Lamotrigine vs levetiracetam in female patients of childbearing age with juvenile absence epilepsy: A Bayesian reanalysis.

OBJECTIVE: Women of childbearing age with juvenile absence epilepsy (JAE) face treatment challenges due to limited access to safe and effective anti-seizure medications (ASMs). In a previous study we compared the effectiveness of levetiracetam (LEV) and lamotrigine (LTG) in women with idiopathic generalized epilepsy (IGE), highlighting a superiority of LEV in juvenile myoclonic epilepsy. In this study, we specifically reanalyzed, through a Bayesian approach and by expanding the previously published cohort, the comparative effectiveness of these ASMs as initial monotherapy in JAE. METHODS: We conducted a multicenter, retrospective, comparative effectiveness study on women of childbearing age diagnosed with JAE and prescribed LEV or LTG as the initial ASM. Inverse probability treatment weighting (IPTW) Bayesian Cox proportional hazard models were employed to evaluate treatment failure (TF) due to ineffectiveness and ASM retention. The patients' center of provenance and year of prescription were considered as random effect factors. Posterior probabilities and relative log-risk distribution were computed, and the distribution of posterior draws was analyzed to assess the evidence supporting LTG superiority over LEV. RESULTS: Of 123 patients, those treated with LTG (n = 67) demonstrated lower TF and higher ASM retention than those treated with LEV (n = 56), with the IPTW-weighted Bayesian Cox proportional hazards model showing a 99.2% posterior probability of LTG being superior on TF and a 99.5% probability on ASM retention. Additional analyses on ≥50% and ≥75% seizure reduction through IPTW-weighted Bayesian logistic regression largely confirmed these findings, whereas the two ASMs did not show evident differences in terms of seizure freedom. The two ASMs showed comparable safety profiles, with only a minority of patients discontinuing treatment due to side effects. SIGNIFICANCE: Bayesian reanalysis supports LTG as first-line monotherapy for JAE in women of childbearing age, emphasizing the importance of individualized treatment strategies in women with IGE. This study underscores the value of Bayesian methods in refining clinical research and treatment decisions.

Status epilepticus in Auckland, New Zealand: Treatment patterns and determinants of outcome in a prospective population-based cohort.

OBJECTIVE: Determination of the real-world performance of a health care system in the treatment of status epilepticus (SE). METHODS: Prospective, multicenter population-based study of SE in Auckland, New Zealand (NZ) over 1 year, with data recorded in the EpiNet database. Focus on treatment patterns and determinants of SE duration and 30-day mortality. The incidence, etiology, ethnic discrepancies, and seizure characteristics of this cohort have been published previously. RESULTS: A total of 365 patients were included in this treatment cohort; 326 patients (89.3%) were brought to hospital because of SE, whereas 39 patients (10.7%) developed SE during a hospital admission for another reason. Overall, 190 (52.1%) had a known history of epilepsy and 254 (70.0%) presented with SE with prominent motor activity. The mean Status Epilepticus Severity Score (STESS) was 2.15 and the mean SE duration of all patients was 44 min. SE self-terminated without any treatment in 84 patients (22.7%). Earlier administration of appropriately dosed benzodiazepine in the pre-hospital setting was a major determinant of SE duration. Univariate analysis demonstrated that mortality was significantly higher in older patients, patients with longer durations of SE, higher STESS, and patients who developed SE in hospital, but these did not maintain significance with multivariate analysis. There was no difference in the performance of the health care system in the treatment of SE across ethnic groups. SIGNIFICANCE: When SE was defined as 10 continuous minutes of seizure, overall mortality was lower than expected and many patients had self-limited presentations for which no treatment was required. Although there were disparities in the incidence of SE across ethnic groups there was no difference in treatment or outcome. The finding highlights the benefit of a health care system designed to deliver universal health care.

Sustained effort network for treatment of status epilepticus/European academy of neurology registry on adult refractory status epilepticus (SENSE-II/AROUSE).

BACKGROUND: Status Epilepticus (SE) is a common neurological emergency associated with a high rate of functional decline and mortality. Large randomized trials have addressed the early phases of treatment for convulsive SE. However, evidence regarding third-line anesthetic treatment and the treatment of nonconvulsive status epilepticus (NCSE) is scarce. One trial addressing management of refractory SE with deep general anesthesia was terminated early due to insufficient recruitment. Multicenter prospective registries, including the Sustained Effort Network for treatment of Status Epilepticus (SENSE), have shed some light on these questions, but many answers are still lacking, such as the influence exerted by distinct EEG patterns in NCSE on the outcome. We therefore initiated a new prospective multicenter observational registry to collect clinical and EEG data that combined may further help in clinical decision-making and defining SE. METHODS: Sustained effort network for treatment of status epilepticus/European Academy of Neurology Registry on refractory Status Epilepticus (SENSE-II/AROUSE) is a prospective, multicenter registry for patients treated for SE. The primary objectives are to document patient and SE characteristics, treatment modalities, EEG, neuroimaging data, and outcome of consecutive adults admitted for SE treatment in each of the participating centers and to identify factors associated with outcome and refractoriness. To reach sufficient statistical power for multivariate analysis, a cohort size of 3000 patients is targeted. DISCUSSION: The data collected for the registry will provide both valuable EEG data and information about specific treatment steps in different patient groups with SE. Eventually, the data will support clinical decision-making and may further guide the planning of clinical trials. Finally, it could help to redefine NCSE and its management. TRIAL REGISTRATION: NCT number: NCT05839418.

Patient-Centered Management of Brain Tumor-Related Epilepsy.

PURPOSE OF REVIEW: Brain tumor-related epilepsy is a heterogenous syndrome involving variability in incidence, timing, pathophysiology, and clinical risk factors for seizures across different brain tumor pathologies. Seizure risk and disability are dynamic over the course of disease and influenced by tumor-directed treatments, necessitating individualized patient-centered management strategies to optimize quality of life. RECENT FINDINGS: Recent translational findings in diffuse gliomas indicate a dynamic bidirectional relationship between glioma growth and hyperexcitability. Certain non-invasive measures of hyperexcitability are correlated with survival outcomes, however it remains uncertain how to define and measure clinically relevant hyperexcitability serially over time. The extent of resection, timing of pre-operative and/or post-operative seizures, and the likelihood of tumor progression are critical factors impacting the risk of seizure recurrence. Newer anti-seizure medications are generally well-tolerated with similar efficacy in this population, and several rapid-onset seizure rescue agents are in development and available. Seizures in patients with brain tumors are strongly influenced by the underlying tumor biology and treatment. An improved understanding of the interactions between tumor cells and the spectrum of hyperexcitability will facilitate targeted therapies. Multidisciplinary management of seizures should occur with consideration of tumor-directed therapy and prognosis, and anti-seizure medication decision-making tailored to the individual priorities and quality of life of the patient.

Quality of life in people with epilepsy: The associations of anti-seizure medications and biopsychosocial variables.

People with epilepsy, on average, experience lower quality of life (QOL) than healthy controls. This study examined the associations between specific anti-seizure medications, biopsychosocial factors, and QOL in people with epilepsy. Analysis of covariance revealed that individuals taking three or more anti-seizure medications had significantly lower QOL than those taking levetiracetam. Findings also demonstrated that when examining biopsychosocial factors as predictors of QOL in hierarchical regression, anxiety, depression, and daytime sleepiness were significant predictors of QOL. Once these factors were entered into the model, number of medications was no longer significant. The final model predicted 59.6% of the variance in QOL. In clinical settings, providers should take a patient-centered approach that includes regular assessment of QOL and an emphasis on good psychological care for those coping with anxiety, depression, and sleep difficulty. These findings underscore the importance of addressing psychological health and sleep factors within the epilepsy population.

Impaired executive functioning in children of women with epilepsy.

OBJECTIVE: While neurodevelopmental symptoms are often seen in children of mothers with epilepsy, research specifically addressing executive function (EF) in this population is limited. This study aims to investigate EF in children of mothers with epilepsy, both with and without fetal exposure to anti-seizure medications, compared to typically developing children whose mothers do not have epilepsy. METHODS: We evaluated EF in children aged 8 to 17 years born to mothers with clinically validated diagnoses of epilepsy, using the Behavior Rating Inventory of Executive Function completed by the mothers. The results were then compared to a typically developing control group at the same age living in the same geographic area. RESULTS: The results showed significantly higher levels of EF problems in children of mothers with epilepsy who were exposed (p = 0.005, d = 0.63), and unexposed (p = 0.001, d = 0.74) to anti-seizure medications during pregnancy, compared to typically developing children. There was no significant difference in EF problems between the exposed and unexposed groups. These findings remained statistically significant after adjusting for mothers' education levels, and when excluding participants exposed to valproate during pregnancy. SIGNIFICANCE: This study highlights the increased risk of EF problems in children of mothers with epilepsy, independent of exposure to anti-seizure medications. Findings underscore the importance of continuous monitoring of EF in these children and highlights the need for further research into the diverse factors affecting EF development in this group.

Predictors and associated factors with adverse drug reaction in people with epilepsy.

OBJECTIVES: There is a need for early identification and intervention of Adverse Drug Reaction (ADR) to alleviate the unacceptably growing burden, morbidity, and mortality associated with People With Epilepsy (PWE). This study is aimed at identifying associated factors and predictors of ADR among PWE. METHODS: It is an interviewer-administered questionnaire-based study consisting of 940 consenting participants aged 16 years and above attending epilepsy clinics for 5 years with diagnosis confirmed by International League against Epilepsy (ILAE) criteria and supported by Electroencephalography (EEG). Twenty-one-item Liverpool Adverse Effect Profile (LAEP) and 8-item Morinsky Medication Adherence Scale (MMAS) were used to assess ADR and adherence respectively. RESULTS: The highest reported ADR in PWE were nervousness (34.3%), aggression (33.6%), and weight gain (32.3%). Specifically, 20.1% of the participants complained of memory problems. On the other hand, ADR associated with skin, mouth/gum and hair loss was 9.3%, 8.9%, and 7.2% respectively, and these were the lowest reported ADRs. Using the MMAS, 545(90.2%), 28(4.6%), and 31(5.1%) of PWE in this study were classified as having high, medium, and low adherence, respectively. Duration of Anti-Seizure Medication (ASM) use and duration of epilepsy were the major determinants of ADR in PWE on the regression model. CONCLUSION: Duration of ASM use and duration of epilepsy are the major determinants of ADR in PWE. Effective strategies to identify and reduce ADR should be incorporated into the management of PWE by Health Care Providers (HCPs) to improve their quality of life.

Tolerability of perampanel: A retrospective study at the department of psychiatry.

PURPOSE: We aimed to identify factors that contribute to the discontinuation of perampanel. METHODS: We retrospectively analyzed patients with epilepsy at the Department of Psychiatry, Hokkaido University Hospital. We evaluated the factors contributing to perampanel discontinuation as primary outcomes using Cox proportional hazards regression. Then, we explored the components contributing to the primary outcomes using logistic regression analysis. RESULTS: A total of 118 patients were included, 44.9% of whom discontinued participation, 22.0% had intellectual disability, and 23.7% had a psychiatric disorder other than intellectual disability. Adverse effects occurred in 65% of the patients, 23.7% had psychiatric adverse effects (PAE), and 49.2% had common adverse effects (CAE). The effect of PER to suppress seizures was confirmed in 65.3% of them. Discontinuation was influenced by non-response (Hazard Ratio (HR) 6.70, 95% Confidence Interval (CI) 3.42-13.1), the occurrence of PAE (HR 3.68, 95% CI 1.89-7.16), CAE (HR 1.90, 95% CI 1.06-3.41), and comorbid psychiatric disorders (HR 2.35, 95% CI 1.21-4.59). Moreover, comorbid intellectual disability correlated with a low risk of PAE (OR 0.19, 95% CI 0.04-0.89). CONCLUSION: The discontinuation of perampanel is influenced by poor efficacy and the occurrence of common/psychiatric adverse effects. The discontinuation of perampanel is influenced by poor efficacy and the occurrence of common/psychiatric adverse effects. Consideration of factors contributing to perampanel discontinuation may assist in determining the indication for perampanel treatment.

Structural connectivity as a predictive factor for responsiveness to levetiracetam treatment in epilepsy.

PURPOSE: To investigate whether structural connectivity or glymphatic system function is a potential predictive factor for levetiracetam (LEV) response in patients with newly diagnosed epilepsy. METHODS: We enrolled patients with newly diagnosed epilepsy who were administered LEV as initial monotherapy and underwent diffusion tensor imaging (DTI) at diagnosis. We categorized the patients into drug response. We used graph theory to calculate the network measures for structural connectivity based on the DTI scans in patients with epilepsy. Additionally, we evaluated glymphatic system function by calculating the DTI analysis along the perivascular space (DTI-ALPS) index based on DTI scans. RESULTS: We enrolled 84 patients with epilepsy. The clinical factors and DTI-ALPS index did not differ between the groups. However, some of the structural connectivity measures significantly differ between the groups. The poor responders exhibited a higher mean clustering coefficient, global efficiency, and small-worldness index than the good responders (p = 0.003, p = 0.048, and p = 0.038, respectively). In the receiver operating characteristic curve analysis, the mean clustering coefficient exhibited the highest performance in predicting the responsiveness to LEV (area under the curve of 0.677). In the multiple logistic regression analysis, the mean clustering coefficient of the structural connectivity measures was the only significant predictor of LEV response (p = 0.014). Furthermore, in the survival analysis, the mean clustering coefficient was the only significant predictor of LEV response (p = 0.026). CONCLUSION: We demonstrated that structural connectivity is a potential predictive factor for responsiveness to LEV treatment in patients with newly diagnosed epilepsy.

Clinical characteristics of people with intellectual disability admitted to hospital with constipation: identifying possible specific high-risk factors.

BACKGROUND: People with intellectual disabilities (ID) die on an average 20 years earlier to the general population. They have higher rates of multimorbidity and polypharmacy. Around 25% of people with ID report chronic constipation. The England Learning Disabilities Mortality Review found that nearly 25% of deaths identified constipation as a long-term health problem. However, the likely risk factors for constipation related harm are poorly enumerated. We sought to identify possible specific high-risk factors by examining the clinical characteristics of people with ID admitted to hospital with constipation. METHODS: Data of people with ID admitted with constipation in two general hospitals covering a population of 1.3 million from 2017 to 2022 were reported using the STROBE guideline for cohort studies. Collected data included age, gender, intellectual disability severity, recorded medication, presenting complaint and co-morbidities. The medication anticholinergic burden was calculated using the anticholinergic burden scale. Continuous variables were summarised by mean and standard deviation if normally distributed, with categorical variables summarised by the number and percentage in each category. RESULTS: Of 46 admissions (males 52%), 57% had moderate to profound ID, 37% had epilepsy, 41% prescribed antiseizure medication (ASM) and 45% were on laxatives. Average age was 46 years. The anticholinergic burden score mean was 2.3 and median, one. CONCLUSIONS: We can hypothesise that people with more severe ID, suffering from epilepsy and on ASM may be more at risk of developing severe constipation. Some admissions may be avoided with earlier use of laxatives in the community.

Migraine - a borderland disease to epilepsy: near it but not of it.

BACKGROUND: Migraine and epilepsy are two paroxysmal chronic neurological disorders affecting a high number of individuals and being responsible for a high individual and socioeconomic burden. The link between these disorders has been of interest for decades and innovations concerning diagnosing and treatment enable new insights into their relationship. FINDINGS: Although appearing to be distinct at first glance, both diseases exhibit a noteworthy comorbidity, shared pathophysiological pathways, and significant overlaps in characteristics like clinical manifestation or prophylactic treatment. This review aims to explore the intricate relationship between these two conditions, shedding light on shared pathophysiological foundations, genetic interdependencies, common and distinct clinical features, clinically overlapping syndromes, and therapeutic similarities. There are several shared pathophysiological mechanisms, like CSD, the likely underlying cause of migraine aura, or neurotransmitters, mainly Glutamate and GABA, which represent important roles in triggering migraine attacks and seizures. The genetic interrelations between the two disorders can be observed by taking a closer look at the group of familial hemiplegic migraines, which are caused by mutations in genes like CACNA1A, ATP1A2, or SCN1A. The intricate relationship is further underlined by the high number of shared clinical features, which can be observed over the entire course of migraine attacks and epileptic seizures. While the variety of the clinical manifestation of an epileptic seizure is naturally higher than that of a migraine attack, a distinction can indeed be difficult in some cases, e.g. in occipital lobe epilepsy. Moreover, triggering factors like sleep deprivation or alcohol consumption play an important role in both diseases. In the period after the seizure or migraine attack, symptoms like speech difficulties, tiredness, and yawning occur. While the actual attack of the disease usually lasts for a limited time, research indicates that individuals suffering from migraine and/or epilepsy are highly affected in their daily life, especially regarding cognitive and social aspects, a burden that is even worsened using antiseizure medication. This medication allows us to reveal further connections, as certain antiepileptics are proven to have beneficial effects on the frequency and severity of migraine and have been used as a preventive drug for both diseases over many years. CONCLUSION: Migraine and epilepsy show a high number of similarities in their mechanisms and clinical presentation. A deeper understanding of the intricate relationship will positively advance patient-oriented research and clinical work.

Transcranial magnetic stimulation-evoked electroencephalography responses as biomarkers for epilepsy: A review of study design and outcomes.

Transcranial magnetic stimulation (TMS) with electroencephalography (EEG), that is TMS-EEG, may assist in managing epilepsy. We systematically reviewed the quality of reporting and findings in TMS-EEG studies on people with epilepsy and healthy controls, and on healthy individuals taking anti-seizure medication. We searched the Cochrane Library, Embase, PubMed and Web of Science databases for original TMS-EEG studies comparing people with epilepsy and healthy controls, and healthy subjects before and after taking anti-seizure medication. Studies should involve quantitative analyses of TMS-evoked EEG responses. We evaluated the reporting of study population characteristics and TMS-EEG protocols (TMS sessions and equipment, TMS trials and EEG protocol), assessed the variation between protocols, and recorded the main TMS-EEG findings. We identified 20 articles reporting 14 unique study populations and TMS methodologies. The median reporting rate for the group of people with epilepsy parameters was 3.5/7 studies and for the TMS parameters was 13/14 studies. TMS protocols varied between studies. Fifteen out of 28 anti-seizure medication trials in total were evaluated with time-domain analyses of single-pulse TMS-EEG data. Anti-seizure medication significantly increased N45, and decreased N100 and P180 component amplitudes but in marginal numbers (N45: 8/15, N100: 7/15, P180: 6/15). Eight articles compared people with epilepsy and controls using different analyses, thus limiting comparability. The reporting quality and methodological uniformity between studies evaluating TMS-EEG as an epilepsy biomarker is poor. The inconsistent findings question the validity of TMS-EEG as an epilepsy biomarker. To demonstrate TMS-EEG clinical applicability, methodology and reporting standards are required.

Verbal fluency functional magnetic resonance imaging detects anti-seizure effects and affective side effects of perampanel in people with focal epilepsy.

Perampanel, a noncompetitive antagonist of the postsynaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor, is effective for controlling focal to bilateral tonic-clonic seizures but is also known to increase feelings of anger. Using statistical parametric mapping-derived measures of activation and task-modulated functional connectivity (psychophysiologic interaction), we investigated 14 people with focal epilepsy who had verbal fluency functional magnetic resonance imaging (fMRI) twice, before and after the add-on treatment of perampanel. For comparison, we included 28 people with epilepsy, propensity-matched for clinical characteristics, who had two scans but no change in anti-seizure medication (ASM) regimen in-between. After commencing perampanel, individuals had higher task-related activations in left orbitofrontal cortex (OFC), fewer task-related activations in the subcortical regions including the left thalamus and left caudate, and lower task-related thalamocaudate and caudate-subtantial nigra connectivity. Decreased task-related connectivity is observed between the left OFC and precuneus and left medial frontal lobe. Our results highlight the brain regions associated with the beneficiary therapeutic effects on focal to bilateral tonic-clonic seizures (thalamus and caudate) but also the undesired affective side effects of perampanel with increased anger and aggression (OFC).

Which is more deleterious to cognitive performance? Interictal epileptiform discharges vs anti-seizure medication.

Children with epilepsy commonly have comorbid neurocognitive impairments that severely affect their psychosocial well-being, education, and future career prospects. Although the provenance of these deficits is multifactorial, the effects of interictal epileptiform discharges (IEDs) and anti-seizure medications (ASMs) are thought to be particularly severe. Although certain ASMs can be leveraged to inhibit IED occurrence, it remains unclear whether epileptiform discharges or the medications themselves are most deleterious to cognition. To examine this question, 25 children undergoing invasive monitoring for refractory focal epilepsy performed one or more sessions of a cognitive flexibility task. Electrophysiological data were recorded to detect IEDs. Between repeated sessions, prescribed ASMs were either continued or titrated to <50% of the baseline dose. Hierarchical mixed-effects modeling assessed the relationship between task reaction time (RT), IED occurrence, ASM type, and dose while controlling for seizure frequency. Both presence (ß ± SE = 49.91 ± 16.55 ms, p = .003) and number of IEDs (ß ± SE = 49.84 ± 12.51 ms, p < .001) were associated with slowed task RT. Higher dose oxcarbazepine significantly reduced IED frequency (p = .009) and improved task performance (ß ± SE = -107.43 ± 39.54 ms, p = .007). These results emphasize the neurocognitive consequences of IEDs independent of seizure effects. Furthermore, we demonstrate that inhibition of IEDs following treatment with select ASMs is associated with improved neurocognitive function.

Efficacy and tolerability of immediate switch from sodium channel blockers to Lacosamide.

Lacosamide (LCM) is a new-generation anti-seizure medication approved for monotherapy and add-on therapy for focal-onset epilepsy. It has novel pharmacodynamics and favorable pharmacokinetic qualities with good clinical response. This study aims to evaluate the effectiveness and tolerability of LCM when used in the immediate switch from sodium channel blockers in patients with focal-onset and generalized-onset epilepsies. This retrospective, multicenter observational study was conducted with adult patients who received LCM as mono- or polytherapy through immediate switch with 6 to 52 months follow-up. The clinical data obtained during the follow-up period were analyzed to assess retention rate, seizure freedom, more than 50% seizure reduction, and adverse effects. A total of 32 patients (eight females, 24 males) with a median age of 49.75 (range, 23-86) years, median age at epilepsy onset of 32.58 (range, 0.5-85) years, and median epilepsy duration of 17.17 (range, 1-46) years were included in this study. Seizure frequency was between 1 and 90 in the past 6 months. Seven (21.9%) of the patients had structural brain lesions and 27 (84.4%) of the patients had EEG abnormalities. The adverse effects leading to switching were hyponatremia, rash, elevated liver enzymes, pain, and erectile dysfunction. At 14.34 (range, 6-52) months follow-up, 30 (93.75%) patients in total retained LCM, 20 (66.7%) of them were seizure-free, and 13 were on LCM monotherapy. Responder rate was 81.25%. Eight (25%) of the patients experienced adverse effects after the immediate switch. One patient with generalized-onset epilepsy needed to quit LCM due to an increase in seizures. Seizure frequency did not change in three patients in the focal-onset group. Immediate switch to LCM showed favorable outcomes with a significant reduction in seizure frequency, high retention rates, and tolerable adverse effect profiles in both focal-onset and generalized-onset seizures.

Changes in seizure frequency and anti-seizure medication therapy during pregnancy and one year postpregnancy.

Seizure control in women with epilepsy (WWE) during pregnancy is a vital concern. The aim of this study was to compare changes in seizure frequency and anti-seizure medication (ASM ) therapy in WWE in a real-world setting over three epochs (prepregnancy, pregnancy, and postpregnancy). We screened WWE who were pregnant between 1 January 2010 and 31 December 2020 from the epilepsy follow-up registry database of a tertiary hospital in China. We reviewed and collected follow-up data for the following time periods: 12 months before pregnancy (epoch 1), throughout pregnancy and the first 6 weeks postpartum (epoch 2), and from 6 weeks to 12 months postpartum (epoch 3). Seizures were classified into two categories: tonic‒clonic/focal to bilateral tonic‒clonic seizures and non-tonic‒clonic seizures. The main indicator was the seizure-free rate over the three epochs. Using epoch 1 as a reference, we also compared the percentage of women with an increased seizure frequency, as well as changes in ASM treatment, in epochs 2 and 3. Ultimately, 271 eligible pregnancies in 249 women were included. The seizure-free rates in epoch 1, epoch 2, and epoch 3 were 38.4%, 34.7%, and 43.9%, respectively (P = 0.09). The top three ASMs used in the three epochs were lamotrigine, levetiracetam, and oxcarbazepine. Using epoch 1 as a reference, the percentages of women with increased frequencies of tonic‒clonic/focal to bilateral tonic‒clonic seizures in epoch 2 and epoch 3 were 17.0% and 14.8%, respectively, while the percentages of women with an increased frequency of non-tonic‒clonic seizures in epoch 2 and epoch 3 were 31.0% and 21.8% (P = 0.02). The percentage of women whose ASM dosages were increased in epoch 2 was higher than that in epoch 3 (35.8% vs. 27.3%, P = 0.03). The seizure frequency during pregnancy may not differ significantly from that during prepregnancy and postpregnancy if WWE are treated according to the guidelines.

Clinical factors associated with late seizure remission after failed epilepsy surgery.

BACKGROUND: Some patients who initially fail epilepsy surgery later become seizure-free, but it is not clear how the clinical characteristics of the patients or post-operative modifications of anti-seizure medication (ASM) regimens contribute to late seizure remission. METHODS: We performed a retrospective chart review of patients undergoing epilepsy surgery at the University of Washington Regional Epilepsy Center between 2007 and 2017, including patients receiving neocortical resection, temporal lobectomy, and hippocampal laser interstitial therapy (LITT) ablation. We assessed seizure freedom, ASM changes, seizure frequency at the first and last follow-up, and type of lesion. Two-tailed Fisher's exact test and Mann-Whitney U test were used for statistical analyses. RESULTS: Two hundred and fifteen patients undergoing epilepsy surgery between 2007 and 2017 had both first and last follow-ups. Ninety-eight (46%) were not seizure-free at the first follow-up (mean 1.1 years post-operative). By the last follow-up (mean 4.7 years post-operative), 20% of those not initially seizure-free had become so. Those who were seizure-free at the last visit had lower median seizures per month in the first post-operative year (0.21 versus 0.95 per month in those not seizure-free, p < 0.001). There was also a significantly higher proportion of patients with cavernomas who were seizure-free at the last visit (25% vs. 1% of those not seizure-free at the last visit; p = 0.001), but no other differences in clinical characteristics. Of the 98 patients who had seizures at the first follow-up, 63% underwent post-operative modification of their ASM regimens. The rate of late seizure freedom was similar for patients with or without ASM changes: 21% were seizure-free at the last visit with ASM changes and 19% without ASM changes. There were no significant differences in which ASMs were changed between those who became seizure-free and those who did not, but patients who were subjected to further medical management were less likely to have had mesial temporal sclerosis (MTS) than those who were not. A number of patients not initially seizure-free who underwent ASM changes achieved seizure freedom as long as 10 years post-surgery. CONCLUSION: A substantial proportion of patients who initially fail epilepsy surgery will have late seizure remission. Those with cavernous hemangiomas were more likely to achieve late remission from seizures as were those with lower rates of seizures in the first year after surgery. The chances of achieving remission were similar in those with or without modification of their ASM regimens, but those with pre-operative MTS were more likely to achieve late seizure freedom without medication changes. At the individual level, patients may still achieve seizure freedom with ASM changes as long as ten years after the initial surgery.

The course of sleep habits in newly diagnosed epilepsy in children: A prospective study.

BACKGROUND: Epilepsy and sleep have a close, complex, and reciprocal relationship. Sleep may also be adversely affected by epilepsy and anti-seizure medication (ASM). This study sought to determine sleep-related problems before and after six months of treatment with ASMs follow-up in children with epilepsy, to reveal changes in sleep habits, and to determine the effect of ASMs on sleep in different types of epilepsy. METHODS: This is a prospective study that included 61 children, aged 4-18 years with newly diagnosed epilepsy, who regularly had follow-up checks and used ASM for six months, and completed the Children's Sleep Habits Questionnaire (CSHQ). Children's Sleep Habits Questionnaire was completed before and after six months of ASM, allowing for assessments based on treatment group and type of epilepsy. RESULTS: The mean ages of 61 children were 10.6 ± 3.9 years. The participants' post-treatment total scores on the CSHQ decreased by 2.9 ± 7.8 units on average compared to their pretreatment scores (p = 0.008; p < 0.01). In the levetiracetam group, post-treatment CSHQ subscale scores showed a mean decrease for bedtime resistance (p = 0.001), sleep duration (p = 0.005), sleep anxiety (p = 0.030), and total scores (p = 0.012) (p < 0.05). In the valproic acid group, post-treatment CSHQ subscale scores showed a mean decrease in sleep duration (p = 0.007) and a mean increase in daytime sleepiness (p = 0.03) (p < 0.05). CONCLUSION: Our study found that children diagnosed with epilepsy had significantly higher rates of pretreatment sleep problems, which significantly decreased in patients who regularly attended follow-up examinations and received treatment. Except for the daytime sleepiness factor, our study found that sleep-related problems improved with treatment. It was observed that the initiation of epilepsy treatment had a positive effect on the patient's sleep, regardless of the type of treatment or epilepsy.

Disability assessment among persons with epilepsy in Mahenge, an onchocerciasis-endemic area in Tanzania: A cross-sectional study.

BACKGROUND: A high prevalence of epilepsy has been observed in the onchocerciasis-endemic focus of Mahenge, Tanzania. This study sought to assess the degree of disability experienced by persons with epilepsy (PWE) in Mahenge and identify associations with sociodemographic and clinical features. METHOD: This cross-sectional study was conducted in Mahenge, Tanzania, between February and July 2020. PWE were recruited from the Mahenge epilepsy clinic and four neighbouring rural villages (Mdindo, Mzogezi, Mzelezi and Sali). Data were collected using the 36-item version of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) questionnaire for adults. For children aged 5-17 years, we used the Module on Child Functioning developed by UNICEF and the Washington Group. Questionnaires were administered by trained research assistants. Descriptive statistics were performed, and multivariable analyses (gamma and logistic regressions) were conducted. RESULTS: A total of 321 adults (45.5% males) and 48 children (55.3% males) with epilepsy participated. The overall median WHODAS 2.0 score was 4.8% (IQR: 0.9-18.9). The most affected disability domain was 'participating in the society' (median score: 12.5%, IQR: 0-29.2). Fifteen (31.3%) of the children with epilepsy had a disability in at least one domain of the child functioning module, with the 'accepting change' domain harbouring the highest proportion of disabled children (12.5%). Higher seizure frequency and longer epilepsy duration were associated with more disability. CONCLUSION: PWE in Mahenge experience variable degrees of disability. The affected domains indicate the need for societal rehabilitation of PWE in various community and/or social activities. Peer-support groups were instituted at the study sites to address these needs.

Paradoxical effects of levetiracetam in people with epilepsy with rhythmic epileptiform discharges.

OBJECTIVE: To elucidate the incidence and risk factors for paradoxical effects (i.e., increased seizure frequency, increased seizure severity, or onset of new seizure types) of levetiracetam (LEV) in people with epilepsy (PWE) and identify the usefulness of electroencephalography (EEG) in predicting these effects. METHODS: We examined data for consecutive PWE treated with LEV. All PWE underwent EEG and magnetic resonance imaging (MRI) before LEV administration. We also evaluated the incidence of paradoxical LEV effects and conducted multivariate logistic regression analyses to identify the associated factors. RESULTS: In total, 210 (66.2%) of 317 PWEs treated in our department had a history of LEV use. The incidence of paradoxical LEV effects was 5.2% (n = 11) and was significantly associated with a high LEV dose (p = 0.029), high seizure frequency (p = 0.005), temporal lobe epilepsy (p = 0.004), focal awareness seizure (p = 0.004), focal impaired awareness seizure (p = 0.007), spike (p = 0.015), rhythmic epileptiform discharges (REDs; p = 0.003), and MRI-identified focal cortical dysplasia (FCD; p < 0.0001). Multivariate analyses revealed that REDs (odds ratio [OR] = 5.35, p = 0.048, 95% confidence interval [CI]: 1.01-28.21) were independently associated with paradoxical LEV effects. CONCLUSIONS: Paradoxical LEV effects occurred in PWE, particularly in those with drug-resistant focal epilepsy. Furthermore, the occurrence of REDs in EEG was an independent factor associated with the paradoxical effects of LEV in PWE.