Antiseizure Research Articles

Prehospital seizure management protocols need standardized guidelines. A descriptive study from Norway

BackgroundPatients with convulsive seizures constitute a significant group in acute neurology. No common European clinical practice guidelines on prehospital seizure management exist, and today most patients are brought to hospital for seizure treatment, with great variation in which prehospital treatment is provided. Only 33 % of status epilepticus patients receive a benzodiazepine as first anti-seizure medication (ASM). The aim of this study is to assess the prehospital seizure control protocols in the Emergency Medical Services (EMS) in Norway, and compare these with current evidence for acute management. MethodWe performed a descriptive analysis of the 18 regional EMS protocols in Norway and compared the findings with recent evidence on prehospital treatment. We analysed recommended drug and dosage, route of medication administration, number of additional rescue doses permitted, requirements for registration of type of seizures and seizure duration. ResultsThe protocols vary in terms of preferred medication, administration method, dosage and recommendations regarding first- and second-line therapies. 33 % of protocols explicitly define status epilepticus according to contemporary guidelines, and 16.7 % have an operational definition of when to administer benzodiazepines. All protocols showed variations in dosing and administration instructions and only 28 % had a clearly stated first line treatment. ConclusionThere are disparities in the prehospital seizure management protocols within the Norwegian healthcare system, a system comparable to other European countries. To improve seizure management there is a need for standardised guidelines for prehospital treatment.

Unpacking the Effects of Decriminalization: Understanding Drug Use Experiences and Risks among Individuals Who Use Drugs in British Columbia

ObjectivesOn January 31, 2023, a three-year exemption from the Controlled Drugs and Substances Act was granted to the Canadian province British Columbia (BC), allowing the cumulative possession of 2.5 g of specific unregulated drugs amongst adults. The goals of the policy are to reduce health, social, and economic harms associated with criminalization, stigma, drug overdose deaths, as well as drug seizures, arrests, and associated enforcement and court costs. As the inaugural year has passed, we aimed to assess people who use drugs’ awareness and knowledge of the, as well as the policy’s impact on their drug use patterns and overdose risk.MethodsWe conducted 100 telephone-based semi-structured interviews with people who use drugs from across BC, exploring changes in drug use experiences and perceived overdose risk since the implementation of the policy. Participants also completed an interviewer-administered survey assessing socio-demographics and substance use patterns. We utilized a qualitative content analysis approach to analyze the interview data.ResultsOur findings indicate a general awareness of the policy among participants, although some policy details were often misunderstood, and participants expressed the need for more widespread dissemination of policy information. While the majority of participants reported that their drug use patterns remained unchanged after decriminalization, some made subtle adjustments, such as carrying under the 2.5 g threshold to minimize the risk of criminalization. Participants highlighted several policy benefits and concerns, including its potential to reduce criminalization and stigmatization, but also increase public drug consumption. Participants offered suggestions for policy improvement.ConclusionThese findings underscore the need for ongoing monitoring of the impacts of decriminalization regarding its potential impact on people who use drugs’ drug use patterns and related risks. Reevaluation of the possession threshold and efforts to enhance education and awareness about the policy could help achieve the policy’s goals.

Subclinical hypothyroidism and plasma levels of commonly prescribed anti-seizure medications

Background: Epilepsy remains the most common neurological problem worldwide. Most commonly prescribed antiseizure medications (ASMs) like phenytoin, sodium valproate, and carbamazepine show high inter-individual variability in bioavailability due to genetic and epigenetic factors resulting in either therapeutic failure or toxicity. In our study, we aim to determine the association between subclinical hypothyroidism and the plasma levels of these commonly prescribed ASMs, leading to either therapeutic failure or adverse drug reactions. Methods: We collected demographic data, details about the antiepileptic medication, and plasma levels of ASMs (phenytoin, carbamazepine, and sodium valproate) from patients on antiseizure medications who came for routine therapeutic drug monitoring (TDM). High-performance liquid chromatography (HPLC) estimated plasma levels of the antiseizure medications as per the TDM laboratory standard operating procedure (SOP) and thyroid function test (TSH) by a standard enzyme-linked immune-sorbent assay (ELISA) kit. Results: Of the 158 patients who had TDM, 75.31% were taking sodium valproate, 15.18% were on phenytoin, and 9.49% were on carbamazepine monotherapy. In our study, we found that 12 patients (7.59%) had TSH levels between 4 to 10 mIU/l, indicating subclinical hypothyroidism (SCH). The plasma drug levels of all 12 patients who had SCH were found to be below the therapeutic range. Conclusions: This study has established a significant association between ASMs, particularly sodium valproate, and thyroid dysfunction, specifically SCH, in patients with epilepsy. Our findings suggest that prolonged ASM therapy can lead to thyroid disturbances, warranting careful monitoring of thyroid function in these patients.

Cardiac dysfunction associated with lacosamide in a premature infant with Hypoxic Ischemic Encephalopathy: A case report.

Lacosamide [Vimpat® Harris FRC Corporation. © 2022 UCB, Inc. Smyrna, GA 30080] is an antiseizure medication which acts through blockage of voltage-gated neuronal sodium channels. Its recent implementation in the neonatal population has been extrapolated from adult and pediatric data suggesting a favorable safety profile. (1) Of note, preterm infants have unique developmental characteristics that may predispose them to increased risk of adverse reactions. We present a case of a preterm neonate who developed left ventricular (LV) dysfunction coinciding with the initiation of lacosamide.

Element Changes Occurring in Brain Point at the White Matter Abnormalities in Rats Exposed to the Ketogenic Diet During Prenatal Life.

A large number of clinical studies demonstrate that the ketogenic diet (KD) may be an effective approach to the reduction of epileptic seizures in children and adults. Such dietary therapy could also help pregnant women with epilepsy, especially since most antiseizure drugs have teratogenic action. However, there is a lack of medical data, considering the safety of using KD during gestation for the progeny. Therefore, we examined the influence of KD used prenatally in rats on the elemental composition of the selected brain regions in their offspring. For this purpose, synchrotron radiation-induced X-ray fluorescence (SR-XRF) microscopy was utilized, and elements such as P, S, K, Ca, Fe, and Zn were determined. Moreover, to verify whether the possible effects of KD are temporary or long-term, different stages of animal postnatal development were taken into account in our experiment. The obtained results confirmed the great applicability of SR-XRF microscopy to track the element changes occurring in the brain during postnatal development as well as those induced by prenatal exposure to the high-fat diet. The topographic analysis of the brains taken from offspring of mothers fed with KD during pregnancy and appropriate control individuals showed a potential influence of such dietary treatment on the brain levels of elements such as P and S. In the oldest progeny, a significant reduction of the surface of brain areas characterized by an increased P and S content, which histologically/morphologically correspond to white matter structures, was noticed. In turn, quantitative elemental analysis showed significantly decreased levels of Fe in the striatum and white matter of 30-day-old rats exposed prenatally to KD. This effect was temporary and was not noticed in adult animals. The observed abnormalities may be related to the changes in the accumulation of sphingomyelin and sulfatides and may testify about disturbances in the structure and integrity of the myelin, present in the white matter.

Intensive treatment course to identify pseudoresistant epilepsy and expedite surgery referrals - A prospective intervention study

IntroductionA significant proportion of patients do not achieve seizure freedom despite treatment attempts with two different anti-seizure medications (ASMs). A subset may not truly have drug-resistant epilepsy (“pseudoresistant”), while rapid referral of patients with genuine drug-resistant epilepsy to surgery is mandated. This study was designed to evaluate a structured and intensive treatment course with the objective of promptly identifying cases of pseudoresistance and accelerating the time to referral to epilepsy surgery. MethodsFrom May 2017 to February 2021, this prospective interventional study recruited consecutive adult patients with epilepsy treated at Odense University Hospital, Denmark, who had at least one seizure per month despite attempts with two or more ASMs. The predefined endpoint was improvement in seizure activity. Secondary endpoints were referral to epilepsy surgery, patients with pseudoresistance, and achievement of seizure freedom. ResultsOf the 41 patients enrolled, 39 completed the study. The intervention comprised a initial seizure documentation, specialist evaluation, EEG monitoring as required, and an individualized plan for intensive treatment. The plans included e.g., optimization of medical treatment, seizure classification, and improvement of medication adherence. The subsequent intensive treatment (1–4 contacts/month; 1–13 contacts in total) was led by epilepsy nurses that executed the treatment plan. The intervention significantly improved seizure control, with 41.1 % of patients achieving seizure freedom and an additional 17.8 % of patients experiencing reduced seizure frequency. One-third of the patients turned out to be “pseudoresistant” due to various reasons, including wrong classification of seizures and inadequate adherence to ASMs. Ten patients were offered a referral for epilepsy surgery at the end of the study after an average of 34.8 weeks. ConclusionThis study demonstrates the efficacy of a standardized, intensive treatment course involving epilepsy nurses in identifying and managing patients with persisting seizures despite treatment attempts with two ASMs. This approach led to favourable seizure outcomes and facilitated expedited referrals for epilepsy surgery where appropriate.

Seizure outcomes in patients with brain metastases and epilepsy: A systematic review on the efficacy of antitumor treatment and antiseizure medication

Abstract Background Epilepsy is a common symptom in patients with brain metastases (BMs), and because of the rising incidence of BMs, adequate seizure management is warranted. We conducted a systematic review on seizure outcomes after antitumor treatment and antiseizure medication (ASM) in patients with BMs from solid tumors and epilepsy. Methods A literature search was performed in six databases up to February 2024. Extracted outcomes were rates for (1) seizure freedom; (2) ≥50% seizure reduction; and (3) treatment failure (for ASM only). Weighted averages (WAs) were calculated for outcomes after surgery at 6 months follow-up. Quality assessment of the included studies was performed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. Results We retrieved 2244 references, of which 16 studies were eligible for inclusion. Eight studies were at critical, and 8 studies at serious risk of bias. The WA of seizure freedom rates at 6 months after surgical resection was 64% (based on 3 studies at serious risk of bias, n=151 patients). Results on ASM efficacy and tolerability were unreliable, as all eligible studies for these outcomes were at critical risk of bias. Conclusions Limited available evidence from heterogeneous study populations demonstrated that in the majority of patients with epilepsy due to BMs, seizure freedom 6 months after surgical resection may be reached. No substantial evidence on ASM efficacy and tolerability in patients with epilepsy due to BMs is available. High-quality cohort studies are warranted to expand the evidence on seizure outcomes after antitumor and ASM treatment.

Fifteen Years of Neonatal Therapeutic Hypothermia: Clinical Trends Show Unchanged Post-Rewarming Outcomes despite Reduction in Hypoxic-Ischemic Encephalopathy Severity

Introduction: Hypoxic-ischemic encephalopathy (HIE) affects 1–2 per 1,000 births and is associated with mortality and long-term neurodevelopmental challenges. At present, therapeutic hypothermia (TH) is the only neuroprotective intervention for these infants. This study examines whether HIE severity, clinical management during TH, and post-rewarming outcomes have changed since its introduction 15 years ago. Methods: Neonatal characteristics, HIE severity, management during TH, and post-rewarming MRI of all infants with HIE undergoing TH between 2008 and 2023 were compared across three five-year epochs. Linear regression was used to estimate annual changes over time. Results: In total, 252 infants underwent TH. Median gestational age (39.5 weeks), birth weight (3,376 g), and time to start TH (4.25 h) remained stable over time. Apgar score at 5 min (p = 0.031) and lowest pH <1 h postpartum (p = 0.020) increased over time. Thompson score at 1–3 h decreased across epochs (p = 0.046). There was an increase in percentage with normal-mild aEEG background patterns on admission (p = 0.041) and a decrease in aEEG-confirmed seizures (p < 0.001) and antiseizure medication (p < 0.001). Inotropic support decreased (p = 0.007), and use of invasive mechanical ventilation decreased over the last 5 years. Mortality (28.6%) and post-rewarming composite adverse outcome (i.e., neonatal mortality and/or adverse MRI score) (37.9%) remained unchanged. Number of infants seen at 2-year follow-up increased (p < 0.001). Conclusion: Over the last 15 years, we treated more infants with milder HIE, as indicated by lower Thompson and milder aEEG scores, and the need for invasive cardiorespiratory support declined. However, there were no improvements in composite adverse outcome (mortality and/or adverse MRI score).

The hydroxycarboxylic acid receptor HCA2 is required for the protective effect of ketogenic diet in epilepsy.

One third of epilepsy patients are resistant to treatment with current anti-seizure medications. The ketogenic diet is used to treat some forms of refractory epilepsy, but the mechanism of its action has not yet been elucidated. In this study, we aimed to investigate whether the hydroxycarboxylic acid receptor 2 (HCA2), a known immunomodulatory receptor, plays a role in mediating the protective effect of this diet. We demonstrate for the first time that selective agonists at this receptor can directly reduce seizures in animal models. Agonists also reduce network activity in rodent and human brain slices. Ketogenic diet is known to increase circulating levels of endogenous HCA2 agonists, and we show that the effect of ketogenic diet in reducing seizures in the 6 Hz seizure model is negated in HCA2-deficient mice. Our data support the potential of HCA2 as a target for the treatment of epilepsy and potentially for neurodegenerative diseases.

Sinapinic acid as a potential therapeutic agent for epilepsy through targeting NMDA receptors and nitrite level

Epilepsy, a widespread neural ailment considered by prolonged neuronal depolarization and repetitive discharge, has been linked to extreme stimulus of N-methyl-D-aspartate receptors (NMDARs). Despite the availability of approved anti-seizure medications (ASMs) in many developed nations, approximately 30% of epilepsy patients continue to experience drug-resistant seizures. Thus, a growing interest in discovering natural compounds as potential sources for new medications is growing. Sinapinic acid, a natural derivative of cinnamic acid found in food sources, is known for its neuroprotective properties. This study investigated how sinapinic acid interacts with NMDA receptors and its potential role in providing anticonvulsant effects. Male mice were randomly allocated into nine groups: a control group receiving normal saline (1 ml/kg), groups treated with sinapinic acid at doses of 1, 3, and 10 mg/kg, a group treated with diazepam at 10 mg/kg, a group treated with an NMDA agonist at 75 mg/kg, a group treated with an NMDA antagonist at 0.5 mg/kg, a group receiving the ineffective dose of sinapinic acid (1 mg/kg) along with the NMDA antagonist, and a group receiving the effective dose of sinapinic acid (10 mg/kg) along with the NMDA agonist. Sinapinic acid and other treatments were administered intraperitoneally 30 min prior to inducing seizures with PTZ injection. Seizure onset time was recorded following PTZ injection. Blood and brain samples were collected after anesthesia to determine serum and brain nitrite levels. Real-time PCR assessed NMDAR gene expression in the prefrontal cortex (PFC). Data were analyzed using Prism software. The time seizures began was notably extended in groups treated with sinapinic acid at doses of 3 and 10 mg/kg compared to those treated with saline (P < 0.05). Additionally, in the receiving group of an ineffective dose of sinapinic acid alongside ketamine, the beginning of seizure time was significantly prolonged compared to the group that received the ineffective dose of sinapinic acid alone (P < 0.05). Serum and prefrontal cortex (PFC) nitrite levels were significantly lower in mice treated with sinapinic acid at doses of 1, 3, and 10 mg/kg compared to the saline-treated group (P < 0.05). The gene expression of the NMDAR NR2B subunit in the PFC was decreased in groups treated with sinapinic acid at 1 and 10 mg/kg compared to the saline-treated group. Furthermore, co-administration of sinapinic acid (10 mg/kg) with NMDA resulted in significantly lower NR2A gene expression than the group treated with 10 mg/kg of sinapinic acid alone. Conversely, co-administration of ketamine with sinapinic acid (1 mg/kg) significantly increased NR2B subunit gene expression compared to the group treated with sinapinic acid at 1 mg/kg alone. Sinapinic acid showed anticonvulsant effects through reduced serum and PFC nitrite and modulation of glutamatergic signaling.

Generation and Characterization of Three Novel Mouse Mutant Strains Susceptible to Audiogenic Seizures.

The mechanisms of epileptogenesis after brain injury, ischemic stroke, or brain tumors have been extensively studied. As a result, many effective antiseizure drugs have been developed. However, there are still many patients who are resistant to therapy. The molecular and genetic bases regarding such drug-resistant seizures have been poorly elucidated. In many cases, heavy seizures are instigated by brain development malformations and often caused by gene mutations. Such malformations can be demonstrated in mouse models by generating mutant strains. One of the most potent mutagens is ENU (N-ethyl-N-nitrosourea). In the present study, we describe three novel mutant strains generated by ENU-directed mutagenesis. Two of these strains present a very strong epileptic phenotype triggered by audiogenic stimuli (G9-1 and S5-1 strains). The third mouse strain is characterized by behavioral disorders and hyperexcitation of neuronal networks. We identified changes in the expression of those genes encoding neurotransmission proteins in the cerebral cortexes of these mice. It turned out that the G9-1 strain demonstrated the strongest disruptions in the expression of those genes encoding plasma membrane channels, excitatory glutamate receptors, and protein kinases. On the other hand, the number of GABAergic neurons was also affected by the mutation. All three lines are characterized by increased anxiety, excitability, and suppressed motor and orientational-exploratory activities. On the other hand, the strains with an epileptic phenotype-G9-1 and S5-1ave reduced learning ability, and the A9-2 mice line retains high learning ability.

Recent Advances in Pharmacologic Treatments of Drug-Resistant Epilepsy: Breakthrough in Sight.

Epilepsy affects approximately 1% of the world population. Patients have recurrent seizures, increased physical and psychiatric comorbidities, and higher mortality rate than the general population. Over the last 40 years, research has resulted in 20 new antiseizure medications (ASMs) approved between 1990 and 2018. In spite of this, up to one-third of patients (~ 1 million patients in the USA) have drug-resistant epilepsy (DRE), with little change between 1982 and 2018, a period of intense new ASM development. A minority of patients with DRE may benefit from surgical treatment, but this specialized care remains challenging to scale. Therefore, the greatest hope for breakthroughs for patients with DRE is in pharmacologic therapies.Recently, several advances promise to change the outcomes for patients with DRE. Cenobamate, a drug with dual mechanisms of modulating sodium channel currents and GABA-A receptors, achieves 90-100% seizure reduction in 25-33% of patients with focal DRE, a response not observed with other ASMs. Fenfluramine, a serotonin-acting drug, dramatically reduces the frequency ofconvulsive seizuresin Dravet syndrome, a devastating developmental epileptic encephalopathy with severe DRE.Both drugs reduce mortality.In addition, the possibility of DRE prevention was recently raised in patients with tuberous sclerosis complex, a relatively common genetic form of epilepsy. A paradigm shift is emerging in the treatment of epilepsy. Seizure freedom has become attainable in a significant proportion of patients with focal DRE, and dramatic seizure reduction has been achieved in a developmental encephalopathy. Coupled with a rich pipeline of new compounds under clinical development, the long sought-after breakthrough in the treatment of epilepsy may finally be in sight.

Adverse events associated with carbamazepine: a pharmacovigilance study using the FDA Adverse Event Reporting System

ABSTRACT Introduction Carbamazepine (CBZ) is a commonly used antiseizures medications (ASM), but its adverse drug reactions (ADRs) can impact the successful management of epilepsy. There are currently limited systematic studies on ADRs related to CBZ, necessitating further investigation. Areas covered Using the FDA Adverse Event Reporting System (FAERS) database , we extracted reports where CBZ was the primary suspect, conducting subgroup analyses stratified by sex and age. Four risk signal detection methods ROR, PRR, BCPNN, and EGBM were employed to systematically analyze the ADRs associated with CBZ. Expert opinion In the epilepsy population, ADRs related to CBZ often involve examinations, hereditary disorders, and infections. Subgroup analysis showed differences in ADR signals among male, female, elderly, and young patients. Human Herpesvirus 6 Infection and Dermatitis Exfoliative were consistent CBZ-induced ADRs, unaffected by age or sex. The study also identified previously overlooked ADRs such as bone metabolism abnormalities, ocular toxicity, and ototoxicity. Many ADRs linked to CBZ remain underreported. It is crucial to enhance monitoring and information dissemination about CBZ use in epileptic patients. Adjusting medication regimens for high-risk individuals, potentially incorporating acupuncture, traditional Chinese medicine, or alternative anti-seizure medications, should be considered when necessary.

Terminology of medicines used to control seizure disorders: 2024 ILAE Recommendations and profile of real-world term use

Background. The International League Against Epilepsy (ILAE) has provided recommendations on the terminology of medicines for control of seizure disorders, which should be adapted into different languages.Objective: to evaluate the usage profile of terms describing the effects of medicines used in patients with epilepsy.Material and methods. The search query analysis systems Google Trends and Yandex Wordstat as well as PubMed/MEDLINE, Google Scholar and eLibrary databases were used to evaluate the general public and professional usage profile, respectively.The following terms in Russian and English were studied: “antiepileptic”, “antiepileptic drug”, “antiseizure”, “antiseizure drug”. In order to ascertain a prevailing opinion within professional and patient communities, a questionnaire survey was conducted on the public online resources of the non-profit partnership “The Association of Epileptologists and Patients” carried out via the cloud-based cross-platform social media as well as instant messaging service Telegram and the social media platform VK.Results. In the English-speaking internet segment, the term “antiepileptic” is used more than 5 times frequently than “antiseizure” by the general public. Conversely, in the Russian-language segment, the term “antiseizure” is almost 2.5 times more common. The term “antiepileptic” is more prevalent in scientific community in both segments. This finding aligns with the profile of terminology usage observed among epileptologists and epilepsy patients. The questionnaire survey results revealed that 56.42% of 179 respondents were in favor of the terms “antiepileptic drug”, “AED” and “antiepileptic therapy”, whereas as few as 17.32% of those endorsed the ILAE-proposed terminology.Conclusion. In light of the established practice of terminology use in both professional scientific community and among practicing epileptologists and epileptic patients, as well as the differences in the semantics of English- and Russian-language terms and the identified lack of precision in the ILAE definition of epilepsy, it can be concluded that for the Russian-speaking population, the terms “antiepileptic drug”, “AED” are more preferable rather than the terms “antiseizure medication”, “ASM”. Additionally, it is preferable to use the terms “convulsive ictus” and “epileptic ictus” due to negative connotation with term “seizure” in Russian. The terms “antiseizure” and “antiepileptic” should not be regarded as mutually exclusive in the context of treatment that has a direct impact on epilepsy course. Finally, it is necessary to further refine epilepsy definition and classification.

Development and Validation of a Clinical Score to Predict Epilepsy After Cerebral Venous Thrombosis

One of 10 patients develop epilepsy in the late phase after cerebral venous thrombosis (CVT) diagnosis but predicting the individual risk is difficult. To develop and externally validate a prognostic score to estimate the individual risk of post-CVT epilepsy. This observational cohort study included both retrospective and prospective patients enrolled from 1994 through 2022. For development of the DIAS3 score, data from the International CVT Consortium (n = 1128), a large international hospital-based multicenter CVT cohort, were used. For validation, data from 2 independent multicenter cohorts, the ACTION-CVT (n = 543) and the Israel CVT study (n = 556), were used. Of 2937 eligible, consecutively enrolled adult patients with radiologically verified CVT, 710 patients with a history of epilepsy prior to CVT, follow-up less than 8 days, and missing late seizure status were excluded. The prediction score (DIAS3) was developed based on available literature and clinical plausibility and consisted of 6 readily available clinical variables collected during the acute phase: decompressive hemicraniectomy, intracerebral hemorrhage at presentation, age, seizure(s) in the acute phase (excluding status epilepticus), status epilepticus in the acute phase, and subdural hematoma at presentation. Time to a first late seizure, defined as occurring more than 7 days after diagnosis of CVT. Of 1128 patients included in the derivation cohort (median age, 41 [IQR, 30-53] years; 805 women [71%]), 128 (11%) developed post-CVT epilepsy during a median follow-up of 12 (IQR, 3-26) months. According to the DIAS3 score, the predicted 1-year and 3-year risk of epilepsy in individual patients ranged from 7% to 68% and 10% to 83%, respectively. Internal and external validation showed adequate discrimination in the derivation cohort (1 year and 3 years: C statistic, 0.74; 95% CI, 0.70-0.79) and the 2 independent validation cohorts, (ACTION-CVT) 1 year: C statistic, 0.76; 95% CI, 0.67-0.84; 3 years: C statistic, 0.77; 95% CI, 0.66-0.84; and Israel CVT study 1 year: C statistic, 0.80; 95% CI, 0.75-0.86. Calibration plots indicated adequate agreement between predicted and observed risks. The DIAS3 score (freely available online) is a simple tool that can help predict the risk of post-CVT epilepsy in individual patients. The model can improve opportunities for personalized medicine and may aid in decision-making regarding antiseizure medication, patient counseling, and facilitation of research on epileptogenesis in CVT.

Stiripentol for the treatment of refractory status epilepticus

BackgroundStatus epilepticus (SE) is one of the most common neurological emergencies and an acutely life-threatening condition characterized by high mortality and morbidity. Despite the well-established staged therapy of status epilepticus, especially stages 1 and 2, more than one third of patients develop (super-) refractory SE. Despite a large variety of potential treatment options for super-refractory SE, there is an unmet clinical need of potential new treatment ideas in this often desperate clinical situation.A number of studies have demonstrated the safety and efficacy of stiripentol (STP) in patients with Dravet syndrome (DS) and in children with focal epilepsy and generalized epilepsies. Some smaller series and case reports have documented the use of STP in the treatment of status epilepticus in adult patients.MethodsWe retrospectively analyzed all patients who were admitted to the Department of Neurology at Marburg University Hospital between 2013 and 2023 with a diagnosis of (super)-refractory status epilepticus and who received additional treatment of SE with STP. All patients who received STP during the SE were included, regardless of previous medication.ResultsSE ceased in 64% of 25 patients (13 female and 12 male). The mean age was 58.6 ± 21.9 years (mean ± SD). 72% had a structural epilepsy. In 20% of patients, SE was terminated by the administration of STP alone in 32% of cases, while in a further 32% of patients, the simultaneous administration of multiple anti-seizure medications (ASMs) including STP was potentially responsible for the cessation of the SE, with valproic acid (VPA), benzodiazepines and STP, being the most frequently implicated ASMs. In 12% of patients, there was at least a temporary improvement in the electroencephalogram (EEG). Stiripentol had to be discontinued in three cases due to a reduction in vigilance or hypercalcemia.ConclusionsStiripentol may represent a promising additional treatment option for refractory and super-refractory status epilepticus. The tolerability of this treatment has already been demonstrated in previous studies, and was also reflected in these data. Further prospective investigation in larger patient populations are necessary to ascertain the efficacy of stiripentol in SE.Trial registrationNCT06540378, retrospectively registered.

Coexistence of epilepsy or seizure and multiple sclerosis; review of the literature with a single center experience

ObjectivesThere is evidence that the inflammatory demyelinating disorder in Multiple Sclerosis (MS) is associated with acute seizures and epilepsy. Additionally, the likelihood of developing epilepsy increases with neurodegeneration. This study aims to reveal the clinical and radiological features of MS-epilepsy/seizure coexistence. MethodsAmong all patients diagnosed with MS that we followed in our center between April 2002 and July 2023, patients with a single seizure history or diagnosed with epilepsy (MS-seizure/epilepsy) were randomized 1:1 in terms of age and gender with MS patients without a diagnosis of epilepsy or seizures. Clinical (comorbidities, annualized relapse rate, disability, seizures during attacks, initial diagnosis, disease duration, disease-modifying therapies (DMTs), refractory epilepsy, anti-seizure drugs), electroencephalography (EEG) and MRI (lesion localization and new lesion(s)) data were retrospectively evaluated. ResultsThe mean EDSS was 4.07±2.81. 29.4 % of patients had progressive MS (n = 10). Refractory epilepsy was 52.9 % (n = 18), and SE history was 14.7 % (n = 5). Pathology was detected in 69.7 % (n = 23) of patients in the EEG. The most common slow wave activation was detected in 51.5 % (n = 17). Refractory epilepsy was more common in cases under 45 and patients with lesions in thalamic localization. Lesions in the temporal and thalamic regions and cerebral atrophy were more common in the MS-seizure/epilepsy group. ConclusionPatients with demyelinating lesions in the temporal and thalamic regions should be questioned more carefully for epilepsy, and an EEG should be performed in case of clinical suspicion. Since thalamus lesions are more common in patients with refractory epilepsy, anti-seizure treatment strategies should be applied more carefully. The presence of atrophy on MRI confirms the link between neurodegeneration processes and the development of epilepsy.

Effects of sleeve gastrectomy and Roux-en-Y gastric bypass on pharmacokinetics of lamotrigine and valproate: A cohort study

BackgroundBariatric surgeries may affect the pharmacokinetics of medications through alterations of the gastrointestinal physiology. Pharmacokinetic changes of first-line antiseizure medications such as lamotrigine and valproate following bariatric treatment have received little research attention so far. MethodsIn our prospective case study we included lamotrigine- or valproate-treated patients undergoing bariatric surgery at hospitals in Central Norway. Lamotrigine and valproate concentrations were assessed using serial blood samples over a dose interval, before and one, six and twelve months following surgery. Primary outcomes included changes in area under the time-concentration curve (AUC) with secondary outcomes comprising full pharmacokinetic profiling. ResultsSix lamotrigine-treated obese patients undergoing Roux-en-Y gastric bypass (RYGB) (n = 3) and sleeve gastrectomy (SG) (n = 3), as well as two valproate-treated patients (one undergoing RYGB and one SG) were included. Largest changes for dose-adjusted AUC values after surgery were seen in RYGB-treated patients on lamotrigine (average increases of 38 % one month and 32 % 12 months postoperatively). In the patients on valproate, AUC values were decreased by 22 % after 6 months and by 30 % after 12 months. The interindividual variation was high. Formal statistical testing was not done due to few cases. ConclusionPostoperative pharmacokinetic changes for lamotrigine and valproate were modest, but for lamotrigine changes may be larger in patients undergoing RYGB than in those undergoing SG. Given the substantial interindividual variation, therapeutic drug monitoring should be used to capture pharmacokinetic changes and guide dose adjustments after bariatric surgery.

An advocacy based cross sectional study of healthcare professionals of factors impacting on medication adherence across nine Sub-Saharan African countries

BackgroundAdherence to anti-seizure medication (ASM) by people diagnosed with epilepsy in sub-Saharan Africa remains low. The factors for low adherence are not well understood. To improve adherence, it is important to understand the perceptions and views of healthcare professionals delivering epilepsy care to this population. The aim was to investigate the factors influencing ASM adherence. MethodsThis study uses a brief online questionnaire which asked healthcare professionals (both from nursing and medical backgrounds) who work in sub-Saharan African countries to rate a set of pre-established options designed with the feedback of a local focus group of epilepsy experts from countries targeted. The questionnaire consisted of six questions and was a mix of multiple choice and Likert scale questions. ResultsThere were 217 healthcare professionals who replied to the questionnaire. The most important factors believed to be influencing adherence from a healthcare professional perspective are; lack of availability of medication for epilepsy (71 %), affordability of medication (60 %), the patient, family, carer lacking in understanding of medication (43 %), cultural misconceptions about epilepsy (40 %) and side effects of the medication (32 %). The survey was answered by many different healthcare professionals; 65 participants were doctors and 152 were other healthcare professionals such as nurses (59 %) pharmacists (10 %) and when comparing them, the three most important categories were consistent across groups. ConclusionHealthcare workers in Sub-Saharan Africa identify that the primary factors impacting adherence to ASMs, in their view, is affordability and availability of ASMs.Addressing this issue may reduce the treatment gap.

Gabapentin for Seizures

What Is the Issue? Gabapentin is 1 of many antiseizure medications available for the treatment of epilepsy in adults; however, there are potential risks associated with its use. Therefore, it is important to determine the place of therapy of gabapentin in the treatment of epilepsy. What Did We Do? To help determine the potential place in therapy for gabapentin in the treatment of epilepsy in adults, we sought to identify and summarize studies of the clinical- and cost-effectiveness of gabapentin as well as recommendations from evidence-based guidelines. We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2014. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included publications, and narratively summarized the findings. What Did We Find? We identified 1 systematic review and 1 randomized controlled trial (RCT) that evaluated the efficacy of gabapentin in adults with epilepsy. We identified 5 evidence-based guidelines that included recommendations on the use of gabapentin for epilepsy. We did not identify any studies that evaluated its cost-effectiveness. Seizure-free retention at 3 months may be better in adults with epilepsy who were treated with lamotrigine than gabapentin or carbamazepine. There were no differences in other seizure outcomes (such as time to seizure, seizure freedom, or seizure-free retention) for adults with epilepsy treated with gabapentin versus lamotrigine or carbamazepine. Adults with epilepsy treated with gabapentin were more likely to experience fair or poor health perception than those treated with oxcarbazepine. There were no differences in other quality of life outcomes (such as anxiety, depression, or worry about seizures) between those treated with gabapentin versus lamotrigine, carbamazepine, oxcarbazepine, or topiramate. Withdrawals because of adverse events were similar between adults with epilepsy treated with gabapentin and lamotrigine. There were more systemic toxicities in adults treated with gabapentin than carbamazepine or lamotrigine but there were no differences in neurotoxicities between groups. One guideline recommends against the use of gabapentin in people with myoclonic seizures or people with epilepsy with myoclonic-atonic seizures. One guideline states that there is insufficient evidence to consider gabapentin instead of carbamazepine in patients with new-onset focal epilepsy or unclassified generalized tonic-clonic seizures. Three guidelines recommend the use of gabapentin in older adults with epilepsy. One guideline recommends the use of gabapentin in people with intellectual disability and epilepsy, if the benefits outweigh the risks or as a second-line option. What Does It Mean? There were few differences in outcomes between adults with epilepsy treated with gabapentin versus other active comparators in the studies we identified. The included guidelines recommended for or against the use of gabapentin depending on patient factors such as age and type of epilepsy or seizures. Decision-makers may wish to consider individual patient factors such as age and type of epilepsy or seizures as well as the availability of other treatment options when making decisions on the use of gabapentin for the treatment of epilepsy.