New Pharmacological Therapies in the Treatment of Epilepsy in the Pediatric Population.

Epilepsy is a disorder characterized by abnormal brain neuron activity, predisposing individuals to seizures. The International League Against Epilepsy (ILAE) categorizes epilepsy into the following groups: focal, generalized, generalized and focal, and unknown. Infants are the most vulnerable pediatric group to the condition, with the cause of epilepsy development being attributed to congenital brain developmental defects, white matter damage, intraventricular hemorrhage, perinatal hypoxic-ischemic injury, perinatal stroke, or genetic factors such as mutations in the Sodium Channel Protein Type 1 Subunit Alpha (SCN1A) gene. Due to the risks associated with this condition, we have investigated how the latest pharmacological treatments for epilepsy in children impact the reduction or complete elimination of seizures. We reviewed literature from 2018 to 2024, focusing on the age group from 1 month to 18 years old, with some studies including this age group as well as older individuals. The significance of this review is to present and compile research findings on the latest antiseizure drugs (ASDs), their effectiveness, dosing, and adverse effects in the pediatric population, which can contribute to selecting the best drug for a particular patient. The medications described in this review have shown significant efficacy and safety in the studied patient group, outweighing the observed adverse effects. The main aim of this review is to provide a comprehensive summary of the current state of knowledge regarding the newest pharmacotherapy for childhood epilepsy.

Seizure control and adverse outcomes of lamotrigine use during pregnancy: A systematic review and meta-analysis.

OBJECTIVE: This review aims to summarize existing evidence on the adverse pregnancy outcomes and seizure control effects of using lamotrigine (LTG) monotherapy in pregnancy women with epilepsy (WWE) during pregnancy. METHODS: A comprehensive search was conducted in various databases including Cochrane, Web of Science, CBM, PubMed, Embase, CNKI, and Pregnancy Registration Center databases to identify relevant studies. The search was concluded up to January 2024. Studies comparing LTG with other antiseizure medications (ASMs) for treating epilepsy in pregnant women were included, with no language or regional restrictions. RESULTS: A total of 19 studies were included for analysis, with 16 studies reporting adverse pregnancy outcomes and 6 studies reporting seizure control outcomes. Meta-analysis showed that compared to monotherapy with carbamazepine (CBZ), sodium valproate (VPA), and levetiracetam (LEV), LTG monotherapy had a slightly weaker ability to control seizures during pregnancy, with ORs and 95 %CIs of 0.65 (0.57-0.75; CBZ), 0.50 (0.32-0.79; VPA), and 0.55 (0.36-0.84; LEV). Regarding adverse pregnancy outcomes, the occurrence rate of LTG monotherapy was significantly lower than that of CBZ, VPA, phenytoin (PHT), and phenobarbital (PHB), with ORs and 95 %CIs ranging from 0.30 (0.25-0.35; VPA) to 0.68 (0.56-0.81; CBZ). CONCLUSION: Based on meta-analysis, LTG and LEV appear to be preferred medications for controlling seizures during pregnancy. This review provides further support for the use of LTG monotherapy in pregnant WWE, building upon existing evidence for clinical practitioners.

About 1.5 million community-dwelling US adults with active epilepsy reported uncontrolled seizures in the past 12 months, and seizure control varied by annual family income-National Health Interview Survey, United States 2021 and 2022.

Uncontrolled seizures among people with epilepsy increase risk of adverse health and social outcomes including increased risk of death. Previous population-based studies have reported suboptimal seizure control and disparities in seizure control among U.S. adults with active epilepsy (self-reported doctor-diagnosed epilepsy and taking anti-seizure medicine or with ≥ 1 seizures in the past 12 months) by annual family income. This brief is based upon data from the 2021 and 2022 National Health Interview Survey (NHIS) to provide updated national estimates of the percentages of adults with active epilepsy with and without seizure control (0 seizures in past 12 months) vs. ≥ 1) by anti-seizure medication use and by annual family income. Annual family income was operationalized with NHIS poverty-income ratio (PIR) categories (i.e., total family income divided by the US Census Bureau poverty threshold given the family's size and number of children): PIR < 1.0, 1.0 ≤ PIR < 2.0; PIR ≥ 2.0. Among the 1.1 % of US adults with active epilepsy in 2021/2022 (estimated population about 2.9 million), 49.2 % (∼1.4 million) were taking antiseizure medication and reported no seizures (seizure control), 36.2 % (∼1.1 million) were taking antiseizure medication and reported ≥ 1 seizures (uncontrolled seizures), and 14.7 % (∼400,000) were not taking antiseizure medication and had ≥ 1 seizures (uncontrolled seizures). The prevalence of seizure control among those with active epilepsy varied substantially by annual family income, with a larger percentage of adults with PIR ≥ 2.0 reporting seizure control compared with those with PIR < 1.0. Opportunities for intervention include improving provider awareness of epilepsy treatment guidelines, enhancing access and referral to specialty care, providing epilepsy self-management supports, and addressing unmet social needs of people with epilepsy with uncontrolled seizures, especially those at lowest family income levels.

Clinical characteristics and surgical outcomes of low-grade epilepsy-associated brain tumors.

Background: Low-grade epilepsy-associated brain tumors (LEATs) are found to be the second most common lesion-related epilepsy. Malignant potential of LEATs is very low and the overall survival is good, so the focus of treatment is focused more on seizure outcome rather than oncological prognosis. Objectives: This study was conducted to evaluate the risk factors of seizure outcomes after resection in patients with LEATs. Design: A retrospective study. Methods: A retrospective analysis of patients with LEATs who underwent resective surgery in our three epilepsy centers between October 2010 and April 2023 with a minimum follow-up of 1 year. Demography, clinical characters, neurophysiology, and molecular neuropathology were assessed for association with postoperative seizure outcomes at 1-, 2-, and 5-year follow-up. Synthetic minority oversampling technique (SMOTE) algorithm model was performed to handle the imbalance of data distribution. Gaussian Naïve Bayes (GNB) algorithms were created as a basis for classifying outcomes according to observation indicators. Results: A total of 111 patients were enrolled in the cohort. The most common pathology was ganglioglioma (n = 37, 33.3%). The percentage of patients with seizure freedom was 91.0% (101/111) at 1-year follow-up, 87.5% (77/88) at 2-year follow-up, and 79.1% (53/67) at 5-year follow-up. Partial resection had a significantly poor seizure outcome compared to total resection and supratotal resection (p < 0.05). The epileptiform discharge on post-resective intraoperative electrocorticography (ECoG) or postoperative scalp electroencephalography (EEG) were negative factors on postoperative seizure freedom at 1-, 2-, or 5-year follow-ups (p < 0.05). The area under the receiver-operating characteristic curve value of the GNB-SMOTE model was 0.95 (95% CI, 0.876-1.000), 0.892 (95% CI, 0.656-0.934), and 0.786 (95% CI, 0.491-0.937) at 1-, 2-, and 5-year follow-up, respectively. Conclusion: The partial resection, post-resective intraoperative ECoG, and postoperative scalp EEG were valuable indicators of poor seizure outcomes. The utilization of post-resective intraoperative ECoG is beneficial to improve seizure outcomes. Based on the data diversity and completeness of three medical centers, a multivariate correlation analysis model was established based on GNB algorithm.

Feasibility of mobile phone application "Epilepsy care" for self-management of children and adolescents with epilepsy in Phramongkutklao hospital: A randomized controlled trial.

Epilepsy is a common neurological disorder in children. Mobile applications have shown potential in improving self-management for patients with chronic illnesses. To address language barriers, we developed the first Thai version of the "Epilepsy care" mobile application for children and adolescents with epilepsy in Thailand. A prospective, randomized controlled trial with 220 children and adolescents living with epilepsy who had a smartphone and were treated at the pediatric neurology clinic was conducted, with one group using the mobile application and the other receiving standard epilepsy guidance. The primary outcome assessed epilepsy self-management using the Pediatric Epilepsy Self-Management Questionnaire (PEMSQ) in the Thai version, which comprised 27 questions. These questions aimed to determine knowledge, adherence to medications, beliefs about medication efficacy, and barriers to medication adherence. The secondary outcome evaluated seizure frequency at baseline, 3, and 6 months after initiation of an application. Eighty-five participants who were randomized to a mobile application achieved significantly higher PEMSQ scores in the domain of barriers to medication adherence (p < 0.05) at 6 months follow-up. Other domains of PEMSQ showed no statistically significant difference. Baseline median seizure frequencies per month were 7 in the control group and 5.5 in the intervention group. At 3 and 6 months, these decreased significantly to 1.5 and 1 for the control group and 2.5 and 1 for the intervention group (p < 0.001). In addition, the study revealed that 94.9 % of the participants in a mobile application group were highly satisfied with using application. These findings suggest that the mobile application "Epilepsy care" may serve as an effective adjunctive therapy to enhance self-management and seizure control in children and adolescents with epilepsy.

The Clinical Characteristics and Outcomes of Infantile Seizures in the First Year of Life: A Single-Center Study.

BACKGROUND: Epilepsy has a high incidence among infants during their first year of life, yet the prognosis can vary significantly. Although considerable research has been conducted on infantile spasms, studies examining infantile-onset epilepsy, excluding infantile spasms, remain limited, particularly concerning the factors influencing outcomes. Therefore, our study aims to elucidate seizure control, developmental outcomes, and prognostic factors in infants with epilepsy during their first year of life, within a single-center study in Malaysia. METHODS: We retrieved data from patients who experienced seizures before age 12 months and were followed for over two years, using electronic patient records at Hospital Raja Perempuan Zainab II in Kelantan, a state in Malaysia's east coast. We retrospectively reviewed these records and assessed clinical outcomes based on the last follow-up. RESULTS: Of 75 patients, 61 (81.3%) achieved good seizure control or remission. At the last follow-up, 24 (32%) exhibited developmental delay, whereas 19 (25.3%) displayed abnormal neuroimaging. Patients with abnormal background electroencephalographic (EEG) activity, as well as abnormal radiological findings, were more likely to experience poor seizure control and unfavorable developmental outcomes (P < 0.05). CONCLUSIONS: Our study underscores that most infants with epilepsy can achieve seizure remission. However, poor seizure control and developmental delay are associated with abnormal EEG background and characteristics, as well as neuroimaging abnormalities. The management of infantile-onset epilepsies may necessitate substantial resources and precise interventions to enhance overall outcomes.

Oral microbiome alterations in epilepsy and after seizure control.

Background: The existing diagnostic methods of epilepsy such as history collection and electroencephalogram have great limitations in practice, so more reliable and less difficult diagnostic methods are needed. Methods: By characterizing oral microbiota in patients diagnosed with epilepsy (EPs) and patients whose seizures were under control (EPRs), we sought to discover biomarkers for different disease states. 16S rRNA gene sequencing was performed on 480 tongue swabs [157 EPs, 22 EPRs, and 301 healthy controls (HCs)]. Results: Compared with normal individuals, patients with epilepsy exhibit increased alpha diversity in their oral microbiota, and the oral microbial communities of the two groups demonstrate significant beta diversity differences. EPs exhibit a significant increase in the abundance of 26 genera, including Streptococcus, Granulicatella, and Kluyvera, while the abundance of 14 genera, including Peptostreptococcus, Neisseria, and Schaalia, is significantly reduced. The area under the receiver operating characteristic curve (AUC) of oral microbial markers in the training cohort and validation cohort was 98.85% and 97.23%, respectively. Importantly, the AUC of the biomarker set achieved 92.44% of additional independent validation sets. In addition, EPRs also have their own unique oral community. Conclusion: This study describes the characterization of the oral microbiome in EP and EPR and demonstrates the potential of the specific microbiome as a non-invasive diagnostic tool for epilepsy.

The Evolving Landscape of Therapeutics for Epilepsy in Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is a rare multisystem genetic disorder characterized by benign tumor growth in multiple organs, including the brain, kidneys, heart, eyes, lungs, and skin. Pathogenesis stems from mutations in either the TSC1 or TSC2 gene, which encode the proteins hamartin and tuberin, respectively. These proteins form a complex that inhibits the mTOR pathway, a critical regulator of cell growth and proliferation. Disruption of the tuberin-hamartin complex leads to overactivation of mTOR signaling and uncontrolled cell growth, resulting in hamartoma formation. Neurological manifestations are common in TSC, with epilepsy developing in up to 90% of patients. Seizures tend to be refractory to medical treatment with anti-seizure medications. Infantile spasms and focal seizures are the predominant seizure types, often arising in early childhood. Drug-resistant epilepsy contributes significantly to morbidity and mortality. This review provides a comprehensive overview of the current state of knowledge regarding the pathogenesis, clinical manifestations, and treatment approaches for epilepsy and other neurological features of TSC. While narrative reviews on TSC exist, this review uniquely synthesizes key advancements across the areas of TSC neuropathology, conventional and emerging pharmacological therapies, and targeted treatments. The review is narrative in nature, without any date restrictions, and summarizes the most relevant literature on the neurological aspects and management of TSC. By consolidating the current understanding of TSC neurobiology and evidence-based treatment strategies, this review provides an invaluable reference that highlights progress made while also emphasizing areas requiring further research to optimize care and outcomes for TSC patients.

Changes over 24 years in a pregnancy register - Teratogenicity and epileptic seizure control.

OBJECTIVES: To trace (i) changes in Australian Pregnancy Register (APR) records concerning antiseizure medications (ASMs) prescribed for women with epilepsy (WWE) over the course of 24 years and correlate the changes with (ii) rates of occurrence of pregnancies involving foetal malformations, (iii) the body organs involved in the malformations, and (iv) freedom from epileptic seizures. RESULTS: Use of valproate and carbamazepine decreased progressively, use of lamotrigine remained relatively static, and the use of levetiracetam increased progressively, whereas the use of topiramate first increased and then fell again, associated with a temporary increase in malformation-associated pregnancy rate. More serious malformations, such as spina bifida, became less frequent, whereas more trivial ones tended to increase, whereas epileptic seizure freedom rates improved. CONCLUSIONS: The increasing use of newer ASMs in pregnant women has been associated with overall advantages in relation to the frequency and severity of foetal malformation and with advantages in relation to freedom from epileptic seizures.

Interaction between vitamin D level, antiseizure medications (ASM) and seizure control in epilepsy adult patients.

OBJECTIVE: To investigate vitamin D levels and factors associated with seizure control in adult patients with epilepsy (APE). METHOD: Cross-sectional study with APE in routine outpatient follow-up at a neurology clinic. Clinical variables, antiseizure medications (ASM) and vitamin D were investigated. Data were analyzed using the Chi2 or Fisher's exact tests, Mann-Whitney, Spearman's correlation coefficient, ROC curve and univariate and multiple logistic regression analysis. RESULTS: Mean age was 46.5±15.1 years and disease duration was 27.5±17.0 years; 52.7% (n=49) of patients used one ASM and 47.3% (n=44) used≥2 ASM. There was a significant difference in the level of vitamin D according to the number of ASM and it was higher in patients who used a single ASM (26.02±10.22 versus 22.50±8.69; P=0.048). In the logistic regression, when vitamin D level was set at 20ng/mL, the chance of seizure control for patients using a single ASM was 6.99 times greater than for those using≥2 ASM. When vitamin D level was set at 40ng/mL, the number of ASM did not modify seizure control. There was no correlation between vitamin D and disease duration, patient age and age at the time of the first seizure. In the logistic regression, it was observed that satisfactory levels of vitamin D did not modify potential seizure control. CONCLUSION: Thirty-three percent (33%) of patients presented with vitamin D deficiency (values below 20ng/mL) and 80% had vitamin D levels below what is recommended (30ng/mL). The use of ASM, when associated with different levels of vitamin D, modified the probability of seizure control in APE. Vitamin D levels and intrinsic epilepsy factors are associated with failure to effectively control seizures.

Factors influencing community pharmacists' knowledge about women's issues in epilepsy.

Background: Previous studies have highlighted instances where pharmacists lacked knowledge regarding women's health issues related to epilepsy. Objectives: To assess UAE community pharmacists' knowledge, toward women's issues in epilepsy. Methods: a cross-sectional research method was employed. A team of seven pharmacy students in their final year visited a randomly selected sample of community pharmacies in the UAE and face-to-face interviews were conducted with the pharmacists using a structured questionnaire. The questionnaire includes two parts; Eight questions designed to elicit data about the demographics of the study participants and 12 questions eliciting insights into the participants' knowledge of women's issues in epilepsy. Results: A total of 412 community pharmacist were recruited in the study. The overall level of knowledge about women's issues in epilepsy was good and the average knowledge score was 81% with a 95% confidence interval (CI) [79.1, 82.7%]. The results of multivariate analysis showed higher knowledge scores in chain pharmacies (OR 1.37; 95% CI 1.12-1.67), Chief pharmacists (OR 1.44; 95% CI 1.01-2.06), Pharmacists in charge (OR 3.46; 95% CI 2.7-4.45), pharmacists with 1-5 Years of experience (OR 2.87; 95% CI 1.71-4.82), pharmacists with 6-10 Years (OR 2.63; 95% CI 1.58-4.38), pharmacists with >10 years (OR 3.13; 95% CI 2.03-4.83), graduation form regional universities (OR 1.37; 95% CI 1.12-1.67), graduation form international universities (OR 1.73; 95% CI 1.36-2.20) and receiving a training on epilepsy (OR 1.36; 95% CI 1.12-1.67). Conclusion: While the findings reveal an overall promising level of knowledge among community pharmacists regarding the issues faced by women with epilepsy, pinpointing which clinical and demographic factors have the most significant impact on this knowledge would permit the implementation of tailored educational interventions. Workshops and modules targeting the issues faced by women with epilepsy would further raise the knowledge and competence among community pharmacists in this area, ensuring better pharmaceutical care for this population.

The number of antiseizure medications taken and not the lipid profile was associated with seizure control in adult patients with epilepsy.

Previous studies show changes in lipid metabolism in epilepsy. The aim of this study was to investigate the association between lipid profile and clinical variables in adult patients with epilepsy (APE). Seventy-two APE participated in this pilot study at an outpatient neurology service. The lipid profile (total cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoproteins (VLDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides), age at disease onset, disease duration, seizures frequency, and the number of antiseizure medications (ASM) used were investigated. Data were analyzed using the Chi-square, Fisher, Mann-Whitney, Spearman coefficient, and logistic regression tests. There were significant differences in HDL (p = 0.0023) and total cholesterol (p = 0.0452) levels in connection with the number of ASM used. There was a significant difference in seizure control among the different numbers of ASM used (p = 0.0382). Higher HDL values were found in females (p = 0.0170). The logistic regression showed that only the number of ASM used was associated with seizure control (p = 0.0408; OR = 2.800; 95% CI = 1.044; 7.509). The number of ASM taken and not the lipid profile was associated with seizure control in APE.

Sustainability of seizure reduction and seizure control with adjunctive cenobamate: Post hoc analysis of a phase 3, open-label study.

OBJECTIVE: In this post hoc analysis of a subset of patients from a long-term, open-label phase 3 study, we assessed ≥50%, ≥75%, ≥90%, and 100% seizure reduction and sustainability of these responses with cenobamate using a time-to-event analytical approach. METHODS: Of 240 patients with uncontrolled focal seizures who had adequate seizure data available, 214 completed the 12-week titration phase and received ≥1 dose of cenobamate in the maintenance phase (max dose 400 mg/day) and were included in this post hoc analysis. Among patients who met an initial given seizure-reduction level (≥50%, ≥75%, ≥90%, or 100%), sustainability of that response was measured using a time-to-event methodology. An event was defined as the occurrence of a study visit at which the seizure frequency during the interval since the prior study visit exceeded the initially attained reduction level. Study visits during the maintenance phase occurred at 3-month intervals. RESULTS: Of the 214 patients analyzed, 188 (88%), 177 (83%), 160 (75%), and 145 (68%) met ≥50%, ≥75%, ≥90%, and 100% seizure-reduction responses, respectively, for at least one study visit interval during the maintenance phase. The median (95% confidence interval [CI]) time to first visit without a ≥50% seizure reduction was not reached by 30 months of follow-up (53% of patients maintained their initial ≥50% seizure reduction). Median (95% CI) time to first visit without sustaining the initial ≥75%, ≥90%, or 100% seizure reduction was 13.0 (7.5-21.9) months, 7.5 (5.4-11.6) months, and 7.0 (5.3-10.4) months, respectively. Among the 145 patients who had 100% seizure reduction during at least one study visit, 22% remained seizure-free for at least 30 months and 63% had ≤3 study visits with seizures. SIGNIFICANCE: Adjunctive treatment with cenobamate led to sustained seizure reductions during the maintenance phase of the phase 3 safety study.

Can the Gut Microbiota Serve as a Guide to the Diagnosis and Treatment of Childhood Epilepsy?

BACKGROUND: To investigate the activity of the gut-brain axis in the pathogenesis of childhood epilepsy and to define biomarkers capable of assisting with determining new strategies in that context. METHODS: Twenty children with epilepsy of "unknown etiology" and seven healthy controls in the same age group were included in the study. The groups were compared using a questionnaire. Stool samples were stored in tubes containing DNA/RNA Shield (Zymo Research) with a sterile swab. Sequencing was carried out using the MiSeq System (Illumina). The 16S rRNA sequencing of samples using next-generation sequencing involved V4 variable region polymerase chain reaction amplification concluded by 2 × 250-bp paired-end sequencing of amplicons and at least 50,000 reads (>Q30) per sample. DNA sequences were classified at the genus level using the Kraken program. Bioinformatics and statistical analysis were then performed. RESULTS: Individuals' gut microbiota relative abundance values differed between the groups at the genus, order, class, family, and phylum levels. Flavihumibacter, Niabella, Anoxybacillus, Brevundimonas, Devosia, and Delftia were seen only in the control group, whereas Megamonas and Coriobacterium were observed only in the epilepsy group. The linear discriminant analysis effect size method identified 33 taxa as important in differentiating the groups. CONCLUSIONS: We think that bacterial varieties (such as Megamonas and Coriobacterium) that differ between the two groups can be employed as useful biomarkers in the diagnosis and follow-up of epileptic patients. We also predict that, in addition to epilepsy treatment protocols, the restoration of eubiotic microbiota may increase the success of treatment.

Living with epilepsy during COVID-19 pandemic restrictions: A longitudinal perspective.

The purpose of our study was to explore how people with epilepsy fared during two of the most stringent 4-month society-wide COVID-19-related pandemic restrictions in Ireland, in 2020 and one year later in 2021. This was in the context of their seizure control, lifestyle factors, and access to epilepsy-related healthcare services. A 14-part questionnaire was administered to adults with epilepsy during virtual specialist epilepsy clinics in a University Hospital in Dublin, Ireland at the end of the two lockdowns. People with epilepsy were questioned on their epilepsy control, lifestyle factors, and quality of epilepsy-related medical care, compared to pre-COVID times. The study sample consisted of two separate cohorts of those diagnosed with epilepsy (100 (51.8%) in 2020, and 93 (48.2%) in 2021, with similar baseline characteristics. There was no significant change in seizure control or lifestyle factors from 2020 to 2021, except for deterioration in anti-seizure medication (ASM) adherence in 2021 compared to 2020 (p = 0.028). There was no correlation between ASM adherence and other lifestyle factors. Over the two years, poor seizure control was significantly associated with poor sleep (p < 0.001) and average seizure frequency in a month (p = 0.007). We concluded that there was no significant difference between seizure control or lifestyle factors between the two most stringent lockdowns in Ireland, in 2020 and 2021. Furthermore, people with epilepsy reported that throughout the lockdowns access to services was well maintained, and they felt well supported by their services. Contrary to the popular opinion that COVID lockdowns greatly affected patients with chronic diseases, we found that those with epilepsy attending our service remained largely stable, optimistic, and healthy during this time.

Poor Seizure Control Among Children Attending a Tertiary Hospital in South Western Uganda - A Retrospective Study.

Background: Seizure control among children with epilepsy (CWE) receiving anti-seizure medications (ASMs) remains a challenge in low-resource settings. Uncontrolled seizures are significantly associated with increased morbidity and mortality among CWE. This negatively impacts their quality of life and increases stigma. Aim: This study determined seizure control status and described the factors associated among CWE receiving ASMs at Mbarara Regional Referral Hospital (MRRH). Methods: In a retrospective chart review study, socio-demographic and clinical data were obtained from 112 medical records. CWE receiving ASMs for at least six months and regularly attending the clinic were included in the study. Physical or telephone interviews were conducted with the immediate caregivers of the CWE to establish the current seizure control status of the participants. Results: A total of 112 participants were enrolled. Of these, three-quarters had generalized onset seizures, 23% had focal onset seizures, while 2% had unknown onset motor seizures. About 60.4% of the study participants had poor seizure control. Having a comorbidity (p-value 0.048, AOR 3.2 (95% CI 1.0-9.9)), history suggestive of birth asphyxia (p-value 0.014, AOR 17.8 (95% CI 1.8-176.8)), and being an adolescent (p-value 0.006, AOR 6.8 (95% CI 1.8-26.6)) were significantly associated with poor seizure control. Conclusion: Seizure control among CWE receiving ASMs at MRRH remains poor. Efforts geared to addressing seizure control and optimizing drugs are needed, especially among children with comorbidities, those with history of birth asphyxia, and adolescents.

Epilepsia y gestación. Factores asociados con la presencia de crisis en la gestación / Epilepsy and pregnancy. Factors associated with epileptic seizures during pregnancy

Introducción: El manejo de la epilepsia durante la gestación requiere un control óptimo de las crisis, evitando los potenciales efectos teratogénicos del tratamiento antiepiléptico.ObjetivosDescribir las características clínicas y los resultados perinatales de las pacientes con epilepsia gestantes. Analizar los factores que se asocian a la presencia de crisis durante la gestación. Describir los fármacos antiepilépticos más utilizados y analizar los cambios en el régimen terapéutico en dos periodos: de 2000-2010 y 2011-2018.MétodosSe realizó un estudio prospectivo observacional de pacientes con epilepsia que notificaron su gestación en el periodo de 2000-2018. Se evaluó a las pacientes en el primer y segundo trimestre de gestación, tras el parto y al año. Se recogieron variables demográficas, relacionadas con la epilepsia, perinatales y obstétricas.ResultadosSe incluyeron 101 gestaciones. La edad media fue de 32,6 años, el 55,4% tenía una epilepsia focal, el 38,6% una epilepsia generalizada y el 5,9% indeterminada. Se registraron 90 nacidos vivos, nueve abortos espontáneos y cinco malformaciones congénitas, cuatro de ellas en monoterapia con valproato. En 40 gestaciones (39,6%) se registraron crisis, siendo tónico-clónicas generalizadas en 16 (40%). Las variables asociadas con la presencia de crisis durante el embarazo fueron el mal control el año previo a la gestación (66,7% vs. 15,1%, p < 0,001), el tratamiento con dos o más fármacos antiepilépticos (30% vs. 14,8% p < 0,001) y no recibir tratamiento (25% vs. 0% p < 0,001). Los fármacos antiepilépticos más utilizados en monoterapia fueron lamotrigina (n = 19, 27,1%), valproato (n = 17, 24,2%) y levetiracetam (n = 12, 17,1%). En el periodo más reciente (2011-2018) se encontró una mayor proporción de monoterapias (81,5% vs. 55,3%), además de un descenso en el uso de carbamazepina (23,1% vs. 2,3%) y valproato (30,8% vs. 20,5%); y un aumento marcado de levetiracetam (0% vs. 27,3%). (AU)

Introduction: The management of epilepsy during pregnancy requires optimal seizure control, avoiding the potential teratogenic effects of antiepileptic drugs.ObjectivesThis study aims to describe the clinical characteristics and perinatal outcomes of pregnant patients with epilepsy; to analyse the factors associated with seizures during pregnancy; to describe the most commonly used antiepileptic drugs in these patients; and to analyse changes in treatment regimens in 2 periods, 2000-2010 and 2011-2018.MethodsWe conducted a prospective observational study of patients with epilepsy who reported their pregnancy between 2000 and 2018. Patients were evaluated in the first and second trimesters of pregnancy, after delivery, and at one year. Data were collected on demographic variables, epilepsy, and perinatal and obstetric variables.ResultsA total of 101 pregnancies were included. Patients’ mean age was 32.6 years; 55.4% had focal epilepsy, 38.6% had generalised epilepsy, and 5.9% had undetermined epilepsy. We recorded 90 live births, 9 miscarriages, and 5 cases of congenital malformations, 4 of which were born to women who received valproate monotherapy. Forty patients (39.6%) presented seizures, with 16 (40%) presenting generalised tonic-clonic seizures. The variables associated with seizures during pregnancy were poor seizure control in the year prior to pregnancy (66.7% vs. 15.1%; P < .001), treatment with 2 or more antiepileptic drugs (30% vs. 14.8%; P < .001), and untreated epilepsy (25% vs. 0%; P < .001). The antiepileptic drugs most widely used in monotherapy were lamotrigine (n = 19; 27.1%), valproate (n = 17; 24.2%), and levetiracetam (n = 12; 17.1%). In the most recent period (2011-2018), we observed a greater proportion patients receiving monotherapy (81.5%, vs. 55.3%), as well as a decrease in the use of carbamazepine (2.3%, vs. 23.1%) and valproate (20.5%, vs. 30.8%); and a marked increase in the use of levetiracetam (27.3%, vs. 0%). (AU)

Seizure forecasting: Where do we stand?

A lot of mileage has been made recently on the long and winding road toward seizure forecasting. Here we briefly review some selected milestones passed along the way, which were discussed at the International Conference for Technology and Analysis of Seizures-ICTALS 2022-convened at the University of Bern, Switzerland. Major impetus was gained recently from wearable and implantable devices that record not only electroencephalography, but also data on motor behavior, acoustic signals, and various signals of the autonomic nervous system. This multimodal monitoring can be performed for ultralong timescales covering months or years. Accordingly, features and metrics extracted from these data now assess seizure dynamics with a greater degree of completeness. Most prominently, this has allowed the confirmation of the long-suspected cyclical nature of interictal epileptiform activity, seizure risk, and seizures. The timescales cover daily, multi-day, and yearly cycles. Progress has also been fueled by approaches originating from the interdisciplinary field of network science. Considering epilepsy as a large-scale network disorder yielded novel perspectives on the pre-ictal dynamics of the evolving epileptic brain. In addition to discrete predictions that a seizure will take place in a specified prediction horizon, the community broadened the scope to probabilistic forecasts of a seizure risk evolving continuously in time. This shift of gears triggered the incorporation of additional metrics to quantify the performance of forecasting algorithms, which should be compared to the chance performance of constrained stochastic null models. An imminent task of utmost importance is to find optimal ways to communicate the output of seizure-forecasting algorithms to patients, caretakers, and clinicians, so that they can have socioeconomic impact and improve patients' well-being.

Glioma features and seizure control during long-term follow-up.

Background: An epileptic seizure is a common presenting symptom of glioma, or epilepsy may develop later during the disease. Epileptic seizures affect the quality of life in patients with glioma. Good seizure control during 6-12 months follow-up has been associated with gross total resection, radiation therapy and chemotherapy of gliomas. Little is known about seizure control during long-term follow-up and about factors which may affect the prognosis of epilepsy in glioma patients. Methods: We identified retrospectively all adult patients with diffuse glioma (grade 2-4) associated epilepsy (n = 123) living in Helsinki, who received treatment at Helsinki University Hospital neuro-oncology center during 2013-2015. We excluded patients with histopathological diagnosis prior to 2005. Data was collected from medical records for five years after diagnosis of glioma, or until death. Results: In this patient cohort 49 (39.8 %) had grade 2 glioma, 19 (15.4 %) had grade 3 glioma and 55 (44.7 %) had grade 4 glioma. 29 (23.6 %) of tumors were astrocytomas, 24 (19.5 %) were oligoastrocytomas, 15 (12.2 %) were oligodendrogliomas and 55 (44.7 %) were glioblastomas. A seizure was the presenting symptom in 87 (70.7 %) of the patients. The majority, 68 (57.6 %) patients were seizure-free for at least 12 months at some point during follow-up and 47 (39.8 %) patients were seizure-free during the last year of follow-up. Survival for five years from glioma diagnosis (p < 0.001), lower grade of tumor (p < 0.001), IDH mutation (p < 0.001), epilepsy as first symptom (p < 0.001), younger age (p < 0.001) and lack of progression (p = 0.021) correlated with seizure freedom at the end of follow-up. When the results were analyzed separately in survivors and deceased patients, only progression correlated negatively with seizure freedom at the end of follow-up in surviving patients (p = 0.008). In 5-year survivors, longer seizure-free periods were achieved by patients without progression of glioma (p = 0.040) vs patients with progression, or without focal aware (p 0.003) or focal impaired awareness seizures (p = 0.002) vs patients with only focal to bilateral tonic-clonic seizures. In deceased patients, progression (p < 0.001) and lower grade of glioma (p = 0.003) correlated positively and focal aware seizures negatively (p = 0.021) with a longer seizure-free period. In all patients, freedom of seizures at the end of follow-up was less likely for patients who had focal aware (p = 0.015) than for patients without focal aware seizures. Conclusion: There are differences in seizure-free times in patients with grade 2-4 glioma and epilepsy. The results suggest that the prognosis of glioma may be the most important factor influencing the prognosis of epilepsy.

Magnitude of uncontrolled seizures and associated factors among people with epilepsy. Data from a major teaching hospital in Southwest Ethiopia.

BACKGROUND: Epilepsy is a major public health problem affecting 70 million people worldwide. 90% of global people with epilepsy were living in developing regions like Ethiopia. Due to the lack of clear guidelines for treatment selection and the difficulty of individualizing care in resource-poor settings, achieving seizure control can be challenging. Seizure control status among epileptic patients is affected by different factors. Accordingly, this study aimed to assess the magnitude of uncontrolled seizures and associated factors among people with epilepsy attending the outpatient clinic of Jimma Medical Center, Southwest Ethiopia. METHODS: A hospital-based retrospective chart review and a respective patient interview conducted among people with epilepsy from October 2020 to June 2021. Sociodemographic, behavioral-related factors, medication adherence, and medication belief were obtained through patient interviews. Seizure control status in the last two years before the study period was retrospectively evaluated and recorded from the charts. Data were entered into Epi Data manager version 4.6 and then exported to SPSS version 23.0 for analysis. A backward logistic regression analysis was done to identify factors associated with uncontrolled seizures. RESULTS: From a total of 314 medical charts reviewed, 149(47.5 %) of patients were with uncontrolled seizures. 28.7 %,12.8 %, and 6 % of the patients experienced 1-5,6-10, and >10 seizure episodes during the last two years respectively. Comorbidity [adjusted odds ratio [(AOR): 2.13, 95 % confidence interval (CI):1.26-3.58], nonadherence [AOR: 2.41, 95 %CI: 1.46-3.9], possible adverse drug reaction (ADR) [AOR:1.79, 95 %CI: 1.107-3.01], and drug interaction [AOR: 3.06, 95 %CI: 1.24-7.57] were associated with an uncontrolled seizure. CONCLUSION AND RECOMMENDATION: Our study showed that a substantial proportion of the patients were with uncontrolled seizures. Epileptic patients with comorbidities, nonadherence, adverse drug reactions, and drug interactions were more prone to have uncontrolled seizures. Hence, to overcome these problems, strategies like community-based education, treatment intensification, and routine assessment of adverse drug reactions and drug interaction may help to improve seizure control status.