Significance of MDR1 gene polymorphism C3435T in predicting drug response in epilepsy.

Antiepileptic drug (AED) treatment in epilepsy is often compromised by the unpredictability of efficacy and inter-individual variability among patients, which at least in part is the result of genetic variation. The idea to determine an individual's response to a prescribed medicine came into inception around 29 years ago. Pharmacogenetics is used to predict the drug response and efficacy, as well as potential adverse effects. We investigated the functional significance of the C3435T polymorphism of the MDR1 gene in a South Indian population. The patients were divided into responders and non-responders based on their clinical outcome and AED response. The risk of drug resistance was significantly higher in patients bearing TT genotype in comparison to carriers of the homozygous CC genotype [TT vs. CC, χ(2)=12.52; p=0.001, Odds ratio=2.34 (95% CI: 1.942-11.32)]. We suggest that the influence of the C3435T polymorphism in predicting the drug-resistance in epilepsy, might be significant and further investigations focusing on carbamazepine and phenytoin, in various ethnic populations are necessary to clarify the effect of C3435T polymorphism on the multidrug resistance in epilepsy patients.

Risk factors, clinical profile, and long-term outcome of 428 patients of cerebral sinus venous thrombosis: insights from Nizam's Institute Venous Stroke Registry, Hyderabad (India).

BACKGROUND: With the widespread use of neuroimaging and hematological workup, many of the previously held concepts about cerebral sinus venous thrombosis (CSVT) are changing. OBJECTIVE: The objective of this study was to investigate the risk factors, clinical profile, and outcome of the fully investigated cases of CSVT from a major university referral hospital in South India. MATERIALS AND METHODS: Consecutive patients of CSVT confirmed by definite neuroimaging criteria and fully investigated for prothrombotic states, between June 2002 and September 2010, were prospectively studied in the Venous Stroke Registry of Nizam's Institute of Medical Sciences, Hyderabad, South India. RESULTS: Of the 428 patients, 230 (53.7%) were men and the mean age was 31.3 years (range 8-65 years). Seizures were noted in 126 (29.4%) patients, stroke like presentation was found in 122 (28.5%) patients, and benign intracranial hypertension like presentation was found in 78 (18.2%) patients. Common risk factors were anemia in 79 (18.4%), hyperhomocysteinemia in 78 (18.2%), alcoholism in 67 (15.6%), oral contraceptive pill intake in 49 (11.4%), postpartum state in 42 (9.8%), anticardiolipin antibodies in 31 (7.2%), and protein S deficiency in 53 (12.3%) patients. Good outcome at 90 days (modified Rankin Scale £ 2) was observed in 273 (71.2%) of 383 patients available for follow-up. In-house mortality was noted in 33 (7.7%) and recurrence in 22 (5.1%) patients. CONCLUSIONS: Compared to the previous studies, prevalence of CSVT was higher in men. Anemia, hyperhomocysteinemia, alcoholism, oral contraceptive use, and postpartum state were the most common risk factors. Overall prognosis was good, but a small percentage of patients died or showed recurrence.

Predictors of major neurological improvement after intravenous thrombolysis in acute ischemic stroke: a hospital-based study from south India.

BACKGROUND: Despite the increasing use of recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke, uncertainty persists about the short- and long-term outcome of the thrombolysed patients. OBJECTIVE: To identify predictors of major neurological improvement at 24 h after intravenous rt-PA administration in patients of acute ischemic stroke and their relationship with outcome at 12 months. MATERIALS AND METHODS: We analyzed the data of the patients with acute ischemic stroke treated as per the National Institute of Neurological Disorders and Stroke (NINDS) criteria with intravenous rt-PA between January 2000 and June 2009 at a tertiary care center in south India. Major neurological improvement was defined by an 8-point improvement in National Institute of Health Stroke Scale (NIHSS) score or an NIHSS score of 0 or 1 at 24 h. Good outcome was defined as a 12-month modified Rankin Scale (mRS) of 0 to 1. RESULTS: Of the 72 patients with acute ischemic stroke treated with intravenous rt-PA, 23 (32%) patients had major neurological improvement at 24 h. Age <60 years (OR 1.9, 95% CI 1.7 to 3.2), admission glucose levels <8 mmol/L (OR 3.87, 95% CI 1.9 to 9.2) and mild to moderate baseline stroke severity (NIHSS median score 10+ 6) were associated with major neurological improvement after adjusting for co variables. Major neurological improvement at 24 h was an independent predictor of good outcome (mRS=1) at 12 months (OR 13.9, 95% CI 6.84 to 40.2). CONCLUSIONS: Age <60 years, glucose levels <8 mmol/L and mild to moderate stroke severity (NIHSS median score 10+/-6) was associated with major neurological improvement after intravenous rt-PA. Major neurological improvement at 24 h after the administration of intravenous thrombolysis independently predicted good outcome at 12 months.