Homocysteine Metabolism and Hematological Parameters in Early Stage of Phenytoin Treated Epileptic Children.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Serum Homocysteine, Folate, and Vitamin B12 Levels in Carbamazepine Treated Epileptic Children.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Evaluate the Effect of Valproate Monotherapy on the Serum Homocysteine, Folate and Vitamin B12 Levels in Epileptic Children.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Subclinical hypothyroidism and its association with cardiovascular risk factors.

BACKGROUND: Subclinical hypothyroidism (SH) represents the mildest form of thyroid hormone deficiency and may be associated with adverse consequences [Subclinical hypothyroidism was defined as a TSH level > 4.0 mIU/L and a normal free thyroxine level 0.6-1.8 ng/dL]. The identification of patients with subclinical hypothyroidism having an increased cardiovascular risk (CVR) is important. The aim of the study was to evaluate atherosclerotic risk factors in patients with subclinical hypothyroidism. METHODS: Forty patients with subclinical hypothyroidism and forty healthy euthyroid controls, age and gender matched were included in the study. Serum total triiodothyronine (T3), thyroxine (T4), TSH, free T3 (FT3) and free T4 (FT4) were measured by enzyme linked immunosorbent assay (ELISA). Atherosclerotic risk factors measured were high sensitivity-CRP (hs-CRP), Lipoprotein (a) [Lp (a)] and lipid parameters. Lipid parameters (triglycerides, total cholesterol and high density lipoprotein cholesterol) were analysed by enzymatic colorimetric, endpoint method whereas the hs-CRP and Lp (a) were measured by quantitative latex turbidimetric method. RESULTS: Patients with subclinical hypothyroidism had significantly higher levels of serum hs-CRP, Lp (a), total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) when compared to same parameters of controls. Further, a significant positive correlation was observed between TSH and hs-CRP, Lp (a), LDL-C and TC in subjects with subclinical hypothyroidism. However, TG levels showed no significant correlation with TSH levels. CONCLUSIONS: We concluded that the SH patients presented increased concentration of some CVR factors. The potential benefits of diagnosis and treatment of subclinical hypothyroidism may have possible advantages firstly by preventing the progression to overt hypothyroidism and secondly decrease the risk of death from cardiovascular disease (CVD) by starting appropriate therapy to improve lipid parameters. Further research is needed on subclinical hypothyroidism and the associated atherosclerotic risk factors.