Number Of Antiepileptic Drugs Research Articles

The treatment of epilepsy in pregnancy: The neurodevelopmental risks associated with exposure to antiepileptic drugs.

A number of antiepileptic drugs (AEDs) have been confirmed as teratogens due to their association with an increased malformation rate. The majority of research to date does not find an association between prenatal exposure to monotherapy carbamazepine, lamotrigine or phenytoin and neurodevelopmental outcome in comparison to control children and noted higher abilities in comparison to children exposed to valproate; but further work is needed before conclusions can be drawn. Data for levetiracetam was limited to one study, as was the evidence for topiramate. Sodium valproate exposure appeared to carry a dose dependent risk to the developing brain, with evidence of reduced levels of IQ, poorer verbal abilities and increased rate of autistic spectrum disorder both in comparison to control children and children exposed to other AEDs. The severity of the neurodevelopmental deficits associated with prenatal exposure to valproate highlight the critical need to consider neurodevelopmental outcomes as a central aspect of teratological research.

Corpus callosotomy outcomes in pediatric patients: Asystematic review.

Corpus callosotomy is a palliative neurosurgical treatment for patients with either generalized or multifocal refractory epilepsy and injurious drop attacks. This report aims to systematically review the pediatric literature. Medline, Embase, Web of Knowledge, and Scopus were searched systematically for published articles on treatment outcomes of corpus callosotomy for refractory epilepsy. Studies were included if the patient population was younger than 18 at the time of surgery and median follow-up was >1year. Studies were excluded if resective surgery was also performed. A total of 12 articles met inclusion criteria. All articles were retrospective case series, with the exception of one being a prospectively designed retrospective case series. There was very little agreement among authors on the definition of a good seizure outcome. Articles that used the Engel classification found that 88.2% of total corpus callosotomy patients had a worthwhile reduction in seizures compared with 58.6% of patients who underwent anterior corpus callosotomy (p<0.05). Drop attacks improved from corpus callosotomy more than other generalized seizure types. Reported complications were minor in all but one patient, and one death was reported. Transient disconnection syndrome was significantly more likely in total corpus callosotomy than in anterior corpus callosotomy (12.5% vs. 0%; p<0.05). Improvements in quality of life, behavior, and intelligence/development quotient, as well as parental satisfaction, were generally correlated with seizure outcome. There was no postcallosotomy change in the number of antiepileptic drugs. Total corpus callosotomy was significantly more likely to result in a reduction in seizures. Anterior corpus callosotomy was unlikely to result in disconnection syndrome. Although all of the papers drew a similar conclusion, the quality of evidence was low. At best, the evidence raises the hypothesis that corpus callosotomy is a safe and effective treatment for refractory generalized epilepsy. It is clear that a case-control or randomized trial is warranted.

Systematic Adverse Drug Reaction Monitoring of Patients Under Newer Antiepileptic Drugs Using Routine Clinical Data of Inpatients.

BackgroundBased on data of clinical trials, new agents are receiving approval to the pharmaceutical market, for which information concerning safety issues under real-life conditions is not yet available.ObjectivesThe aim was to evaluate the tolerability of newer antiepileptic drugs (AEDs), such as topiramate, levetiracetam, zonisamide, pregabalin, extended-release oxcarbazepine, lacosamide and eslicarbazepine, under real-life conditions by means of an assessment of routine clinical data of inpatients.MethodOver 2.75 years data of all inpatients receiving one of the newer AEDs were documented. Occurring adverse drug reactions (ADRs) were classified according to the WHO-UMC Causality Assessment concerning their likely relationship to the prescribed AEDs. For each AED, the total number of patients without and with ADRs, assessed as at least possibly related to the particular drug, was calculated and corresponding incidences compared with reference data provided in the Summary of Product Characteristics (SmPC). For statistical evaluation Spearman correlation (rs), estimated relative risk and logistic regression analysis were used.ResultsIn total, the data of 562 patients were assessed, of which 90 % received up to six different AEDs. The proportion of off-label use with regard to dosage varied between 6.4 and 64.7 %. Levetiracetam and oxcarbazepine as an extended-release formulation were most commonly used, and levetiracetam showed the best tolerance. By using logistic regression, the occurrence of ADRs was significantly associated with the number of AEDs (p < 0.001) as well as the defined daily doses (p = 0.003). In total, ADRs of AEDs were documented for 318 patients (56.6 %). The most common referred to electrolyte imbalance, e.g., low sodium (n = 79, 14.1 %) and potassium (n = 25, 4.4 %) levels, the central nervous system, including dizziness (n = 61, 10.9 %), disturbed vision (n = 47, 8.4 %), fatigue (n = 40, 7.1 %), nystagmus (n = 36, 6.4 %) and ataxia (n = 29, 5.2 %), or cognitive deficits, especially disturbance of speech (n = 37, 6.6 %), memory impairment (n = 36, 6.4 %) and mental slowing (n = 32, 5.7 %). By comparing the assessed ADR incidences with specification data, for some ADRs, a probable underestimation by the SmPC of respective risk could be assumed.ConclusionDuring inpatient treatment, valuable data are generated, which are currently rarely utilized for pharmacoepidemiologic or pharmacovigilance purposes. A systematic evaluation of these data can increase the probability of detecting ADRs and can promote real-life–related drug surveillance.Electronic supplementary materialThe online version of this article (doi:10.1007/s40801-016-0077-2) contains supplementary material, which is available to authorized users.

Quality of life in epilepsy in Bhutan

PurposeTo assess the quality of life in epilepsy (QOLIE) among adults in the lower middle-income country of Bhutan and assess the potential demographic and clinical associations with better QOLIE. MethodsPeople with clinically diagnosed epilepsy were prospectively enrolled at the Jigme Dorji Wangchuck National Referral Hospital in Thimphu (2014–2015). Regression models were constructed to assess the potential impact of age, sex, residence in the capital city, wealth quintile, educational attainment, seizure in the prior year, seizures with loss of consciousness, self-reported stigma score, and need for multiple antiepileptic drugs. ResultsThe mean Bhutanese QOLIE-31 score among 172 adults (mean age 31.1 years, 93 female) was 48.9/100±17.7. Younger age, lower educational attainment level, and increased self-perceived stigma were each observed to have an independent, negative association with QOLIE (p<0.05), while a patient's wealth quintile, sex, seizure frequency, seizure type and number of antiepileptic drugs were not. Education appeared to be most strongly associated with QOL at the high school and college levels. ConclusionsThere are potentially modifiable associations with low QOLIE. Addressing the educational level and self-perceived stigma of PWE may have an especial impact. The low QOLIE in Bhutan may reflect cultural approaches to epilepsy, health services, or other factors including those outside of the health sector.

Virtual car accidents of epilepsy patients, interictal epileptic activity, and medication.

To investigate effects of interictal epileptic activity (IEA) and antiepileptic drugs (AEDs) on reactivity and aspects of the fitness to drive for epilepsy patients. Forty-six adult patients with demonstration of focal or generalized bursts of IEA in electroencephalography (EEG) readings within 1 year prior to inclusion irrespective of medication performed a car driving computer test or a single light flash test (39 patients performed both). Reaction times (RTs), virtual crashes, or lapses (RT ≥ 1 s in the car or flash test) were measured in an IEA burst-triggered fashion during IEA and compared with RT-measurements during unremarkable EEG findings in the same session. IEA prolonged RTs both in the flash and car test (p < 0.001) in individual patients up to 200 ms. Generalized IEA with spike/waves (s/w) had the largest effect on RT prolongation (p < 0.001, both tests), whereas mean RT during normal EEG, age, gender, and number of AEDs had no effect. The car test was better than the flash test in detecting RT prolongations (p = 0.030). IEA increased crashes/lapses >26% in sessions with generalized IEA with s/w. The frequency of IEA-associated RT >1 s exceeded predictions (p < 0.001) based on simple RT shift, suggesting functional impairment beyond progressive RT prolongation by IEA. The number of AEDs correlated with prolonged RTs during normal EEG (p < 0.021) but not with IEA-associated RT prolongation or crashes/lapses. IEA prolonged RTs to varying extents, dependent on IEA type. IEA-associated RTs >1 s were more frequent than predicted, suggesting beginning cerebral decompensation of visual stimulus processing. AEDs somewhat reduced psychomotor speed, but it was mainly the IEA that contributed to an excess of virtual accidents.

Epileptiform K-Complexes and Sleep Spindles: An Underreported Phenomenon in Genetic Generalized Epilepsy.

To study the frequency of epileptiform K-complexes and sleep spindles as well as clinical variables influencing those abnormalities. We prospectively performed 24-hour ambulatory EEGs in a cohort of patients with genetic generalized epilepsy diagnosed and classified according to the International League against Epilepsy criteria. Overlapping of epileptiform discharges with K-complexes and sleep spindles was defined as epileptiform K-complexes and epileptiform sleep spindles. The presence of epileptiform K-complexes and sleep spindles was tabulated for each patient, and frequencies were calculated. We performed multiple regression analysis to study the influence of clinical predictors on the occurrence of epileptiform K-complexes and sleep spindles. The predictor variables tested in the model were seizure-free duration, epilepsy duration, genetic generalized epilepsy syndrome, number of antiepileptic drugs, use of sodium valproate, and use of lamotrigine. A total of 107 patients (37 males and 70 females) were studied. The mean age was 28.5 ± 10.7 years (range, 13-58). Juvenile absence epilepsy was the most common epilepsy syndrome in the cohort (31.8%), followed by generalized epilepsy with tonic-clonic seizures only (26.2%), juvenile myoclonic epilepsy (26.2%), and childhood absence epilepsy (14%). Epileptiform K-complexes and sleep spindles were seen in 65.4% and 10.3% of patients, respectively. None of the clinical variables had any significant impact on the occurrence of epileptiform K-complexes and sleep spindles in our multivariable analysis. Epileptiform K-complexes are common in the sleep EEGs of patients diagnosed with genetic generalized epilepsy. This underreported phenomenon highlights the important association of arousals and epileptiform discharges in genetic generalized epilepsy.

Combined surgical intervention with vagus nerve stimulation following corpus callosotomy in patients with Lennox-Gastaut syndrome.

Lennox-Gastaut syndrome (LGS) is a drug-resistant pediatric epilepsy characterized by multiple seizure types, including drop attacks (DAs). Palliative procedures such as corpus callosotomy (CC) and vagus nerve stimulation (VNS) may be effective for adequate seizure control in LGS patients who are not candidates for resective surgery. We evaluated the efficacy of the combination of these two procedures for LGS-related seizures. Ten patients with LGS (age 3-30 years at VNS implantation) underwent CC and subsequent VNS. We evaluated surgical outcomes, particularly with respect to the efficacy of VNS on seizure reduction rates for different residual seizure types after CC. We compared clinical parameters, including sex, age, seizure duration, history, MRI findings, extent of CC, number of antiepileptic drugs, and neuropsychological states, between VNS responders and non-responders to predict satisfactory seizure outcomes with respect to residual seizures after CC. VNS was effective for residual seizures regardless of seizure type (except for DAs) after CC in patients with LGS. Six of ten (60%) patients had a satisfactory seizure outcome (≥50% seizure reduction) for all residual seizure types after VNS. Two of ten (20%) patients were seizure-free at 12 months post-VNS. Even those patients that were non-responders, with respect to all seizures including DAs, after prior CC showed favorable responses to subsequent VNS. Compared to VNS, excellent seizure outcomes for DAs were achieved after CC in seven of nine (77.8%) patients with DAs. Among the clinical parameters, only conversation ability before VNS was significantly different between responders and non-responders (p = 0.033). Combined VNS and prior CC produced satisfactory seizure outcomes in LGS patients with different seizure types, including DAs. Even non-responders to prior CC responded to subsequent VNS for residual seizures, except for DAs. There is a greater likelihood that these procedures may be more feasible in patients who possess conversation ability prior to VNS.

Factors affecting burden of main caregivers in children with epilepsy

ObjectiveThe purpose of the study was to evaluate burden of main caregivers in children with epilepsy and to identify factors associated with caregiver burden.MethodMain caregivers of pediatric patients with epilepsy were enrolled four general hospitals in several cities of Korea. One hundred and twenty-fou caregivers of patients were included in this cross-sectional study. Sociodemograhic/clinical characteristics of patients and sociodemographic characteristics of caregivers were collected. The caregivers were assessed using the Korean version Zarit burden Interview (ZBI), Center for Epidemiological Studies of Depression Scale (CES-D) and social support/conflict scale. Multiple linear regression methods were used to evaluate factors contributing to burden of caregivers.ResultsOf the 124 participants, 98(81.7%) were the mothers. The mean score on the ZBI and CES-D were 23.66 (± 19.15) and 13.87 (± 12.95) points, respectively. Factors affecting of caregiver burden were the number of antiepileptic drugs (AEDs), which patients are taking, and CES-D score by multiple linear regression analysis.ConclusionsHigher number of AEDs prescribed and depression of caregivers are main factors contributing to burden of caregivers in children with epilepsy.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Associations of impaired sleep quality, insomnia, and sleepiness with epilepsy: A questionnaire-based case-control study.

The purpose of this study was to document the frequency of sleep problems including poor sleep quality, excessive daytime sleepiness, and insomnia in subjects with epilepsy compared with healthy controls and to determine the factors associated with these sleep disturbances. We recruited 180 patients with epilepsy (age: 43.2 ± 15.6 years, men: 50.0%) and 2836 healthy subjects (age: 44.5 ± 15.0 years, men: 49.8%). Sleep and the anxiety/mood profiles were measured using the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Insomnia Severity Index, Goldberg Anxiety Scale, and Patient Health Questionnaire-9 depression scale. Associations of sleep problems with epilepsy and other factors were tested by multiple logistic regression analysis, adjusted for age, gender, body mass index, alcohol intake, smoking, perceived sleep insufficiency, and habitual snoring. Sleep disturbances were more common in the group with epilepsy than in the controls (53.3% vs. 25.5%; p<0.001). Poor sleep quality, excessive daytime sleepiness, and insomnia were significantly associated with epilepsy (odds ratio [95% confidence interval]: 3.52 [2.45-5.05], 2.10 [1.41-3.12], 5.91 [3.43-10.16], respectively). Depressive mood, anxiety, and perceived sleep insufficiency contributed to the presence of sleep disturbances. In the group with epilepsy, seizure remission for the past year related to a lower frequency of insomnia, whereas age, sex, type of epilepsy, and number of antiepileptic drugs were not correlated with sleep problems. Epilepsy was significantly associated with the higher frequency of sleep disturbances, which supports the importance of screening sleep problems in patients with epilepsy and providing available intervention.

Prescription patterns of antiepileptic drugs in young women: development of a tool to distinguish between epilepsy and psychiatric disorders.

Antiepileptic drugs (AEDs) are also prescribed for therapeutic indications other than epilepsy (EPI), namely, psychiatric disorders (PSY). Our aim was to develop an algorithm able to distinguish between EPI and PSY among childbearing age women based on differences in AED exposure in these patient groups. Two groups of women (18-45 years) with EPI or PSY treated with AEDs in the first semester of 2010 or 2011 were extracted from paper or electronic medical charts of specialized centers. Through the prescription database of Bologna Local Health Authority (Italy), AEDs, treatment schedule and co-treatments were collected for each patient. A prescription-based hierarchical classification system was developed. The algorithm obtained was subsequently validated on internal and external data. Eighty-one EPI and 94 PSY subjects were recruited. AED monotherapy was the most common choice in both groups (69% EPI vs 79% PSY). Some AEDs were used only in EPI, others exclusively in PSY. Co-treatments with antipsychotics (6% vs 67%), lithium (0% vs 9%), and antidepressants (7% vs 70%) were fewer in EPI than in PSY. The hierarchical classification system identified antipsychotics, SSRIs (Selective Serotonin Reuptake Inhibitors), and number of AEDs as variables to discriminate EPI and PSY, with an overall error rate estimate of 9.7% (95%CI: 5.3% to 14.1%). Among the differences between EPI and PSY, prescription data alone allowed an algorithm to be developed to diagnose each childbearing age woman receiving AEDs. This approach will be useful to stratify patients for risk estimates of AED-treated patients based on administrative databases. Copyright © 2016 John Wiley & Sons, Ltd.

Calcium Imaging of Neuronal Activity in Drosophila Can Identify Anticonvulsive Compounds.

Although there are now a number of antiepileptic drugs (AEDs) available, approximately one-third of epilepsy patients respond poorly to drug intervention. The reasons for this are complex, but are probably reflective of the increasing number of identified mutations that predispose individuals to this disease. Thus, there is a clear requirement for the development of novel treatments to address this unmet clinical need. The existence of gene mutations that mimic a seizure-like behaviour in the fruit fly, Drosophila melanogaster, offers the possibility to exploit the powerful genetics of this insect to identify novel cellular targets to facilitate design of more effective AEDs. In this study we use neuronal expression of GCaMP, a potent calcium reporter, to image neuronal activity using a non-invasive and rapid method. Expression in motoneurons in the isolated CNS of third instar larvae shows waves of calcium-activity that pass between segments of the ventral nerve cord. Time between calcium peaks, in the same neurons, between adjacent segments usually show a temporal separation of greater than 200 ms. Exposure to proconvulsants (picrotoxin or 4-aminopyridine) reduces separation to below 200 ms showing increased synchrony of activity across adjacent segments. Increased synchrony, characteristic of epilepsy, is similarly observed in genetic seizure mutants: bangsenseless1 (bss1) and paralyticK1270T (paraK1270T). Exposure of bss1 to clinically-used antiepileptic drugs (phenytoin or gabapentin) significantly reduces synchrony. In this study we use the measure of synchronicity to evaluate the effectiveness of known and novel anticonvulsive compounds (antipain, isethionate, etopiside rapamycin and dipyramidole) to reduce seizure-like CNS activity. We further show that such compounds also reduce the Drosophila voltage-gated persistent Na+ current (INaP) in an identified motoneuron (aCC). Our combined assays provide a rapid and reliable method to screen unknown compounds for potential to function as anticonvulsants.

Attention Deficit Hyperactivity Disorder in Adolescents With Epilepsy

BackgroundWe examined attention-deficit hyperactivity disorder in adolescents with epilepsy and the association with seizure-related and sociodemographic variables. MethodsStrengths and Weakness of Attention-Deficit Hyperactivity Disorder Symptoms and Normal Behaviors rating scale was administered to 122 children with epilepsy and 50 children with asthma, aged 10 to 18 years attending mainstream schools. ResultsTwenty-nine (23.7%) adolescents with epilepsy compared with five (10%) with asthma had attention deficit hyperactivity disorder (P = 0.037). Adolescents with epilepsy had a significantly higher score in the inattention subscale when compared with those with asthma (−0.25 ± 1.2 vs −0.64 ± 1.07, P = 0.049). Combined subtype was most frequent in the epilepsy group. Oppositional defiant disorders were more prevalent in those having attention deficit hyperactivity disorder. Psychiatric assistance had only been provided to one third of our patients with epilepsy and attention deficit hyperactivity disorder at the time of study. There was a negative correlation between attention deficit hyperactivity disorder scores and age of seizure onset. A positive correlation was observed between the number of antiepileptic drugs and the inattentive subscale score. The impact of various correlates on individual subtypes was not identical. Independent risk factors associated with attention deficit hyperactivity disorder were medical comorbidities (odds ratio = 12.82, 95% confidence interval 4.44, 37.03, P < 0.0001) and age at seizure onset (odds ratio = 0.73, 95% confidence interval 0.56, 0.94, P = 0.016). ConclusionsAttention deficit hyperactivity disorder is overrepresented in adolescents with epilepsy; screening for its symptoms should be an integral part of management in adolescents with epilepsy.

Social Behavioral Problems and the Health-Related Quality of Life in Children and Adolescents with Epilepsy.

ObjectiveThe purpose of this study was to investigate the impact of specific behavioral problems on the health-related quality of life (HRQOL) in children and adolescents with epilepsy.MethodsChildren and adolescents with epilepsy (n=92; age range=6–17 years) and their mothers completed questionnaires about behavioral problems, HRQOL, socio-demographics, and epilepsy-related variables. To determine significant predictor variables of the HRQOL, the stepwise regression analyses and partial correlations were performed to adjust for other behavioral problems and covariates.ResultsThe analyses revealed that an increase in social behavioral problems and delinquent behavior was associated with a decrease in the HRQOL. Lower levels of maternal education and the number of antiepileptic drugs were also associated with a decline in the HRQOL; the HRQOL and social behavioral problems remained significantly correlated after adjusting for maternal education level, number of antiepileptic drugs, and non-social behavioral problems.ConclusionParents and practitioners should provide intervention if behavioral problems, particularly social behavioral problems, are observed in children or adolescents with epilepsy.

Drug utilization pattern of antiepileptic drugs in a tertiary care teaching rural hospital

Background: Antiepileptic drugs (AEDs) are also commonly used therapy for other conditions like prophylaxis for a manicdepressive disorder, to relieve neuralgic pain and for many more conditions apart from epilepsy. Data suggest that 45% of AEDs prescriptions were for conditions other than epilepsy. All of these uses are off-label except for some AEDs approved for limited indications. Aims and Objective: To study the AEDs utilization pattern in a tertiary care teaching rural hospital in India. Materials and Methods: Patients who prescribed AEDs by treating physician from the various outpatient departments of a tertiary care hospital were enrolled in the study irrespective of their diagnosis. Their demographic data, clinical profile and drug use related details were obtained from the case files and history and analyzed. Results: Out of total 160 patients enrolled, the majority were male 103 (64.4%), in the age group of 18-65 years (123, 76.9%), and from neuromedicine 149 (93.1%) department. 81 (50.63%), 45 (28.12%), and 10 (6.25%) were diagnosed as epilepsy, pain, and psychomotor disorders, respectively, and remaining patients having a dual indication for AEDs prescription. Partial epilepsy (45, 47.87%) was the most common type and cryptogenic (44, 46.80%) was most common aetiological factor among epileptic patients. Average number of AEDs prescribed per patient was 1.331. 113 (70.6%) patients were managed by monotherapy. Most frequently prescribed AEDs were pregabalin (20.19%) followed by phenytoin (16.90%). Conventional AEDs (78.95%) were prescribed more frequently than newer AEDs (21.05%) for epilepsy; while newer AEDs (68.10%) were frequently prescribed in patients suffering from non-epileptic condition. 52% of drugs were prescribed by generic name. No fixed dose combinations of AEDs were prescribed throughout this study period. Conclusions: The use of AEDs not limited to epilepsy only. AEDs were prescribed more frequently in neuropathic pain and psychiatric disorders other than epilepsy. AEDs are usually prescribed as monotherapy and by generic name and not as fixed dose combination. Awareness about off-label use of ADEs is essential for its appropriate use.

The pattern of adverse drug events to antiepileptic drugs: A cross-sectional study at a tertiary care teaching hospital

Background: The goal of antiepileptic therapy is to achieve complete seizure control with minimum adverse effects impacting negatively on the quality of life. The drugs available in the market for the treatment of epilepsy have their own new and unique adverse drug reaction profile. Aims and Objective: To study the pattern of adverse drug events (ADEs) to antiepileptic drugs (AEDs) in a tertiary care teaching rural hospital in India. Materials and Methods: Data of all the patients visited the Outpatient Department of Neuromedicine, Neurosurgery, and Paediatric Department of the Shree Krishna Hospital in the study duration and who received AEDs as treatment, irrespective of diagnosis, age or sex were collected after obtaining written informed consent from the patients. All the adverse events reported spontaneously as well as founded by researcher during the interview at each visit were recorded in the case record form with all necessary information. Results: Total 112 ADEs were reported from 58 (36.25%) patients in 6-month follow-up. Central nervous system was most frequently affected with 68 (60.71%) ADEs followed by the gastrointestinal system (68, 60.71%). Phenytoin was most commonly suspected AEDs (with 39 cases) followed by carbamazepine (in 23 cases). Causality assessment by the WHO-UMC criteria most common association was possible in 75 (66.96%) cases, probable 21 (18.75%), certain 6 (5.36%), and conditional/unclassified 10 (8.93%). Similar result was obtained by Naranjo’s criteria as possible 84 (75.00%), probable 22 (19.64%), and definite 6 (5.36%). 91 (80.36%) ADEs were not preventable by modified Schumock and Thornton scale. Severity assessment by Hartwig’s criteria showed 79 (70.53%) ADEs as mild. Number of AEDs given per patient had a statistical correlation with ADEs. Conclusions: There are higher chances of development of ADEs in patients taking AEDs. However, at individualized regimens, the burden of ADEs is likely to be related more to individual responsiveness, type of AEDs/AED combinations chosen, and physician treatment skills, intensive therapeutic surveillance, education about epilepsy and the importance of drug compliance, and psychosocial interventions.

An analysis of prescription pattern and adverse drug reaction profile in children treated with antiepileptic drugs in a tertiary care teaching hospital

Background: Epilepsy is a clinical diagnosis made after a child has had two (or) more unprovoked seizures. Ideal goal in the management of childhood epilepsy is complete control with minimal side effects. The incidence of adverse effects is an important issue with antiepileptic drugs (AEDs). We took up this study to analyse the pattern of AEDs prescribed and adverse drug reaction (ADR) profile in children with epilepsy being treated at a tertiary care Teaching hospital of South Tamil Nadu.Methods: Children of both sexes, 1 to 12 years of age and on AEDs for at least 3 months were included for the study. Patients with febrile seizures, status epilepticus, seizures associated with paralytic stroke, head injury and cerebral palsy were excluded. Demographic data, treatment history and adverse drug events were recorded. Serum liver function tests, complete blood count and peripheral smear and causality analysis of ADRs were done.Results: Out of 203 patients 122 (60.1%) were males. Average number of AED prescribed per patient was 1.37. About 68% received monotherapy. 26.6% required two drugs and 5.4% patients required triple drugs. Out of 75 ADRs reported 3 are probable and 72 are possible reactions. The prevalence of ADRs (p=0.014*) and anorexia (p=0.0004*) were more in patients on polytherapy.Conclusions: ADRs were more common in patients with combination therapy which insists the need for a newer AED with less toxicity especially for paediatric patients.

Clinical profile and treatment outcome of febrile infection-related epilepsy syndrome in South Indian children.

Purpose:To describe the clinical features and outcome of febrile infection-related epilepsy syndrome (FIRES), a catastrophic epileptic encephalopathy, in a cohort of South Indian children.Materials and Methods:We performed a retrospective chart review of a cohort of children with previously normal development who presented with status epilepticus or encephalopathy with recurrent seizures following a nonspecific febrile illness during the period between January 2007 and January 2012. They were divided into two groups super refractory status epilepticus (SRSE) and refractory status epilepticus (RSE) depending on the duration and severity of the seizures.Key Findings:Fifteen children who met the inclusion criteria were included for the final analysis. The age of the children at presentation ranged 3-15 years (median 6.3 years). All the children presented with prolonged or recurrent seizures occurring 1-12 days (median 4 days) after the onset of fever. Eight children had SRSE while seven children had refractory seizures with encephalopathy. Cerebrospinal fluid (CSF) analysis was done in all the children in the acute phase, and the cell count ranged 0-12 cells/μL (median 2 cells/μL) with normal sugar and protein levels. Initial neuroimaging done in all children (MRI in 10 and CT in 5), and it was normal in 13 children. Treatment modalities included multiple antiepileptic drugs (AEDs) (4-9 drugs) (median 5 drugs). Midazolam (MDZ) infusion was administered in seven patients. Eight patients required barbiturate coma to suppress the seizure activity. The duration of the barbiturate coma ranged 2-90 days (median 3 days). Steroids were used in 14 children and intravenous immunoglobulin (2 g/kg) in 7 children. Three children died in the acute phase. All children were maintained on multiple AEDs till the last follow-up, the number of AEDs ranged 1-6 (median 5 AEDs). The patients with super refractory status in the acute phase were found to be more severely disabled at the follow-up; the median score of these patients on the Glasgow Outcome Scale (GOS) was 2 compared to 5 in the RSE group.Significance:This study reports one of the largest single center cohorts from India, with an adverse long-term developmental and seizure outcome. The duration and severity of seizures in the acute period correlated directly with the short-term and long-term clinical outcomes. There is an urgent need for developing new effective therapeutic strategies to treat this acute catastrophic epileptic syndrome.

The Croatian Model of Integrative Prospective Management of Epilepsy and Pregnancy

Epilepsy is the most common neurological complication in pregnancy. Women with epilepsy have a higher risk of complications in pregnancy. In Croatia, women with epilepsy are treated by neurologists at tertiary centers according to the place of residence. We prospectively followed-up pregnancies in women with epilepsy and healthy controls, and analyzed the factors responsible for their delivery outcomes and development of their babies. Healthy pregnant women had a higher level of education and economic status, but pregnant women with epilepsy took folic acid in a higher proportion than controls, possibly due to timely preconception counseling. Complications during pregnancy depended on the number of antiepileptic drugs and epilepsy control. We noticed some behavioral and cognitive aspects in children exposed in utero to valproic acid, which required follow up. The rate of congenital malformations was not increased. In conclusion, women with epilepsy should receive preconception counseling about the risk for pregnancy, but also about the possibilities to minimize that risk. We have introduced a model of integrative management of pregnancy and epilepsy based on close collaboration among different clinical experts in Croatia, in order to provide prompt counseling and timely intervention.

Therapeutic hypothermia for perinatal asphyxia in an Urban Tertiary Referral Center in South India: Our experience

Objective: To study the outcomes after starting therapeutic hypothermia in our unit. Primary Outcomes: Mortality in Neonatal Intensive Care Unit, neurological examination at discharge, seizures, encephalopathy duration, and mortality up to 18 months were the primary outcomes. Secondary Outcomes: Number of anti-epileptic drugs (AED) at discharge, duration of mechanical ventilation, hospital cost, feeding patterns, duration of hospital stay, and neurodevelopmental outcome at 18 months were the secondary outcomes. Setting: The study was conducted at the NICU, Dr. Mehta's Children Hospital, Chennai. Study Period: October 2013 to December 2015. Conclusion: Therapeutic hypothermia resulted in better survival and neurodevelopmental outcomes though there was no significant reduction in MRI and EEG abnormalities.

Systematics and principles of therapy for depressive disorders in epilepsy

Relying on a comprehensive investigation, the author proposes the typology of depressive disorders in epilepsy by identifying ictal, preictal, interictal, and postictal conditions. Risk factors for depressive symptoms are considered. Main approaches to therapy for depressions are offered. Particular emphasis is placed on the normothymic activity of a number of anticonvulsants. Valproates, and depakine in particular, as a normothymic agent are shown to be beneficial in treating affective disorders.