Antiseizure Research Articles

Antiseizure Medication Withdrawal, Risk of Epilepsy, and Longterm EEG Trends in Acute Symptomatic Seizures or Epileptic EEG Patterns.

Patients with acute symptomatic seizures (ASyS) and acute epileptiform findings on EEG are common. They are often prescribed long-term antiseizure medications (ASMs); it is unknown whether or when this is necessary. Primary outcome was late unprovoked seizure occurrence and association with ASM taper. The secondary outcome was EEG pattern evolution over time. This is a retrospective cohort study of patients from 2015 to 2021 with ASyS (clinical or electrographic) and/or epileptiform findings on index hospitalization EEGs who were discharged on ASMs and had subsequent follow-up including an outpatient EEG at Yale New Haven Hospital. All patients were seen in our postacute symptomatic seizure (PASS) clinic after hospital discharge. We also developed a simple predictive score, Epilepsy-PASS (EPI-PASS), using variables independently associated with seizure recurrence based on stepwise regression; each of the 3 identified variables was assigned a score of 0 (absent) or 1 (present), for a total score of 0-3. Of 190 patients screened, 58 were excluded, leaving a final cohort of 112 patients. Twenty-four percent (27/112) patients developed a late unprovoked seizure (i.e., epilepsy). Independent predictors of epilepsy were persistence of epileptiform abnormalities on follow-up EEGs [56% developed epilepsy vs 19% without, 0.002, OR 7.18 (1.36-37.88)], clinical ASyS [32% vs 13%, p = 0.002, OR 7.45 (2.31-54.36)], and cortical involvement on imaging [40% vs 11%, p = 0.003, OR 7.63 (1.96-29.58)]. None of the 23 patients with none of these predictors (0 points on EPI-PASS) developed epilepsy, vs 13% with 1 predictor (EPI-PASS = 1) and 46% with 2 or 3 predictors (EPI-PASS = 2-3) at 1-year follow-up. ASM taper was not associated with seizure recurrence. Abnormal EEG findings in the index hospitalization usually resolved [54/69 (78%) patients] on subsequent EEGs. Most patients with clinical ASyS or acute epileptiform EEG findings do not require long-term ASMs. Index hospitalization EEG findings usually resolve, but if they do not, there is a >50% chance of developing epilepsy. Other predictors of epilepsy are cortical involvement on imaging and clinical ASyS. A simple 4-point scale using these 3 predictors (EPI-PASS) may help predict the risk of developing epilepsy but requires independent validation.

Association between Frequency of Seizures and Number of Antiseizure Medications (ASM) in Patients with Epilepsy.

The literature has shown the relevance of nutritional and metabolic aspects in patients with epilepsy. This study evaluated the relationship between clinical variables and plasma proteins and compared the variables between seizure frequency and neurological examination. A pilot study was carried out with eighty-four (n = 84) adults patients with epilepsy. The relationship between clinical variables of the disease (age at disease onset, neurological examination, current type and frequency of seizures, duration of disease, amount of antiseizure medications-ASM used and type and etiology of epilepsy) and plasma proteins (albumin and transferrin) was investigated. In the statistical analysis, the chi-square, Fisher, Mann-Whitney, Kruskal-Wallis tests, Spearman coefficient and univariate logistic regression were used. There was a significant association between the use of antiseizure medications (ASM) (p = 0.0105) and altered neurological examination (p = 0.0049), compared with the frequency of seizures, and between albumin and gender (p = 0.0005), and albumin and etiology of epilepsy (p = 0.0186). There was a significant low-intensity and inverse linear correlation (coefficient = -0.31363, p = 0.0037) between albumin and disease duration. In the logistic regression model, a significant association was only observed between the number of ASM and the frequency of seizures (p = 0.0120; OR = 3.368; 95% CI = 1.305-8.691). There was no association between plasma proteins and the outcomes of seizure frequency and neurological examination. The number of ASM and not protein metabolism was associated with frequency of seizures in patients with epilepsy.

Antiseizure medication practices in the adult traumatic brain injury patient population

BackgroundAntiseizure medication (ASM) use in traumatic brain injuries (TBI) reduces the risk of early post-traumatic seizure (PTS). Agent selection and dosing strategies remain inconsistent among trauma centers in the United States. ObjectiveThe purpose of this study was to identify and characterize the most common PTS prophylaxis regimens among adult trauma centers in brain injured patients throughout the United States. MethodsA survey assessing PTS prophylaxis practices of trauma centers was created and distributed in March 2023. Data was then evaluated based on practice site demographics and various sub-group analyses including academic vs. non-academic centers, trauma center designation, geographic practice location, and total number of TBI activations annually. ResultsA total of 84 different trauma centers responded of which, 82 (97.6 %) respondents reporting levetiracetam (LEV) as their ASM of choice for PTS prophylaxis. The most reported dosing regimen included an initial dose of 1000 mg (n = 24, 46.2 %) followed by a maintenance dose of 500 mg BID (n = 39, 48.8 %). There were no statistically significant differences in practice between sub-group analyses evaluated. Conclusion and relevanceThis multicenter, survey study, identified variances in practice for PTS prophylaxis for brain injured patients throughout the U.S. Interestingly, the overwhelming majority of trauma centers do not conform to the Brain Trauma Foundation guidelines and utilize LEV as their agent of choice. Further studies should evaluate ideal patient selection for PTS prophylaxis, optimal agent, and dosing schemes within this cohort.

Retrospective characterization of seizure semiology and treatment using continuous video‐EEG monitoring in neonatal encephalopathy in Uganda

AbstractObjectiveNeonatal encephalopathy (NE) is a leading cause of childhood death and disability, particularly in sub‐Saharan Africa. Detection of NE‐related seizures is challenging. We explored NE seizure semiology and management in Uganda.MethodsVideo‐EEG was recorded (days 1–5), seizure semiology reviewed according to ILAE classification and administration of antiseizure medication (ASM) evaluated. Clinicians treated seizures based on the clinical presentation alone.ResultsAmong 50 participants, 52% (26) had EEG‐confirmed seizures; 70% (18) combined electroclinical/electrographic; 4% (1) exclusively electroclinical; 22% (6) electrographic. Of those with electroclinical seizures (19), 42% displayed >1 semiology. Distribution of seizure semiology was; clonic 34% (11); autonomic 24% (8, of which 6 had prolonged ictal apnea); automatisms 18% (6); behavioral arrest 12% (4); and sequential 12% (4). ASM was administered to 64% (32/50). Of those with EEG‐confirmed seizures, only 62% (16/26) received ASM. In the non‐seizure group, 38% (9/24) received ASM during monitoring. ASM was administered 42 times, of which 45% (19) were considered appropriate.SignificanceIn this Ugandan NE population, incidence of seizures was high and clinical manifestations frequent. Clonic, autonomic and automatisms were most common. Clinical management was challenging, with both under and overtreatment evident. Respiratory impairment due to autonomic seizures frequently went unrecognized and is a prominent concern, particularly in settings without neonatal intensive care.

Characteristics of patients with drug-resistant epilepsy in a tertiary hospital

Drug-resistant epilepsy has a cumulative incidence between 14 and 20% of patients with epilepsy. It is associated with more comorbidities and with higher healthcare expenditure and impact on quality of life. A retrospective longitudinal descriptive study was performed covering the period from 01/01/2010 to 02/28/2024. All patients with epilepsy seen in the Pediatric Neurology unit of our center were collected and a review of medical records was carried out to collect the characteristics and evolution during the study period. The classification and definitions used were those established by the International League Against Epilepsy. A total of 325 patients with epilepsy were identified, with a cumulative incidence of DRE of 29%. The most frequent etiology was structural both in all patients with epilepsy (22%), and in drug-resistant epilepsy (36%). A statistically significant association was established between refractoriness and genetic and structural causes, and between having status epilepticus and the development of drug-resistant epilepsy. Seventy-nine percent of patients with drug-resistant epilepsy developed epileptic encephalopathy. The most commonly used antiseizure drug was valproic acid (90%), 19% received a ketogenic diet and 4.2% received epilepsy surgery. In our setting the incidence of drug-resistant epilepsy is high, more so than previously described. Genetic and structural etiologies are associated with a higher incidence. Having suffered status epilepticus is associated with refractoriness. A higher incidence was observed in patients with defined electroclinical syndromes, probably influenced by epileptic and developmental encephalopathies.

Antiseizure medication use during pregnancy and children's neurodevelopmental outcomes.

The teratogenic potential of valproate in pregnancy is well established; however, evidence regarding the long-term safety of other antiseizure medications (ASMs) during pregnancy remains limited. Using routinely collected primary care data from the UK and nationwide Swedish registries to create a cohort of 3,182,773 children, of which 17,495 were exposed to ASMs in pregnancy, we show that those exposed to valproate were more likely to receive a diagnosis of autism, intellectual disability, and ADHD, when compared to children not exposed to ASMs. Additionally, children exposed to topiramate were 2.5 times more likely to be diagnosed with intellectual disability (95% CI: 1.23-4.98), and those exposed to carbamazepine were 1.25 times more likely to be diagnosed with autism (95% CI: 1.05-1.48) and 1.30 times more likely to be diagnosed with intellectual disability (95% CI: 1.01-1.69). There was little evidence that children exposed to lamotrigine in pregnancy were more likely to receive neurodevelopmental diagnoses. While further research is needed, these findings may support considering safer treatment alternatives well before conception when clinically appropriate.

Determinants of health-related quality of life of patients with focal epilepsy: A systematic literature review.

Focal epilepsy can have significant negative impacts on a person's health-related quality of life (HRQoL). Although studies have been published on HRQoL in persons with focal epilepsy (PWFE), determinants of HRQoL have not been comprehensively examined. This systematic literature review (SLR) queried existing literature to identify aspects associated with HRQoL in PWFE without focus on resective epilepsy surgery, with an interest in identifying modifiable determinants for medical/nonmedical interventions. This SLR was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Searches were conducted in PubMed and Google Scholar for articles published from January 1, 1900, to February 19, 2023, reporting on the association between HRQoL or employability and a range of demographic, psychosocial, or epilepsy-related factors and comorbidities in PWFE. A total of 879 abstracts were identified, with 126 manuscripts reviewed and 37 studies selected for inclusion that quantified the relationship between HRQoL and the variable of interest by multivariate (N = 21) or univariate only (N = 15) methods; 10 multivariate models also included univariate data. In adjusted models, the most commonly examined determinants of HRQoL included depression (n = 15/21), number of antiseizure medications (ASMs; n = 13/21), seizure frequency (continuous seizure count, n = 11/21; seizure freedom, n = 5/21), anxiety (n = 10/21), duration of disease (n = 9/21), and cognition (n = 9/21). Depression, anxiety, and cognition were frequently seen as significant contributors to HRQoL when studied (14/15 [93%], 9/10 [90%], and 7/9 [78%], respectively). Among concepts studied less frequently, ASM severity/adverse event burden was significant each time examined (in 5/19 studies). Attainment of seizure freedom and employability was significant 75% (n = 3/4) and 72% (n = 5/7) of the time, respectively. Poor HRQoL in PWFE can be attributed to a multitude of factors, including depression, anxiety, factors in disease management, and employability. An unmet need remains in addressing elements associated with poor HRQoL in this population.

Epilepsy-pregnancy registries: An update.

This report is the first comprehensive update on the activities of existing epilepsy-pregnancy registries since 2010. The primary aim of these registries, which were initiated by independent international research groups some 25 years ago, has been to assess the risk of major congenital malformations (MCMs) in offspring exposed in utero to different antiseizure medications (ASMs). Progress reports are provided here from the five original registries (the International Registry of Antiepileptic Drugs and Pregnancy EURAP, the North American Antiepileptic Drug Pregnancy Registry, the UK and Ireland Epilepsy and Pregnancy Register, the Kerala Registry of Epilepsy and Pregnancy, and the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs) plus the more recently initiated West China Registry. Since their inception, the registries have published a wealth of data revealing important differences in risks across the most frequently used ASM treatments, thereby facilitating rational management of women with epilepsy who are of childbearing potential. Although the number of pregnancies enrolled in the different registries has more than doubled since the 2010 report, many questions remain. These include outcomes following prenatal exposure to most of the newer ASMs or different ASM combinations, as well as associations with specific MCMs rather than MCMs as a collective. All the registries, therefore, remain active and continue to enroll pregnancies. Administrative health care databases have been utilized more recently for the assessment of MCM risks and other adverse pregnancy outcomes associated with in utero exposure to ASMs. Although these can provide population-based complementary information, they cannot replace the specific epilepsy-pregnancy registries with their more detailed validated individual information. Given the multiple newer ASMs that are increasingly used and the continuing multiple knowledge gaps for the older ASMs, epilepsy-pregnancy registries will continue to play an important role in the future.

A multicenter, cross-sectional analysis to assess the safety and usage pattern of brivaracetam in the management of partial-onset seizure with BAEs-BREEZE study: A post-hoc analysis.

Brivaracetam (BRV), a third-generation anti-seizure medication (ASM) offers strong conformational receptor domain binding, faster blood brain barrier (BBB) permeability and better tolerability making it potential therapeutic option as an initial line or initial line add-on strategy for focal onset seizure (FoS). The following study was planned to further understand the role and relevance of BRV in the real world settings of India. This was a multicentric, cross-sectional, and non-interventional study conducted in patients with FoS across India. The study was approved by central independent ethics committee. Descriptive and analytical statistics employed using SPSS version 29.0.1.0. Per protocol (PP) analysis included 8479 eligible patients from 1069 sites, gender; 5771 (68.06%) male and 2708 (31.94%) female with mean age 41.21 ± 12.74 years. Total 8019 (94.57%) patients had FoS and 460 (5.43%) patients had focal to bilateral tonic-clonic seizures (FBTCs). In FoS, 4105 (51.19%) patients switched from LEV to BRV whereas 3914 (48.81%) switched from other ASMs to BRV. BAEs accounted for 2059 (50.16%) patients in LEV to BRV switch versus 133 (3.39%) in other ASM to BRV switch. Post switch, LEV-associated BAEs reduced irrespective of being used as monotherapy 85.65% (p < 0.001) or as an adjuvant therapy 83.71% (p < 0.001) at BRV dosage of 50 to 100 mg BID. This RWE showed the utility of BRV as mono component as an initial add-on strategy in FoS cases. BRV remains a pertinent therapeutic choice for FoS for the treatment naïve and/or BAE cases. Exposure of LEV leads to considerable BAEs compared to patients without LEV exposure. Patients who switched to BRV due to LEV-induced BAEs significantly improved tolerability with BRV irrespective being used as monotherapy or as adjuvant therapy. Current study was planned to understand the clinical role and relevance of third-generation anti-seizure medication (ASM), brivaracetam (BRV) in the real world settings of India. Outcome of the study highlighted that BRV is an emerging, potential and safe ASM treatment option for epilepsy in Indian context. Many patients with epilepsy who are not able to tolerate the other ASM including levetiracetam (LEV) primarily due to behavioral side effects improves tolerability post switch to BRV, additionally results are consistent either BRV being used as an adjuvant therapy or as monotherapy therapy.

Prevalence and Determinants of Complementary and Alternative Medicine Use among Children living with Epilepsy in Port Harcourt, Nigeria

Introduction: Epilepsy is a common neurologic disorder in children with its management centered on the use of anti-seizure medications (ASM). However, many children do not achieve seizure control despite being on the appropriate ASM. Hence, caregivers may seek complementary and alternative medicines (CAMs) therapies. The aim of this study is to investigate the prevalence and types of CAM used by children with epilepsy in a tertiary hospital in Port Harcourt, Nigeria, and the factors that determines their use. Methods: A descriptive cross-sectional study was conducted among children diagnosed with epilepsy and their caregivers. Participants were recruited using a convenient sampling method, a structured questionnaire was used to collect data. Descriptive statistic was performed using IBM SPSS while Pearson’s chi-square test was used to identify significant associations. Results: The prevalence of CAM use was found to be 84.3%, the use of CAM is a risk for poor adherence to ASM. Family members were the main influencers in the decision to use CAM, and the majority of parents/caregivers did not consult their children’s healthcare providers before incorporating these therapies. Significant factors influencing the use of CAM includes: being a male (P=0.01), higher seizure frequency (P=0.002), multiple ASM use (P=0.01), and the presence of comorbidities (P=0.04). The most common CAMs used were prayers, kernel or crude oil and scarifications. Conclusion: CAM use among children with epilepsy is common and is a cause of poor adherence to ASMs with its untoward effects. It is crucial for healthcare providers to proactively inquire about the use of CAM with caregivers during the management of childhood epilepsy and to educate them on the possible risks specifically regarding drug adherence, compliance and poor seizure control.

GLIOMA-RELATED EPILEPSY

Diffuse low-grade gliomas (LGGs), originating from glial tissue, have a propensity to progress to higher-grade tumors over time, presenting a complex challenge in clinical management. Glioma-associated epilepsy is a significant clinical indicator influencing both treatment strategies and prognostication. This study aims to assess the impact of glioma-related epilepsy on treatment outcomes and explore the current management guidelines. Material and Methods A retrospective analysis was conducted on 38 patients diagnosed with LGGs (WHO grades 2 and 3) treated in our neurosurgical department from 2013 to 2023. The focus was on glioma-related epileptic seizures, with outcomes evaluated using the Engel classification six months post-surgery. Additionally, anti-seizure medication (ASM) regimens were reviewed, and current National Institute for Health and Care Excellence (NICE) guidelines on low-grade gliomas were synthesized. Results Of the 38 patients, 30 had diffuse astrocytoma and 8 had oligodendroglioma. Among those with glioma-related epilepsy (n=25), management strategies included biopsy only (8%), gross total resection (GTR) (40%), subtotal resection (StR) (32%), and partial resection (PaR) (20%). No significant correlation was found between seizures and tumor volume, growth rate, or histological findings. However, a positive correlation between the extent of surgical resection and improved Engel outcomes was observed. Discussion Existing research suggests that early seizures may be a favorable prognostic indicator for malignant progression-free and overall survival. Epilepsy significantly impacts the quality of life for glioma patients. Exploring targeted epilepsy surgery for glioma-related seizures could potentially enhance patient outcomes and quality of life posttreatment. Conclusion Advancing approaches in epilepsy surgery for glioma-related seizures holds promise for improving patient quality of life and treatment efficacy. Further investigation into these strategies is warranted.

High-dose folic acid use and cancer risk in women who have given birth: A register-based cohort study.

This study was undertaken to study whether high-dose folic acid (>1 mg daily) use is associated with an increased risk of cancer in all women who have given birth and in women with epilepsy. High-dose folic acid supplementation during pregnancy has been linked to increased cancer risk in children born to mothers with epilepsy. We identified women with their first pregnancy in Denmark (1997-2017), Norway (2005-2017), and Sweden (2006-2017) using medical birth registers, linking individual data across nationwide health registers and statistical agencies. Exposure was defined as filled prescriptions for high-dose folic acid, considered time-varyingly. The primary outcome was the first malignant cancer diagnosis. Hazard ratios (HRs) of cancer after high-dose folic acid exposure were estimated using Cox proportional hazard models with 95% confidence intervals (CIs), adjusted for confounders including antiseizure medication (ASM) use, and stratified by maternal epilepsy diagnosis. A 6-month time lag was applied, as cancer is unlikely to develop immediately. With up to 21 years of follow-up, we identified 1 465 785 women who gave birth, including 64 485 (4.4%) exposed to high-dose folic acid. In the exposed group, 755 cancer cases were observed (208 per 100 000 person-years, 95% CI = 193.8-223.5), compared with 18 702 cases in the unexposed group (164 per 100 000 person-years, 95% CI = 161.5-166.2), yielding a 20% increased cancer risk overall (adjusted HR = 1.2, 95% CI = 1.1-1.2). This risk was attenuated after the 6-month lag analysis (adjusted HR = 1.1, 95% CI = 1.04-1.2). The risk for non-Hodgkin lymphoma was increased in all analyses (n = 28, adjusted HR = 2.0, 95% CI = 1.3-2.9). The association between high-dose folic acid use and overall cancer risk was similar in those with epilepsy regardless of ASM use (adjusted HR = 1.3, 95% CI = 1.0-1.8). High-dose folic acid use was associated with increased overall cancer risk in women who have given birth, with a consistent association with non-Hodgkin lymphoma, including those with epilepsy, regardless of ASM use.

Post-Asphyxial Aftercare and Management of Neonates in Low- and Middle-Income Countries: A Systematic Evidence Synthesis

Introduction: Effective post-resuscitation care is crucial for improving outcomes in neonates post-asphyxia. This review aimed to provide a comprehensive overview of post-asphyxial aftercare strategies and forms part of a supplement describing an extensive synthesis of effective newborn interventions in low- and middle-income countries (LMICs). Methods: Evidence was generated by performing de novo reviews, updates to reviews via systematic searches, and reanalyses of studies conducted in LMICs from existing reviews. Results: Sixty-one trials recruiting 5,046 term infants post-asphyxia were included across all intervention domains. Limited studies were available from LMICs related to fluid restriction, antiseizure medications, and early interventions to improve developmental outcomes. Our reanalysis of whole-body cooling trials in LMICs found effects on neonatal mortality and mortality or neurological disability in infancy differed significantly based on the care center and type of cooling device used. Pharmacological therapies for neuroprotection evaluated in 27 trials in middle-income countries had varied effects in neonates with encephalopathy. Majority of the trials (60%) focused on magnesium sulfate therapy and showed significant improvements in short-term mortality and morbidities. Conclusion: The sample sizes of included trials were relatively small, and the certainty of evidence ranged from very low to moderate. Evidence on long-term survival and neurodevelopmental outcomes was limited. Further research on promising neuroprotective therapies and factors affecting their implementation in low-resource contexts is required. To reduce the high burden related to asphyxia in LMICs, this review underscores the need for a paradigm shift toward prevention, and strategies that emphasize improving antenatal and obstetric care.

Trends of antiseizure medication utilization among pregnant people in four Canadian provinces from 1998 to 2023; a study from the Canadian mother-child cohort active surveillance initiative (CAMCCO)

BackgroundEpilepsy management during pregnancy is crucial for both the mother and fetus. The use of antiseizure medications (ASMs) during pregnancy requires careful consideration due to their potential effects on maternal and fetal health.MethodsThis study analyzed trends in ASMs use among pregnant people in four Canadian provinces over 20 years (Manitoba, Saskatchewan, Alberta, and Quebec). Descriptive statistics were utilized to examine the characteristics of the population, with the frequency and patterns of ASM use estimated throughout each trimester. Linear regression models were developed to analyze yearly patterns of ASM utilization for the overall study population, as well as for people with and without epilepsy.ResultsAmong 1,317,141 pregnant individuals across four provinces, 0.7% had epilepsy. Of the total pregnancies, 1.7% (n = 22,783) were exposed to ASMs, comprising 4,392 from pregnant people with epilepsy (PPWE) and 18,391 from those without epilepsy (PPWOE). Results demonstrated varying trends in ASM usage between provinces, with an overall increase in usage among people without epilepsy in Manitoba, Saskatchewan, and Alberta. ASM use among PPWOE surged significantly in Manitoba (24.2–149.1 per 10,000 pregnant people), Saskatchewan (29.4–107.0 per 10,000), and Alberta (65.7–241.7 per 10,000) (p &amp;lt; 0.05). In Alberta, PPWE’s ASM exposure also rose, from 23.6 in 2008 to 43.0 per 10,000 pregnant people in 2021, while Quebec witnessed a decrease from 59.2 in 1998 to 45.5 per 10,000 pregnancies in 2015. Analysis of ASM use by trimester illustrated a substantial decline among PPWOE from 365 days pre-pregnancy to the third trimester in all provinces. ASM utilization by drug class showcased significant shifts, with second-generation ASMs experiencing a notable rise. Carbamazepine, once prominent, declined, making way for lamotrigine. Regional variations underscore diverse preferences, such as clonazepam’s sustained popularity in Manitoba and Quebec.ConclusionThe study identified increasing trends in ASM use, particularly the increased use of second-generation ASMs, and differences in prescription patterns for pregnant individuals with and without epilepsy. These findings reveal changing ASM use patterns, including increased second-generation ASM use and regional disparities, providing valuable insights into real-world prescription practices.

Advances in Therapy for Refractory Epilepsy.

Drug-resistant epilepsy (DRE) is defined as failure to achieve sustained seizure control with adequate trials of two appropriate antiseizure medications (ASMs). DRE affects one-third of patients with epilepsy and is associated with significant morbidity and mortality. Newer ASMs provide pharmacological therapy that is better tolerated but not necessarily more effective than older ASMs. Resective brain surgery is the gold standard to treat DRE and achieve seizure freedom, with laser ablation offering an alternative with less morbidity but lower effectiveness. For patients who are not candidates for resection or ablation, multiple neuromodulation options can reduce seizure burden. These neuromodulation devices have shown comparable effectiveness in randomized clinical trials, but the results vary in open-label follow-up cohorts, as do the risks of complications and associated costs. Dietary therapies can help, particularly in pediatric genetic epilepsies. Innovative genetic therapy approaches are being pursued, offering the promise of precision medicine.

Clinical efficacy of low-dose Perampanel correlates with neurophysiological changes in familial adult myoclonus epilepsy 2.

Familial adult myoclonus epilepsy (FAME) management relies on antiseizure medications (ASMs), which inadequately address myoclonus and cortical tremor. This study evaluates Perampanel (PER), an AMPA-receptor antagonist, for treating FAME symptoms. Fifteen FAME2 patients participated in an observational prospective study. They received up to 6 mg daily of PER and underwent Unified-Myoclonus-Rating-Scale (UMRS) before and after treatment. Neurophysiological evaluations, including somatosensory evoked potentials (SEPs) and transcranial magnetic stimulation (TMS), assessed PER's impact on cortical glutamatergic excitatory and GABAergic inhibitory circuits. PER treatment significantly reduced UMRS total scores (p = 0.001) and action-myoclonus subscores (p = 0.002), irrespective of disease duration, age at onset, or testing time (p >0.05). Patients with more severe baseline myoclonus demonstrated significant improvements. Neurophysiological assessments revealed a PER-induced decrease in sensorimotor hyperexcitability, characterized by diminished N33 amplitudes, attenuated glutamatergic facilitation, and enhanced GABAergic inhibition in the motor cortex. In conclusion, low-dose PER is well tolerated and effective in alleviating myoclonus in FAME2 patients, supported by its modulatory effects on glutamatergic and GABAergic neuronal circuits. Plain Language Summary: This study investigated the effects of low-dose perampanel in individuals with Familial Adult Myoclonus Epilepsy2 (FAME2), a hereditary condition characterized by epilepsy and tremors. Perampanel, an antiepileptic drug, blocks AMPA receptors in the brain, reducing excessive neural activity that causes seizures and abnormal movements. The results showed significant symptom improvement, which correlated with changes in brain activity as measured by neurophysiological tests. This study suggests that perampanel helps regulate abnormal brain signals and may help managing FAME2 symptoms.

Rasmussen Encephalitis: Clinical Features, Pathophysiology, and Management Strategies—A Comprehensive Literature Review

Rasmussen encephalitis (RE) is a rare and progressive form of chronic encephalitis that typically affects one hemisphere of the brain and primarily occurs in pediatric individuals. The current study aims to narratively review the literature about RE, including historical information, pathophysiology, and management of this condition. RE often occurs in individuals with normal development, and it is estimated that only a few new cases are identified each year in epilepsy centers. Approximately 10% of cases also occur in adolescents and adults. The hallmark feature of RE is drug-resistant focal seizures that can manifest as epilepsia partialis continua. Also, patients with RE usually develop motor and cognitive impairment throughout the years. Neuroimaging studies show progressive damage to the affected hemisphere, while histopathological examination reveals T-cell-dominated encephalitis with activated microglial cells and reactive astrogliosis. The current therapy guidelines suggest cerebral hemispherotomy is the most recommended treatment for seizures in RE, although significant neurological dysfunction can occur. Another option is pharmacological management with antiseizure medications and immunomodulatory agents. No significant progress has been made in understanding the pathophysiology of this condition in the last decades, especially regarding genetics. Notably, RE diagnosis still depends on the criteria established by Bien et al., and the accuracy can be limited and include genetically different individuals, leading to unexpected responses to management.

Prevalence of epilepsy: a population-based cohort study in Denmark with comparison to Global Burden of Disease (GBD) prevalence estimates

BackgroundThe Global Burden of Disease Study (GBD) produces prevalence estimates for ‘idiopathic epilepsy’ (ie, of unknown aetiology) and ‘secondary epilepsy’ (ie, with known aetiology) but does not report prevalence by...

Seizures and Epilepsy in Association With Neurocysticercosis: A Nosologic Proposal.

Neurocysticercosis is one of the main risk factors of seizures and epilepsy in many regions of the world, which are Taenia solium-endemic but resource-constrained to control the parasite. The nosology of seizures and the classification of epilepsy in the context of neurocysticercosis are somewhat uncertain. Many seizures associated with the infection are customarily referred to as "acute symptomatic seizures." The term, however, seems unsuitable. Neither is the condition acute nor does it allow the avoidance of long-term antiseizure medications, as is the case with acute symptomatic seizures, for instance, associated with traumatic brain injury. We propose that seizures be classified according to the evolutionary stage of parenchymal cysticercosis in addition to the conventional classification of seizures and epilepsy and identification of the epileptogenic zone. An often-ignored aspect is the identification of comorbidities, many of which are specific to neurocysticercosis.

Cannabinoid-like compounds found in non-cannabis plants exhibit antiseizure activity in genetic mouse models of drug-resistant epilepsy.

The cannabinoid cannabidiol has established antiseizure effects in drug-resistant epilepsies such as Dravet syndrome and Lennox-Gastaut syndrome. Amorfrutin 2, honokiol, and magnolol are structurally similar to cannabinoids (cannabis-like drugs) but derive from non-cannabis plants. We aimed to study the antiseizure potential of these compounds in various mouse seizure models. In addition, we aimed to characterize their molecular pharmacology at cannabinoid CB1 and CB2 receptors and at T-type calcium channels, which are known targets of the cannabinoids. Brain and plasma pharmacokinetic profiles were determined. Antiseizure activity was assessed against hyperthermia-induced seizures in a Scn1a+/- mouse model of Dravet syndrome. We then elaborated on the most promising compounds in the maximal electroshock (MES) test in mice and the Gabrb3+/D120N mouse model of Lennox-Gastaut syndrome. Fluorescence-based assays were used to examine modulatory activity at cannabinoid CB1 and CB2 receptors and T-type calcium channel subtypes CaV3.1, CaV3.2, and CaV3.3 overexpressed in mammalian cells. Automated patch-clamp electrophysiology was then used to confirm inhibitory activity on CaV3.1, CaV3.2, and CaV3.3 channels. Magnolol and honokiol had high brain-to-plasma ratios (3.55 and 7.56, respectively), unlike amorfrutin 2 (0.06). Amorfrutin 2 and magnolol but not honokiol significantly increased the body temperature threshold at which Scn1a+/- mice had a generalized tonic-clonic seizure. Both amorfrutin 2 and magnolol significantly decreased the proportion of mice exhibiting hindlimb extension in the MES test. Furthermore, magnolol reduced the number and duration of atypical absence seizures in Gabrb3+/D120N mice. The three compounds inhibited all T-type calcium channel subtypes but were without specific activity at cannabinoid receptors. We show for the first time that amorfrutin 2 and magnolol display novel antiseizure activity in mouse drug-resistant epilepsy models. Our results justify future drug discovery campaigns around these structural scaffolds that aim to develop novel antiseizure drugs for intractable epilepsies.