Seizure Control Research Articles

Susceptibility to Pentylenetetrazole-Induced Seizures in Mice with Distinct Activity of the Endogenous Opioid System.

Currently, pharmacotherapy provides successful seizure control in around 70% of patients with epilepsy; however, around 30% of cases are still resistant to available treatment. Therefore, effective anti-epileptic therapy still remains a challenge. In our study, we utilized two mouse lines selected for low (LA) and high (HA) endogenous opioid system activity to investigate the relationship between down- or upregulation of the opioid system and susceptibility to seizures. Pentylenetetrazole (PTZ) is a compound commonly used for kindling of generalized tonic-clonic convulsions in animal models. Our experiments revealed that in the LA mice, PTZ produced seizures of greater intensity and shorter latency than in HA mice. This observation suggests that proper opioid system tone is crucial for preventing the onset of generalized tonic-clonic seizures. Moreover, a combination of an opioid receptor antagonist-naloxone-and a GABA receptor agonist-diazepam (DZP)-facilitates a significant DZP-sparing effect. This is particularly important for the pharmacotherapy of neurological patients, since benzodiazepines display high addiction risk. In conclusion, our study shows a meaningful, protective role of the endogenous opioid system in the prevention of epileptic seizures and that disturbances in that balance may facilitate seizure occurrence.

Long-Term Outcome in Adult Patients with Drug-Resistant Epilepsy Submitted to Vagus Nerve Stimulation.

Epilepsy treatment primarily involves antiseizure medications (ASMs) to eliminate seizures and improve the quality of life, but many patients develop drug-resistant epilepsy (DRE), necessitating alternative interventions. This study aimed to evaluate the long-term efficacy and safety of vagus nerve stimulation (VNS) in managing DRE. We retrospectively analyzed data from 105 adult patients treated at Agostino Gemelli Hospital from 1994 to 2022. Among the 73 patients with follow-up data, 80.8% were responders, experiencing significant reductions in seizure frequency over an average follow-up period of 9.4 years. Although 19.2% were non-responders, many of these patients still opted for generator replacements due to improvements in quality of life, such as fewer falls and shorter post-ictal periods. The overall complication rate was 12.3%, with most complications being mild and manageable. These findings suggest that VNS offers substantial long-term benefits for patients with DRE, improving seizure control and quality of life. This study underscores the importance of VNS as a viable long-term treatment option for DRE, highlighting its potential to significantly enhance patient outcomes and quality of life.

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.

EEG Ictal Power Dynamics, Function-Structure Associations, and Epilepsy Surgical Outcomes.

Postoperative seizure control in drug-resistant temporal lobe epilepsy (TLE) remains variable, and the causes for this variability are not well understood. One contributing factor could be the extensive spread of synchronized ictal activity across networks. Our study used novel quantifiable assessments from intracranial EEG (iEEG) to test this hypothesis and investigated how the spread of seizures is determined by underlying structural network topological properties. We evaluated iEEG data from 157 seizures in 27 patients with TLE: 100 seizures from 17 patients with postoperative seizure control (Engel score I) vs 57 seizures from 10 patients with unfavorable surgical outcomes (Engel score II-IV). We introduced a quantifiable method to measure seizure power dynamics within anatomical regions, refining existing seizure imaging frameworks and minimizing reliance on subjective human decision-making. Time-frequency power representations were obtained in 6 frequency bands ranging from theta to gamma. Ictal power spectrums were normalized against a baseline clip taken at least 6 hours away from ictal events. Electrodes' time-frequency power spectrums were then mapped onto individual T1-weighted MRIs and grouped based on a standard brain atlas. We compared spatiotemporal dynamics for seizures between groups with favorable and unfavorable surgical outcomes. This comparison included examining the range of activated brain regions and the spreading rate of ictal activities. We then evaluated whether regional iEEG power values were a function of fractional anisotropy (FA) from diffusion tensor imaging across regions over time. Seizures from patients with unfavorable outcomes exhibited significantly higher maximum activation sizes in various frequency bands. Notably, we provided quantifiable evidence that in seizures associated with unfavorable surgical outcomes, the spread of beta-band power across brain regions is significantly faster, detectable as early as the first second after seizure onset. There was a significant correlation between beta power during seizures and FA in the corresponding areas, particularly in the unfavorable outcome group. Our findings further suggest that integrating structural and functional features could improve the prediction of epilepsy surgical outcomes. Our findings suggest that ictal iEEG power dynamics and the structural-functional relationship are mechanistic factors associated with surgical outcomes in TLE.

Electrocorticographic Patterns in Frontal Epilepsy and Long-Term Outcomes [RETRACTED

The prognostic significance of tailored resection guided with intraoperative electrocorticography (iECoG) in frontal lobe epilepsy surgery has not been fully elucidated. To analyze influence of preresection and postresection iECoG patterns on long-term seizure control of adults with frontal lobe epilepsy undergoing epilepsy surgery. We retrospectively analyzed 27 patients undergoing epilepsy surgery from two centers with preresection and postresection iECoG and reported clinical variables, preresection and postresection iECoG patterns, and outcome using the Engel Outcome Scale. Descriptive statistics, Kaplan-Meier, the logistic regression model, and analysis of variance tests were used. Fifteen males (55.6%), a mean and mode follow-up after surgery of 43 (range 2-117) and 19 months, respectively. At 6 months, seizure frequency outcome according to Engel Scale was I 74.1% (20/27), II 7.4% (2/27), III 3.7% (1/27), and IV 14.8% (4/27). We found that 51.9% (14/27) and 40.8% (11/27) of patients without residual epileptiform discharges in postresective iECoG become seizure-free at 6 and 12 months of follow-up, respectively, compared with other postresective iECoG patterns. Disregarding the presence of lack of residual epileptiform discharges (interictal epileptiform discharges) after resection, Engel I outcome was seen between 74.1% and 63% at 6- and 12-month postresection follow-up, suggesting the outcome might be in relation with other factors.

A retrospective study of the yield of next-generation sequencing in the diagnosis of developmental and epileptic encephalopathies and epileptic encephalopathies in 0-12 years aged children at a single tertiary care hospital in South India.

Studies on the genetic yield of developmental and epileptic encephalopathy and Epileptic encephalopathies using next-generation sequencing techniques are sparse from the Indian subcontinent. Hence, the study was conducted to assess the yield of genetic testing and the proportion of children where a positive genetic yield influenced treatment decisions. In this retrospective observational study, electronic medical records of children (0-12 years) with suspected genetic epilepsy who underwent genetic testing using whole exome sequencing, focused exome sequencing and epilepsy gene panels were retrieved. Genetic yield was ascertained based on the detection of pathogenic and likely pathogenic variants. A total of 100 patients with epilepsy underwent genetic testing. A yield of 53.8% (42/78) was obtained. Pathogenic variants were identified in 18 (42.8%) cases and likely pathogenic variants in 24 (57.1%) cases. Yield was 66.6% each through whole exome sequencing, focused exome sequencing and 40% through Epilepsy gene panels (p = .07). Yield was not statistically significant across different age groups (p = .2). It was however found to significantly vary across different epilepsy syndromes with maximum yield in Epilepsy in infancy with migrating focal seizures in 2 (100%), followed by developmental and epileptic encephalopathy unspecified in 14 (77.7%), Dravet syndrome in 14 (60.8%), early infantile developmental and epileptic encephalopathy in 3 (60%), infantile epileptic spasm syndrome in 5 (35.7%), and other epileptic encephalopathies in 4 (30.7%) cases (p = .04). After genetic diagnosis and drug optimization, drug-refractory proportion reduced from 73.8% to 45.3%. About half of the cases achieved seizure control. A reasonably high yield of 53.8% was obtained irrespective of the choice of panel or exome or age group using next-generation sequencing-based techniques. Yield was however higher in certain epilepsy syndromes and low in Infantile epileptic spasms syndrome. A specific genetic diagnosis facilitated tailored treatment leading to seizure freedom in 28.6% and marked seizure reduction in 54.7% cases.

The contribution of NaV1.6 to the efficacy of voltage-gated sodium channel inhibitors in wild type and NaV1.6 gain-of-function (GOF) mouse seizure control.

Inhibitors of voltage-gated sodium channels (NaVs) are important anti-epileptic drugs, but the contribution of specific channel isoforms is unknown since available inhibitors are non-selective. We aimed to create novel, isoform selective inhibitors of Nav channels as a means of informing the development of improved antiseizure drugs. We created a series of compounds with diverse selectivity profiles enabling block of NaV1.6 alone or together with NaV1.2. These novel NaV inhibitors were evaluated for their ability to inhibit electrically evoked seizures in mice with a heterozygous gain-of-function mutation (N1768D/+) in Scn8a (encoding NaV1.6) and in wild-type mice. Pharmacologic inhibition of NaV1.6 in Scn8aN1768D/+ mice prevented seizures evoked by a 6-Hz shock. Inhibitors were also effective in a direct current maximal electroshock seizure assay in wild-type mice. NaV1.6 inhibition correlated with efficacy in both models, even without inhibition of other CNS NaV isoforms. Our data suggest NaV1.6 inhibition is a driver of efficacy for NaV inhibitor anti-seizure medicines. Sparing the NaV1.1 channels of inhibitory interneurons did not compromise efficacy. Selective NaV1.6 inhibitors may provide targeted therapies for human Scn8a developmental and epileptic encephalopathies and improved treatments for idiopathic epilepsies.

Comparative Analysis of Antihypertensive and Anticonvulsant Regimens in Managing Pre-eclampsia and Eclampsia: Insights from a Sudanese Retrospective Study.

BACKGROUND Preeclampsia presents with gestational proteinuria, usually after 20 weeks of gestation, and can be complicated by generalized tonic-clonic seizures of eclampsia. Particularly in countries with limited healthcare resources, preeclampsia and eclampsia are major causes of maternal morbidity and mortality. This retrospective study aimed to evaluate the presentation, management, and outcomes of 185 women with preeclampsia and eclampsia in 2 maternity hospitals in Omdurman, Sudan, between January and December 2020. MATERIAL AND METHODS An analytical retrospective study was conducted in 2 main maternity hospitals in Omdurman, Sudan, between January and December 2020. The study included 185 pregnant women with preeclampsia or eclampsia. Data on clinical and obstetric characteristics (history of the illness, comorbid diseases, parity, gravida, multifetal pregnancy, and laboratory investigations), medications used, and maternal and neonatal outcomes were obtained for the diagnosis. The data were analyzed using the SPSS version 27. RESULTS Results: The mean age was 27.2±6.3 years, with 42.7% primigravida, 30% had a triple-drug regimen, nifedipine was the most common antihypertensive (60.5%), and 17.3% of patients underwent observation only. The seizure rate was 20%, with 92.73% controlled with magnesium sulfate. The antihypertensive regimen before delivery was significantly associated with the mode of delivery (P=0.001) and maternal outcomes (P=0.047); the regimen used after delivery significantly achieved blood pressure control (P=0.043) and improved maternal outcomes (P=0.007), but not fetal outcomes. CONCLUSIONS Maternal outcomes were markedly affected by the antihypertensive drug regimens used and the patient's seizure control status, and use of anti-convulsants successfully controlled all seizures.

Characteristics of malignant brain tumor-associated epileptic spasms.

Although epilepsy is the most common comorbidity of brain tumors, epileptic spasms rarely occur. Brain tumors associated with epileptic spasms are mostly low-grade gliomas. To date, few studies in the literature have reported on malignant (Grades 3-4) brain tumors associated with epileptic spasms. Thus, we aimed to investigate the characteristics of malignant brain tumor-associated epileptic spasms. We retrospectively reviewed patients with malignant brain tumors and epileptic spasms in our institution. Data on demographics, tumor histology, magnetic resonance imaging, epileptic spasm characteristics, electroencephalography, and treatment responsiveness were also collected. Six patients were included. In all cases, the brain tumors occurred in infancy in the supratentorial region and epileptic spasm onset occurred after the completion of brain tumor treatment. Anti-seizure medication did not control epileptic spasms; two patients were seizure-free after epileptic surgery. Although all patients had developmental delays caused by malignant brain tumors and their treatment, developmental regression proceeded after epileptic spasm onset. Two patients who achieved seizure-free status showed improved developmental outcomes after cessation of epileptic spasms. This is the first report of the characteristics of malignant brain tumor-associated epileptic spasms. Our report highlights a difficulties of seizure control and possibillity of efficacy of epileptic surgery in this condition. In malignant brain tumor-associated epileptic spasms, it is important to proceed with presurgical evaluation from an early stage, bearing in mind that epileptic spasms may become drug-resistant.

Effects of ganaxolone on non-seizure outcomes in CDKL5 Deficiency Disorder: Double-blind placebo-controlled randomized trial

CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy. Ganaxolone, a neuroactive steroid, reduces the frequency of major motor seizures in children with CDD. This analysis explored the effect of ganaxolone on non-seizure outcomes. Children (2–19 years) with genetically confirmed CDD and ≥ 16 major motor seizures per month were enrolled in a double-blind randomized placebo-controlled trial. Ganaxolone or placebo was administered three times daily for 17 weeks. Behaviour was measured with the Anxiety, Depression and Mood Scale (ADAMS), daytime sleepiness with the Child Health Sleep Questionnaire, and quality of life with the Quality of Life Inventory-Disability (QI-Disability) scale. Scores were compared using ANOVA, adjusted for age, sex, number of anti-seizure mediations, baseline 28-day major motor seizure frequency, baseline developmental skills, and behaviour, sleep or quality of life scores. 101 children with CDD (39 clinical sites, 8 countries) were randomized. Median (IQR) age was 6 (3–10) years, 79.2 % were female, and 50 received ganaxolone. After 17 weeks of treatment, Manic/Hyperactive scores (mean difference 1.27, 95%CI –2.38,-0.16) and Compulsive Behaviour scores (mean difference 0.58, 95%CI -1.14,-0.01) were lower (improved) in the ganaxolone group compared with the placebo group. Daytime sleepiness scores were similar between groups. The total change in QOL score for children in the ganaxolone group was 2.6 points (95%CI -1.74,7.02) higher (improved) than in the placebo group but without statistical significance. Along with better seizure control, children who received ganaxolone had improved behavioural scores in select domains compared to placebo.

IL-6 is associated with poor seizure control in low-grade glioma patients undergoing primary resection

In this study, 198 patients with low-grade gliomas (LGGs) undergoing primary resection were evaluated for seizure status at 24months after primary resection with the Engel classification of seizures, and 120 patients had good seizure control (class I) while 78 patients had poor seizure control (class II-IV). Multivariate analysis showed that cortex involvement, subtotal resection, serum IL-6 concentration, and neutrophil to lymphocyte ratio (NLR) were associated with poor seizure control. The area under curve (AUC) of serum IL-6 concentration, NLR and their combination applied in predicting poor seizure control was 0.756, 0.714, and 0.857, respectively. The AUC of combination prediction was significantly higher than those of individual prediction. Therefore, elevated serum IL-6 concentration was associated with poor seizure control in LLG patients undergoing primary resection and could be applied in predicting seizure control, and the predictive value could be elevated through adding other serum indices to IL-6.

A Systematic Review of the Predictive and Diagnostic Uses of Neuroinflammation Biomarkers for Epileptogenesis.

A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the role of inflammatory mediators in epileptogenesis, its association with seizure severity, and its correlation with drug-resistant epilepsy (DRE). The study analysed articles published in JCR journals from 2019 to 2024. The search strategy comprised the MESH, free terms of "Neuroinflammation", and selective searches for the following single biomarkers that had previously been selected from the relevant literature: "High mobility group box 1/HMGB1", "Toll-Like-Receptor 4/TLR-4", "Interleukin-1/IL-1", "Interleukin-6/IL-6", "Transforming growth factor beta/TGF-β", and "Tumour necrosis factor-alpha/TNF-α". These queries were all combined with the MESH terms "Epileptogenesis" and "Epilepsy". We found 243 articles related to epileptogenesis and neuroinflammation, with 356 articles from selective searches by biomarker type. After eliminating duplicates, 324 articles were evaluated, with 272 excluded and 55 evaluated by the authors. A total of 21 articles were included in the qualitative evaluation, including 18 case-control studies, 2 case series, and 1 prospective study. As conclusion, this systematic review provides acceptable support for five biomarkers, including TNF-α and some of its soluble receptors (sTNFr2), HMGB1, TLR-4, CCL2 and IL-33. Certain receptors, cytokines, and chemokines are examples of neuroinflammation-related biomarkers that may be crucial for the early diagnosis of refractory epilepsy or may be connected to the control of epileptic seizures. Their value will be better defined by future studies.

Diagnostic pathway and management of first seizures in infants with Sturge-Weber syndrome.

Sturge-Weber syndrome (SWS) is a rare neurocutaneous syndrome, frequently associated with pharmaco-resistant, early-onset epilepsy. Optimal seizure control is paramount to maximize neurodevelopment. A single-centre case series of 49 infants explored early SWS care. Ninety-two per cent of children developed seizures aged 0 to 3 years; 55% of cases were before diagnostic magnetic resonance imaging (MRI) or tertiary referral. Delay in SWS diagnosis affected 31% of infants because of a lack of gadolinium enhancement for initial MRI. First seizures were frequently prolonged, with phenytoin administration necessary in 46%. Presymptomatic antiseizure medication prophylaxis (n = 8/49) decreased seizure burden. No patients on antiseizure medication prophylaxis suffered status epilepticus for longer than 30 minutes, and half of them (n = 4) had not developed seizures at last follow-up (aged 2-10 years). A parental survey enabled further service evaluation. Eighty-three per cent of parents considered local clinicians' understanding of SWS inadequate: 61% felt insufficiently informed about SWS and 81% received no epilepsy education before seizures. To overcome the identified shortfalls, guidelines towards improving and standardizing SWS management are proposed.

Effectiveness and Safety of Adjunctive Cenobamate in People with Focal-Onset Epilepsy: Evidence from the First Interim Analysis of the BLESS Study.

Despite new anti-seizure medications (ASMs) being introduced into clinical practice, about one-third of people with epilepsy do not reach seizure control. Cenobamate is a novel tetrazole-derived carbamate compound with a dual mechanism of action. In randomized controlled trials, adjunctive cenobamate reduced the frequency of focal seizures in people with uncontrolled epilepsy. Studies performed in real-world settings are useful to complement this evidence and better characterize the drug profile. The Italian BLESS ("Cenobamate in Adults With Focal-Onset Seizures") study is an observational cohort study aimed to evaluate the effectiveness, tolerability, and safety of adjunctive cenobamate in adults with uncontrolled focal epilepsy in the context of real-world clinical practice. The study is ongoing and conducted at 50 centers in Italy. This first interim analysis includes participants enrolled until June 2023 and with 12-week outcome data available. Forty participants with a median age of 36.5 (interquartile range [IQR] 26.0-47.5) years were included. The median monthly seizure frequency at baseline was 6.0 (IQR 2.5-17.3) seizures and 31 (77.5%) participants had failed four or more ASMs before cenobamate. At 12 weeks from starting cenobamate, the median reduction in monthly seizure frequency was 52.8% (IQR 27.1-80.3%); 22 (55.0%) participants had a ≥ 50% reduction in baseline seizure frequency and six (15.0%) reached seizure freedom. The median number of concomitant ASMs decreased from 3 (IQR 2-3) at baseline to 2 (IQR 2-3) at 12 weeks and the proportion of patients treated with > 2 concomitant ASMs decreased from 52.5% to 40.0%. Seven (17.5%) patients reported a total of 12 adverse events, 11 of which were considered adverse drug reactions to cenobamate. In adults with uncontrolled focal seizures, the treatment with adjunctive cenobamate was well tolerated and was associated with improved seizure control and a reduction of the burden of concomitant ASMs. NCT05859854 (ClinicalTrials.gov Identifier).

Genotype and Phenotype Characteristics of 58 Cases of Mitochondrial Epilepsy with Nuclear DNA Mutations in Children.

Identify the genotype and clinical characteristics of mitochondrial epilepsy caused by nDNA mutations in Chinese children and explore the treatment and prognosis of the condition. This is a retrospective cohort study conducted at a single center, including patients diagnosed with an established nDNA mutation-associated primary mitochondrial disease between October 2012 and March 2023 who also met the practical clinical definition of epilepsy published by the ILAE in 2014. Of the 58 patients identified, 74.1% had an onset before the age of 1year and 63.8% had seizures as their initial symptom. Developmental and epileptic encephalopathy (DEE) (31%) are the most common phenotypes. The most frequently observed MRI abnormalities include abnormal signal asymmetry in the bilateral basal ganglia and/or brainstem (34.7%), as well as brain atrophy, myelin sheath dysplasia, and corpus callosum dysplasia (32.7%). Of the 40 patients followed, seizure treatment was effective in 18 of the cases, while it was ineffective in 22. The mitochondrial DNA depletion syndrome (MDS) was found to be more difficult to control seizures than other phenotypes (P < 0.05). Additionally, the MDS was associated with a significantly higher mortality rate compared to alternative phenotypes (P < 0.05). The onset of mitochondrial epilepsy due to nDNA mutations is early and seizures are the most common initial symptom. DEE is the most common phenotype. Characteristic MRI abnormalities in the brain may be helpful in the diagnosis of primary mitochondrial disease. People with MDS typically face challenges in seizure control and have a poor prognosis.

Evaluating the effectiveness of the maximum permitted dose of midazolam in seizure termination: Insights from New South Wales, Australia.

Out-of-hospital seizures demand rapid management. Midazolam plays a key role in stopping seizures. At times the first dose of midazolam proves insufficient, necessitating additional doses. Within the New South Wales Ambulance (NSWA) service, the upper limit for midazolam administration is set at 15 mg. However, the outcomes and safety of using midazolam at this maximum dosage have not been thoroughly investigated. A retrospective analysis of out of hospital electronic health records from New South Wales, Australia, over the year 2022, was conducted. The study manually reviewed cases where adult patients received the maximum dose of midazolam for seizure management by paramedics. It focused on seizure cessation success rates and the incidence of adverse effects to evaluate the clinical implications of high-dose midazolam administration. Of 818 790 individual attendances by NSWA clinicians, a total of 11 392 (1.4%) adults had seizures noted, of which midazolam was administered in 2565 (22.5%). An algorithm shows that in 2352 (91.7%) instances the midazolam was associated with the apparent termination of seizures. Analysis revealed that 176 (1.5%) proportion of all adult's seizure patients required the maximum dose of midazolam for seizure control. These higher doses successfully terminate seizures in about half of the instances. AEs following the maximum dose of midazolam included hypoxia in 26.7% of patients and respiratory depression in 9.7%, indicating significant side effects at higher dosages. In New South Wales, Australia, administering the maximum dose of midazolam to seizure patients is rare but proves effective in approximately half of the refractory seizure cases. Therefore, assessing the potential for additional doses of midazolam or the use of a second-line agent is advisable.

Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medication: Practice Guideline From the AAN, AES, and SMFM.

This practice guideline provides updated evidence-based conclusions and recommendations regarding the effects of antiseizure medications (ASMs) and folic acid supplementation on the prevalence of major congenital malformations (MCMs), adverse perinatal outcomes, and neurodevelopmental outcomes in children born to people with epilepsy of childbearing potential (PWECP). A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies through August 2022. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. The following are some of the major recommendations. When treating PWECP, clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, at the earliest possible opportunity preconceptionally. Clinicians must minimize the occurrence of convulsive seizures in PWECP during pregnancy to minimize potential risks to the birth parent and to the fetus. Once a PWECP is already pregnant, clinicians should exercise caution in attempting to remove or replace an ASM that is effective in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures. Clinicians must consider using lamotrigine, levetiracetam, or oxcarbazepine in PWECP when appropriate based on the patient's epilepsy syndrome, likelihood of achieving seizure control, and comorbidities, to minimize the risk of MCMs. Clinicians must avoid the use of valproic acid in PWECP to minimize the risk of MCMs or neural tube defects (NTDs), if clinically feasible. Clinicians should avoid the use of valproic acid or topiramate in PWECP to minimize the risk of offspring being born small for gestational age, if clinically feasible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ, in children born to PWECP, clinicians must avoid the use of valproic acid in PWECP, if clinically feasible. Clinicians should prescribe at least 0.4 mg of folic acid supplementation daily preconceptionally and during pregnancy to any PWECP treated with an ASM to decrease the risk of NTDs and possibly improve neurodevelopmental outcomes in the offspring.

ФАКТОРЫ РИСКА РЕЗИСТЕНТНОСТИ ЮНОШЕСКОЙ МИОКЛОНИЧЕСКОЙ ЭПИЛЕПСИИ

Abstract. Introduction. Juvenile myoclonic epilepsy is the most common form of genetic generalized epilepsy, which is included in the group of idiopathic generalized epilepsies. The etiology of drug-resistant forms of juvenile myoclonic epilepsy, which represent a serious clinical problem, is currently a controversial issue. Aim. To reveal the most significant risk factors of resistance in juvenile myoclonic epilepsy. Materials and Methods. The observational retrospective study included 56 patients, 46 (82%) women and 10 (18%) men. Inclusion criteria: patients diagnosed with juvenile myoclonic epilepsy based on the criteria of the International League Against Epilepsy, treatment for at least 2 years. The type and frequency of epileptic seizures, the onset and course of the disease, concomitant diseases, family history, all available results of 1-2 hours video electroencephalographic monitoring with sleep, and magnetic resonance imaging results were analyzed. Depending on the treatment effect, all patients were divided into two groups: 1 – without seizures, 2 – with seizures. Lack of complete seizure control for at least 2 years was considered intractable epilepsy. Risk ratios as outcomes for dichotomous variables in two compared groups for various characteristics and their confidence intervals were calculated using the Review Manager program (v5.3). Differences were considered significant at P&lt;0.05. Results and Discussion. As a result, there were obtained data on the resistance of juvenile myoclonic epilepsy depending on the age of disease onset, the type of epileptic seizures, changes in the electroencephalogram, and the type of antiepileptic treatment. Conclusions. The most significant risk factors of resistance in juvenile myoclonic epilepsy have been identified: frequent generalized tonic-clonic seizures (more than 5 times a year) accompanying the basic disease, depression, anxiety, and lack of response to the treatment with valproic acid. At the same time, non-compliance, sleep disturbances, consumption of alcohol and energy drinks during therapy are factors that can be controlled during the physician’s individual work with the patient aimed at the explanation and prevention of risks in treatment.

Hemispherectomy at The Hospital for Sick Children: expanded indications and lessons learned over 35 years

OBJECTIVE Functional hemispherectomy is an effective surgical intervention for select patients with drug-resistant epilepsy. The last several decades have seen dramatic evolutions in preoperative evaluation, surgical techniques, and postoperative care. Here, the authors present a retrospective review of the medical records of 146 children who underwent hemispherectomy between 1987 and 2022 at The Hospital for Sick Children, providing a unique overview of the evolution of the procedure and patient outcomes over 35 years. METHODS The medical records of all children who underwent hemispherectomy at The Hospital for Sick Children between 1987 and 2022 were reviewed. Demographic information, preoperative clinical features, short-term and long-term seizure outcomes, and details regarding postoperative complications were recorded. RESULTS The seizure outcomes of 146 children were analyzed. There were 68 females and 78 males with a mean age of 5.08 years, 123 of whom demonstrated seizure freedom (Engel class IA) in the short-term postoperative follow-up period and 89 in the long term. The effectiveness of hemispherectomy in achieving long-term seizure control has improved over time (β = 0.06, p &lt; 0.001). Factors associated with overall seizure freedom included younger age at the time of hemispherectomy and stroke as the etiology of seizures, as well as complete disconnection during the first surgery. Additionally, the etiologies of epilepsy for which hemispherectomy is performed have expanded over time, while complication rates have remained unchanged. CONCLUSIONS Hemispherectomy is an increasingly effective treatment for certain cases of drug-resistant epilepsy. The etiologies of epilepsy for which hemispherectomy is performed are broadening, with no change in its safety profile. Seizure outcomes are better when the etiology of epilepsy is an ischemic injury, and the most common complication after the procedure is hydrocephalus. These findings reinforce the ongoing use of hemispherectomy as a safe and effective treatment option for certain individuals with drug-resistant epilepsy, support its application to a broader range of etiologies, and highlight areas of future investigation.

Cerebral Palsy Phenotypes in Genetic Epilepsies

BackgroundAlthough there are established connections between genetic epilepsies and neurodevelopmental disorders like intellectual disability, the presence of cerebral palsy (CP) in genetic epilepsies is undercharacterized. We performed a retrospective chart review evaluating the motor phenotype of patients with genetic epilepsies. MethodsPatients were ascertained through a research exome sequencing study to identify genetic causes of epilepsy. We analyzed data from the first 100 individuals with molecular diagnoses. We determined motor phenotype by reviewing medical records for muscle tone and motor function data. We characterized patients according to CP subtypes: spastic diplegic, spastic quadriplegic, spastic hemiplegic, dyskinetic, hypotonic-ataxic. ResultsOf 100 individuals with genetic epilepsies, 14% had evidence of possible CP, including 5% characterized as hypotonic-ataxic CP, 5% spastic quadriplegic CP, 3% spastic diplegic CP, and 1% hemiplegic CP. Presence of CP did not correlate with seizure onset age (P = 0.63) or seizure control (P = 0.07). CP occurred in 11% (n = 3 of 27) with focal epilepsy, 9% (n = 5 of 54) with generalized epilepsy, and 32% (n = 6 of 19) with combined focal/generalized epilepsy (P = 0.06). ConclusionsIn this retrospective analysis of patients with genetic epilepsies, we identified a substantial portion with CP phenotypes, representing an under-recognized comorbidity. These findings underscore the many neurodevelopmental features associated with neurogenetic conditions, regardless of the feature for which they were ascertained for sequencing. Detailed motor phenotyping is needed to determine the prevalence of CP and its subtypes among genetic epilepsies. These motor phenotypes require clinical management and represent important targeted outcomes in trials for patients with genetic epilepsies.