Comparative Analysis of Hemispherotomy in Adults versus Children- A Prospective Observational Series.

BACKGROUND: Hemispherotomy (HS) is an effective treatment for unilateral hemispheric onset epilepsy. There are few publications for HS in adults, and there is no series comparing adults and pediatric patients of HS. OBJECTIVE: To compare the hemispherotomies done in adult patients with pediatric ones in terms of efficacy and safety. METHODS: Data was prospectively collected for HS patients (up to 18 years and more) from Aug 2014 to Aug 2018. Comparison between the groups was made for seizure onset, duration of epilepsy, frequency of seizures, number of drugs, intraoperative blood loss, postoperative seizure control, postoperative stay, postoperative motor functions, and preoperative and postoperative intelligence quotient. Follow-up was one year. RESULTS: A total of 61 pediatric and 11 adults underwent HS. The seizure onset was earlier in children, and the duration of epilepsy was longer in adults. The frequency of seizures per day was more in children being 14.62 ± 26.34 in children, and 7.71 ± 5.21 per day in adults (P - 0.49). The mean number of drugs was similar in the preoperative and postoperative periods in both. Class I seizure outcome was similar in both the groups being 85.24% in children and 90.9% in adults (P - 0.56). Blood loss, postoperative stay, was similar in both the groups. No patient had a new permanent motor deficit. Power worsened transiently in 1 pediatric patient and in 4 adult patients. The visual word reading and object naming improved in both the groups (no intergroup difference), and IQ remained the same in both groups. One adult patient had meningitis, and another had hydrocephalus requiring shunt placement. CONCLUSION: Hemispherotomy is a safe and effective procedure in adults as in children in appropriately selected patients.

Effectiveness of Yoga Intervention in Reducing Felt Stigma in Adults With Epilepsy: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Persons with epilepsy are afflicted with comorbidities such as stigma, anxiety, and depression which have a significant impact on their quality of life. These comorbidities remain largely unaddressed in resource-limited countries. This randomized controlled trial (RCT) aimed to investigate whether yoga and psychoeducation were effective in reducing felt stigma (primary outcome), neuropsychiatric outcomes, and seizure frequency, as compared with sham yoga and psychoeducation in persons with epilepsy. METHODS: This was an assessor-blinded, sham yoga-controlled RCT. Patients clinically diagnosed with epilepsy, aged 18-60 years, and scoring higher than the cutoff score for felt stigma as measured by the Kilifi Stigma Scale (KSS) in our population were randomly assigned to receive either yoga therapy plus psychoeducation (intervention) or sham yoga therapy plus psychoeducation (comparator) for a duration of 3 months. The primary outcome was a significant decrease in felt stigma as compared with the comparator arm as measured by the KSS. Primary and secondary outcomes (seizure frequency, quality of life, anxiety, depression, mindfulness, trait rumination, cognitive impairment, emotion regulation) were assessed at baseline, 3 months, and 6 months. Parametric/nonparametric analysis of covariance and the χ2 test were used to compare the 2 arms. RESULTS: A total of 160 patients were enrolled in the trial. At the end of the follow-up period (6 months), the intervention arm reported significant reduction in felt stigma as compared with the control arm (Cohen's d = 0.23, 95% CI -0.08 to 0.55, p = 0.006). Significantly higher odds of >50% seizure reduction (odds ratio [OR] 4.11, 95% CI 1.34-14.69, p = 0.01) and complete seizure remission (OR 7.4, 95% CI 1.75-55.89, p = 0.005) were also observed in the intervention group. The intervention group showed significant improvement in symptoms of anxiety, cognitive impairment, mindfulness, and quality of life relative to the control group at the end of follow-up period (p < 0.05). DISCUSSION: Yoga can alleviate the burden of epilepsy and improve the overall quality of life in epilepsy by reducing perceived stigma. TRIAL REGISTRATION INFORMATION: Clinical Trials Registry of India (CTRI/2017/04/008385). CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that yoga reduces felt stigma in adult patients with epilepsy.

VE-MMODE - A randomized controlled trial of Venlafaxine versus Escitalopram for treatment of mild to moderate depression in persons with epilepsy.

OBJECTIVES: Depression in persons with epilepsy (PWE) goes undiagnosed and untreated. Despite being common, there are no direct efficacy comparisons of available antidepressants in PWE. Our aim was to compare the effectiveness of Venlafaxine (VEN) and Escitalopram (ESCIT) in comorbid depression in PWE. METHODS: In a single-center, prospective, double-blinded randomized controlled trial (RCT) 90 PWE (age ≥18 years) with mild to moderate depression, were randomized in a 1:1 ratio to receive ESCIT (5-20 mg/day) or VEN (37.5-150 mg/day) for 8 weeks. The primary outcome was to study differences in the efficacy, based on the change in scores of the Hamilton depression rating scale (HAM-D) at 8 weeks. Seizure frequency, QOLIE-31, adverse event profile, and medication adherence were secondary outcome measures. RESULTS: Using the NDDI-E scale, we screened 350 PWE, 90 were enrolled. ITT analysis included all participants and the PP analysis included 40 participants to VEN group and 42 to ESCIT group. Baseline mean (±SD) HAM-D scores for both groups were similar (13.53 ± 3.27; 13.02 ± 3.57). The mean difference (95%CI) on HAM-D scores at 8 weeks was found to be significant within both groups (ITT/PP- VEN: 7.75(6.75, 8.79)/7.92 (7.06, 8.78); p < 0.001, ESCIT: 8.21 (7.39, 9.03)/8.23(7.43, 9.04); p < 0.001). However, there was no significant difference in the efficacy of VEN versus ESCIT at 8 weeks. A significant improvement in QOLIE-31 index and seizure frequency was observed from baseline in both the groups. 90% of those on VEN and 92.9% of those using ESCITadhered to the treatment at week 8. Adverse events were more in VEN group than the ESCIT group. CONCLUSIONS: This study found that HAMD scores improved significantly in the ESCIT and VEN groups, despite the fact that there was no clinically meaningful difference observed between the two groups. Trials with a larger sample size and longer duration are required to establish whether ESCIT or VEN is superior.

Role of Gut Microbiota in Neurological Disorders and Its Therapeutic Significance.

In humans, the gut microbiota (GM) are known to play a significant role in the metabolism of nutrients and drugs, immunomodulation, and pathogen defense by inhabiting the gastrointestinal tract (GIT). The role of the GM in the gut-brain axis (GBA) has been documented for different regulatory mechanisms and associated pathways and it shows different behaviors with individualized bacteria. In addition, the GM are known as susceptibility factor for neurological disorders in the central nervous system (CNS), regulating disease progression and being amenable to intervention. Bidirectional transmission between the brain and the GM occurs in the GBA, implying that it performs a significant role in neurocrine, endocrine, and immune-mediated signaling pathways. The GM regulates multiple neurological disorders by supplementing them with prebiotics, probiotics, postbiotics, synbiotics, fecal transplantations, and/or antibiotics. A well-balanced diet is critically important for establishing healthy GM, which can alter the enteric nervous system (ENS) and regulate multiple neurological disorders. Here, we have discussed the function of the GM in the GBA from the gut to the brain and the brain to the gut, the pathways associated with neurology that interacts with the GM, and the various neurological disorders associated with the GM. Furthermore, we have highlighted the recent advances and future prospects of the GBA, which may require addressing research concerns about GM and associated neurological disorders.

Safety, Efficacy, and Tolerability of Modified Atkins Diet in Persons With Drug-Resistant Epilepsy: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Modified Atkins diet (MAD) has emerged as an adjuvant therapy in drug-resistant epilepsy (DRE). Most studies are in children; there is limited evidence for DRE in adults. This study aimed to investigate whether MAD along with standard drug therapy (SDT) was indeed more effective than SDT alone in reducing seizure frequency and improving psychological outcomes at 6 months in adolescents and adults with DRE (nonsurgical). METHODS: A prospective randomized controlled trial was conducted at tertiary care referral center in India. Persons with DRE aged 10-55 years attending outpatient epilepsy clinics between August 2015 and April 2019, who had more than 2 seizures per month despite using at least 3 appropriate antiseizure medications (ASMs) at their maximum tolerated doses and had not been on any form of diet therapy for the past 1 year, were enrolled. Patients were assessed for the eligibility and randomly assigned to receive SDT plus MAD (intervention arm) or SDT alone (control arm). The primary outcome was >50% reduction in seizure frequency, and the secondary outcomes were quality of life (QOL), behavior, adverse events, and rate of withdrawal at 6 months. Intention-to-treat analysis was performed. RESULTS: A total of 243 patients were screened for eligibility; 160 patients (80 adults and 80 adolescents) were randomized to either the intervention or control arm. Demographic and clinical characteristics in both groups were comparable at baseline. At 6 months, >50% seizure reduction was seen in 26.2% in the intervention group vs 2.5% in the control group (95% CI 13.5-33.9; p < 0.001). Improvement in QOL was 52.1 ± 17.6 in the intervention group vs 42.5 ± 16.4 in the control group (mean difference, 9.6; 95% CI 4.3 to 14.9, p < 0.001). However, behavior scores could be performed in 49 patients, and improvement was seen in the intervention vs control group (65.6 ± 7.9 vs 71.4 ± 8.1, p = 0.015) at the end of the study. One patient had weight loss; 2 patients had diarrhea. DISCUSSION: The MAD group demonstrated improvement in all aspects (reduction in seizure frequency and behavioral problems) compared with the control group at the end of the study. MAD is an effective modality in controlling seizures; further research is required to assess its efficacy in terms of biomarkers along with descriptive metabolomics studies. TRIAL REGISTRATION INFORMATION: The clinical trial registry of India: CTRI/2015/07/006048. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the MAD increases the probability of seizure reduction in adolescents and adults with DRE.

Anti-seizure medications and quality of life in person with epilepsy.

Objective: The goal of this study was to determine the effects of mono-, bi-, and polytherapy anti-seizure medications (ASMs) in terms of seizure reduction and quality of life (QOL) in persons with epilepsy (PWE). Methods: A cross-sectional observational study was conducted. All PWE with age <75 years were recruited and further classified into two groups: responders and non-responders, based on the response of the ASMs to the treatments for reduced seizure frequency since the last one year. Other demographic and clinical data such as seizure frequency, type of seizures, age at onset of seizures, and information about ASMs with their daily doses were assessed for the descriptive analysis. The quality of life was assessed in randomly selected PWE (n = 100) using the quality of life in epilepsy inventory-31 (QOLIE-31) in adults. Results: With a total of 486 PWE, the median age (years) was comparable in both groups. Out of these the non-responders group was found to be significantly higher (77.8%) than the responders group (22.2%). In the responders group, the percentage of PWE who were on monotherapy was significantly higher (51.85 %) than those who were on polytherapy (17.59%), whereas in the non-responders group, 21.16% of PWE were on monotherapy and 44.86% were on polytherapy. The duration of epilepsy was similar in both groups, but the average seizure frequency was significantly higher in the non-responders. In QOL assessments, 43% of PWE were observed in the responders group, whereas 57% of PWE were found in the non-responders group. The overall comparative QOL scores were also significantly higher (p < 0.0001) in the responders group as compared to the non-responders group. Conclusion: Our findings revealed that those PWE who were on monotherapy showed better reduction in seizure frequency and improved QOL in responder groups as compared to non-responder groups.

Impact of exercise as a complementary management strategy in people with epilepsy: A randomized controlled trial.

OBJECTIVE: To measure the impact of 12 weeks of physical exercise as complementary management strategy on quality of life (QOL) in people with epilepsy (PWE). METHODS: In a parallel-group, randomized controlled study with blinded outcome assessment, PWE of 18-65 years old, smartphone users were randomized into two groups. The exercise group was advised minimum 150 min per week of moderate-intense aerobic activity, as per current WHO recommendation [1], in addition to standard medical care; the control group received only standard medical care. QOL was assessed using Quality of Life in Epilepsy (QOLIE-31) inventory [2,3]; physical activity, with Global Physical Activity Questionnaire version 2 (GPAQ), and Pedometer Step Counter (a smartphone-based activity tracker application), at baseline and after 12 weeks. Body weight, body mass index, seizure frequency, and stigma scores (Epilepsy Stigma Scale Austin and colleagues) [4] were also noted. RESULTS: One hundred and seventeen PWE were recruited (58 exercise, 59 control). Although there was an improvement in the physical activity correlates after 12 weeks compared to mean values at baseline, the differences were not significant between the groups. The total QOL mean scores at baseline in the exercise and control groups were 64.9 and 63.7 (p = 0.597) and after 12 weeks, 68.4 and 66.9 (p = 0.660), respectively. However, intragroup comparison of energy/fatigue score in the exercise group showed significant change with a p value of 0.009 and intragroup comparison of Overall QOL score in the control group showed a significant change with a p value of 0.003. Similar improvement was seen in stigma scores (p = 0.500) and seizure frequency (p = 0.388) at 12 weeks in exercise and control groups. After 12 weeks, mean values of METS ((metabolic equivalents) were 794.81 and 714.27 (p = 0.159), steps per day were 4018.32 and 3730.0 (p = 0.314), calories spent per day were 173.85 and 159.68 (p = 0.320 and distance walked per day in meters were 2576.52 and 2198.42 (p = 0.072), in the exercise and control groups, respectively. SIGNIFICANCE: Regular physical activity for at least 150 min per week, in the form of moderate-intense aerobic exercises resulted in positive yet non-significant improvement of QOL, seizure frequency, and stigma in PWE.

Endoscope-assisted (with robotic guidance and using a hybrid technique) interhemispheric transcallosal hemispherotomy: a comparative study with open hemispherotomy to evaluate efficacy, complications, and outcome.

OBJECTIVEEndoscope-assisted hemispherotomy (EH) has emerged as a good alternative option for hemispheric pathologies with drug-resistant epilepsy.METHODSThis was a prospective observational study. Parameters measured included primary outcome measures (frequency, severity of seizures) and secondary outcomes (cognition, behavior, and quality of life). Blood loss, operating time, complications, and hospital stay were also taken into account. A comparison was made between the open hemispherotomy (OH) and endoscopic techniques performed by the senior author.RESULTSOf 59 cases (42 males), 27 underwent OH (8 periinsular, the rest vertical) and 32 received EH. The mean age was 8.65 ± 5.41 years (EH: 8.6 ± 5.3 years; OH: 8.6 ± 5.7 years). Seizure frequency per day was 7 ± 5.9 (EH: 7.3 ± 4.6; OH: 15.0 ± 6.2). Duration of disease (years since first episode) was 3.92 ± 1.24 years (EH: 5.2 ± 4.3; OH: 5.8 ± 4.5 years). Number of antiepileptic drugs per patient was 3.9 ± 1.2 (EH: 4.2 ± 1.2; OH: 3.8 ± 0.98). Values for the foregoing variables are expressed as the mean ± SD. Pathologies included the following: postinfarct encephalomalacia in 19 (EH: 11); Rasmussen's syndrome in 14 (EH: 7); hemimegalencephaly in 12 (EH: 7); hemispheric cortical dysplasia in 7 (EH: 4); postencephalitis sequelae in 6 (EH: 2); and Sturge-Weber syndrome in 1 (EH: 1). The mean follow-up was 40.16 ± 17.3 months. Thirty-nine of 49 (79.6%) had favorable outcomes (International League Against Epilepsy class I and II): in EH the total was 19/23 (82.6%) and in OH it was 20/26 (76.9%). There was no difference in the primary outcome between EH and OH (p = 0.15). Significant improvement was seen in the behavioral/quality of life performance, but not in IQ scores in both EH and OH (p < 0.01, no intergroup difference). Blood loss (p = 0.02) and hospital stay (p = 0.049) were less in EH.CONCLUSIONSEH was as effective as the open procedure in terms of primary and secondary outcomes. It also resulted in less blood loss and a shorter postoperative hospital stay.

Does surgery help in reducing stigma associated with drug refractory epilepsy in children?

INTRODUCTION: Epilepsy has several comorbidities and associated stigma. Stigma associated with epilepsy is well known and prevalent worldwide. Surgical treatment is an established treatment for drug refractory epilepsy. Following surgery in children, it is possible that the stigma may reduce, but such an effect has not been studied earlier. MATERIALS AND METHODS: Analysis of prospectively collected data was performed for pediatric patients at a single tertiary center for treating epilepsy. Child stigma scale, as described by Austin et al., was used to evaluate stigma both pre- and postoperatively. Analysis was done using Paired t test. RESULTS: In this study, following surgery, there was significant reduction of stigma (P<0.001). This was proportional to the reduction in seizures, though there were 9 (30%) patients, who due to persistent neurodisability did not have any reduction of stigma despite having good seizure outcome. CONCLUSION: Surgery in drug-resistant epilepsy helps in reducing stigma. Seizure reduction is probably not the only factor responsible for a change in stigma outcome.

Surgery for Drug-Resistant Epilepsy in Children.

BACKGROUND: Neurosurgical treatment may improve seizures in children and adolescents with drug-resistant epilepsy, but additional data are needed from randomized trials. METHODS: In this single-center trial, we randomly assigned 116 patients who were 18 years of age or younger with drug-resistant epilepsy to undergo brain surgery appropriate to the underlying cause of epilepsy along with appropriate medical therapy (surgery group, 57 patients) or to receive medical therapy alone (medical-therapy group, 59 patients). The patients in the medical-therapy group were assigned to a waiting list for surgery. The primary outcome was freedom from seizures at 12 months. Secondary outcomes were the score on the Hague Seizure Severity scale, the Binet-Kamat intelligence quotient, the social quotient on the Vineland Social Maturity Scale, and scores on the Child Behavior Checklist and the Pediatric Quality of Life Inventory. RESULTS: At 12 months, freedom from seizures occurred in 44 patients (77%) in the surgery group and in 4 (7%) in the medical-therapy group (P<0.001). Between-group differences in the change from baseline to 12 months significantly favored surgery with respect to the score on the Hague Seizure Severity scale (difference, 19.4; 95% confidence interval [CI], 15.8 to 23.1; P<0.001), on the Child Behavior Checklist (difference, 13.1; 95% CI, 10.7 to 15.6; P<0.001), on the Pediatric Quality of Life Inventory (difference, 21.9; 95% CI, 16.4 to 27.6; P<0.001), and on the Vineland Social Maturity Scale (difference, 4.7; 95% CI, 0.4 to 9.1; P=0.03), but not on the Binet-Kamat intelligence quotient (difference, 2.5; 95% CI, -0.1 to 5.1; P=0.06). Serious adverse events occurred in 19 patients (33%) in the surgery group, including hemiparesis in 15 (26%). CONCLUSIONS: In this single-center trial, children and adolescents with drug-resistant epilepsy who had undergone epilepsy surgery had a significantly higher rate of freedom from seizures and better scores with respect to behavior and quality of life than did those who continued medical therapy alone at 12 months. Surgery resulted in anticipated neurologic deficits related to the region of brain resection. (Funded by the Indian Council of Medical Research and others; Clinical Trial Registry-India number, CTRI/2010/091/000525 .).

Concentration of antiepileptic drugs in persons with epilepsy: a comparative study in serum and saliva.

AIM OF THE STUDY: The monitoring of antiepileptic drugs (AEDs) in clinical setting is important for measuring the efficacy of drugs and their safety and in personalizing drug therapy. We investigated the levels of AED, carbamazepine (CBZ), phenytoin (PHT) and phenobarbital (PHB), to understand their association in saliva compared with those in serum during the therapy. MATERIALS AND METHODS: In this study, we performed a prospective study of 116 persons with epilepsy (PWE; mean age 26.90 ± 11.83 years). Serum and saliva samples were collected at trough levels from the patients, who were under the treatment of CBZ, PHT and PHB either alone or in combination of these drugs for at least three months. The drug levels were assessed by high-performance liquid chromatography. RESULTS AND CONCLUSIONS: The number of males (n = 88; 75.86%) was higher than females (n = 28; 24.14%) among the recruited patients. The intake of CBZ, PHT and PHB was observed in 49.14%, 68.10% and 38.79% of PWE, respectively. The levels of these AEDs showed a significant correlation (p < 0.05) between serum and saliva. Interestingly, the levels of mono-therapy or bi-therapy showed a significant association (p < 0.05) between serum and saliva, however, there was no significant association in case of poly-therapy. This is the first report in the Indian population on simultaneous estimation of the three commonly used AEDs, such as CBZ, PHT and PHB in serum and saliva implicating their associations, either in mono-therapy or bi-therapy in PWE.

Endoscopic-Assisted (Through a Mini Craniotomy) Corpus Callosotomy Combined With Anterior, Hippocampal, and Posterior Commissurotomy in Lennox-Gastaut Syndrome: A Pilot Study to Establish Its Safety and Efficacy.

BACKGROUND: Corpus callosotomy is a palliative procedure especially for Lennox-Gastaut semiology without localization with drop attacks. OBJECTIVE: To describe endoscopic-assisted complete corpus callosotomy combined with anterior, hippocampal, and posterior commissurotomy. METHODS: Patients with drug refractory epilepsy having drop attacks as the predominant seizure type, bilateral abnormalities on imaging, and moderate to severe mental retardation were included. All underwent a complete workup (including magnetic resonance imaging). RESULTS: Patients (n = 16, mean age 11.4 ± 6.4 years, range 6-19 years) had a mean seizure frequency of 24.5 ± 19.8/days (range 1-60) and a mean intelligence quotient of 25.23 ± 10.71. All had syndromic diagnosis of Lennox-Gastaut syndrome, with the following etiologies: hypoxic insult (10), lissencephaly (2), bilateral band heterotropia (2), and microgyria and pachygyria (2). Surgery included complete callosotomy and the section of anterior and posterior commissure by microscopic approach through a mini craniotomy (11) and endoscopic-assisted approach (5). Complications included meningitis (1), hyperammonemic encephalopathy (2), and acute transient disconnection (5). There was no mortality or long-term morbidity. Mean follow-up was 18 ± 4.7 months (range 16-27 months). Drop attacks stopped in all. Seizure frequency/duration decreased >90% in 10 patients and >50% in 5 patients, and increased in 1 patient. All patients attained presurgical functional levels in 3 to 6 months. Child behavior checklist scores showed no deterioration. Parental questionnaires reported 90% satisfaction attributed to the control of drop attacks. The series was compared retrospectively with an age/sex-matched cohort (where a callosotomy only was performed), and showed better outcome for drop attacks (P < .003). CONCLUSION: This preliminary study demonstrated the efficacy and safety of complete callosotomy with anterior, hippocampal, and posterior commissurotomy in Lennox-Gastaut syndrome (drop attacks) with moderate to severe mental retardation.

Endoscopy-assisted interhemispheric transcallosal hemispherotomy: preliminary description of a novel technique.

BACKGROUND: Various hemispherotomy techniques have been developed to reduce complication rates and achieve the best possible seizure control. OBJECTIVE: To present a novel and minimally invasive endoscopy-assisted approach to perform this procedure. METHODS: Endoscopy-assisted interhemispheric transcallosal hemispherotomy was performed in 5 children (April 2013-June 2014). The procedure consisted of performing a small craniotomy (4 × 3 cm) just lateral to midline using a transverse skin incision. After dural opening, the surgery was performed with the assistance of a rigid high-definition endoscope, and bayoneted self-irrigating bipolar forceps and other standard endoscopic instruments. Steps included a complete corpus callosotomy followed by the disconnection of the hemisphere at the level of the basal nuclei and thalamus. The surgeries were performed in a dedicated operating room with intraoperative magnetic resonance imaging and neuronavigation. Intraoperative magnetic resonance imaging confirmed a total disconnection. RESULTS: The pathologies for which surgeries were performed included sequelae of middle a cerebral artery infarct (n = 2), Rasmussen syndrome (n = 1), and hemimegalencephaly (2). Four patients had an Engel class I and 1 patient had a class II outcome at a mean follow-up of 10.2 months (range, 3-14 months). The mean blood loss was 80 mL, and mean operating time was 220 minutes. There were no complications in this study. CONCLUSION: This study describes a pilot novel technique and the feasibility of performing a minimally invasive, endoscopy-assisted hemispherotomy.

Correlation of saliva and serum free valproic acid concentrations in persons with epilepsy.

PURPOSE: Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) in serum is frequently used in clinical settings however saliva could be an alternative to measure free concentration of drugs. In the present study, we observed the possible correlation of VPA concentration between serum and saliva in persons with epilepsy (PWE). METHODS: A total of 59 paired serum and saliva samples were assayed from 65 consecutive PWE (51 males and 14 females; age range 9-65 years). Patients were subjected to either VPA monotherapy or its combination with other AEDs for at least three months. Steady state trough concentration of unbound VPA drug was quantified using HPLC. The correlation between serum and saliva free VPA concentration was evaluated. RESULTS: Out of 65 patients, 27 were on monotherapy of VPA and 38 were on VPA with other antiepileptic drugs. Saliva VPA concentration significantly correlated with serum free VPA concentration (p<0.05). Poor correlation was observed between serum and saliva VPA concentration with the daily dose (p>0.05) respectively. CONCLUSIONS: Our study reveals that serum and saliva VPA concentrations are significantly associated in PWE. These associations may facilitate monitoring and evaluation of VPA levels non-invasively for PWE.

Applicability of the new ILAE classification for epilepsies (2010) in persons with epilepsy at a tertiary care center in India.

PURPOSE: To test the applicability of the new International League Against Epilepsy (ILAE) 2010 classification for epilepsies and to compare it with the ILAE 1989 classification and the ILAE 2001 diagnostic scheme in developing countries with limited resources such as India. METHODS: Prospective data of 500 consecutive patients with epilepsy, presenting in neurology department of All India Institute of Medical Sciences, was collected from January 2011 to June 2012 and analyzed according to the three systems proposed by ILAE in 1989, 2001, and 2010. KEY FINDINGS: All 500 patients could be classified in the ILAE 1989 classification system, but only 413 in the ILAE 2001 diagnostic scheme (in axes 3 and 4) and 420 in the ILAE 2010 classification system. Leading categories were localization-related epilepsies, symptomatic focal epilepsies, perinatal insult, and epilepsies attributed to structural and metabolic cause in ILAE 1989, 2001 axis 3, 2001 axis 4, and 2010 systems, respectively. The ILAE 1989 classification system could categorize significantly greater numbers of patients compared to the 2001 and 2010 systems, whereas the latter two remained similar. SIGNIFICANCE: A large group of patients remained unclassified in the new classification system despite our tremendous gain in knowledge through improved imaging, genomics, and molecular biology, and so on, which could be attributed to lack of availability of facilities in developing countries. Dichotomy of localization-related and generalized epilepsy still makes for a fundamental and pragmatic working diagnosis and guides the physician about the extent of investigations and treatment especially in "epilepsies of unknown cause."

Do gene polymorphism in IL-1ß, TNF-α and IL-6 influence therapeutic response in patients with drug refractory epilepsy?

PURPOSE: Pro-inflammatory cytokines may play an important pathophysiological role in patients with epilepsy. To understand the role of genes encoding pro-inflammatory cytokines in epilepsy, this study aimed to evaluate the polymorphisms of the promoter regions of IL-1ß-511C>T (rs16944), TNF-α-308G>A (rs1800629) and IL-6-174G>C (rs1800795) genes and to look into the interaction between these genes in influencing seizure susceptibility, seizure frequency and response to therapy. METHODS: The comparative frequency of polymorphism was determined in rs16944, rs1800629 and rs1800795 using PCR-RFLP in a group of 120 persons with epilepsy (PWE) and 110 ethnically matched healthy subjects of comparable age and sex in the North Indian population. RESULTS: Alleles and genotypes of rs16944, rs1800629 and rs1800795 were not found to influence the odds ratio of having susceptibility to epilepsy. Also gene-gene interaction of possible nine combinations of these genes did not show any positive association with epilepsy. The genotype and allelic frequency of rs1800795 showed a significant association (p<0.05) in seizure frequency (number of seizures/6-months) and drug refractory epilepsy. However, the genotype and allelic frequency of rs16944 and rs1800629 were not found to have such effect. CONCLUSION: This study demonstrates that the rs16944, rs1800629 and rs1800795 polymorphism does not act as a strong susceptibility factor for epilepsy in North Indian population. The genotypic association of rs1800795 with seizure frequency and drug-refractory epilepsy raises the issue that a specific set of polymorphic genes can influence seizures and therapeutic response in epilepsy.