Parampreet Kharbanda

Pharmacokinetic interaction of single dose of piperine with steady-state carbamazepine in epilepsy patients.

Piperine, the active principle of piper species, is commonly used as a spice and adjuvant in various traditional systems of medicine. It has been known as a bioavailability‐enhancer. The present study aimed at evaluating the effect of piperine on the steady‐state pharmacokinetics of a single dose of carbamazepine in poorly controlled epilepsy patients on carbamazepine monotherapy. Patients (n = 10 each) receiving either 300 mg or 500 mg dose of carbamazepine twice daily were selected. After administration of carbamazepine, venous blood samples were collected at 0, 0.5, 1, 2, 4, 6, 9, 12 h. Subsequently, piperine (20 mg p.o.) was administered along with carbamazepine and samples were collected similarly. The pharmacokinetic parameters were compared by Students t‐test. Piperine significantly increased the mean plasma concentrations of carbamazepine at most of the time points in both dose groups. There was a significant increase in AUC0‐12hr (p < 0.001), average Css (p < 0.001), t1\2el (p < 0.05) and a decrease in Kel (p < 0.05), in both the dose groups, whereas changes in Ka and t1\2a were not significant. Cmax (p < 0.01) and tmax (p < 0.01) were increased significantly following piperine administration in the 500 mg dose group; however, these parameters were not significant in the lower dose group. Piperine could significantly enhance the oral bioavailability of carbamazepine, possibly by decreasing the elimination and/or by increasing its absorption. Copyright

Sodium Valproate, Hyperandrogenism and Altered Ovarian Function in Indian Women with Epilepsy: A Prospective Study

Summary:  Purpose: To assess the association of long‐term sodium valproate therapy with reproductive endocrine disorders in Indian women with generalized epilepsy.

Seizure type, antiepileptic drugs, and reproductive endocrine dysfunction in Indian women with epilepsy: a cross-sectional study.

Background:  There is paucity of data regarding occurrence of reproductive endocrine disorders in Asian women with epilepsy (WWE) on antiepileptic drug (AED) therapy.

Peripheral neuropathy in liver cirrhosis

Background and Aims:  Neuropathy in association with chronic liver disease, including cirrhosis, is recognized; however, there are differences in the incidence and type of neuropathy reported. The causal relationship of liver disease to neuropathy has been questioned. This study was designed to evaluate the incidence and character of peripheral neuropathy in patients with liver cirrhosis. The effect of alcohol consumption, severity of liver disease and encephalopathy on the incidence and severity of neuropathy were also studied.

Sleep disturbances in drug naïve Parkinson's disease (PD) patients and effect of levodopa on sleep.

Context: Parkinsons disease (PD) is associated with sleep disturbances, attributed to the neurodegenerative process and therapeutic drugs. Studies have found levodopa to increase wakefulness in some patients while increasing sleepiness in others. Aims: To confirm sleep disturbances in drug naïve PD patients and understand the impact of levodopa on their sleep. Materials and Methods: Twenty-three drug naïve PD patients and 31 age-gender matched controls were compared using the Parkinsons Disease Sleep Scale (PDSS) and Epworth Sleepiness Scale (ESS). A polysomnogram objectively compared sleep quality. Of the 23 patients, the 12 initiated on levodopa were reassessed subjectively and through polysomnography after 2 months of therapy. Statistical Analysis: Data was expressed as mean ± standard deviation, median, and range. Continuous variables were analyzed by Students T test for normally distributed data and Mann–Whitney U test for skewed data. Discrete variables were compared by Chi Square tests (Pearson Chi square Test or Fishers Exact Test). Wilcoxon signed ranks test was applied in the analysis of paired data pre- and post-levodopa. A P value < 0.05 was considered as statistically significant. Statistical analysis of the data was done using the Statistical Package for the Social Sciences (SPSS) version 12. Results: Drug naïve PD patients had lower PDSS scores than controls. The sleep architecture changes observed on polysomnogram were reduced NREM Stage III and REM sleep and increased sleep latency and wake after sleep onset time. Following levodopa, improved sleep efficiency with reduced sleep latency and wake after sleep onset time was noted, coupled with improved PDSS scores. However, NREM Stage III and REM sleep duration did not increase. Discussion: PD patients take longer to fall asleep and have difficulty in sleep maintenance. Sleep maintenance is affected by nocturia, REM behavioral disorder, nocturnal cramps, akinesia, and tremors, as observed in PDSS scores. Levodopa improves sleep efficiency by improving motor scores without altering sleep architecture. Conclusions: Poor sleep quality and sleep architecture changes occur secondary to the neurodegenerative process in PD patients. Though levodopa improves sleep quality by reducing rigidity and tremor, it does not reverse sleep architecture changes.

The dilemma of arranged marriages in people with epilepsy. An expert group appraisal.

INTRODUCTION Matrimony remains a challenging psychosocial problem confronting people with epilepsy (PWE). People with epilepsy are less likely to marry; however, their marital prospects are most seriously compromised in arranged marriages. AIMS The aim of this study was to document marital prospects and outcomes in PWE going through arranged marriage and to propose optimal practices for counseling PWE contemplating arranged marriage. METHODS A MEDLINE search and literature review were conducted, followed by a cross-disciplinary meeting of experts to generate consensus. RESULTS People with epilepsy experience high levels of felt and enacted stigma in arranged marriages, but the repercussions are heavily biased against women. Hiding epilepsy is common during marital negotiations but may be associated with poor medication adherence, reduced physician visits, and poor marital outcome. Although divorce rates are generally insubstantial in PWE, divorce rates appear to be higher in PWE undergoing arranged marriages. In these marriages, hiding epilepsy during marital negotiations is a risk factor for divorce. CONCLUSIONS In communities in which arranged marriages are common, physicians caring for PWE are best-equipped to counsel them about their marital prospects. Marital plans and aspirations should be discussed with the family of the person with epilepsy in a timely and proactive manner. The benefits of disclosing epilepsy during marital negotiations should be underscored.

Neurocysticercosis: An uncommon cause of drug-refractory epilepsy in North Indian population.

Being a common cause of epilepsy in endemic areas, neurocysticercosis (NCC) is expected to account for a sizable proportion of patients with drug‐refractory epilepsy (DRE) as well. However, data regarding prevalence of DRE in NCC are sparse. This study aimed to determine the prevalence of DRE as well as identification of clinical and radiologic factors that lead to DRE in patients with NCC.

Acute Flaccid paralysis in adults: Our experience.

Acute flaccid paralysis (AFP) is a complex clinical syndrome with a broad array of potential etiologies that vary with age. We present our experience of acute onset lower motor neuron paralysis. Materials and Methods: One hundred and thirty-three consecutive adult patients presenting with weakness of duration less than four weeks over 12 months period were enrolled. Detailed history, clinical examination, and relevant investigations according to a pre-defined diagnostic algorithm were carried out. The patients were followed through their hospital stay till discharge or death. Results: The mean age was 33.27 (range 13-89) years with male preponderance (67.7%). The most common etiology was neuroparalytic snake envenomation (51.9%), followed by Guillain Barre syndrome (33.1%), constituting 85% of all patients. Hypokalemic paralysis (7.5%) and acute intermittent porphyria (4.5%) were the other important conditions. We did not encounter any case of acute polio mylitis in adults. In-hospital mortality due to respiratory paralysis was 9%. Conclusion: Neuroparalytic snakebite and Guillain Barre syndrome were the most common causes of acute flaccid paralysis in adults in our study.

Phenotypic interaction of simultaneously administered isoniazid and phenytoin in patients with tuberculous meningitis or tuberculoma having seizures.

Treatment of tuberculous meningitis or tuberculoma has become complicated because of adverse drug interactions found amongst antitubercular and anticonvulsant drugs. The aim of the study is to evaluate the effect of simultaneously administered isoniazid (300 mg/day) and phenytoin (300 mg/day) on 60 patients with tuberculous meningitis or tuberculoma having seizures. Plasma samples were analyzed for isoniazid, acetylated-isoniazid (AcINH) and phenytoin levels by high performance liquid chromatography at 3h of drugs administration and patients were classified as rapid or slow acetylator on the basis of metabolic ratio of isoniazid (Rm) and percentage of acetylated-isoniazid (%AcINH). Out of 60 patients studied, 23 were slow acetylators and 37 were rapid acetylators. Slow acetylators revealed higher plasma isoniazid levels and lower plasma AcINH levels, metabolic ratio and %AcINH as compared to rapid acetylators. Plasma phenytoin levels were found to be significantly higher (above therapeutic range) in slow acetylators as compared to rapid acetylators. Plasma phenytoin concentration was moderately strong, negatively correlated with metabolic ratio (r=-0.439, P<0.001) and %AcINH (r=-0.729, P<0.001). Eight comatose patients (34.8%) also showed significantly higher plasma phenytoin levels. Our results suggest that assessment of acetylator status and plasma phenytoin level is critical for dose optimization of isoniazid and phenytoin and to predict the patients at risk of intoxication.

N-acetyltransferase 2 (NAT2) gene polymorphism as a predisposing factor for phenytoin intoxication in tuberculous meningitis or tuberculoma patients having seizures - A pilot study

Background & objectives: Simultaneous administration of phenytoin and isoniazid (INH) in tuberculous meningitis (TBM) or tuberculoma patients with seizures results in higher plasma phenytoin level and thus phenytoin intoxication. N-acetyltransferase 2 (NAT2) enzyme catalyses two acetylation reactions in INH metabolism and NAT2 gene polymorphism leads to slow and rapid acetylators. The present study was aimed to evaluate the effect of allelic variants of N-acetyltransferase 2 (NAT2) gene as a predisposing factor for phenytoin toxicity in patients with TBM or tuberculoma having seizures, and taking INH and phenytoin simultaneously. Methods: Sixty patients with TBM or tuberculoma with seizures and taking INH and phenytoin simultaneously for a minimum period of seven days were included in study. Plasma phenytoin was measured by high performance liquid chromatography. NAT2 gene polymorphism was studied using restriction fragment length polymorphism and allele specific PCR. Results: The patients were grouped into those having phenytoin intoxication and those with normal phenytoin level, and also classified as rapid or slow acetylators by NAT2 genotyping. Genotypic analysis showed that of the seven SNPs (single nucleotide polymorphisms) of NAT2 gene studied, six mutations were found to be associated with phenytoin intoxication. For rs1041983 (C282T), rs1799929 (C481T), rs1799931 (G857A), rs1799930 (G590A), rs1208 (A803G) and rs1801280 (T341C) allelic variants, the proportion of homozygous mutant was higher in phenytoin intoxicated group than in phenytoin non-intoxicated group. Interpretation & conclusions: Homozygous mutant allele of NAT2 gene at 481site may act as a predisposing factor for phenytoin intoxication among TBM or tuberculoma patients having seizures.