Single Antiepileptic Drug Research Articles

Insights into Anti-Epileptic Drug Therapy: A Cross-Sectional Comparison of Adverse Drug Reactions in Monotherapy vs. Polytherapy at a Tertiary Care Hospital

Epilepsy, a widespread neurological disorder, poses significant challenges to effective treatment, often resulting in a diminished quality of life for affected individuals. Despite its prevalence, managing epilepsy remains a complex task, as many patients experience treatment non-compliance due to adverse effects or perceived lack of efficacy. The conventional approach to treatment involves monotherapy, wherein a single anti-epileptic drug (AED) is prescribed. However, this method often leads to adverse effects necessitating dose escalation, which can ultimately prompt treatment cessation. In recent years, polytherapy has emerged as an alternative strategy for managing epilepsy. Polytherapy involves combining multiple AEDs at reduced doses to mitigate adverse effects and enhance therapeutic efficacy. While monotherapy is favored for its simplicity and historical effectiveness, there is growing interest in exploring the comparative effectiveness and safety between monotherapy and polytherapy.1 Understanding the nuances of these treatment approaches is essential for clinicians and patients alike to make informed decisions regarding epilepsy management, considering factors such as seizure control, adverse effects, and overall quality of life. This review aims to provide a comprehensive analysis of the efficacy and safety profiles of monotherapy and polytherapy in epilepsy treatment. By evaluating existing evidence and clinical outcomes, this study offers valuable insights that can guide clinicians in tailoring treatment regimens to individual patient needs, ultimately improving outcomes and enhancing the overall quality of care for individuals living with epilepsy. Results from our study have established that out of the 563 patients included in our study, about 50% have developed some sort of adverse drug reaction (ADR). Of these 282 patients that have developed an ADR, about 62% of patients were on monotherapy and the remaining 38% were on polytherapy. Establishing the fact that monotherapy is more effective than polytherapy in reducing the incidence of adverse drug reactions.

Remote Monitoring for Seizures During Therapeutic Hypothermia in Neonates With Hypoxic-Ischemic Encephalopathy

Neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH) frequently experience seizures, which are associated with adverse outcomes. Efforts to rapidly identify seizures and reduce seizure burden may positively change neurologic and neurodevelopmental outcomes. To describe the onset, treatment, and evolution of seizures in a large cohort of newborns with HIE during TH assisted by a telehealth model and remote neuromonitoring approach. This was a prospective, observational, multicenter cohort study performed between July 2017 and December 2021 in 32 hospitals in Brazil. Participants were newborns with HIE meeting eligibility criteria and receiving TH. Data were analyzed from November 2022 to April 2023. Infants with HIE receiving TH were remotely monitored with 3-channel amplitude-integrated electroencephalography (aEEG) including raw tracing and video imaging, and bedside clinicians received assistance from trained neonatologists and neurologists. Data on modified Sarnat examination, presence, timing and seizure type, aEEG background activity, sleep-wake cycling, and antiepileptic drugs used were collected. Descriptive statistical analysis was used with independent t test, χ2, Mann-Whitney test, and post hoc analyses applied for associations. A total of 872 cooled newborns were enrolled; the median (IQR) gestational age was 39 (38-40) weeks, 518 (59.4%) were male, and 59 (6.8%) were classified as having mild encephalopathy by modified Sarnat examination, 504 (57.8%) as moderate, and 180 (20.6%) as severe. Electrographic seizures were identified in 296 newborns (33.9%), being only electrographic in 213 (71.9%) and clinical followed by electroclinical uncoupling in 50 (16.9%). Early abnormal background activity had a significant association with seizures. Infants with flat trace had the highest rate of seizures (58 infants [68.2%]) and the greatest association with the incidence of seizures (odds ratio [OR], 12.90; 95% CI, 7.57-22.22) compared with continuous normal voltage. The absence of sleep-wake cycling was also associated with a higher occurrence of seizures (OR, 2.22; 95% CI, 1.67-2.96). Seizure onset was most frequent between 6 and 24 hours of life (181 infants [61.1%]); however, seizure occurred in 34 infants (11.5%) during rewarming. A single antiepileptic drug controlled seizures in 192 infants (64.9%). The first line antiepileptic drug was phenobarbital in 294 (99.3%). In this cohort study of newborns with HIE treated with TH, electrographic seizure activity occurred in 296 infants (33.9%) and was predominantly electrographic. Seizure control was obtained with a single antiepileptic drug in 192 infants (64.9%). These findings suggest neonatal neurocritical care can be delivered at remote limited resource hospitals due to innovations in technology and telehealth.

Feasibility of Telemedicine for Follow up of Children with Established Seizure Disorder- A Tertiary Care Center Prospective Study

Introduction: Medical information exchanged via electronic communications to improve a patient’s clinical health status by a physician without in-patient visit is telemedicine. Control of seizures with antiepileptic drugs, reassurance for compliance to drugs, regular monitoring of adverse effects of drugs in patient with established seizure can be possible through telemedicine. The main objective of this study was to evaluate feasibility of telemedicine for follow up of children with established seizure disorder.
 Methods: This study was conducted among children of age one to 16 years with an established seizure due to any cause presenting to the Paediatric Neurodevelopmental OPD of Tribhuvan University Teaching Hospital (TUTH) between October 1, 2018 and September 30, 2020. Mobile phone as a modality of telemedicine was used to inquire about seizure every month for 12 months and whenever necessary.
 Results: When parameters as seizure control, total cost and time spent per hospital visit, distance to TUTH were analyzed, more than 75% caregivers were satisfied with telemedicine. Greater age, appropriate development, focal onset of seizure, normal electroencephalogram and seizure adequately controlled by single antiepileptic drug were the favorable factors in better seizure control in children using telemedicine.
 Conclusions: Telemedicine for follow up of children with established seizure disorder seems to be a feasible and satisfactory option when implemented with caution and proper patient selection as it decreases unnecessary high expenses and time to hospital visit

Clinico-Etiological Profile and Outcome of Neonatal Seizures - A Hospital-Based Cross-Sectional Study in Western Nepal

INTRODUCTION
 Neonatal seizure, a common problem encountered in neonatal intensive care unit (NICU) setting, is an important determinant of outcome of neurological disorders in newborn period. The aim of the study was to study the clinical and etiological profile of neonatal seizures along with their outcomes.
 MATERIAL AND METHODS
 A prospective observational study was conducted in the NICU of Department of Pediatrics at Universal College of Medical Sciences, Bhairahawa, Nepal from November 2019 to March 2021. Babies with neonatal seizures were enrolled in the study after obtaining written consent from parents.
 RESULTS
 Out of 870 admitted neonates, 9.7% (n=85) developed clinical seizures where 62.4% were males. Most cases (87.1%) had seizures within 48-hour of life with subtle seizures (92.9%) being the commonest. About 43.5% cases had single episode of seizure followed by multiple episodes. Perinatal asphyxia (92.9%) either alone and/or associated with hypocalcemia (80%) followed by sepsis (40%) and hyponatremia (18.8%) were common etiologies for neonatal seizures. Most of the seizures (76.5%) were aborted with use of single anti-epileptic drug. About 86% (n=73) survived and rest expired.
 CONCLUSION
 Subtle seizures were common and perinatal asphyxia was the predominant etiology for neonatal seizures. Thus, strengthening the healthcare facility during delivery of the newborn, proper newborn care and nutrition must be emphasized to decrease the incidence of seizures in developing nations like Nepal.

Autoimmune complications and clinical outcomes of herpes simplex encephalitis in children: A case series

Objective: To report the neurologic prognosis and autoimmune complications of 16 cases of childhood herpes simplex virus encephalitis. Methods: The study was conducted at Şanlıurfa Training and Research Hospital, Turkey from June 2017 to August 2019. The study included 16 pediatric patients aged between 6 months and 17 years (median age 77.7 months) who were diagnosed with herpes simplex virus type 1 encephalitis by pediatric infectious disease and pediatric neurology clinics. Patients were followed using patient records, and interviews at the pediatric neurology clinic or via the telephone. Clinical and demographic data, received therapies, neurologic prognosis and complications were evaluated. Results: Patients with and without autoimmune encephalitis were compared in terms of age, sex, symptom duration before treatment, initial cerebrospinal fluid protein, glucose, red blood count and white blood count but no significant difference was found. Autoimmune complications were seen in four patients. N-methyl-D-aspartate encephalitis was observed in three patients and choreoathetosis was seen in one patient. The average follow-up period was 48.3 months. Twenty-five percent of the patients were receiving multiple antiepileptic drug (AED) treatment, 43.8% were receiving single AED treatment and 31.3% were not receiving AED treatment at the end of the follow-up. Motor disability was observed in 12.5% and drug-resistant epilepsy was observed in 6.3% who had autoimmune complications. Conclusions: Seizures and movement disorders were controlled with immunotherapy and autoantibodies should be studied routinely. Treatment should be started early upon recognition of autoimmune complications through follow-up by measuring autoantibody levels and clinical examination results. Effective prevention and curative treatment modalities are needed to avoid herpes simplex virus encephalitis complications.

Role of Magnetic Resonance Imaging of Brain in Evaluation of Pediatric Seizure Disorder

Seizure disorder in children is commonly seen in clinical practice and in the assessment of these patients. Magnetic Resonance Imaging (MRI) is found to be the ideal and first imaging modality of choice for pediatric seizure disorder because of lack of radiation exposure. This work aims to assess the role of MRI of the brain in the evaluation of pediatric seizure disorder. Before undergoing MRI, all of the patients received EEG to detect the epileptogenic center. On the superconductive 1.5-Tesla Siemens Avanto Magnetom MR system, patients underwent a brain MRI scan. Percentages and proportions were used in the statistical analysis. Around 70% of children with seizures were found to be controlled by the use of a single antiepileptic drug (AED). Electroencephalogram (EEG) findings were abnormal in 82% of patients. The MRI findings were normal in 45 patients (45%) and abnormal in 55 patients (55%). The common abnormalities were gliosis (45.4%), periventricular leukomalacia (12.7%), neurodegenerative changes in white/grey matter (7.3%), focal cortical dysplasia (FCD) (7.3%), arteriovenous malformations (AVM) (7.3%), polymicrogyria (5.5%), mesial temporal sclerosis (MTS) (5.5%), abnormal spectroscopy (3.6%), space-occupying lesion (SOL) (3.6%) and megalencephaly (1.8%). Our study showed about 55% of children with seizures had MRI abnormalities and common abnormalities were gliosis and periventricular leukomalacia. Improvements in perinatal care, hygiene, and socio-economic status can help in reducing the incidence and thus morbidity associated with a seizure disorder. Thus, MRI plays a pivotal role in the workup of pediatric patients with a seizure disorder.

Epilepsy in Pregnancy-Management Principles and Focus on Valproate.

An estimated 60 million people worldwide suffer from epilepsy, half of whom are women. About one-third of women with epilepsy are of childbearing age. The childbirth rate in women with epilepsy is about 20–40% lower compared to that of the general population, which may be partly due to a lower number of these women being in relationships. Lower fertility in women with epilepsy may be linked to the disease itself, but it is mainly a result of the treatment provided. Valproate, as an antiepileptic drug inhibiting histone deacetylases, may affect the expression of genes associated with cell cycle control and cellular differentiation. Evidently, this drug is associated with the risk of malformations although other antiepileptic drugs (AEDs) may also trigger birth defects, however, to a lower degree. Valproate (and to a certain degree other AEDs) may induce autism spectrum disorders and attention deficit hyperactivity disorder. The main mechanism responsible for all negative effects of prenatal exposure to valproate seems inhibition of histone deacetylases. Animal studies show a reduction in the expression of genes involved in social behavior and an increase in hippocampal cytokines. Valproate-induced oxidative stress may also contribute to neural tube defects. Interestingly, paternal exposure to this AED in mice may trigger neurodevelopmental disorders as well although a population-based cohort study does not confirm this effect. To lower the risk of congenital malformations and neurodevelopmental disorders, a single AED at the optimal dose and supplementation with folic acid is recommended. VPA should be avoided in women of childbearing age and especially during pregnancy.

A Cross-sectional Observational Study to Find out the Pattern of Drug Utilization and Medication Adherence of Anti-Epileptic Drugs (AEDs) among Epileptic Patients at a Tertiary Care Teaching Hospital

Background: Antiepileptic drugs (AEDs) are the mainstay of the therapy for epilepsy, despite the development in recent years of new therapeutic options, such as brain stimulation or Surgery. Objective: To understand the pattern of drug utilization and medication adherence of anti-epileptic drugs (AEDs) among epileptic patients at a tertiary care teaching hospital.
 Methodology: A cross-sectional observational study of a total of 120 subjects receiving anti-epileptics was done. All the patients with epilepsy were prescribed with anti-epileptic drug who visited, admitted, or referred to the Department of Neurology. All inpatients and outpatients of epilepsy were screened for the study.
 Results: A total of 120 patients were included in our study into which (38.33%) were inpatients and (61.67%) were outpatient. The male (56%) patients were more as compared to female (44%) patients. A maximum number of patients were from the age group of 21-40 (41%) year. The majority of the patient were suffered from focal epilepsy (63%), remaining were having a generalized seizure. The highest comorbidities were found to be HTN and diabetes mellitus. Monotherapy was highly prescribed as compare to polytherapy. Among single AED, the maximum prescribed drug was Carbamazepine [30% (N=17)] followed by 25% (N=14) of phenytoin and levetiracetam 21% (N=12). In two AED Combinations, the most prescribed drugs were clobazam + Levetiracetam and Midazolam + phenytoin 12% (N=5) followed by sodium valproate + clobazam 10% (N=4). Highest combination of three AEDs that were prescribed the highest were carbamazepine + Levetiracetam + clobazam and phenytoin + phenobarbitone + sodium Valproate 20% (N=2)
 The highest medication adherence was found in patients who were on single AEDs and the lowest adherence was found in the patients who were on more than two AEDs.
 Conclusion: Antiepileptic drug monotherapy was highly prescribed as compare to polytherapy. Phenytoin was the most commonly prescribed AEDs followed by carbamazepine and highly prescribed single AEDs were found to be carbamazepine. The patients who were on single epileptic drugs showed the highest adherence as compared to the patients with more than two AEDs.

Syntaxin Binding Protein 1 Related Epilepsies

AbstractSyntaxin binding protein 1 (STXBP1), commonly known as MUNC18–1, is a member of SEC1 family membrane trafficking proteins; their function consists in controlling the soluble N-ethylmaleimide-sensitive factor attachment protein receptors complex assembly, making them essentials regulators of vesicle fusion. The precise function and molecular mechanism through which Munc18–1 contributes to neurotransmitter releasing is not entirely understood, but several evidences suggest its probable role in exocytosis. In 2008, heterozygous de novo mutations in neuronal protein Munc18–1 were first referred as a cause of Ohtahara syndrome development. Currently, a wide examination of the published data proved that 3.1% of patients with severe epilepsy carry a pathogenic de novo mutation including STXBP1 and approximately 10.2% of early onset epileptic encephalopathy is due to an aberrant STXBP1 form codified by the mutated gene. STXBP1 mutations can be associated to a wide clinical heterogeneity. All affected individuals show developmental delay and approximately the 95% of cases have seizures and early onset epileptic encephalopathy, characterized by infantile spasms as the main consistent feature. Burst suppression pattern and hypsarrhythmia are the most frequent EEG anomalies. Other neuronal disorders include Rett syndrome and behavioral and movement disorders. Mild dysmorphic features have been detected in a small number of cases. No genotype–phenotype correlation has been reported. Management of STXBP1 encephalopathy requires a multidisciplinary approach, including epilepsy control and neurological rehabilitation. About 25% of patients are refractory to standard therapy. A single or combined antiepileptic drugs may be required. Several studies described vigabatrin, valproic acid, levetiracetam, topiramate, clobazam, and oxcarbazepine as effective in seizure control. Lamotrigine, zonisamide, and phenobarbital are also commonly used. To date, it remains unclear which therapy is the most effective. Severe morbidity and high mortality are inevitable consequences in some of these patients.

Gabapentin add-on treatment for drug-resistant focal epilepsy.

This is an updated version of the Cochrane Review previously published in 2018. Epilepsy is a common neurological disorder characterised by recurrent seizures. Most people with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug, but up to 30% develop drug-resistant epilepsy, especially people with focal seizures. In this review, we summarised the evidence from randomised controlled trials (RCTs) of gabapentin, when used as an add-on treatment for drug-resistant focal epilepsy. To evaluate the efficacy and tolerability of gabapentin when used as an add-on treatment for people with drug-resistant focal epilepsy. For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid) on 11 August 2020. CRS Web includes randomised or quasi-randomised, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups including Epilepsy. We imposed no language restrictions. Randomised, placebo-controlled, double-blind, add-on trials of gabapentin in people with drug-resistant focal epilepsy. We also included trials using an active drug control group or comparing different doses of gabapentin. Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: seizure frequency, seizure freedom, treatment withdrawal (any reason) and adverse effects. Primary analyses were intention-to-treat. We also undertook sensitivity best-case and worst-case analyses. We estimated summary risk ratios (RR) for each outcome and evaluated dose-response in regression models. We identified no new studies for this update, therefore, the results and conclusions are unchanged. In the previous update of this review, we combined data from six trials in meta-analyses of 1206 randomised participants. The overall risk ratio (RR) for reduction in seizure frequency of 50% or more compared to placebo was 1.89 (95% confidence interval (CI) 1.40 to 2.55; 6 studies, 1206 participants; moderate-certainty evidence). Dose regression analysis (for trials in adults) showed increasing efficacy with increasing dose, with 25.3% (95% CI 19.3 to 32.3) of people responding to gabapentin 1800 mg compared to 9.7% on placebo, a 15.5% increase in response rate (95% CI 8.5 to 22.5). The RR for treatment withdrawal compared to placebo was 1.05 (95% CI 0.74 to 1.49; 6 trials, 1206 participants; moderate-certainty evidence). Adverse effects were significantly associated with gabapentin compared to placebo. RRs were as follows: ataxia 2.01 (99% CI 0.98 to 4.11; 3 studies, 787 participants; low-certainty evidence), dizziness 2.43 (99% CI 1.44 to 4.12; 6 studies, 1206 participants; moderate-certainty evidence), fatigue 1.95 (99% CI 0.99 to 3.82; 5 studies, 1161 participants; low-certainty evidence) and somnolence 1.93 (99% CI 1.22 to 3.06; 6 studies, 1206 participants; moderate-certainty evidence). There was no evidence of a difference for the adverse effects of headache (RR 0.79, 99% CI 0.46 to 1.35; 6 studies, 1206 participants; moderate-certainty evidence) or nausea (RR 0.95, 99% CI 0.52 to 1.73; 4 trials, 1034 participants; moderate-certainty evidence). Overall, the studies were at low to unclear risk of bias due to information on each risk of bias domain not being available. We judged the overall certainty of the evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide CIs. Gabapentin has efficacy as an add-on treatment in people with drug-resistant focal epilepsy, and seems to be fairly well-tolerated. However, the trials reviewed were of relatively short duration and provide no evidence for the long-term efficacy of gabapentin beyond a three-month period. The results cannot be extrapolated to monotherapy or to people with other epilepsy types. Further trials are needed to assess the long-term effects of gabapentin, and to compare gabapentin with other add-on drugs.

SURG-38. SEIZURE OUTCOME AFTER EPILEPSY SURGERY IN CHILDREN WITH BRAIN TUMORS

Abstract INTRODUCTION Epilepsy is a common chronic neurological complication of childhood brain tumors and seizures are refractory to medical therapy in up to 10% of patients. Referral for a diagnostic evaluation is recommended in patients with seizures refractory to ≥2 anti-epileptic drugs (AED). Utility of epilepsy surgery is not established in children with brain tumors. OBJECTIVE Primary aim of this study was to determine seizure outcome after epilepsy surgery in children with childhood brain tumors. METHODS Institutional Review Board’s approval was obtained for this retrospective study. A diagnosis of childhood brain tumor and a referral to the epilepsy monitoring unit (EMU) were required to be included in this study. Seizure outcome was defined according to International League Against Epilepsy (ILAE) outcome scale. Pre and post-operative MRIs were reviewed. RESULTS Forty-two children were referred to the EMU from May 2004 to July 2019. Of the 10 patients that underwent epilepsy surgery, 7 (70%) had pre-surgery frequency of >10 seizures/month and 3(30%) of these had multiple daily seizures; the rest had 3-4 seizures/month. All were taking ≥3 AEDs. Median time from first seizure to surgery was 83.7 months (range 24.3-151.6). At a median follow-up of 67.5 months (range 4.9-133.5) after epilepsy surgery, 60% reported no seizures in the 6-months before the last follow-up. Three (30%) had ILAE class-1 outcome, 4 (40%) class-3, and 3 (30%) were class-4. One child was off AEDs and the others were on a single AED at last follow-up. No post-operative neurological or cognitive deficits were recognized. Focal cortical atrophy was present in 40% of children before and in 30% after surgery. CONCLUSION Epilepsy surgery improved seizure outcome in all children that had epilepsy surgery and reduced the number of AEDs needed to treat seizures. Children with brain tumors and intractable seizures should be referred for epilepsy surgery evaluation.

The clinical characteristics of pregnant women with epilepsy in China.

Epilepsy during pregnancy and puerperium is infrequent, and it can induce severe complications and poor prognosis. Pregnancy in women with epilepsy (WWE) is usually uneventful. Previous studies have mainly focused on the effects of different treatments on prognosis. However, few articles have addressed if different epilepsy types were associated with a higher incidence of seizure breakthrough/recurrence and pregnancy outcomes. In the present study, based on a unique sample with a low incidence of epilepsy, we evaluated the main clinical characteristics of epilepsy patients. Mean age of pregnant WWE was 29.95±4.65 (range, 21-42) years. Pregnancies were at a mean gestational age of 33.80±9.14 (range, 7-41) weeks, and 88.24% (52/61) of WWE were in their third trimester. There was 9.84% (6/61) of pregnant WWE underwent abortion or induced labor in midpregnancy to ensure maternal safety. There was 75.41% (46/61) of pregnant WWE using antiepileptic drugs (AEDs), of which 52.46% (32/61) were taking a single AED and 22.95% (14/61) were using multiple AEDs. There was 47.54% (29/61) of WWE experiencing seizures during their pregnancy. We found that the type of epilepsy did not affect seizures during pregnancy or the prognosis. However, more pregnant WWE with hypertensive disorder had seizures compared with pregnant WWE without hypertensive disorder. The study highlighted a novel direction for effectively improving seizures during pregnancy and the prognosis of pregnancy-associated epilepsy.

Management Strategy of Patients Attending at Epilepsy Clinic in a Tertiary Care Hospital of Bangladesh

Background: Epilepsy is a neuronal disorder that is observed globally but still it is not explored very well in most parts of the world.
 Objective: The aim of our study was to determine the types of epilepsies along with their treatment strategies among patients attending the outdoor epilepsy clinic in a referral tertiary care hospital.
 Methodology: This cross sectional study was carried out from the records of weekly epilepsy clinic of Department of Neurology at National Institute of Neurosciences and Hospital, Dhaka, Bangladesh from January 2018 to August 2019. Data were collected through a predesigned questionnaire containing information about demography, clinical features, EEG and imaging findings and treatment of patients.
 Results: A total number of 1832 patients were recruited. There was a male (55.3%) and urban (61.1%) predominance. Most (75.1%) of the patients were young (age range from 10 to 29 years). A large number of patients were student (44.4%) and 24.2% were unemployed. The duration of epilepsy in most patients were less than 5 years (40.7%). 58.3% patients took various forms of indigenous treatment prior to attending this clinic. 54.7% patients had no comorbid illness. EEG was abnormal in 34.5% patients of which 24.4% had focal abnormality and 10.1% had generalized epileptic discharge. In brain imaging (CT/MRI) only 16.4% showed abnormal findings. 49.5% patients were suffering from generalized epilepsy whereas 44.6% had partial epilepsy. Among the generalized epilepsy group, most of them had generalized tonic clonic seizure (GTCS) (75.4%), while 8.9% had absence seizure and 7.9% had tonic seizure. In partial epilepsy group, the majority were secondary generalized seizure (74.7%), followed by complex partial seizure (CPS) (18.7%) and simple partial seizure (6.6%).42.7% patients got single antiepileptic drug whereas 37.4% patients received dual drug. Polytherapy (three or more drugs) were prescribed in 14% patients. Valproic acid was the highest prescribed drug (29.3%) either as monotherapy or in combination. Carbamazepine (27.4%) was the second common drug followed by Levetiracetam (15.1%).
 Conclusion: Epilepsy affects almost all groups of the society. Most of the patients remain seizure-free with judicious anti-epileptic drugs. Therefore, more effort is needed for early accurate diagnosis and appropriate treatment of epilepsy
 Journal of National Institute of Neurosciences Bangladesh, 2020;6(1): 3-8

Antiepileptic drugs as prophylaxis for postcraniotomy seizures.

This is an updated version of the Cochrane Review previously published in 2018. The incidence of seizures following supratentorial craniotomy for non-traumatic pathology has been estimated to be between 15% to 20%; however, the risk of experiencing a seizure appears to vary from 3% to 92% over a five-year period. Postoperative seizures can precipitate the development of epilepsy; seizures are most likely to occur within the first month of cranial surgery. The use of antiepileptic drugs (AEDs) administered pre- or postoperatively to prevent seizures following cranial surgery has been investigated in a number of randomised controlled trials (RCTs). To determine the efficacy and safety of AEDs when used prophylactically in people undergoing craniotomy and to examine which AEDs are most effective. For the latest update we searched the following databases on 29 September 2019: Cochrane Epilepsy Group Specialized Register, CENTRAL, MEDLINE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). We did not apply any language restrictions. We included RCTs of people with no history of epilepsy who were undergoing craniotomy for either therapeutic or diagnostic reasons. We included trials with adequate randomisation methods and concealment; these could either be blinded or unblinded parallel trials. We did not stipulate a minimum treatment period, and we included trials using active drugs or placebo as a control group. Three review authors (JW, JG, YD) independently selected trials for inclusion, extracted data and assessed risk of bias. We resolved any disagreements through discussion. Outcomes investigated included the number of participants experiencing seizures (early (occurring within first week following craniotomy), and late (occurring after first week following craniotomy)), the number of deaths and the number of people experiencing disability and adverse effects. Due to the heterogeneous nature of the trials, we did not combine data from the included trials in a meta-analysis; we presented the findings of the review in narrative format. Visual comparisons of outcomes are presented in forest plots. We included 10 RCTs (N = 1815), which were published between 1983 and 2015. Three trials compared a single AED (phenytoin) with placebo or no treatment. One, three-armed trial compared two AEDs (phenytoin, carbamazepine) with no treatment. A second three-armed trial compared phenytoin, phenobarbital with no treatment. Of these five trials comparing AEDs with placebo or no treatment, two trials reported a statistically significant advantage for AED treatment compared to controls for early seizure occurrence; all other comparisons showed no clear or statistically significant differences between AEDs and control treatment. None of the trials that were head-to-head comparisons of AEDs (phenytoin versus sodium valproate, phenytoin versus phenobarbital, levetiracetam versus phenytoin, zonisamide versus phenobarbital) reported any statistically significant differences between treatments for either early or late seizure occurrence. Only five trials reported incidences of death. One trial reported statistically significantly fewer deaths in the carbamazepine and no-treatment groups compared with the phenytoin group after 24 months of treatment, but not after six months of treatment. Incidences of adverse effects of treatment were poorly reported; however, three trials did show that significantly more adverse events occurred on phenytoin compared to valproate, placebo, or no treatment. No trials reported any results relating to functional outcomes such as disability. We considered the evidence to be of low certainty for all reported outcomes due to methodological issues and variability of comparisons made in the trials. There is limited, low-certainly evidence to suggest that AED treatment administered prophylactically is either effective or not effective in the prevention of postcraniotomy (early or late) seizures. The current evidence base is limited due to the different methodologies employed in the trials and inconsistencies in the reporting of outcomes including deaths and adverse events. Further evidence from good-quality, contemporary trials is required in order to assess the clinical effectiveness of prophylactic AED treatment compared to placebo or no treatment, or other AEDs in preventing postcraniotomy seizures in this select group of patients.

Reflex Epilepsy with Hot Water: Clinical and EEG Findings, Treatment, and Prognosis in Childhood.

Hot water epilepsy (HWE) is a subtype of reflex epilepsy in which seizures are triggered by the head being immersed in hot water. Hot water or bathing epilepsy is the type of reflex epilepsy most frequently encountered in our clinic. We describe our patients with HWE and also discuss the clinical features, therapeutic approaches, and prognosis. Eleven patients (10 boys, 1 girl), aged 12 months to 13 years, admitted to the pediatric neurology clinic between January 2018 and August 2019, and diagnosed with HWE or bathing epilepsy based on International League Against Epilepsy (ILAE)-2017, were followed up prospectively for ∼18 months. Patients' clinical and electroencephalography (EEG) findings and treatment details were noted. All 11 patients' seizures were triggered by hot water. Age at first seizure was between 2 months and 12 years. Seizure types were generalized motor seizures, absence, and atonic. EEG was normal in two patients, but nine patients had epileptiform discharges. Magnetic resonance imaging of the brain was performed and reported as normal (except in one case). Histories of prematurity were present in two patients, unprovoked seizures in one, and low birth weight and depressed birth in the other. Patients with HWE have normal neuromuscular development and neurological examination results, together with prophylaxis or seizure control with a single antiepileptic drug, suggesting that it is a self-limited reflex epilepsy.

Antiepileptic Drug Treatment Outcomes and Seizure-Related Injuries Among Adult Patients with Epilepsy in a Tertiary Care Hospital in Ethiopia.

ObjectiveAnti-epileptic drugs (AEDs) are the primary therapeutic modalities for epilepsy management. However, one-third of epileptic patients continue to experience seizure even with appropriate AED use. Patients with epilepsy are at increased risk for seizure-related injury and they have higher incidences of home, street and work accidents. There is a paucity of data on AED use pattern and treatment outcomes among patients with epilepsy in the tertiary hospitals of Ethiopia. Therefore, the aim of this study was to assess AED use pattern, treatment outcome, and prevalence of seizure-related injury among patients with epilepsy in Tikur Anbessa specialized Hospital (TASH), Ethiopia.Patients and MethodsAn institution-based cross-sectional study was carried out on 291 patients with epilepsy attending the neurology clinic of TASH. A semi-structured questionnaire and data abstraction format were used to collect data through patient interview and medical chart review. Binary logistic regression was utilized to identify the associated factors of treatment outcome.ResultsAbout 172 (59%) of the patients were taking a single AED, in which phenobarbital, 195 (67%), and phenytoin, 97 (33.3%), were the most frequently prescribed AEDs as monotherapy and combination therapy. Headache, depressed mood and epigastric pain were frequently reported as adverse drug reactions. Seizure-related injury was reported among 78 (26.8%) patients and head injury 15 (5.2%), desntal injury 15 (5.2%), soft tissue injury 14 (4.8%) and burns 10 (3.4%) were the commonest. About two-thirds (191, 65.6%) of the study participants had uncontrolled seizure. Medication adherence and multiple AEDs were significantly associated with treatment outcome.ConclusionAll the study participants were put on old generation AEDs with phenobarbital being the most frequently used. About two-thirds of the patients had uncontrolled seizure and seizure-related injury is still a serious concern among patients with epilepsy.

Impact of adherence to antiepileptic medications on quality of life of epileptic patients in the Eastern Province of Saudi Arabia: A cross-sectional study

Background: Epilepsy is one of the most common neurological diseases, characterized by recurrent epileptic seizures. Adherence to antiepileptic drugs (AEDs) is vital in establishing seizure control. The adherence, in turn, impacts the quality of life (QoL) in epileptic patients. Methodology: This was a hospital-based cross-sectional study conducted at King Fahd Hospital of the University, Qatif Central Hospital, and Dammam Central Hospital in the Eastern region of Saudi Arabia during the period from January 2018 to April 2018. Epileptic patients from all age groups treated with at least single AED and who had follow-up in hospital for the past 6 months were included in the study. Patients with intellectual disabilities and those who received AEDs for other indications were excluded. The participants were interviewed in Arabic, and validated translated version of questionnaire was completed under the following sections: sociodemographic characteristics, adherence assessment using the General Medication Adherence Scale (GMAS), and QoL in epilepsy patients using EQ-5D-5L. Results: We report 48% of participants with high adherence, 34% with moderate adherence, while 19% exhibited low adherence toward AEDs. Of 80 participants, 25 (31%) reported perfect health status (11,111) and 2 (3%) reported extremely worst health status (55,555). Further, the study revealed a significant (P = 0.045 and 0.035) improvement of QOL in patients with moderate and high adherence compared to patients with low adherence. Conclusion: This study reports high health-related quality index (QoL) in participants with moderate–high adherence. The relationship between adherence and overall HRQoL was directly proportional.

Early versus late antiepileptic drug withdrawal following temporal lobectomy

PurposeTo compare the seizure outcome following early and late complete antiepileptic drug (AED) withdrawal following anterior temporal lobectomy (ATL) for mesial temporal lobe epilepsy (MTLE). MethodAll the patients who were seizure free for one year following ATL were offered early or late AED withdrawal. AEDs were discontinued starting at one year in those who opted for early withdrawal. Patients who opted for late withdrawal were continued on single AED for three years following surgery before attempting complete discontinuation. ResultsOf the 135 study patients, 65 opted for early AED withdrawal and 70 for late withdrawal. The mean postoperative follow-up duration was 10.4 ± 1.3 (Range, 8–12) years. At three years following surgery, seizure recurrence occurred in 23 (35.4 %) patients in the early withdrawal group and in 10 (14.3 %) patients in late withdrawal group (p = 0.005; relative risk [RR], 2.48; 95 % confidence interval [CI], 1.28–4.80). At last follow-up, 27 (41.5 %) patients in the early withdrawal group and 26 (37.1 %) in late withdrawal group had recurrence (p = 0.60; RR, 1.12, 95 % CI, 0.74–1.70). At last followup, 80 (59.3 %) patients were off AEDs. During the terminal one year, 123 (91 %) patients were seizure free, similar in the two groups. ConclusionsThis nonrandomized controlled study suggests that early complete AED withdrawal starting one year following ATL is associated with a higher risk of early seizure recurrence. However, long term seizure outcome is similar in early and late AED withdrawal groups.

Losigamone add-on therapy for focal epilepsy.

Epilepsy is a common neurologic disorder, affecting approximately 50 million people worldwide; nearly a third of these people have epilepsy that is not well controlled by a single antiepileptic drug (AED) and they usually require treatment with a combination of two or more AEDs. In recent years, many newer AEDs have been investigated as add-on therapy for focal epilepsy; losigamone is one of these drugs and is the focus of this systematic review. This is an update of a Cochrane Review first published in 2012 and updated in 2018. To investigate the efficacy and tolerability of losigamone when used as an add-on therapy for focal epilepsy. For the latest update on 20 August 2019, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE. CRS Web includes randomized or quasi-randomized, controlled studies from the Specialized Registers of Cochrane Review Groups including Cochrane Epilepsy, CENTRAL, PubMed, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (ICTRP). Previously we searched trials registers and contacted themanufacturer of losigamone and authors of included studies for additional information. We did not impose any language restrictions. Randomized controlled, add-on studies comparing losigamone with placebo for focal epilepsy. Two review authors independently assessed study quality and extracted data. The primary outcomes were 50% or greater reduction in seizure frequency and seizure freedom; the secondary outcomes were treatment withdrawal and adverse events. Results are presented as risk ratios (RRs) with 95% confidence intervals (CIs) or 99% CIs (for the individual listed adverse events to make an allowance for multiple testing). Two studies involving a total of 467 participants, aged over 18 years, were eligible for inclusion. Both studies assessed losigamone 1200 mg/day or 1500 mg/day as an add-on therapy for focal epilepsy. We assessed one study as being of good methodological quality while the other was of uncertain quality. For the efficacy outcomes, results showed that participants taking losigamone were significantly more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.76, 95% CI 1.14 to 2.72; 2 studies, 467 participants; moderate-quality evidence), but associated with a significant increase of treatment withdrawal when compared with those taking placebo (RR 2.16, 95% CI 1.28 to 3.67; 2 studies, 467 participants; moderate-quality evidence). For the tolerability outcomes, results indicated that the proportion of participants who experienced adverse events in the losigamone group was higher than in the placebo group (RR 1.34, 95% CI 1.00 to 1.80; 2 studies, 467 participants; moderate-quality evidence). Dizziness was the only adverse event significantly reported in relation to losigamone (RR 3.82, 99% CI 1.69 to 8.64; 2 studies; 467 participants; moderate-quality evidence). Neither study reported the proportion of participants achieving seizure freedom. A subgroup analysis according to different doses of losigamone showed that a higher dose of losigamone (1500 mg/day) was associated with a greater reduction in seizure frequency than lower doses, but was also associated with more dropouts due to adverse events. The results of this review showed that losigamone did reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with focal epilepsy. However, the included studies were of short-term duration and uncertain quality. Future well-designed randomized, double-blind, placebo-controlled studies with a longer-term duration are needed. We did not find any new studies since the last version of this review. We judged the overall quality of the evidence for the outcomes assessed as moderate.

Topiramate add-on therapy for drug-resistant focal epilepsy.

The majority of people with epilepsy have a good prognosis and their seizures are controlled by a single antiepileptic drug. However, up to 20% of patients from population-based studies, and up to 30% from clinical series (not population-based), develop drug-resistant epilepsy, especially those with focal-onset seizures. In this review, we summarise the current evidence regarding topiramate, an antiepileptic drug first marketed in 1996, when used as an add-on treatment for drug-resistant focal epilepsy.This is an update of a Cochrane Review first published in 1999, and last updated in 2014. To evaluate the efficacy and tolerability of topiramate when used as an add-on treatment for people with drug-resistant focal epilepsy. For the latest update of this review we searched the following databases on 2 July 2018: Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (Ovid, 1946- ); ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP). We imposed no language restrictions. We also contacted the manufacturers of topiramate and researchers in the field to identify any ongoing or unpublished studies. Randomised, placebo-controlled add-on trials of topiramate, recruiting people with drug-resistant focal epilepsy. Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: (1) 50% or greater reduction in seizure frequency; (2) seizure freedom; (3) treatment withdrawal (any reason); (4) adverse effects. Primary analyses were intention-to-treat (ITT), and summary risk ratios (RRs) with 95% confidence intervals (95% CIs) are presented. We evaluated dose-response in regression models. We carried out a 'Risk of bias' assessment for each included study using the Cochrane 'Risk of bias' tool and assessed the overall certainty of evidence using the GRADE approach. We included 12 trials, representing 1650 participants. Baseline phases ranged from four to 12 weeks and double-blind phases ranged from 11 to 19 weeks. The RR for a 50% or greater reduction in seizure frequency with add-on topiramate compared to placebo was 2.71 (95% CI 2.05 to 3.59; 12 studies; high-certainty evidence). Dose regression analysis showed increasing effect with increasing topiramate dose demonstrated by an odds ratio (OR) of 1.45 (95% CI 1.28 to 1.64; P < 0.001) per 200 mg/d increase in topiramate dosage. The proportion of participants achieving seizure freedom was also significantly increased with add-on topiramate compared to placebo (RR 3.67, 95% CI 1.79 to 7.54; 8 studies; moderate-certainty evidence). Treatment withdrawal was significantly higher for add-on topiramate compared to placebo (RR 2.37, 95% CI 1.66 to 3.37; 12 studies; high-certainty evidence). The RRs for the following adverse effects indicate that they are significantly more prevalent with topiramate, compared to placebo: ataxia 2.29 (99% CI 1.10 to 4.77; 4 studies); concentration difficulties 7.81 (99% CI 2.08 to 29.29; 6 studies; moderate-certainty evidence); dizziness 1.52 (99% CI 1.07 to 2.16; 8 studies); fatigue 2.08 (99% CI 1.37 to 3.15; 10 studies); paraesthesia 3.65 (99% CI 1.58 to 8.39; 7 studies; moderate-certainty evidence); somnolence 2.44 (99% CI 1.61 to 3.68; 9 studies); 'thinking abnormally' 5.70 (99% CI 2.26 to 14.38; 4 studies; high-certainty evidence); and weight loss 3.99 (99% CI 1.82 to 8.72; 9 studies; low-certainty evidence). Evidence of publication bias for the primary outcome was found (Egger test, P = 0.001). We rated all studies included in the review as having either low or unclear risk of bias. Overall, we assessed the evidence as moderate to high certainty due to the evidence of publication bias, statistical heterogeneity and imprecision, which was partially compensated for by large effect sizes. Topiramate has efficacy as an add-on treatment for drug-resistant focal epilepsy as it is almost three times more effective compared to a placebo in reducing seizures. The trials reviewed were of relatively short duration and provided no evidence for the long-term efficacy of topiramate. Short-term use of add-on topiramate was shown to be associated with several adverse events. The results of this review should only be applied to adult populations as only one study included children. Future research should consider further examining the effect of dose.