in a 3-month double-blind randomized trial testing oral folic acid supplementation (1 mg/day) versus placebo.. Hyperhomocysteinemia (tHcy >10.4 micromol/L) was present in 19 of 123 patients. Patients with hyperhomocysteinemia were older (13.7 +/- 4 vs. 11.0 +/- 3.9 years) and had significantly lower folate and cobalamin concentrations. Multidrug (two or more) AED treatment and duration of therapy correlated significantly with elevated total homocysteine (tHcy) and low folate. In contrast, polymorphisms in the methylene tetrahydrofolate reductase gene (MTHFR 677 C-->T, 1298 A-->C, 1793 G-->A) had no significant impact on tHcy. Nine of 19 patients with hyperhomocysteinemia were randomized to placebo, whereas the remaining 10 patients received folic acid supplementation. Folic acid supplementation resulted in a significant increase of folate and decrease of tHcy, whereas both parameters remained unchanged in the placebo group.. Hyperhomocysteinemia is present in 15.5% of children receiving long-term AED treatment. Multidrug treatment and long duration of therapy enhance the risk for hyperhomocysteinemia. Folic acid supplementation significantly reduces tHcy. We recommend assessment of serum folate and plasma tHcy in children receiving AEDs.

Topics: Anticonvulsants; Child; Dietary Supplements; Double-Blind Method; Drug Therapy, Combination; Epilepsy; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; Treatment Outcome; Vitamin B 12

Serum triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), vitamin B12 and folic acid levels were studied in 16 children with epilepsy who had been receiving carbamazepine (CBZ), and in 16 healthy children. Our purpose was to determine whether there was any effect of CBZ therapy on serum lipids, vitamin B12 and folic acid levels. Age ranged from 5 to 19 years (12.25 +/- 3.79 years) and 5.5 to 18 years (12.16 +/- 3.53 years) in the study and control groups, respectively. The duration of CBZ therapy in the patients was between 1 and 4.5 years (3.01 +/- 1.04 years). Serum CBZ level varied between 4 and 12 microg/ml (6.26 +/- 2.07 microg/ml). There was no statistically significant difference in serum triglycerides, TC, HDL-C, LDL-C, VLDL-C or vitamin B12. However, mean folic acid level was found to be lower in the study group than that of the control group (p < 0.05). Nonetheless, serum folic acid levels were within the normal range in all patients. Our study demonstrated that CBZ therapy does not affect serum lipids, vitamin B12 and folic acid levels, and may safely be used with regard to these parameters in children.

Topics: Adolescent; Adult; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Cholesterol; Cholesterol, HDL; Cholesterol, VLDL; Colorimetry; Epilepsy; Female; Folic Acid; Humans; Lipids; Long-Term Care; Male; Triglycerides; Vitamin B 12

Patients on antiepileptic drugs (AEDs) may have elevated levels of plasma total homocysteine (p-tHcy). The aim of this study was to assess the effect of B-vitamin supplementation on the levels of p-tHcy and markers of endothelial activation and lipid peroxidation. A total of 33 adult patients on AEDs were identified with either fasting (Group 1, n=23) or post methionine load (PML) (Group 2, n=10) hyperhomocysteinemia. Subjects were supplemented with B-vitamins for 30 days: folic acid 0.4 mg, pyridoxine 120 mg and riboflavin 75 mg per day. After supplementation, serum folate and pyridoxal phosphate had increased, while fasting and PML p-tHcy had decreased (P<0.0001) by 36 and 26%, respectively. Prior to supplementation, the Group 1 patients had elevated levels of P-selectin and von Willebrand factor (vWF) (P=0.05 and 0.03, respectively). After supplementation, the levels of intercellular cell adhesion molecules had decreased (P=0.01) and E-selectin decreased nonsignificantly (P=0.07). However, the levels of vascular cell adhesion molecules had increased (P<0.0001), while lipid peroxidation were unchanged. In conclusion, the combined supplementation with folic acid, pyridoxine and riboflavin reduced fasting and PML hyperhomocysteinemia in patients on AEDs. Patients with fasting hyperhomocysteinemia had elevated levels of P-selectin and vWF, which may indicate an increased risk of cardiovascular disease. Furthermore, B-vitamin supplementation influenced endothelial activation, although the clinical implication is uncertain.

Topics: Adult; Anticonvulsants; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Epilepsy; Fasting; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Intercellular Adhesion Molecule-1; Male; Malondialdehyde; Methionine; Middle Aged; Pyridoxic Acid; Riboflavin; Selectins; Vascular Cell Adhesion Molecule-1; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Seventy-two epileptic patients receiving phenytoin (PHT) alone or in combination with phenobarbital for more than 4 years were divided into four groups, the first taking two placebo tablets per day; the second folate (5 mg/day) and placebo; the third placebo and thiamine (50 mg/day); and the fourth both vitamins. The clinical trial lasted 6 months. At baseline assessment, 31% of the patients had subnormal blood thiamine levels and 30% had low folate. The vitamin deficiencies were independent phenomena. It was found that thiamine improved neuropsychological functions in both verbal and non-verbal IQ testing. In particular, higher scores were recorded on the block design, digit symbol, similarities and digit span subtests. Folate treatment was ineffective. These results indicate that, in epileptics chronically treated with PHT, thiamine improves neuropsychological functions, such as visuo-spatial analysis, visuo-motor speed and verbal abstracting ability.

Topics: Adult; Brain; Double-Blind Method; Drug Therapy, Combination; Education; Electroencephalography; Epilepsy; Female; Folic Acid; Humans; Male; Middle Aged; Phenobarbital; Phenytoin; Thiamine; Vitamin B 12; Wechsler Scales

Folic acid (FA) and vitamin B12 have been measured prospectively in 110 children that were under treatment with anticonvulsants. The control group consisted of 59 healthy children. A statistically significant difference in levels of serum FA and mean corpuscular volume (MCV) was observed between groups. Children under anticonvulsant treatment had lower serum FA levels and higher MCV. No significant difference was observed between the two groups in levels of serum vitamin B12. All children with serum FA levels lower than 3 ng/ml were given folate and no adverse side effects were observed due to treatment. Anticonvulsant drugs decrease serum FA levels; therefore, FA should be determined periodically in children under long-term anticonvulsant treatment.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Epilepsy; Female; Folic Acid; Folic Acid Deficiency; Humans; Infant; Long-Term Care; Male; Vitamin B 12

Topics: Anticonvulsants; Blood-Brain Barrier; Clinical Trials as Topic; Epilepsy; Folic Acid; Folic Acid Deficiency; Humans; Phenobarbital; Phenytoin; Primidone; Seizures; Tetrahydrofolates; Vitamin B 12

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticonvulsants; Clinical Trials as Topic; Epilepsy; Erythrocytes; Female; Folic Acid; Folic Acid Deficiency; Humans; Male; Middle Aged; Placebos; Vitamin B 12

Topics: Adult; Aggression; Anticonvulsants; Behavior; Clinical Trials as Topic; Epilepsy; Female; Folic Acid; Humans; Male; Motor Activity; Placebos; Vitamin B 12

Topics: Clinical Trials as Topic; Epilepsy; Folic Acid; Humans; Vitamin B 12

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticonvulsants; Clinical Trials as Topic; Epilepsy; Folic Acid; Humans; Middle Aged; Placebos; Vitamin B 12

HCFC1 encodes transcriptional co-regulator HCF-1, which undergoes an unusual proteolytic maturation at a centrally located proteolysis domain. HCFC1 variants were associated with X-linked cobalamin metabolism disorders and mental retardation-3. This study aimed to explore the role of HCFC1 variants in common epilepsy and the mechanism underlying phenotype heterogeneity.. Whole-exome sequencing was performed in a cohort of 313 patients with idiopathic partial (focal) epilepsy. Functional studies determined the effects of the variants on the proteolytic maturation of HCF-1, cell proliferation and MMACHC expression. The role of HCFC1 variants in partial epilepsy was validated in another cohort from multiple centers.. We identified seven hemizygous HCFC1 variants in 11 cases and confirmed the finding in the validation cohort with additional 13 cases and six more hemizygous variants. All patients showed partial epilepsies with favorable outcome. None of them had cobalamin disorders. Functional studies demonstrated that the variants in the proteolysis domain impaired the maturation by disrupting the cleavage process with loss of inhibition of cell growth but did not affect MMACHC expression that was associated with cobalamin disorder. The degree of functional impairment was correlated with the severity of phenotype. Further analysis demonstrated that variants within the proteolysis domain were associated with common and mild partial epilepsy, whereas those in the kelch domain were associated with cobalamin disorder featured by severe and even fatal epileptic encephalopathy, and those in the basic and acidic domains were associated with mainly intellectual disability.. HCFC1 is potentially a candidate gene for common partial epilepsy with distinct underlying mechanism of proteolysis dysfunction. The HCF-1 domains played distinct functional roles and were associated with different clinical phenotypes, suggesting a sub-molecular effect. The distinct difference between cobalamin disorders and idiopathic partial epilepsy in phenotype and pathogenic mechanism, implied a clinical significance in early diagnosis and management.

Topics: Epilepsies, Partial; Epilepsy; Gene Expression Regulation; Humans; Oxidoreductases; Proteolysis; Vitamin B 12

The aim of this study was to investigate possible associations between MTHFR polymorphism and seizure control of epileptic patients with hyperhomocysteinaemia.. A total of 81 epileptic patients with hyperhomocysteinaemia treated with oxcarbazepine monotherapy were enrolled in this study. All patients were offered vitamin B supplementation (2.5 mg/d folate and 1.5 mg/d mecobalamine) for six months. MTHFR C677T and A1298C polymorphisms, serum homocysteine, folate and vitamin B12 levels as well as seizure frequency and score based on the Hamilton depression scale (HAMD) were evaluated at baseline and after six months of follow-up.. Spearman correlation analysis showed that the extent of decline of seizure frequency positively correlated with a dynamic change in serum homocysteine concentration between baseline and after six months of follow-up (t=0.241, p=0.015 [Spearman’s coefficient]). For the MTHFR C677T polymorphism, compared to the CC genotype, the TT genotype was associated with a significant downtrend of homocysteine (19.69 vs 10.28 mmol/L, p=0.006) and uptrend of folate (6.21 vs 2.49 ng/mL; p=0.004). The decrease in homocysteine (17.94 vs 12.52 mmol/L, p=0.001) and increase of folate (5.08 vs 2.86 ng/mL; p=0.003) were significantly greater in patients with the T allele compared to those with the C allele. Also, the TT genotype (2.33 vs 1.4, p=0.056) and T allele (1.95 vs 1.38, p=0.037) were associated with a greater decrease in seizure frequency compared to the CC genotype or C allele. The A1298C polymorphism alone was not associated with elevated homocysteine or decreased folate levels at baseline, and showed little association with response to vitamin B supplementation in epileptic patients with hyperhomocysteinaemia. However, in patients with combined 677TT/1298AA or 677TT/1298AC polymorphisms, the changes in homocysteine and folate levels and seizure frequency were more obvious.. MTHFR C677T polymorphism was associated with seizure control in epileptic patients with hyperhomocysteinaemia; individuals with the 677TT genotype or T allele demonstrated better seizure control.

Topics: Epilepsy; Folic Acid; Genotype; Homocysteine; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Genetic; Seizures; Vitamin B 12; Vitamins

The purpose of this study was to prevent anaemia caused on long-term phenytoin treatment among Epileptic patients. Therefore, two groups were categorised based on the duration of phenytoin namely, cases and control. The duration of Phenytoin treatment for case was > 2 years while control had < 1 year. The estimation of serum Folate and Vitamin B12 was carried out and the association between the deficiency of Vitamins with the duration of treatment were evaluated using Linear Regression Analysis. The statistical results shown that the mean value of Folate (2.61 ± 1.81) and the mean value of Vitamin B12 (284.68 ± 110.12) were considered to be low as the duration of Phenytoin treatment increases (> 2 years) compare to control with the Folate concentration of (7.01 ± 4.40) which was statistically significant (p < 0.000). The experimental results have proved that a long-term phenytoin treatment significantly affects the concentration of Folate and Vitamin B12 among the Epileptic patients vigorously.

Topics: Adult; Anticonvulsants; Epilepsy; Female; Folic Acid; Humans; Male; Middle Aged; Phenytoin; Vitamin B 12

Folic acid supplementation during the periconceptual period has been shown to improve cognitive outcomes in children of women with epilepsy taking anti-seizure medications (ASMs). The dose of folic acid necessary to provide positive cognitive outcomes is unclear. In many countries including the United States, food is fortified with folic acid, but no data exist on how food fortification may affect cognition in children with fetal-ASM exposure. This study evaluated the effect of dietary folate from natural folates plus folic acid fortification, separate from folic acid vitamin supplements, on age-6 year IQ in children with fetal-ASM exposure.. Data from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study were retrospectively analyzed for this investigation. Assessment of nutrient intake was conducted using the Block Food Frequency Questionnaire-98. The primary outcome of the present study was to assess association of maternal prepregnancy nutrient levels to child age-6 IQ.. Folate from food alone without supplement was not associated with improvement of age-6 IQ in children with fetal ASM exposure (95% CI: -11.7-2.3, p = 0.187). Periconceptual folate supplement use was associated with a 10.1-point higher age-6 IQ (95% CI: 5.2-15.0, p < .001). Total combined folate from food plus supplement also showed that higher intake of folate was associated with higher age-6 IQ (Coefficient: 4.5, 95% CI: 2.0-6.9, p < .001). Six other nutrients from food and supplements were analyzed (Vitamin C, Vitamin D, Vitamin E, Omega 3, Gamma Tocopherol, and Vitamin B12) and had no significant association with age 6-IQ.. Dietary content of folate, even in a country where food is fortified with folic acid, is not sufficient to provide improved cognitive outcomes for children of women taking ASMs during pregnancy. Folate supplementation is needed for significant improvement in cognitive outcomes, specifically age-6 IQ.

Topics: Child; Dietary Supplements; Epilepsy; Female; Folic Acid; Humans; Pregnancy; Retrospective Studies; United States; Vitamin B 12

Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism. MTHFR C677T and A1298C polymorphisms are best-defined variants of MTHFR that were reported to be associated with epilepsy development. The aim of the study was to determine the incidence of interictal epileptiform discharges on electroencephalography (EEG) in asymptomatic children with C677T and A1298C polymorphisms who had no history of seizure.. Children with MTHFR C677T or A1298C polymorphisms who had normal neurological examination without a history of seizure were included in the study. Blood samples for serum folate, vitamin B12, and homocysteine levels were analyzed. Sleep and awake electroencephalograms (EEG) were recorded.. A total of 102 children (50 girls and 52 boys) with a mean age of 59.4 ± 58.7 months were included in the study. Interictal epileptiform EEG discharges were detected in 3 children (2.9%).. There was no increase in the prevalence of interictal epileptiform discharges in seizure-free and asymptomatic children with MTHFR C677T and A1298C polymorphisms.

Topics: Child; Child, Preschool; Electroencephalography; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Infant; Male; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Single Nucleotide; Vitamin B 12

Long-term antiepileptic drug (AED) therapy has been associated with metabolic consequences that lead to an increase in risk of atherosclerosis in patients with epilepsy. Earlier published studies showed conflicting results about the levels of hematological parameters, serum homocysteine, folate, and vitamin B12, in epileptics treated with phenytoin monotherapy. Therefore, we evaluated homocysteine metabolism and hematological parameters in early stage of phenytoin treated epileptic children.. A total of 64 newly diagnosed epileptic children with mean age 10.09 ± 2.56 years were enrolled at the start of study. However, after 3 months follow up, the final total sample size was only 50 epileptic children. Fourteen children dropped out of study due to poor follow up. Serum homocysteine levels were measured by enzyme immunoassay method. Serum folate and vitamin B12 levels were estimated by Competitive Chemiluminescent Enzyme Immunoassay method. Hematological parameters were analysed by an automated hematology analyzer (Cell counter), Sysmex XT-1800i, using commercially available reagents.. In our study the anthropometric and hematological parameters did not show any significant difference after phenytoin monotherapy as compared to before therapy in epileptic children. The serum homocysteine level in epileptic children was found to be significantly increased after phenytoin (PHT) monotherapy as compared to before therapy. Moreover, a highly significant decrease was observed in the serum folate and vitamin B12 levels after phenytoin monotherapy as compared to before therapy in epileptic children.. Phenytoin monotherapy may cause a significant increase in the levels of serum homocysteine and a significant decrease in the serum folate and vitamin B12 levels in children with epilepsy, and the significant changes in above mentioned parameters occur early in the course of treatment. This could be responsible for a higher prevalence of cardiovascular incidents in epileptic children taking phenytoin monotherapy. Therefore, it may be useful to do early screening and treatment of increased serum homocysteine levels in epileptic children under phenytoin monotherapy to prevent atherosclerosis and its complications. Hematological parameters should also be strictly monitored regularly in individuals administered with PHT monotherapy. If there are persistent alterations, the administration of the drugs should be discontinued.

Topics: Anticonvulsants; Carbamazepine; Child; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Male; Phenytoin; Vitamin B 12

Increased blood homocysteine levels are a known cardiovascular risk factor. Epileptic patients on long-term treatment with antiepileptic drugs may present higher homocysteine levels and, consequently, a potential increase in cardiovascular risk.. We conducted an observational case-control study to compare plasma levels of homocysteine, folic acid, and vitamin B. Our study included a total of 88 subjects: 52 patients with epilepsy and 36 controls. Epileptic patients showed higher homocysteine levels (P=.084) and lower levels of folic acid (P<.05).. Homocysteine levels should be monitored in epileptic patients on long-term treatment with antiepileptic drugs. We suggest starting specific treatment in patients with high homocysteine levels.

Topics: Adult; Anticonvulsants; Carbamazepine; Cardiovascular Diseases; Case-Control Studies; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Risk Factors; Vitamin B 12

Antiepileptic drugs (AEDs) have been associated with metabolic consequences that lead to an increase in risk of atherosclerosis in patients with epilepsy. Therefore, we evaluated whether differences exist in homocysteine, folate, and vitamin B12 levels in children receiving carbamazepine (CBZ) monotherapy.. A total of 58 newly diagnosed epileptic children with ages ranging from 2 to 15 years were enrolled at the start of study. However, after 3 months follow up, the final total sample size was only 50 epileptic children. Eight children dropped out of the study due to poor follow up. Serum homocysteine levels were measured by enzyme immunoassay method. Serum folate and vitamin B12 levels were estimated by Competitive Chemiluminescent Enzyme Immunoassay method.. The serum homocysteine level in epileptic children was found to be significantly increased after carbamazepine (CBZ) monotherapy as compared to before therapy. Moreover, a highly significant decrease was observed in the serum folate and vitamin B12 levels, after carbamazepine monotherapy as compared to before therapy in epileptic children.. Carbamazepine monotherapy may cause a significant increase in the levels of homocysteine and a significant decrease in the levels of serum folate and vitamin B12 in children with epilepsy, significant changes in above mentioned parameters occurring early in the course of treatment. The atherogenic effect of increased serum homocysteine level is well established, and patients under carbamazepine monotherapy should be monitored for possible atherogenic effects. Therefore, it may be useful to measure serum homocysteine, folate, and vitamin B12 concentrations routinely in children with epilepsy taking carbamazepine monotherapy and be treated when their levels are found to be disturbed.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Male; Vitamin B 12

The aim of this study was to compare the serum levels of one-carbon metabolism (OCM) nutrients (e.g., folate, homocysteine and vitamin B12) and peripheral blood DNA methylation in epileptic patients under treatment with antiepileptic drugs (AEDs) and in healthy controls.. In this cross-sectional study, 60 patients with epilepsy who were receiving valproate (VPA) (n = 30) or lamotrigine (LTG) (n = 30) monotherapy were enrolled. Thirty age and sex matched healthy subjects served as the controls. Serum concentrations of OCM nutrients and peripheral blood DNA methylation status were measured.. Compared to the control group, the VPA group had higher serum levels of homocysteine (p<0.05). No difference in homocysteine concentration was observed in the LTG group. Patients receiving VPA or LTG had significantly lower serum folate levels in comparison with controls (p<0.001). The level of methylation of long interspersed nucleotide element-1 (LINE-1) in peripheral blood was not significantly different between the AED monotherapy group and healthy controls. A difference in the methylation levels of methylenetetrahydrofolate reductase (MTHFR) amplicon was observed between AED-treated patients with epilepsy and controls (p<0.01). A positive correlation between serum folate levels and peripheral blood MTHFR amplicon methylation status was also observed (r = 0.25, p = 0.023).. Our findings suggest that the effects of AED monotherapy on OCM may induce specific regions of DNA hypomethylation.

Topics: Adolescent; Adult; Anticonvulsants; Case-Control Studies; Cross-Sectional Studies; DNA Methylation; Epilepsy; Female; Folic Acid; Heterocyclic Compounds; Homocysteine; Humans; Lamotrigine; Long Interspersed Nucleotide Elements; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Triazines; Valproic Acid; Vitamin B 12; Young Adult

There are increasing studies indicating neuroprotective effects for vitamin B12. In the present study, the effect of intracortical microinjection of vitamin B12 was investigated on penicillin-induced epileptiform activity. We also examined the effects of intracortical microinjection of diazepam (a GABA-benzodiazepine receptor agonist) and flumazenil (a GABAbenzodiazepine receptor antagonist) to clarify the possible mechanism of vitamin B12. In urethane-anesthetized rats, epileptiform activity was induced by intracortical microinjection of penicillin (300 IU, 1.5 microL), and the number and amplitude of spike waves were analyzed using electroencephalographic (EEG) recordings. Intracortical microinjections of vitamin B12 at doses of 100 and 200 ng/site, diazepam at a dose of 200 ng/site and their ineffective doses (50 ng/site of vitamin B12 with 50 ng/site of diazepam) co-microinjection treatment significantly (P less than 0.05) reduced both the number and amplitude of spike waves. In addition, combined microinjection of effective doses of vitamin B12 (100 ng/site) and diazepam (200 ng/site) produced more antiepileptiform effect in comparison with their alone used doses. The antiepileptic effects induced by microinjection of vitamin B12 and diazepam at a same dose of 200 ng/site were prevented by the same site microinjection of 50 ng/site of flumazenil. The results showed antiepileptiform activities for vitamin B12 and diazepam AT the cerebral cortex level. A central GABA-benzodiazepine receptor complex-mediated mechanism might be involved in the antiepileptiform activity of vitamin B12.

Topics: Animals; Anticonvulsants; Benzodiazepines; Diazepam; Electroencephalography; Epilepsy; Male; Microinjections; Penicillins; Rats, Wistar; Receptors, GABA-A; Vitamin B 12

Comparative analysis of the effect of antiepileptic drugs on the epileptic (tonic clonic seizure type) patient's serum folate and vitamin B12 concentrations.. Consecutively, 84 cases from September 2010 to September 2014 from the Department of Internal Medicine of our hospital were considered to diagnose as epilepsy nerve. Among which, 49 cases received anti epileptic drug treatment (treatment group), 35 cases received treatment without anti epileptic drugs (non-treatment group); At the same period, 42 nonepileptic patients (control group) underwent the analysis of the difference of serum folate and vitamin B12 concentrations of among the three groups of patients before the test, and at the end of test with the contrast analysis of difference of clinical efficiency and thrombosis rate.. Serum folic acid level of patients in the treatment group decreased significantly after test, vitamin B12 level was significantly higher, the differences were statistically significant (P<0.05), but folic acid and vitamin B12 concentration of non-treatment group and the control group did not change, and the differences were not statistically significant (P>0.05). Clinical efficiency of treatment group patients was significantly higher than that of the non-treatment group; the incidence of thrombosis was significantly lower than that of the non-treatment group, and the difference was statistically significant (P<0.05).. Antiepileptic drugs can significantly improve clinical efficacy of the epilepsy tonic clonic seizure type patients, which may be related to the decrease of serum levels of folate and vitamin B12-increased concentration.

Topics: Adult; Anticonvulsants; Biomarkers; Case-Control Studies; Drug Monitoring; Epilepsy; Female; Folic Acid; Humans; Male; Middle Aged; Phenytoin; Risk Factors; Time Factors; Treatment Outcome; Vitamin B 12; Vitamin B Complex

The data regarding Valproate and its influence on serum folate and homocysteine levels are conflicting. The aim of this study was to evaluate whether differences exist in homocysteine, folate, and vitamin B12 levels in children receiving Valproate.. A total of 55 newly diagnosed epileptic children with ages ranging from 2 to 15 years were enrolled at the start of study but after 3 months follow up, the total sample size finally was only 50 epileptic children. 5 children dropped out of study due to poor follow up. 50 age and gender matched healthy control subjects were also studied on enrollment at the start of study. Serum homocysteine levels were analyzed by enzyme immunoassay method using the kits provided by Axis-Shield Diagnostics Ltd (Dundee DD2 1XA, United Kingdom). Serum folate and serum vitamin B12 were estimated by Competitive Chemiluminescent Enzyme Immunoassay method.. The serum homocysteine level in epileptic children was found to be significantly increased after Valproate monotherapy as compared to before therapy. Moreover, a highly significant decrease was observed in the levels of serum folate in epileptic children after Valproate monotherapy as compared to before therapy. But a non significant difference was observed in serum vitamin B12 levels in epileptic children before and after Valproate monotherapy.. Thus, we conclude that there is a significant increase in the levels of homocysteine and a significant decrease in the concentration of serum folate while vitamin B12 decreases non-significantly after Valproate monotherapy. The atherogenic effect of increased serum homocysteine level is well established; the patients under Valproate monotherapy should be monitored for possible atherogenic effects. Considering the above observation and results of children undergoing Valproate monotherapy, these children should be screened for levels of serum homocysteine, folate, and vitamin B12 and treated when their levels are found to be disturbed.

Topics: Adolescent; Age Factors; Anticonvulsants; Case-Control Studies; Child; Child, Preschool; Drug Monitoring; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Male; Risk Factors; Time Factors; Treatment Outcome; Valproic Acid; Vitamin B 12

To investigate biochemical cardiovascular risk factors and vascular endothelial function and structure in children with epilepsy on antiepileptic drugs (AEDs), particularly sodium valproate (VPA) and carbamazepine (CBZ).. Individuals with epilepsy have increased risk factors for vascular disease, particularly lipid abnormalities and elevated total plasma homocyst(e)ine (tHcy). AED induced B-vitamin deficiencies have been suggested to contribute to this risk. Vitamin B supplementation has consequently been recommended for children on AEDs. Early vascular endothelial dysfunction and atherosclerosis are detectable by measuring flow-mediated dilation (FMD) and intima-media thickness (IMT).. Thirty children with epilepsy on AEDs (13.3±2.3 years, 14 male) and 30 controls (13.9±2.9 years, 14 male) were recruited. Fasting tHcy, folate, pyridoxal-5-phosphate (PLP), vitamin B12, glucose and lipids were measured. Vascular function and structure were assessed using FMD (brachial artery) and IMT (carotid/aortic arteries).. No differences were found between children with epilepsy and controls for tHcy, folate, PLP, lipids, FMD, carotid or aortic IMT. Vitamin B12 levels were elevated and glucose reduced in children treated with VPA. Elevated total cholesterol, cholesterol/HDL ratio and triglycerides occurred in children treated with CBZ. Aortic IMT correlated with weight (r=0.75, p<0.001), BMI (r=0.54, p=0.01), and HDL cholesterol (r=-0.58, p=0.006).. We found no early changes in vascular function or structure in children on valproate or carbamazepine. We were also unable to confirm previous reports of tHcy abnormalities in this group. This may be due to higher B-vitamin intake, which compensates for loss of vitamins induced by this AED therapy. Vitamin supplementation in children with epilepsy on valproate and carbamazepine is not required in populations with adequate dietary intake of B vitamins.

Topics: Adolescent; Anticonvulsants; Aorta; Blood Glucose; Brachial Artery; Carbamazepine; Carotid Arteries; Cholesterol; Cholesterol, HDL; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Male; Phosphoric Monoester Hydrolases; Risk Factors; Ultrasonography; Valproic Acid; Vitamin B 12

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. High plasma total Hcy (tHcy) has been quite frequently reported in patients with epilepsy treated with antiepileptic drugs (AEDs) mainly related to plasma folate reduction induced by AEDs themselves. The role of C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene (MTHFR) on the increase of plasma tHcy in patients with epilepsy taking AEDs is still controversial. Cognitive impairment may be associated with epilepsy either as the result of the epileptic syndrome per se or as a side effect induced by the AEDs. High plasma tHcy levels were associated with lower cognitive performances in patients affected by Alzheimer's disease and mild cognitive impairment and in healthy elderly. We searched for a correlation between plasma tHcy levels with the intelligence quotient (IQ) scores in a population of children and young adults with epilepsy treated with old and/or newer AEDs. The study group encompassed 179 patients (92 M, 51.5%) followed at our Unit of Child Neuropsychiatry and aged between 4 and 25years (mean+SD: 14.03±4.25). The inclusion criteria included the following: 1) diagnosis of epilepsy of "unknown cause" (cryptogenic) according to the ILAE classification, 2) age older than 3years, 3) stabilized antiepileptic treatment for at least 6months, and 4) clinical records of cognitive tests, plasma tHcy value, and results of MTHFR polymorphisms. Patients' mean tHcy value was 9.71±3.13μM/L (tHcy<9μM/L as our laboratory cutoff in nonepileptic controls). The mean TIQ score was 85.22 (SD±24.12); the mean VIQ score was 86.32 (SD±20.86); and the mean PIQ score was 86.94 (SD±21.51). C677T and A1298C MTHFR polymorphisms were detected in 74/92 (80%) examined patients and distributed into the following: CT (22.3%), TT (14.9%), CC (10.3%) for C677T, AC (16%), CC (1.1%), and AA (30.3%) for A1298C. Plasma tHcy levels were not significantly related to the IQ scores (TIQ, VIQ, or PIQ). Two significant findings came out. First, patients on AED polytherapy showed significantly lower TIQ, VIQ, and PIQ scores compared with the ones with AED monotherapy (p=0.032; p=0.008; p=0.005, respectively). However, this significant difference was not observed with the plasma tHcy levels compared with AED treatment. Second, patients with the 677TT genotype showed significantly higher tHcy levels versus those with the wt ones (p=0.049). In the latter group of patients, although the m

Topics: Adolescent; Adult; Anticonvulsants; Child; Cognition Disorders; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Intelligence Tests; Male; Methylenetetrahydrofolate Reductase (NADPH2); Neuropsychological Tests; Polymorphism, Genetic; Statistics, Nonparametric; Vitamin B 12; Young Adult

To compare the levels of homocysteine, vitamin B12 and folic acid before and after 6 months of carbamazepine therapy and to correlate them with carbamazepine level at 6 months.. Prospective comparative study.. Tertiary care centre in North India.. 51 children (2-12 years of age) presenting with motor partial seizures.. Carbamazepine (10-20 mg/kg/day) for 6 months.. Change in serum homocysteine, B12, folic acid level.. Fasting venous samples were collected before carbamazepine therapy and after six months. Homocysteine was analyzed using homocysteine enzyme immunoassay. Vitamin B12 and folic acid were estimated using electrochemiluminesence technique. Carbamazepine levels were measured at 6 months.. Of the 51 children, 36 (males-21), were followed up and their data analyzed. Mean homocysteine level was 11.51±3.95 umol/L at recruitment and 11.77±6.65 umol/L at six months (P=0.785). At recruitment 6(16%) children had homocysteine level above 15 umol/L which increased to 10(27%) at 6 months. Mean vitamin B12 at recruitment was 292.1±111.2 pg/mL and 297.8±82.9 pg/mL at 6 months (P=0.764). Mean folic acid at recruitment was 9.98±3.45 ng/mL and 10.66±3.97 ng/mL at 6 months (P=0.358). There was no correlation between carbamazepine levels with homocysteine, vitamin B12 and folic acid (P>0.05). There was no effect of age, sex or dietary pattern on homocysteine levels.. Hence 6 months of carbamazepine therapy did not cause significant change in serum levels of homocysteine, vitamin B12 and folic acid.

Topics: Anticonvulsants; Carbamazepine; Child; Child, Preschool; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Male; Neurocysticercosis; Prospective Studies; Vitamin B 12

Antiepileptic drugs (AEDs) are commonly used in the treatment of epilepsy, psychiatric diseases and pain disorders. Several of these drugs influence blood levels of folate and vitamin B12 and, consequently, homocysteine. This may be relevant for AED effects and side effects. However, not only folate and vitamin B12, but also genetic variants modify homocysteine metabolism. Here, we aimed to determine whether there is a pharmacogenetic interaction between folate, vitamin B12 and genetic variants and homocysteine plasma level in AED-treated patients.. In this mono-center study, we measured homocysteine, folate and vitamin B12 plasma levels in a population of 498 AED-treated adult patients with epilepsy. In addition, we analyzed the genotypes of seven common genetic variants of homocysteine metabolism: methylenetetrahydrofolate reductase (MTHFR) c.677C>T and c.1298A>C, methionine synthase (MTR) c.2756A>G, dihydrofolate reductase (DHFR) c.594+59del19bp, cystathionine β-synthase (CBS) c.844_855ins68, transcobalamin 2 (TC2) c.776C>G and methionine synthase reductase (MTRR) c.66G>A.. On multivariate logistic regression, folate and vitamin B12 levels, but none of the genetic variants, were predictive for homocysteine levels.. These data suggest that, in AED-treated patients, folate and vitamin B12 play important roles in the development of hyperhomocysteinemia, whereas genetic variants of homocysteine metabolism do not and thus do not contribute to the risk of developing hyperhomocysteinemia during AED treatment.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Adult; Anticonvulsants; Cystathionine beta-Synthase; Epilepsy; Female; Ferredoxin-NADP Reductase; Folic Acid; Genetic Variation; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Logistic Models; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Single Nucleotide; Risk Factors; Tetrahydrofolate Dehydrogenase; Transcobalamins; Vitamin B 12

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. An elevated total plasma Hcy concentration (tHcy) is a risk factor for vascular disease. The present study aimed to assess the role of antiepileptic drugs (AEDs) and C677T methylenetetrahydrofolate (MTHFR) polymorphisms on tHcy in pediatric patients with epilepsy treated for at least 6 months with various treatment regimens protocols including the newer AEDs. The study group was recruited from children and adolescents with epilepsy followed up in the Child Neuropsychiatry Clinic of the Second University of Naples, between January 2007 and March 2008. Inclusion criteria were: (1) patients with epilepsy, treated with one or more anticonvulsant drugs for at least 6 months; (2) age between 2 and 16 years. Plasma tHcy concentrations were considered elevated when they exceeded 10.4 μmol/L, and folate concentrations <3 ng/mL were considered deficient. Serum vitamin B12 levels were considered normal between 230 and 1,200 pg/mL. The study group was composed of 78 patients (35 males, 43 females), aged between 3 and 15 years (mean 8.9 years). Thirty-five patients were taking AED monotherapy, 43 polytherapy. Sixty-three healthy sex- and age-matched children and adolescents served as controls. The mean tHcy value in the patient group was higher than the mean value in the control group (12.11 ± 7.68 μmol/L vs 7.4±4.01 μmol/L; p<0.01). DNA analysis for the MTHFR C677T polymorphism showed the CT genotype in 46%, CC in 35% and TT in 17.8% of cases. Decreased folic acid serum levels significantly correlated with increased tHcy levels (p<0.003). Female sex was a less significant risk factor for increased tHcy levels (p=0.039). Our study confirms the association between hyperhomocysteinemia and epilepsy. The elevation of tHcy is essentially related to low folate levels. Correction of poor folate status, through supplementation, remains the most effective approach to normalize tHcy levels in patients on AED mono- or polytherapy.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Folic Acid; Folic Acid Deficiency; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Male; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Genetic; Vitamin B 12

Recent reports have demonstrated elevated serum homocysteine (Hcy) levels in children receiving valproic acid (VPA) therapy. Elevated Hcy levels might play a potential role in the resistance to antiepileptic drugs, and might lead to an increased risk for a vascular disease. It has been reported that elevated total homocysteine (tHcy) levels are associated with elevated asymmetric dimethylarginine (ADMA) levels, which are factors that may be better indicators of endothelial dysfunction compared to serum homocysteine levels, because they are less sensitive to changes, such as fasting status, physical activity, and other factors. In this study, we aim to evaluate serum ADMA, Hcy, lipid, folate, and vitamin B₁₂ levels in epileptic children, receiving VPA monotherapy. Forty-four epileptic children, receiving VPA monotherapy for at least 6 months and 28 healthy children aged between 4 and 16 years, were recruited. Serum lipids, lipoproteins, folate, vitamin B₁₂, Hcy, and ADMA levels were analyzed in both study groups. Serum Hcy, ADMA, and vitamin B₁₂ levels were higher in patients than in controls (p < 0.001 for tHcy and ADMA levels; p < 0.05 for vitamin B₁₂ levels); however, serum lipid, lipoprotein, and folate levels were similar. According to the duration of epilepsy, serum tHcy, ADMA, and triglyceride (TG) levels were higher in patients with epilepsy for ≥ 2 years than in patients with epilepsy for < 2 years (p < 0.001 for serum ADMA levels, p < 0.01 for tHcy levels, and p < 0.05 for serum TG levels). Similarly, with respect to the duration of VPA therapy, serum tHcy, ADMA, and TG levels were higher in patients who had received VPA therapy for more than 2 years (p < 0.001 for serum ADMA levels, p < 0.05 for serum tHcy levels, p < 0.01 for TG levels). Serum ADMA levels were significantly higher in patients receiving VPA at the dose of 25-30 mg/kg/day than in those receiving 20 mg/kg/day (p < 0.01). In conclusion, our study found increased serum ADMA levels and increased tHcy levels in epileptic children receiving VPA monotherapy. Increased serum ADMA levels were demonstrated in epileptic children who have had a seizure history greater than 2 years, and have used VPA therapy for more than 2 years, and have received higher doses of VPA. Routine monitoring of serum ADMA and tHcy levels might have beneficial effects for patients receiving long-term VPA therapy, especially in children who have other potential risk factors for vascular diseases. Further studies ar

Topics: Adolescent; Anticonvulsants; Arginine; Biomarkers; Case-Control Studies; Child; Child, Preschool; Cholesterol; Cross-Sectional Studies; Drug Administration Schedule; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Lipids; Male; Triglycerides; Valproic Acid; Vitamin B 12; Vitamin B Complex

Antiepileptic drugs (AEDs) are important for the treatment of epilepsy, psychiatric diseases, and pain syndromes. Small studies have suggested that AED treatment reduces serum levels of folate and vitamin B12.. This prospective monocenter study aimed at testing the hypothesis that AED treatment is associated with folate and vitamin B12 serum levels in a large population. A total of 2730 AED-treated and 170 untreated patients with epilepsy and 200 healthy individuals were enrolled.. Treatment with carbamazepine, gabapentin, oxcarbazepine, phenytoin, primidone, or valproate was associated with lower mean serum folate levels or with a higher frequency of folate levels below the reference range in comparison with the entire group of patients, untreated patients, or controls. Treatment with phenobarbital, pregabalin, primidone, or topiramate was associated with lower vitamin B12 levels compared with the entire group of patients. Vitamin B12 serum levels were higher in patients treated with valproate compared with the entire group of patients, untreated patients, and healthy controls. Folate or vitamin B12 levels below the reference range were associated with higher mean corpuscular volume (MCV) and higher homocysteine plasma levels. Vitamin substitution for 3 months in 141 patients with folate or vitamin B12 levels below the reference range yielded normal vitamin levels in 95% of the supplemented patients and reduced MCV and homocysteine plasma levels.. Treatment with most of the commonly used AEDs is associated with reduced folate or vitamin B12 serum levels and is a risk factor for hyperhomocysteinemia. Oral substitution is effective to restore vitamin, MCV, and homocysteine levels.

Topics: Analysis of Variance; Anticonvulsants; Epilepsy; Female; Folic Acid; Humans; Male; Prospective Studies; Vitamin B 12

Topics: Epilepsy; Folic Acid; Humans; Hyperhomocysteinemia; Vitamin B 12

Older enzyme-inducing antiepileptic drugs (AEDs) may induce supraphysiologic plasma concentrations of total (t) homocysteine (Hcy). The aim of the present study was to investigate the effect of new AEDs on plasma tHcy levels.. Patients 18-50 years of age, on AEDs monotherapy, with no other known cause of hyper-tHcy were enrolled. Plasma tHcy, folate, vitamin B(12), and AEDs levels were determined by standard high-performance liquid chromatography (HPLC) methods. Methylenetetrahydrofolate-reductase (MTHFR) polymorphisms were checked using Puregene genomic DNA purification system (Gentra, Celbio, Italy). A group of healthy volunteers matched for age and sex was taken as control.. Two hundred fifty-nine patients (151 on newer and 108 on older AEDs) and 231 controls were enrolled. Plasma tHcy levels were significantly higher [mean values, standard error (SE) 16.8, 0.4 vs. 9.1, 0.2 microm; physiologic range 5-13 microm] and folate lower (6.3, 0.1 vs. 9.3, 0.1 nm; normal > 6.8 nm) in patients compared to controls. Patients treated with oxcarbazepine, topiramate, carbamazepine, and phenobarbital exhibited mean plasma tHcy levels above the physiologic range [mean values (SE) 16 (0.8), 19.1 (0.8), 20.5 (1.0), and 18.5 (1.5) microm, respectively]. Conversely, normal tHcy concentrations were observed in the lamotrigine and levetiracetam groups [both 11.1 (0.5) microm].. Oxcarbazepine and topiramate might cause hyper-tHcy, most likely because of the capacity of these agents to induce the hepatic enzymes. Because literature data suggest that hyper-tHcy may contribute to the development of cerebrovascular diseases and brain atrophy, a supplement of folate can be considered in these patients to normalize plasma tHcy.

Topics: Adolescent; Adult; Anticonvulsants; Carbamazepine; Enzyme Induction; Epilepsy; Female; Folic Acid; Fructose; Genotype; Humans; Hyperhomocysteinemia; Lamotrigine; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxcarbazepine; Phenobarbital; Polymorphism, Genetic; Topiramate; Triazines; Vitamin B 12

Some recent studies indicated that administration of antiepileptic drugs (AEDs) is associated with occlusive vascular diseases. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthase inhibitor and increased plasma ADMA levels are associated with cardiovascular morbidity. We hypothesized that elevated plasma ADMA concentrations exist in patients receiving AEDs and administration of AEDs may result in an increased risk of occlusive vascular disease. Thirty five newly diagnosed epilepsy patients participated, patients were classified into two groups according to their antiepileptic drug regimen. In the first group patients were treated with valproic acid (VPA, n=17) (500-1500 mg/day), and in the second group with carbamazepine (CBZ, n=18) (400-1200 mg/day). ADMA levels significantly increased after treatment in both VPA (p=0.002) and CBZ (p=0.024) groups. Homocysteine levels increased in both groups, but the difference was significant only in VPA group (p=0.005). Serum folate levels did not differ in VPA group, but significantly decreased in CBZ group (p=0.006). Vitamin B(12) levels significantly increased in VPA group (p=0.001) but did not differ in CBZ group. Correlation analysis showed that the increases in ADMA and homocysteine levels in the VPA group were higher however the differences between the groups were insignificant. The correlations of the changes between ADMA and other parameters were all insignificant in both VPA and CBZ groups. In conclusion our data suggest that elevated ADMA levels may be responsible for the increased cardiovascular risk in patients with epilepsy under AED therapy.

Topics: Adult; Anticonvulsants; Arginine; Arterial Occlusive Diseases; Carbamazepine; Drug Monitoring; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Male; Statistics, Nonparametric; Valproic Acid; Vitamin B 12

The effects of antiepileptic drugs (AED) on the serum concentration of vitamin B12, folic acid and homocysteine (HMC), and erythrocyte folic acid levels were determined in 45 epileptic patients (30 women, 15 men; mean age 31.7 years) and 23 healthy volunteers (control group; 18 women, five men; mean age 33.4 years). All patients were either on carbamazepine (CMZ), oxcarbazepine (OXZ), or valporate (VP) monotherapy. Serum vitamin B12 levels were low in 17.8% of patients and 8.7% of the controls (P = 0.299). Serum homocysteine levels were high in 17.8% of the patients (P = 0.008). Fifty percent of the patients who had hyperhomocysteinemia, and 75% of the patients who had low serum vitamin B12 level were on CMZ monotherapy. Peripheral blood smears showed hypersegmented neutrophils and macrocytosis in 13.3%, hypochromia and microcytosis in 26.7%, acanthocytes in 2.2%, and thrombocytosis in 2.2% of all patients. The control group had normal peripheral blood smears, except in four cases that showed hypocromia and microcytosis. Long-term administration of AED may cause elevation of homocysteine and development of subnormal serum vitamin B12 levels. Peripheral blood smear abnormalities were frequently seen in patients receiving antiepileptic treatment (P = 0.022), particularly in patients on CMZ monotherapy (P = 0.281). However, homocysteine, vitamin B12, folic acid levels and peripheral blood smear findings did not correlate with the drugs used (P = 0.665, 0.336, 0.249 for CMZ, OXZ, VP, respectively).

Topics: Adolescent; Adult; Aged; Anticonvulsants; Case-Control Studies; Epilepsy; Erythrocytes, Abnormal; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Neutrophils; Vitamin B 12; Vitamin B 12 Deficiency

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. Elevated plasma Hcy concentration is a possible risk factor for vascular disease. Folate and vitamin B-12 are vitamins that are necessary for remethylization of Hcy to methionine. The methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in remethylation of Hcy to methionine and supplies the required 5-methyltetrahydrofolate as the methyl donor for this reaction. It is well known that some antiepileptic drugs (AED) can lead to hyperhomocysteinemia by affecting the levels of folate and vitamin B-12. The C677T variant of MTHFR gene can also lead to hyperhomocysteinemia particularly when serum folate level is decreased. In this study, we investigated the levels of serum folate, vitamin B-12 and Hcy in epileptic patients receiving carbamazepine (CBZ) or valproic acid (VPA) as monotherapy, and we also evaluated the probable contribution of the C677T variant of MTHFR gene in hyperhomocysteinemia. A total of 93 patients with idiopathic epilepsy receiving CBZ or VPA as monotherapy were included in this study. CBZ and VPA groups consisted of 29 and 64 patients, respectively. The control group comprised 62 healthy children. We measured serum folate, vitamin B-12 and Hcy levels in each group. We found that mean serum folate level was statistically lower and mean Hcy level was higher in epileptic patients receiving CBZ or VPA when compared with those of controls'. We also determined the C677T variants of MTHFR gene (as normal, heterozygote or homozygote) in epileptic patients. We compared the variant groups for serum folate, vitamin B-12 and Hcy levels and found no significant differences among them. In conclusion, C677T variants of MTHFR gene have no contribution in hyperhomocysteinemia in epileptic patients receiving CBZ or VPA.

Topics: Adolescent; Analysis of Variance; Anticonvulsants; Carbamazepine; Child; Chromatography, High Pressure Liquid; Electrochemistry; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Genetic; Valproic Acid; Vitamin B 12

Folic acid supplementation reduces the occurrence of neural tube defects (NTDs); however, it is not clear whether it protects against teratogenic effects of antiepileptic drugs.. We report the cases of four pregnant women receiving valproic acid therapy, who all had NTD-affected offspring, despite periconceptional 5 mg/day of folic acid supplementation (cases), and investigated homocysteine metabolism, linked with folate metabolism. Their plasma homocysteine, folates, and vitamin B6 and B12 results were compared with values of two other women, who were also receiving valproic acid and folic acid complement, but who had normal pregnancies (valproic acid controls), and values of 40 pregnant women who had normal pregnancies and were not receiving any therapy (controls without therapy). Because of the possible existence of a genetic susceptibility, polymorphisms in homocysteine metabolism were sought.. Two cases showed a decreased phosphopyridoxal level, compared with levels in the controls not receiving therapy. The genotype TT (C677T) is an NTD genetic susceptibility, but it was observed in only one valproic acid control. Various polymorphisms were observed in the cases, but were also common in the controls. Several studies have reported that valproic acid therapy lowers vitamin B6 levels. Our case with the greatest decrease in plasma phosphopyridoxal, who was taking periconceptional folic acid plus pyridoxine therapy, had a normal second pregnancy outcome.. In addition to folates, other vitamins, such as vitamin B6, may have played a role in NTDs in our patients taking an antiepileptic drug.

Topics: Adult; Anticonvulsants; Epilepsy; Female; Folic Acid; Genetic Predisposition to Disease; Homocysteine; Humans; Neural Tube Defects; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Valproic Acid; Vitamin B 12; Vitamin B 6

The aim of this study is to investigate the homocysteine, folic acid, and vitamin B(12) levels in epileptic children receiving antiepileptic drugs. A total of 25 children with idiopathic epilepsy (8 valproate, 11 carbamazepine, and 6 oxcarbazepine) and 10 healthy children were included in the study. The mean homocysteine, folic acid, and vitamin B(12) levels in the study group were 7.57 +/- 3.78 micromol/L (normal = 5-15 micromol/L), 10.19 +/- 4.05 ng/mL (normal = 3.0-17 ng/mL), and 428.20 +/- 256.12 pg/mL (normal = 193-983 pg/mL), respectively. The differences between the mean plasma homocysteine, folic acid, and vitamin B(12) levels of the study and control groups were not significant (P = .522; P = .855; P = .798, respectively). However, plasma homocysteine levels were higher than the normal cutoff point accepted for childhood in 4 (16%) of the study patients. Out of these 4 children, 3 were from the carbamazepine group and 1 was from the valproate group. Although the number of the study patients is limited, the authors recommend assessment of plasma homocysteine, serum vitamin B(12), and folic acid levels in children receiving enzyme-inducing antiepileptic drugs.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Oxcarbazepine; Valproic Acid; Vitamin B 12

There is emerging evidence to support the unfavorable effects of some anti-epileptic drugs on the plasma homocysteine concentrations. Elevated homocysteine levels induced by anti-epileptic drug administration can theoretically increase not only the risk of vascular occlusive diseases, but also the risk of resistance to anti-epileptics and development of refractory epilepsy. To investigate the effect of common anti-epileptic drugs on the homocysteine metabolism, a total of 75 epileptic patients receiving phenytoin (n=16), carbamazepine (n=19), or valproic acid (n=22) and no anti-epileptic drug (n=18) were enrolled. Eleven age- and sex-matched healthy subjects served as the control group. Blood concentrations of homocysteine, folic acid, Vitamin B12 and pyridoxal 5'-phosphate (active circulating form of Vitamin B6) were measured. Compared to the control group, epileptic patients on anti-epileptic drug had higher blood levels of homocysteine. No difference in homocysteine concentrations was observed among epileptic patients in terms of the anti-epileptic drug used. Patients receiving phenytoin had significantly lower folic acid levels and those receiving carbamazepine had marginally lower pyridoxal 5'-phosphate levels in comparison with those using other anti-epileptic drugs. A negative correlation between homocysteine and folic acid concentrations was detected in epileptic patients on anti-epileptic drug. The duration of anti-epileptic drug use was correlated to the decrease of folic acid levels, but not with changes observed in homocysteine, Vitamin B12 and pyridoxal 5'-phosphate levels. No relationship between seizure frequency and homocysteine levels was observed in epileptic patients. Our results confirm that common anti-epileptic drugs has disadvantageous effects on homocysteine status. Because there was no significant change in homocysteine concentrations in epileptic patients who were not receiving an anti-epileptic drug, and no positive correlation between seizure frequency and homocysteine levels, we suggest that increase of homocysteine levels may be due to anti-epileptic drug use, rather than being epileptic in origin. Additionally, the underlying mechanism for homocysteine increase seems to be a decrease of cofactor molecules in patients using carbamazepine and phenytoin (pyridoxal 5'-phosphate and folic acid, respectively). However, changes observed are not related to the alteration in the levels of cofactors and remain unclear in the patients

Topics: Adolescent; Adult; Anticonvulsants; Carbamazepine; Case-Control Studies; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Phenytoin; Pyridoxal Phosphate; Reference Values; Valproic Acid; Vitamin B 12

Plasma total homocysteine (p-tHcy), serum folate (s-F), serum vitamin B-12 (s-B12) and plasma pyridoxal-5'-phosphate (p-PLP) were measured in epileptic children before and after a 20-week period of sodium valproate (group A, n=32) and carbamazepine (group B, n=20) monotherapy. P-tHcy significantly increased in both groups, s-F and s-B12 significantly increased in group A, while s-F and p-PLP significantly decreased in group B. Our study showed an early effect of antiepileptic drug treatment on homocysteine metabolism.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Male; Prospective Studies; Pyridoxal Phosphate; Valproic Acid; Vitamin B 12

Folate and vitamin B12 are essential cofactors for the methionine/homocysteine cycle in the brain. These vitamins mediate the remethylation of homocysteine (HCY), which affects the production of the universal methyl donor, S-adenosylmethionine (SAM), in the brain among other organs. Acquired or inherited disorders in these metabolic pathways are associated with brain abnormalities and severe neurological symptoms that are mostly irreversible, even after providing the missing cofactors. This review discusses the relationship between brain and blood levels of key vitamins and metabolites related to one carbon metabolism.

Topics: Aquaporins; Brain; Epilepsy; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Muscular Dystrophy, Duchenne; S-Adenosylmethionine; Vitamin B 12; Vitamin B 12 Deficiency

Genetic and clinical data suggest that folate and homocysteine may play a role in the pathogenesis of psychiatric disorders. The total plasma homocysteine level is a sensitive measure of a functional folate deficiency. We thus investigated whether a functional folate deficiency and/or elevated levels of plasma homocysteine may be related to interictal "schizophrenia-like" psychosis (interictal psychosis ) of epilepsy. We studied the plasma folate, vitamin B12, and homocysteine levels of 32 age- and sex-matched epileptic patients with or without interictal psychosis. Each group included 25 localization-related epilepsies and 7 generalized epilepsies. The epileptic patients with interictal psychosis had significantly lower folate levels and higher homocysteine levels than those without interictal psychosis. There were no significant differences in the vitamin B12 levels between the two groups. The present study suggests that low plasma folate and high plasma homocysteine levels may be related to the pathophysiology of interictal psychosis of epilepsy. In future studies, we should investigate whether folate supplementation, in addition to antipsychotics, might play a beneficial role in the treatment of interictal psychosis in epileptic patients. Furthermore, the present findings should be confirmed by prospective longitudinal studies in a larger group of patients with epilepsy.

Topics: Adult; Electroencephalography; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Schizophrenic Psychology; Vitamin B 12

To evaluate whether the administration of lamotrigine (LTG) or valproate (VPA) changes concentrations of plasma total homocysteine (tHcy), plasma and red-cell folate and plasma Vitamin B-12, we measured these indices in a total of 20 patients with epilepsy before and after a 32-week period of monotherapy of LTG or VPA. We found that the 32-week administration of a mean daily dose of 250mg LTG had no significant effect on any of the blood indices. On the other hand, the administration of a mean daily dose of 2070mg of VPA resulted in a 57% increase in plasma Vitamin B-12 concentrations over the baseline value and a 27% decline in plasma tHcy concentrations, although the mechanisms of such changes are unknown. Our data indicate that hyperhomocysteinemia may not be a serious clinical problem among patients with epilepsy, who receive either LTG or VPA.

Topics: Adult; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Lamotrigine; Male; Middle Aged; Triazines; Valproic Acid; Vitamin B 12

Topics: Aged; Anemia, Macrocytic; Comorbidity; Epilepsy; Humans; Male; Polyneuropathies; Vitamin B 12; Vitamin B Deficiency

Homocysteine (HMC) is a sulfur containing amino acid, which plays a role in methionine metabolism. Folic acid (FA) and vitamin B12 (B12) are essential for remethylization of HMC to methionine. HMC level increases in the deficiency of these vitamins. Hyperhomocysteinemia causes vascular endothelial damage, which causes atherosclerosis. The aim of this study is to investigate the effect of valproate (VA) and carbamazepine (CBZ) on the serum levels of HMC, B12, and FA.Thirty-six children receiving CBZ and 30 children receiving VA for epilepsy for the last 1-year period and 29 healthy children as control were the population of this study. After 6 h of fasting serum HMC, B12, and FA levels were measured and results were compared statistically. Mean values of HMC, FA, and B12 levels in control group were 9.2+/-2.7 micromol/l, 9.0+/-2.0 ng/ml, and 342+/-162 pg/ml, in VA group 14.0+/-6.8 micromol/l, 7.3+/-2.9 ng/ml, and 368+/-159 pg/ml, in CBZ group 16.0+/-13.1 micromol/l, 7.5+/-3.3 ng/ml, and 285+/-158 pg/ml, respectively. Serum HMC levels were higher in VA and CBZ groups than control group (P<0.01 and P<0.05, respectively). Serum FA levels were lower in VA and CBZ groups compared to control group (P<0.05). Serum levels of B12 were not different between VA and control groups (P>0.05). In CBZ group serum B12 levels were lower than control group (P<0.05).FA may be added to the treatment protocol (if the patients take only CBZ, then B12 should also be added) for patients taking these antiepileptic drugs to decrease the degenerative effect of VA and CBZ on vascular endothelium.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Male; Reference Values; Valproic Acid; Vitamin B 12

In this study, serum triglyceride, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), vitamin B12 and folic acid levels were studied in children with epilepsy who had been receiving long-term valproate (VPA) therapy. Our purpose was to determine that whether or not there was any affect of VPA therapy on serum lipids, vitamin B12 and folic acid levels. The study includes 26 patients (13 males, 13 females) with epilepsy who had been receiving long-term VPA therapy and in 28 healthy children (14 males, 14 females). The age ranged from 14 months-12 years (8.22 +/- 3.64 years) and 9 months-18 years (8.97 +/- 4.85 years) in the study and control group, respectively. Because serum lipid ranges may be changed according to the age groups in childhood, the children were divided into three groups as follows; younger than < 5 years, between 5-10 years, and older than > 10 years. The duration of VPA use was between 10 months and 7 years (1.83 +/- 1.80 years). Serum VPA level changed between 42-108 micrograms/ml (75.09 +/- 21.42 micrograms/ml). When comparing the results we did not find any significant difference in all parameters including lipid profiles, vitamin B12 and folic acid levels between the groups (P > 0.05). Additionally, we did not find any correlation between lipid profile and age at start of therapy, duration of therapy, serum VPA level (P > 0.05). In conclusion, our findings showed that VPA therapy did not change serum lipids, vitamin B12 and folic acid concentrations; therefore, we suggest that VPA may be safely used with regard to lipid composition, vitamin B12 and folic acid levels in childhood epilepsy.

Topics: Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Folic Acid; Humans; Infant; Lipids; Male; Valproic Acid; Vitamin B 12

To describe epilepsy and EEG findings in the early-onset cobalamin (Cbl) C/D deficiency, an inborn error of intracellular Cbl metabolism characterized by high plasma levels of methylmalonic acid, homocystine, and homocysteine.. Type and frequency of seizures were studied in 10 patients (six boys and four girls) who underwent waking and sleep EEG.. Half of patients had seizures in the first year of life (either concurrent with the other symptoms of disease or some months after the onset of disease); seizures occurred after 2 years in the other half of patients. Convulsive status epilepticus was the initial manifestation in three patients. During the follow-up, nine patients had seizures (mainly partial) despite specific treatment for Cbl C/D deficiency and antiepileptic drugs. Focal or multifocal epileptiform abnormalities during waking EEG that increased during sleep EEG were recorded in the majority of patients. Plasma levels of homocystine and homocysteine were constantly higher than normal, despite therapy institution.. Epilepsy and EEG abnormalities are prominent features in the early-onset type of combined methylmalonic aciduria and homocystinuria due to Cbl C/D deficiency, possibly related to the pathologically and persistently high levels of homocysteine, experimentally proven to induce seizures. Plasma amino acids evaluation and urinary acid organic analysis should be performed in any infant showing seizures associated with feeding difficulties and failure to thrive, at onset during the first year of life, as well as in any child with convulsive status epilepticus and a history of psychomotor developmental delay of unknown origin.

Topics: Age of Onset; Brain; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Homocysteine; Homocystine; Homocystinuria; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Male; Methylmalonic Acid; Sleep; Vitamin B 12; Vitamin B 12 Deficiency; Wakefulness

Low folate levels have consistently been reported in patients with epilepsy on phenytoin (PHT), phenobarbital (PB) and primidone (PRD), while data on valproate (VPA) are conflicting. Furthermore, antiepileptic drugs (AEDs) may be associated with high levels of plasma total homocysteine (p-tHcy). Therefore, we have investigated the levels of p-tHcy, serum folate (S-FA) and erythrocyte folate (E-FA) in patients on PHT, PB and PRD (Group 1, n=21) and VPA (Group 2, n=24). Both groups had their own matched controls. Blood samples were drawn fasting and 6 h post methionine loading (6 h-PML). The Group 1 patients had fasting and 6 h-PML p-tHcy levels significantly higher than their controls (P=0.05 and <0.0001, respectively), and patients without dietary multivitamin supplementation (n=14), had lower fasting S-FA and E-FA levels than their controls (P=0.02 and 0.0003, respectively). The Group 2 patients had fasting and 6 h-PML levels of p-tHcy, S-FA and E-FA not different from their controls. In a multiple stepwise regression model comprising all subjects (n=90), the AEDs of Group 1 and the S-FA levels were independent predictors of p-tHcy levels. Thus, PHT, PB and PRD are associated with high p-tHcy and low folate levels, whereas VPA does not influence S-FA, E-FA and p-tHcy levels in adult patients.

Topics: Adult; Amino Acid Substitution; Anticonvulsants; Cholesterol; Cholesterol, HDL; Confidence Intervals; Cysteine; Epilepsy; Fasting; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Mutation; Predictive Value of Tests; Prevalence; Statistics, Nonparametric; Threonine; Triglycerides; Vitamin B 12

A few reports have shown elevated fasting total plasma homocysteine (tHcy) in patients taking antiepileptic drugs (AEDs). In this study we determined the influence of AEDs on plasma tHcy levels prior to and following methionine loading.. Thirty-four patients on different AEDs and 34 matched controls were recruited. Blood samples were drawn prior to and 6 h post-methionine loading (6h-PML).. The patients on AEDs inducing the cytochrome P450 (carbamazepine, phenytoin, phenobarbital, primidone), had higher fasting and 6h-PML plasma tHcy concentrations than the controls (P = 0.01 and P<0.001). Patients on AED inhibiting the cytochrome P450 (valproate [VPA]), had lower 6h-PML p-tHcy concentrations than controls (P = 0.01).. Our data indicate that not only fasting but also 6h-PML tHcy levels should be determined in order to identify hyperhomocysteinemia among patients on AEDs. Inducer AEDs seem to have an opposite effect than the inhibitor VPA on plasma tHcy, erythrocyte folate and serum folate levels.

Topics: Adult; Aged; Anticonvulsants; Carbamazepine; Case-Control Studies; Cytochrome P-450 Enzyme System; Epilepsy; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Methionine; Middle Aged; Phenobarbital; Phenytoin; Primidone; Treatment Outcome; Valproic Acid; Vitamin B 12

Homocysteine is an experimental convulsant and an established risk factor in atherosclerosis. A nutritional deficiency of vitamin B6, vitamin B12, or folate leads to increased homocysteine plasma concentrations. During treatment with carbamazepine (CBZ), phenytoin, or phenobarbital, a deficiency in these vitamins is common. The objective of the study was to test the hypothesis that antiepileptic drug (AED) treatment is associated with increased homocysteine plasma concentrations.. A total of 51 consecutive outpatients of our epilepsy clinic receiving stable, individually adjusted AED treatment and 51 sex- and age-matched controls were enrolled in the study. Concentrations of total homocysteine and vitamin B6 were measured in plasma; vitamin B12 and folate were measured in the serum of fasted subjects.. Patients and controls differed significantly in concentrations of folate ( 13.5+/-1.0 vs. 17.4+/-0.8 nM and vitamin B6 (39.7+/-3.4 vs. 66.2+/-7.5 nM), whereas serum concentrations of vitamin B12 were similar. The homocysteine plasma concentration was significantly increased to 14.7+/-3.0 microM in patients compared with controls (9.5+/-0.5 microM; p < 0.05, Wilcoxon rank-sum test). The number of patients with concentrations of >15 microM was significantly higher in the patient group than among controls. The same result was obtained if only patients with CBZ monotherapy were included. Patients with increased homocysteine plasma concentrations had lower folate concentrations.. These data support the hypothesis that prolonged AED treatment may increase plasma concentrations of homocysteine, although the alternative explanation that increased homocysteine plasma concentrations are associated with the disease and not the treatment cannot be completely excluded at the moment.

Topics: Age Factors; Ambulatory Care; Anticonvulsants; Carbamazepine; Convulsants; Depression, Chemical; Epilepsy; Fasting; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Male; Middle Aged; Phenobarbital; Phenytoin; Pyridoxine; Risk Factors; Sex Factors; Valproic Acid; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6 Deficiency

Basic haematologic parameters and serum gamma-glutamyl-transferase (GGT) activity were evaluated in a five-year prospective follow-up study of 25 patients with newly diagnosed epilepsy starting treatment with carbamazepine. In addition, we evaluated the effects of replacing carbamazepine by oxcarbazepine on these parameters, erythrocyte folate concentrations and serum vitamin B12 levels in 12 male patients with epilepsy. The mean white blood cell count (WBC) and red blood cell count decreased after 2 months carbamazepine therapy, and remained at this lower level during the first 5 years of medication. The mean erythrocyte volume (MCV) and the serum GGT activity increased progressively during carbamazepine treatment. The serum GGT activity decreased after replacing carbamazepine by oxcarbazepine indicating a normalization of the liver P450 enzyme system induction. Concomitantly, the erythrocyte folate concentrations and serum levels of vitamin B12 increased, and the WBC increased and MCV decreased. It is probable that the changes in folate metabolism and serum vitamin B12 concentrations are due to normalization of the liver P450 enzyme system induction after the change of medication. The haematologic changes during carbamazepine medication, and their normalization after replacing carbamazepine by oxcarbazepine are possibly related to changes in folate and vitamin B12 metabolism.

Topics: Adolescent; Adult; Anticonvulsants; Blood Cell Count; Carbamazepine; Cytochrome P-450 Enzyme System; Epilepsy; Erythrocytes; Folic Acid; gamma-Glutamyltransferase; Humans; Liver; Male; Oxcarbazepine; Vitamin B 12

Plasma total homocysteine (tHcy) and serum folate (FA) concentrations were measured in 130 epileptic patients taking anticonvulsant drugs. A significant inverse correlation was found between FA and tHcy. This was greater in the older group (> or = 15 years) than in the younger group (1 to 14 years). There were four FA-deficient patients (FA concentration < 3 ng/mL regardless of symptoms), including three patients in the older group and one in the younger group. All FA-deficient patients had received long-term treatment (> 7 years) with multiple anticonvulsants. Their tHcy levels were higher than the 90th percentile of those in control subjects. Two patients showed extremely high levels of tHcy (57.9 and 29.1 mumol/L) and subnormal plasma methionine levels. After FA therapy, their tHcy decreased to levels the same as or less than those of control subjects and FA increased to above the normal range. Based on these findings, we conclude that measuring FA and tHcy concentrations may be useful for preventing thrombosis due to hyperhomocysteinemia in epileptic patients taking anticonvulsants, particularly those who receive long-term treatment with multiple agents.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Infant; Male; Vitamin B 12

Two groups of mentally handicapped residents were studied consisting of 32 epileptics on anti-epileptic medication and 32 non-epileptic controls. The epileptic group showed a significantly low serum folate level compared with the non-epileptic control group. Serum vitamin B12 and behaviour rating did not show any significant difference between two groups. Comparison of patients receiving phenytoin and those who were not showed significantly lower serum folate in the sub-group receiving phenytoin, but there was no significant difference between the sub-groups with respect to vitamin B12 or behaviour problem rating.

Topics: Adolescent; Adult; Aged; Epilepsy; Female; Folic Acid; Humans; Intellectual Disability; Male; Mental Disorders; Middle Aged; Phenytoin; Vitamin B 12

Topics: Adult; Anticonvulsants; Biotin; Epilepsy; Erythrocytes; Female; Humans; Male; Pyridoxal Phosphate; Pyridoxine; Riboflavin; Risk; Sex Factors; Thiamine; Vitamin B 12

The frequency of the cases which showed the toxic levels and the relationship between the serum levels and mental symptoms were discussed on the basis of determination of the serum antiepileptic drugs. This was aimed at recognizing the effects of drug therapy in the appearance of some psychiatric symptoms in patients with epilepsy. The serum levels of folate and vitamin B12 were measured simultaneously to examine the relationship with some mental change. The direct cause-and-effect relationship could not be demonstrated between the serum levels and the mental symptoms.

Topics: Anticonvulsants; Barbiturates; Carbamazepine; Epilepsy; Folic Acid; Humans; Kinetics; Mental Disorders; Phenobarbital; Phenytoin; Primidone; Valproic Acid; Vitamin B 12

The relationship between serum folate level and psychological disturbances was studied in a series of 95 chronic epileptic outpatients. All were nondrinkers. Serum folic acid in all cases and vitamin B12 in 83 cases were determined by radioimmunoassay. Only three factors were significantly related with psychological disturbances: serum levels of folic acid were significantly lower and the mean corpuscular volume of the erythrocytes was significantly higher in disturbed patients, particularly in those with the most severe psychiatric syndromes, and the incidence of disturbances was significantly higher in patients treated with three or more drugs. Conversely, variables such as number or type of seizures, duration of epilepsy, duration of treatment, presence of structural neurological lesions, previous mental retardation, or focal temporal lobe disturbances in the EEG did not show any statistical relationship to the presence of psychological disturbances. No relevant relationship was found between serum vitamin B12 and psychological disturbances.

Topics: Adolescent; Adult; Aged; Child; Chronic Disease; Epilepsy; Female; Folic Acid; Humans; Male; Mental Disorders; Middle Aged; Vitamin B 12

A 7 1/2-year-old girl with a rare defect in cobalamin (vitamin B12) metabolism ("cobalamin C" type) developed epileptiform ocular and eyelid movements as the major clinical manifestation of the disease. One of three other patients who have been described with congenital syndrome was similarly noted to have "fluttering" of the eyelids interpreted as epileptic discharges. The metabolic abnormality produced a defect in synthesis of cobalamin coenzymes. It is characterized biochemically by the excreation of methylmalonic acid and homocystine in the urine.

Topics: Child; Child, Preschool; Cobamides; Epilepsy; Eye Movements; Eyelid Diseases; Female; Homocystinuria; Humans; Malonates; Metabolism, Inborn Errors; Methylmalonic Acid; Syndrome; Vitamin B 12

Immunoglubulin concentrations were determined by radial immunodiffusion in sera from 15 epileptic patients before and during phenytoin therapy. Three reaction patterns were recorded: Two patients developed IgA deficiency (less than 0.05 mg/ml) during the first 3-4 months of treatment. Both patients also had a decrease in serum IgG and IgM, but no significant fall or increase in serum IgE. The IgA deficiency state was apparently reversible, since normalization of serum levels occurred after withdrawal of phenytoin. Five patients developed a 35-80 per cent reduction in serum IgA. In these patients, the decline in serum levels of IgG and IgM was inconsistent. Eight patients showed no significant fluctuations in serum immunoglobulins during phenytoin treatment. When a fall in serum IgA occurred, it did not correspond to a fall in serum or in red cell folate. Mean serum IgG was lower (9.37 mg/ml) in epileptic patients who had taken phenytoin for less than 1 year and had a low IgA, than in patients who had taken phenytoin for 10 years or more (11.50 mg/ml).

Topics: Adolescent; Adult; Child; Depression, Chemical; Epilepsy; Erythrocytes; Female; Folic Acid; Humans; Immunoglobulin A; Immunoglobulin E; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Male; Phenytoin; Vitamin B 12

Normal red cells in man were found to contain predominantly folate pentaglutamates with smaller amounts of tetra- and hexapolyglutamates. There was no change in the type of polyglutamate present in red cells from patients with vitamin B12 deficiency and primary folate deficiency. In contrast to the fall in red cell polyglutamate concentration in vitamin B12 deficiency, there was a marked fall in short-chain folates in early folate deficiency (treated non-anaemic epileptics) and a fall in both short chain and long chain polyglutamates in patients with severe folate deficiency and megaloblastic anaemia. These differences in folate distribution within cells exclude a primary failure to transport methylfolate into cells as the lesion in vitamin B12 deficiency. The failure of folate polyglutamate synthesis in ivtamin B12 deficiency arises either from a failure to provide the proper substrate for polyglutamate synthesis or to a direct requirement for vitamin B12 for polyglutamate synthesis.

Topics: Anemia, Pernicious; Epilepsy; Erythrocytes; Folic Acid; Folic Acid Deficiency; Glutamates; Humans; Peptide Biosynthesis; Peptides; Vitamin B 12; Vitamin B 12 Deficiency

Mean motor conduction velocity of posterior tibial nerves was significantly reduced in epileptic patients treated with diphenylhydantoin formore than 10 years or in patients with serum diphenylhydantoin level above 20 mug/ml. Subnormal serum folate was not responsible for this reduction and clinical peripheral neuropathy was infrequent.

Topics: Adolescent; Adult; Epilepsy; Folic Acid; Humans; Male; Middle Aged; Motor Neurons; Neural Conduction; Peripheral Nervous System Diseases; Phenytoin; Time Factors; Vitamin B 12

Serum pyridoxal, folate, and vitamin B12 concentrations were measured in 68 institutionalized patients with severe epilepsy. Twenty-five patients had a reduced level of pyridoxal and thirty-three a reduced level of folate. There was no instance of a low serum vitamin B12 although in three patients the levels were found to be abnormally high. Fifteen patients had both a low serum pyridoxal and a low serum folate but there was no significant correlation. All patients had a normal hemoglobin concentration and a normal mean corpuscular volume. There was no close relationship between reduced serum vitamin levels and single or groups of anticonvulsant agents, although the size of the groups was too small to permit a detailed study.

Topics: Adolescent; Adult; Age Factors; Epilepsy; Female; Folic Acid; Humans; Male; Middle Aged; Pyridoxal; Sex Factors; Vitamin B 12

In 27 drug-treated epileptics there was a significant fall in serum, red cell and CSF folate levels compared with 15 untreated epileptics and 22 neurological controls. The 3 folate parameters were positively correlated with each other and negatively correlated with serum phenobarbitone, diphenylhydantoin and primidone. There was also a significant elevation of CSF 5-hydroxyindoleacetic acid (5HIAA) in the drug-treated epileptics; but this was not seen until "therapeutic" serum levels of phenobarbitone and diphenylhydantoin had been achieved and was most marked in clinically intoxicated patients. Similar trends were observed in CSF homovanillic acid (HVA). CSF 5HIAA and HVA were positively correlated with each other, especially in the drug-treated patients, in whom both amine metabolites were also negatively correlated with CSF folate. A possible relationship between folate and monoamine metabolism is discussed with particular reference to the antiepileptic and toxic effects of phenobarbitone, diphenylhydantoin and primidone.

Topics: Adolescent; Adult; Anticonvulsants; Biogenic Amines; Epilepsy; Erythrocytes; Folic Acid; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Middle Aged; Phenobarbital; Phenytoin; Primidone; Vitamin B 12

Topics: Adult; Aged; Alcohol Amnestic Disorder; Alcoholism; Alkaline Phosphatase; Aspartate Aminotransferases; Biological Assay; Epilepsy; Euglena gracilis; Female; Folic Acid; Folic Acid Deficiency; Hematocrit; Hemoglobins; Humans; Lacticaseibacillus casei; Liver Diseases; Male; Middle Aged; Pyridoxal; Vitamin B 12

Topics: Adult; Aged; Carbamazepine; Electric Stimulation; Electromyography; Epilepsy; Ethosuximide; Evoked Potentials; Female; Folic Acid; Humans; Male; Median Nerve; Middle Aged; Neural Conduction; Peripheral Nerves; Peripheral Nervous System Diseases; Peroneal Nerve; Phenobarbital; Phenytoin; Primidone; Reaction Time; Reflex, Monosynaptic; Sural Nerve; Time Factors; Vitamin B 12

Topics: Anticonvulsants; Biological Assay; Child; Child, Preschool; Epilepsy; Euglena; Folic Acid; Hematocrit; Hemoglobins; Humans; Lacticaseibacillus casei; Leukocyte Count; Phenobarbital; Phenytoin; Primidone; Vitamin B 12

Topics: Adolescent; Adult; Anticonvulsants; Azo Compounds; Child; Epilepsy; Female; FIGLU Test; Folic Acid; Glutarates; Histidine; Humans; Intellectual Disability; Male; Neutrophils; Phenytoin; Vitamin B 12

Topics: Anemia, Macrocytic; Epilepsy; Folic Acid; Folic Acid Deficiency; Humans; Phenobarbital; Phenytoin; Primidone; Vitamin B 12

Topics: Anticonvulsants; Epilepsy; Folic Acid; Humans; Vitamin B 12

Topics: Acetazolamide; Adolescent; Adult; Amphetamine; Anticonvulsants; Epilepsy; Epilepsy, Temporal Lobe; Ethosuximide; Female; Folic Acid; Humans; Lactobacillus; Middle Aged; Thiazines; Vitamin B 12

Serum and red cell folate levels and serum vitamin B(12) levels have been estimated in 33 normal controls; 34 epileptic outpatients, 19 of whom also suffered from psychiatric illness; 33 epileptic inpatients with psychiatric illness; and 30 non-epileptic inpatients with psychiatric illness. Significant lowering of serum folate and red cell folate levels was observed in epileptic patients with psychiatric illness, and a less significant fall in red cell folate levels was found in non-epileptic psychiatric patients. Serum folate levels less than 2·5 ng/ml. were found in two controls, seven outpatient epileptics, 29 inpatients, and 10 non-epileptic patients. Red cell folate levels less than 100 ng/ml. were found in two controls, nine outpatient epileptics, 23 inpatient epileptics, and seven non-epileptic patients. A significant correlation was found between serum and red cell folate values in control, epileptic, and non-epileptic patients. In the epileptic patients there was a significant association between low serum and red cell folate levels and the presence of psychiatric illness. The origin and possible significance of these findings are discussed.

Topics: Adult; Antidepressive Agents; Epilepsy; Erythrocytes; Female; Folic Acid; Folic Acid Deficiency; Humans; Male; Mental Disorders; Middle Aged; Phenobarbital; Phenothiazines; Phenytoin; Vitamin B 12

Topics: Adult; Antidepressive Agents; Barbiturates; Epilepsy; Erythrocytes; Ethosuximide; Female; Folic Acid; Humans; Hydantoins; Male; Phenothiazines; Primidone; Vitamin B 12

Topics: Anticonvulsants; Epilepsy; Folic Acid; Humans; Mental Disorders; Psychotic Disorders; Schizophrenia; Vitamin B 12

Topics: Anticonvulsants; Child; Epilepsy; Folic Acid; Humans; Vitamin B 12

Folate deficiency in 50 epileptic children aged 5 to 18 years was treated with a combination of folic acid and vitamin B(12). Improvement in mental condition occurred from five to eight weeks after beginning treatment in some of the younger children; no change was noticed, however, in 31. Similarly, in 19 children fits became less frequent and less severe. It is recommended that both folic acid and vitamin B(12) should be given as soon as a patient is started on anticonvulsant drugs to prevent mental deterioration.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Folic Acid; Folic Acid Deficiency; Humans; Intellectual Disability; Male; Vitamin B 12

Topics: Adult; Anticonvulsants; Child; Epilepsy; Folic Acid; Humans; Vitamin B 12

Topics: Adult; Aged; Antidepressive Agents; Barbiturates; Chronic Disease; Epilepsy; Female; Folic Acid; Folic Acid Deficiency; Hematologic Diseases; Humans; Male; Middle Aged; Neurocognitive Disorders; Phenothiazines; Schizophrenia; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Epilepsy; Folic Acid; Humans; Vitamin B 12

An assessment of vitamin B(12) absorption in neurological patients has been made by both serum and urine counting of (57)Co cyanocobalamin during the conventional Schilling test. Although patients with pernicious anaemia, some with subacute combined degeneration of the cord, have been studied, emphasis in the discussion is placed on the significantly increased excretion of the radioactive vitamin in a group of patients with pituitary insufficiency. Results are also given for epileptic patients who have developed folate deficiency (as assessed by serum folate levels) coincidental with anticonvulsant therapy, as well as for some patients who have had neurological symptoms or signs following partial gastrectomy operations.

Topics: Adult; Aged; Anemia, Pernicious; Cobalt Isotopes; Epilepsy; Female; Folic Acid Deficiency; Humans; Hypopituitarism; Intestinal Absorption; Male; Middle Aged; Postgastrectomy Syndromes; Schilling Test; Vitamin B 12

Topics: Anticonvulsants; Epilepsy; Female; Folic Acid; Humans; Malabsorption Syndromes; Male; Vitamin B 12

Topics: Anemia; Anticonvulsants; Biological Assay; Epilepsy; Folic Acid; Hemoglobins; Humans; Lactobacillus; Vitamin B 12

Topics: Adolescent; Adult; Anticonvulsants; Epilepsy; Erythrocyte Count; Female; FIGLU Test; Folic Acid; Folic Acid Deficiency; Hematocrit; Humans; Male; Middle Aged; Neutrophils; Phenobarbital; Phenytoin; Primidone; Psychotic Disorders; Vitamin B 12

Topics: Acetazolamide; Adult; Anemia, Macrocytic; Epilepsy; Female; Folic Acid; Humans; Male; Middle Aged; Phenobarbital; Phenytoin; Primidone; Psychophysiologic Disorders; Thiazines; Vitamin B 12

Topics: Age Factors; Anemia, Macrocytic; Anticonvulsants; Brain; Epilepsy; Female; Folic Acid; Folic Acid Deficiency; Humans; Intellectual Disability; Male; Mental Disorders; Peripheral Nerves; Phenobarbital; Phenytoin; Primidone; Psychotic Disorders; Sex Factors; Spinal Cord; Vitamin B 12

Topics: Adult; Anemia, Macrocytic; Epilepsy; Female; Folic Acid; Humans; Intestinal Absorption; Phenobarbital; Phenytoin; Primidone; Vitamin B 12

Topics: Adolescent; Adult; Aged; Anticonvulsants; Biopsy; Celiac Disease; Cobalt Isotopes; Epilepsy; Female; Folic Acid; Gastrointestinal Diseases; Glucose; Histidine; Humans; Intestinal Mucosa; Intestine, Small; Jejunum; Lipid Metabolism; Malabsorption Syndromes; Male; Microscopy, Electron; Middle Aged; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anticonvulsants; Biological Assay; Blood Chemical Analysis; Enterococcus faecalis; Epilepsy; Folic Acid; Folic Acid Antagonists; Humans; Lactobacillus; Phenobarbital; Phenytoin; Primidone; Toxicology; Vitamin B 12

Topics: Anemia; Anemia, Hemolytic; Anemia, Macrocytic; Anemia, Pernicious; Anticonvulsants; Blood; Celiac Disease; Clinical Laboratory Techniques; Epilepsy; Female; FIGLU Test; Folic Acid; Folic Acid Deficiency; Formiminoglutamic Acid; Glutamates; Humans; Lymphoma; Lymphoma, Non-Hodgkin; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Urine; Vitamin B 12; Vitamin B Deficiency

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Brain Diseases; Cysticercosis; Drug Therapy; Epilepsy; Folic Acid; Humans; Iatrogenic Disease; Phenobarbital; Phenytoin; Primidone; Spinal Cord; Toxicology; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Blood Platelet Disorders; Drug Therapy; Epilepsy; Female; Folic Acid; Hemorrhage; Humans; Phenobarbital; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Primidone; Thrombocytopenia; Toxicology; Vitamin B 12

Topics: Amobarbital; Anemia, Macrocytic; Anemia, Megaloblastic; Anticonvulsants; Barbiturates; Epilepsy; Folic Acid; Humans; Metabolism; Phenobarbital; Phenytoin; Primidone; Toxicology; Vitamin B 12

Topics: Blood; Central Nervous System Diseases; Cerebrospinal Fluid; Cysticercosis; Epilepsy; Humans; Hydrocephalus; Meningitis; Neurosyphilis; Peripheral Nervous System Diseases; Polyradiculopathy; Spinal Cord; Sulfonamides; Vitamin B 12

Topics: Anemia; Anemia, Pernicious; Antacids; Anti-Bacterial Agents; Arthritis; Arthritis, Rheumatoid; Blood Pressure; Cortisone; Dibenzylchlorethamine; Dicumarol; Epilepsy; Ergot Alkaloids; Heart Failure; Heparin; Histamine Antagonists; Humans; Hyaluronoglucosaminidase; Hydantoins; Hypersensitivity; Hypertension; Hyperthyroidism; Imidazoles; Iodine; Iodine Isotopes; Kidney; Meperidine; Mephenesin; Methadone; Motion Sickness; Norepinephrine; Organomercury Compounds; Peptic Ulcer; Tetraethylammonium; Therapeutics; Thiouracil; Thrombosis; Veratrum; Vitamin B 12