Use Of Antiseizure Medications Research Articles

Perampanel for the treatment of epilepsy with genetic aetiology: Real-world evidence from the PERMIT Extension study

Genetic factors contribute to the aetiology of epilepsy in >50% of cases, and information on the use of antiseizure medications in people with specific aetiologies will help guide treatment decisions. The PERMIT Extension study pooled data from two real-world studies (PERMIT and PROVE) to investigate the effectiveness and safety/tolerability of perampanel (PER) when used to treat people with focal and generalised epilepsy in everyday clinical practice. This post-hoc analysis of PERMIT Extension explored the use of PER when used to treat individuals presumed to have epilepsy with a genetic aetiology. Assessments included retention rate (evaluated at 3, 6 and 12 months), effectiveness (responder and seizure freedom rates; evaluated at 3, 6, 12 months and the last visit [last observation carried forward) and tolerability (adverse events [AEs]). Of the 6822 people with epilepsy included in PERMIT Extension, 1012 were presumed to have a genetic aetiology. The most common genetic aetiologies were idiopathic generalised epilepsy (IGE; 58.2%), tuberous sclerosis (1.1%), Dravet syndrome (0.8%) and genetic epilepsy with febrile seizures plus (GEFS+; 0.5%). Retention rates at 3, 6 and 12 months in the total genetic aetiology population were 89.3%, 79.7% and 65.9%, respectively. In the total genetic aetiology population, responder rates at 12 months and the last visit were 74.8% and 68.3%, respectively, and corresponding seizure freedom rates were 48.9% and 46.5%, respectively. For the specific aetiology subgroups, responder rates at 12 months and the last visit were, respectively: 90.4% and 84.4% (IGE), 100% and 57.1% (tuberous sclerosis), 100% and 71.4% (Dravet syndrome), and 33.3% and 20.0% (GEFS+). Corresponding seizure freedom rates were, respectively: 73.1% and 64.6% (IGE), 33.3% and 22.2% (tuberous sclerosis), 20.0% and 28.6% (Dravet syndrome), and 0% and 0% (GEFS+). The incidence of AEs was 46.5% for the total genetic aetiology population, 48.8% for IGE, 27.3% for tuberous sclerosis, 62.5% for Dravet syndrome, and 20% for GEFS+. Tolerability findings were consistent with PER’s known safety profile. PER was effective and generally well tolerated when used in individuals with a presumed genetic epilepsy aetiology in clinical practice. PER was effective across a wide range of genetic aetiologies.

Pre-operative predictors of post-operative seizure control in low-grade glioma: a systematic review and meta-analysis.

As many as 80% of low-grade gliomas (LGGs) present with seizures, negatively impacting quality of life. While seizures are associated with gliomas regardless of grade, the importance of minimizing impact of seizures for patients with low grade tumors cannot be understated given the prolonged survival period in this population.The objective of this systematic review and meta-analysis was to summarize existing literature and identify factors associated with post-operative seizure control (defined as Engel I classification) in patients with LGGs, with a focus on pre-operative factors. Patient data extracted include tumor location and histology, pre-operative anti-seizure medication use, extent of resection (EOR), adjuvant treatment, pre-operative seizure type, duration, and frequency, and post-operative Engel classification. A random-effects model was used to calculate the effects of EOR, pre-operative seizure duration, adjuvant radiation, and adjuvant chemotherapy on post-operative seizure control. The effect of tumor location and histology on post-operative Engel I classification was determined using contingency analyses.Thirteen studies including 1628 patients with seizures were included in the systematic review. On meta-analyses, Engel I classification was associated with pre-operative seizure type (OR = 0.79 (0.63-0.99), p = 0.0385, focal versus generalized), frontal lobe LGGs (OR = 1.5 (1.1-2.0), p = 0.0195), and EOR (OR (95% CI) = 4.5 (2.3-6.7), p < 0.0001 gross-total versus subtotal). Pre-operative seizure duration less than one year, adjuvant radiation, adjuvant chemotherapy, and tumor histology were not associated with achieving Engel I classification. In addition to the known effects of EOR, Engel I classification is less likely to be achieved in patients with focal pre-operative seizures and more likely to be achieved in patients with frontal lobe LGGs.

Language impairments in seropositive and seronegative autoimmune encephalitis

Background and objectiveAutoimmune encephalitis (AE) is a rare neuroinflammatory disease affecting the central nervous system. To examine language functions in patients with different subsets of AE consisting of seropositive and seronegative groups.MethodsFifty-two patients were recruited from neurology departments in Melbourne, Australia, who met clinical criteria for possible AE. Language tests include the Naming Test from the Sydney Language Battery (SydBat), the semantic fluency trial from the Controlled Oral Word Association Test (COWAT), and the Vocabulary and Similarities subtests of the Weschler Abbreviated Scale of Intelligence–Second Edition. The results were standardised with normative data.ResultsThe mean age of our cohort was 52.5 years old, with the average time from hospital admission to recruitment being 38.41 months. At an aggregate level, none of the mean language test z-scores were below normative data. At the patient level, impairment rates were 18.37% for COWAT (animals), 28.57% for SydBat (naming), 4.65% for Similarities, and 4.55% for Vocabulary. Chi-squared goodness of fit tests indicated that observed performances were significantly below expected performances for the SydBat (naming) test (p < 0.0001) and COWAT (animals) (p = 0.004).DiscussionWhile, on average, language functions were within normal limits in patients with AE, but a subgroup exhibited lower performance in semantic fluency and visual confrontation naming, with impairment rates below expected norms. To advance understanding of language in chronic AE patients, exploring the impact of seizure burden, antiseizure medication use, and the relationship of language functions with other cognitive functions is crucial.

Benzodiazepines for pediatric epilepsies and their risks in a cohort within the French health care data.

The management of antiseizure treatment in patients with epilepsy relies on the benefit-risk ratio. Data on antiseizure medication (ASM) use in children are limited. We described antiseizure medication use in children with epilepsy (CwE) in France, with a focus on the chronic use of benzodiazepines and related implications. We conducted a 5-year cohort study from January 2012, using data from the French national health care data system (Système National des Données de Santé). We included CwE identified through International Classification of Diseases, 10th Revision codes and medications from January 2012 to December 2015 and followed them until December 2016. We described ASMs and assessed whether the risk of initiating a polytherapy after a bitherapy depends on whether benzodiazepine was included in the bitherapy. We identified 62 885 CwE. Valproate was the most reimbursed ASM (40%), followed by lamotrigine (17.6%), levetiracetam (9.3%), clobazam (6.1%), and carbamazepine (5.8%). Prescriptions were initiated at the hospital in 74.5% of CwE. We observed a decrease in the number of CwE with at least one benzodiazepine reimbursement from 15.3% in 2013 to 10.1% in 2016 (p < .0001). The prevalence of CwE with levetiracetam reimbursements increased, whereas that of CwE with valproate decreased. A switch from a bitherapy to a polytherapy was more likely when the bitherapy included a benzodiazepine (subdistribution hazard ratio [sHR] = 1.20 [1.03-1.39]). The prevalence of CwE with at least one benzodiazepine reimbursement decreased during the study period. Benzodiazepines were associated with an increased use of subsequent ASM polytherapy.

Clinical Implications of Various Electroencephalographic Patterns in Post-Stroke Seizures. The Utility of Routine Electroencephalogram.

Objective: Post-stroke seizures (PSS) are one of the major stroke-related complications. Early therapeutic interventions are critical therefore using electroencephalography (EEG) as a predictive tool for future recurrence may be helpful. We aimed to assess frequencies of different EEG patterns in patients with PSS and their association with seizure recurrence and functional outcomes. Methods: All patients admitted with PSS were included and underwent interictal EEG recording during their admission and monitored for seizure recurrence for 24 months. Results: PSS was reported in 106 patients. Generalized slow wave activity (GSWA) was the most frequent EEG pattern observed (n = 62, 58.5%), followed by Focal sharp wave discharges (FSWDs) (n = 57, 55.8%), focal slow wave activity (FSWA) (n = 56, 52.8%), periodic discharges (PDs) (n = 13, 12.3%), and ictal epileptiform abnormalities (n = 6, 5.7%). FSWA and ictal EAs were positively associated with seizure recurrence (p < .001 and p = .015 respectively) and it remained significant even after adjusting for age, sex, stroke severity, stroke subtype, or use of anti-seizure medications (ASMs). Other positive associations were status epilepticus (SE) (p = .015), and use of older ASM (p < .001). FSWA and GSWA in EEG were positively associated with severe functional disability (p = .055, p = .015 respectively). Other associations were; Diabetes Mellitus (p = .034), Chronic Kidney Disease (p = .002), use of older ASMs (p = .037), presence of late PSS (p = .021), and those with Ischemic stroke (p = .010). Conclusions: Recognition and documentation of PSS-related EEG characteristics are important, as certain EEG patterns may help to identify the patients who are at risk of developing recurrence or worse functional outcomes.

Hormonal Changes in Women with Epilepsy.

Epilepsy is a prevalent neurological disorder among women globally, often requiring long-term treatment. Hormonal fluctuations in women with epilepsy (WWE) can have reciprocal effects on epilepsy and antiseizure medications (ASMs), posing significant challenges for WWE. Notably, WWE commonly experience endocrine alterations such as thyroid dysfunctions, low bone metabolism, and reproductive hormone irregularities. On the one hand, the presence of hormones in women with epilepsy affects their susceptibility to epilepsy as well as the metabolism of antiseizure medications in various ways. On the other hand, epilepsy itself and the use of antiseizure medications impact the production, secretion, and metabolism of hormones, resulting in low fertility, increased risk of pregnancy complications, negative offspring outcomes, and so on. In order to develop more precise treatment strategies in the future, it is necessary to comprehend the explicit relationships between hormones, epilepsy, and antiseizure medications, as well as to elucidate the currently known mechanisms underlying these interactions.

Comparative Risk of Major Congenital Malformations With Antiseizure Medication Combinations vs Valproate Monotherapy in Pregnancy.

Valproate should be avoided in pregnancy, but it is the most effective drug for generalized epilepsies. Alternative treatment may require combinations of other drugs. Our objectives were to describe first trimester use of antiseizure medication (ASM) combinations that are relevant alternatives to valproate and determine whether specific combinations were associated with a lower risk of major congenital malformations (MCM) compared with valproate monotherapy. We conducted a population-based cohort study using linked national registers from Denmark, Finland, Iceland, Norway, and Sweden and administrative health care data from the United States and New South Wales, Australia. We described first trimester use of ASM combinations among pregnant people with epilepsy from 2000 to 2020. We compared the risk of MCM after first trimester exposure to ASM combinations vs valproate monotherapy and low-dose valproate plus lamotrigine or levetiracetam vs high-dose valproate (≥1,000 mg/d). We used log-binomial regression with propensity score weights to calculate adjusted risk ratios (aRRs) and 95% CIs for each dataset. Results were pooled using fixed-effects meta-analysis. Among 50,905 pregnancies in people with epilepsy identified from 7.8 million total pregnancies, 788 used lamotrigine and levetiracetam, 291 used lamotrigine and topiramate, 208 used levetiracetam and topiramate, 80 used lamotrigine and zonisamide, and 91 used levetiracetam and zonisamide. After excluding pregnancies with use of other ASMs, known teratogens, or a child diagnosed with MCM of infectious or genetic cause, we compared 587 exposed to lamotrigine-levetiracetam duotherapy and 186 exposed to lamotrigine-topiramate duotherapy with 1959 exposed to valproate monotherapy. Pooled aRRs were 0.41 (95% CI 0.24-0.69) and 1.26 (0.71-2.23), respectively. Duotherapy combinations containing low-dose valproate were infrequent, and comparisons with high-dose valproate monotherapy were inconclusive but suggested a lower risk for combination therapy. Other combinations were too rare for comparative safety analyses. Lamotrigine-levetiracetam duotherapy in first trimester was associated with a 60% lower risk of MCM than valproate monotherapy, while lamotrigine-topiramate was not associated with a reduced risk. Duotherapy with lamotrigine and levetiracetam may be favored to treat epilepsy in people with childbearing potential compared with valproate regarding MCM, but whether this combination is as effective as valproate remains to be determined. This study provides Class II evidence that in people with epilepsy treated in the first trimester of pregnancy, the risk of major congenital malformations is lower with lamotrigine-levetiracetam duotherapy than with valproate alone, but similar with lamotrigine-topiramate.

Effect of anti-epileptic drugs usage on thyroid profile in Egyptian epileptic children

BackgroundThe long-term use of anti-seizure medications (ASMs) adversely affects thyroid, lipid profile and other metabolic functions. Subclinical hypothyroidism and alterations in thyroid hormone serum levels are reported with older ASMs in adults with limited and conflicting data of the influence of ASMs especially newer one on thyroid function in children. This study aimed to investigate the effects of conventional and newer ASMs whether mono or polytherapy on thyroid profile in children with epilepsy and its impact on lipid profile and metabolic functions.ResultsThis study included 155 children with epilepsy (76 on monotherapy and 79 on polytherapy) with mean age of 9.677 ± 3.981 years (54.84% euthyroid, 31.61% hypothyroid, 9.68% subclinical hyperthyroid and 3.87% subclinical hypothyroid) and 78 healthy controls. Children with epilepsy whether on monotherapy or on polytherapy had a statistically significant thyroid profile abnormalities (hypothyroidism, sub-clinical hypothyroidism or sub-clinical hyperthyroidism), dyslipidemia, delayed growth and increase in DBP compared to control group. There was a statistically significant positive correlation between hypothyroidism and dyslipidemia as well as between hypothyroidism and delayed growth and increase in DBP. There was no statistically significant difference between polytherapy and monotherapy regarding thyroid and lipid parameters but children with epilepsy on polytherapy were associated with more statistically significant delay in growth and increase in DBP compared to monotherapy group. Carbamazepine had a statistically significant association with hypothyroidism, increase in DBP and higher total and LDL-cholesterol. Valproic acid had a statistically significant association with sub-clinical hypothyroidism with a positive dose correlation. Levetiracetam (LEV) was associated with a statistically significant lower HDL-cholesterol. All echocardiography data showed no abnormality.ConclusionASMs whether older or newer generations can affect thyroid and lipid profile differently through different mechanisms that are dose and duration dependent regardless of the seizure type and age of the patient. ASMs mainly conventional ones are associated with hypothyroidism, sub-clinical hypothyroidism, sub-clinical hyperthyroidism, dyslipidemia and consequently delayed growth and diastolic blood pressure abnormalities.

Adaptive Dosage Strategy of Levetiracetam in Chinese Epileptic Patients: Focus on Pregnant Women

There is presently no efficient dose individualization strategy for the use of antiseizure medications in epileptic pregnant patients. This study aimed to develop a population pharmacokinetics model for levetiracetam and propose a tailored adaptive individualized dosage strategy for epileptic pregnant patients. A total of 322 levetiracetam plasma concentrations from 238 patients with epilepsy were included, including 216 women with epilepsy (20.83% of whom were pregnant). The levetiracetam plasma concentration was measured using a validated ultra-performance liquid chromatography-tandem mass spectrometry assay, and the data were modeled using a nonlinear mixed-effects model. The resultant model served as the basis for simulating the dosage adjustment strategy. A one-compartment model with first-order elimination best described the pharmacokinetic data of levetiracetam. The apparent clearance (CL/F) was 3.43 L/h (95% CI 3.30–3.56) and the apparent volume of distribution was 43.7 L (95% CI 40.4–47.0) for a typical individual of 57.2 kg. Pregnancy and body weight were found to be significant covariates of CL/F of levetiracetam. The recommended regimen of levetiracetam could be predicted by the population pharmacokinetic model based on body weight, gestational age, and the daily dose of levetiracetam taken before pregnancy.

Seizures after Subarachnoid Hemorrhage and Clinical Use of Anti-seizure Medication

Seizures after Subarachnoid Hemorrhage and Clinical Use of Anti-seizure Medication

Prophylactic use of anti-seizure medication in patients with Sturge-Weber Syndrome: A systematic literature review

Prophylactic use of anti-seizure medication in patients with Sturge-Weber Syndrome: A systematic literature review

Efficient organisation of the contralateral hemisphere connectome is associated with improvement in intelligence quotient after paediatric epilepsy surgery

ObjectiveAims of epilepsy surgery in childhood include optimising seizure control and facilitating cognitive development. Predicting which children will improve cognitively is challenging. We investigated the association of the pre-operative structural connectome of the contralateral non-operated hemisphere with improvement in intelligence quotient (IQ) post-operatively. MethodsConsecutive children who had undergone unilateral resective procedures for epilepsy at a single centre were retrospectively identified. We included those with pre-operative volume T1-weighted non-contrast brain magnetic resonance imaging (MRI), no visible contralateral MRI abnormalities, and both pre-operative and two years post-operative IQ assessment. The MRI of the hemisphere contralateral to the side of resection was anatomically parcellated into 34 cortical regions and the covariance of cortical thickness between regions was used to create binary and weighted group connectomes. ResultsEleven patients with a post-operative IQ increase of at least 10 points at two years were compared with twenty-four patients with no change in IQ score. Children who gained at least 10 IQ points post-operatively had a more efficiently structured contralateral hemisphere connectome with higher global efficiency (0.74) compared to those whose IQ did not change at two years (0.58, p = 0.014). This was consistent across thresholds and both binary and weighted networks. There were no statistically significant group differences in age, sex, age at onset of epilepsy, pre-operative IQ, mean cortical thickness, side or site of procedure, two year post-operative Engel scores or use of anti-seizure medications between the two groups. ConclusionsSurgical procedures to reduce or stop seizures may allow children with an efficiently structured contralateral hemisphere to achieve their cognitive potential.

Evolution of antiseizure medication use and cost in the United States of America 2006-2021.

To describe the evolution in use and cost of antiseizure medications (ASM) in the United States of America (USA). Retrospective descriptive study using the IBM MarketScan Commercial Database (data of privately-insured patients) for the years 2006 to 2021. We identified patients with epilepsy who were on ASM. We adjusted cost for inflation with the Gross Domestic Product Implicit Price Deflator. We evaluated 347,158 patients (46.9% males; median (p25-p75) age: 33 (17-49) years; 28% with pediatric-onset epilepsy and 72% with adult-onset epilepsy) with a total of 1,385,382 person-years and 588,285,065 ASM prescription days. The most commonly prescribed (as percentage of prescription days) ASMs in 2006 were valproate (18%) and lamotrigine (17%) in pediatric-onset epilepsy and phenytoin (21%) and carbamazepine (17%) in adult-onset epilepsy, but starting in the 2010s, levetiracetam and lamotrigine became the most commonly prescribed ASMs in both pediatric-onset (in 2021, levetiracetam 25%, lamotrigine 16%) and adult-onset (in 2021, levetiracetam 27%, lamotrigine 20%) epilepsy. The proportion of generic ASM use increased 3.6-fold: from 23% of prescription days in 2006 to 83% of prescription days in 2021. The median (p25-p75) average wholesale price (AWP) per person-year increased by 102% from $2,684 ($990-$5,509) in 2006 to $5,417 ($2,858-$12,310) in 2021. The increases were greater in absolute terms for brand-name ASMs by 419%: $3,109 ($1,564-$5,068 in 2006 and $16,149 ($12,950-$23,377) in 2021 than for generic ASMs by 462%: $699 ($457-$1,678) in 2006 and $3,931 ($2,618-$6,081) in 2021. The costs directly borne by the patient (copay, coinsurance, deductibles, and pharmacy processing fees) increased by 69% for brand-name ASMs from $393 ($246-$570) in 2006 to $665 ($335-$1,308) in 2021, but decreased by 37% for generic ASMs from $147 ($98-$213) in 2006 to $92 ($51-$141) in 2021. The median cost of ASMs per person-year approximately doubled from 2006 to 2021. The increase in use of generic ASMs probably helped buffer the growing costs of ASMs. However, generic ASMs already represent 83% of prescription days in 2021, with limited room to further contain costs by just increasing the proportion of generics.

The impact of epilepsy and antiseizure medications on pregnancy and neonatal outcomes: A nationwide cohort study.

Our objective was to assess the adverse outcomes during pregnancy, as well as for the fetus and neonates, in women with epilepsy, both with and without the use of antiseizure medications (ASMs). A cohort of singleton pregnancies between January 1, 2004 and December 31, 2014 was identified using the Taiwan National Health Database. The pregnancies were categorized into ASM exposure, ASM nonexposure, and control (consisting of women without an epilepsy diagnosis) groups. We recorded adverse outcomes in neonates and documented pregnancy complications. The generalized estimating equation with logit link was used to estimate adjusted odds ratios. There were 629 singleton pregnancies in the group exposed to ASMs, 771 in the epilepsy group without ASM exposure, and 2,004,479 in the control group. Women with epilepsy had a significantly higher risk of puerperal cerebrovascular diseases (adjusted odds ratios in the exposure and nonexposure groups=54.46 and 20.37, respectively), respiratory distress syndrome (5.1 and 2.99), mortality (3.15 and 3.22), sepsis (2.67 and 2.54), pregnancy-related hypertension (1.71 and 1.8), preeclampsia (1.87 and 1.79), cesarean delivery (1.72 and 2.15), and preterm labor (1.38 and 1.56). The use of ASMs may increase the risk of eclampsia (adjusted odds ratio=12.27). Compared to controls, fetuses/neonates born to women with epilepsy had a higher risk of unexplained stillbirth (adjusted odds ratios in the exposure and nonexposure groups=2.51 and 2.37, respectively), congenital anomaly (1.37 and 1.33), central nervous system malformation (3.57 and 2.25), low birth weight (1.90 and 1.97), and a low Apgar score at 5 min (2.63 and 1.3). The use of ASMs may introduce an additional risk of small for gestational age; the adjusted odds ratio was 1.51. Women with epilepsy, irrespective of their exposure to ASMs, had a slightly elevated risk of pregnancy and perinatal complications. Puerperal cerebrovascular diseases may be a hidden risk for women with epilepsy.

Treatment of electrographic seizures versus clinical seizures in neonates: A systematic review and meta-analysis

IntroductionElectrographic seizures in neonates are commonly associated with poor neurodevelopmental outcomes. However, there is conflict in evidence whether control of electrographic seizures translate into improved neurodevelopmental outcome. We aimed to evaluate whether treating all electrographic seizures compared with treating clinical seizures leads to a better neurodevelopmental outcome at 18–24 months in neonates. MethodsWe searched four electronic databases (Medline, Cochrane Library, Embase, and Web of Science) for randomized controlled trials (RCTs) published until October 31, 2022. We included RCTs comparing the treatment of electrographic seizures with clinical seizures in neonates with or at risk of seizures. The Risk of Bias version 2 tool was used to assess the risk of bias. The random-effects meta-analysis was performed using RevMan 5.4 software. ResultsOf the 2872 unique records identified by the database search, five trials involving 474 infants were eligible for the review. There was no significant difference in the incidence of neurodevelopmental disability at 18–24 months. Infants in the electrographic seizure group had lower scores in the cognitive domain (2 trials, 186 participants, MD: −5.4; 95% CI:−10.3 to −0.4, I2-0%). There were no significant differences in scores in the motor and language domains, mortality, seizure burden, brain injury scores, antiseizure medication use, and post-neonatal epilepsy. ConclusionsHaving limitations of small number of trials and heterogeneity, the systematic review does not identify evidence demonstrating improved neurodevelopmental outcomes or improved survival in neonates treated for electrographic seizures versus clinical seizures.

Bone health in children with Angelman syndrome at the ENCORE Expertise Center

Angelman syndrome (AS) is a rare genetic disorder due to lack of UBE3A function on chromosome 15q11.2q13 caused by a deletion, uniparental paternal disomy (UPD), imprinting center disorder (ICD), or pathological variant of the UBE3A gene. AS is characterized by developmental delay, epilepsy, and lack of speech. Although fractures are observed frequently in our clinical practice, there are few studies on bone health in AS. The aim of this study is to investigate bone health in children with AS. In this prospective cohort study, we describe bone health in 91 children with AS visiting the ENCORE Expertise Center for AS between April 2010 and December 2021. Bone health was assessed with the bone health index (BHI) in standard deviation score (SDS) measured by digital radiogrammetry of the left hand using BoneXpert software. Risk factors analyzed were age, sex, genetic subtype, epilepsy, anti-seizure medication use, mobility, body mass index (BMI), and onset of puberty. Children with AS had a mean BHI of −1.77 SDS (SD 1.4). A significantly lower BHI was found in children with a deletion (−2.24 SDS) versus non-deletion (−1.02 SDS). Other factors associated with reduced BHI-SDS were inability to walk and late onset of puberty. Children with a history of one or more fractures (22%) had a significantly lower BHI than children without fractures (−2.60 vs −1.56 SDS). Longitudinal analysis showed a significant decrease in BHI-SDS with age in all genetic subtypes. Conclusions: Children with AS have a reduced bone health. Risk factors are deletion genotype, no independent walking, and late onset of puberty. Bone health decreased significantly with age.What is Known:• Children with neurological disorders often have a low bone health and higher risk of fractures.• Little is known about bone health in children with Angelman syndrome (AS).What is New:• Children with AS showed a reduced bone health and this was significantly associated with having a deletion, not being able to walk independently, and late onset of puberty.• Longitudinal analysis showed a significant decrease in bone health as children got older.

Long-term antiseizure medication use in patients after meningioma resection: identifying predictors for successful weaning and failures.

To define risk factors for meningioma-related seizures and predictors of successful weaning of antiseizure medications following meningioma resection. This is a retrospective study of 95 patients who underwent meningioma resection at a single institution. Primary outcome analyzed was ability to achieve seizure freedom without the use of anti-seizure medication at 6-months, 1-year, and last known follow up. Secondary outcome was postoperative seizure freedom. Preoperative seizures (OR: 11.63, 95% CI [3.64, 37.17], p < 0.0001), non-skull base tumor location (OR: 3.01, 95% CI [1.29, 7.02], p = 0.0128), and modified STAMPE score of 3-5 (OR: 5.42, 95% CI [2.18, 13.52], p = 0.0003) were associated with greater likelihood of remaining on antiseizure medication at 6-month follow up. Preoperative seizures (OR: 4.93, 95% CI: [2.00, 12.16 ], p = 0.0008), intratumoral calcifications (OR: 4.19, 95% CI: [1.61, 14.46], p = 0.0055), modified STAMPE score of 3-5 (OR: 5.42, CI [2.18, 13.52], p = 0.0003), and Ki67 greater than 7% (OR: 5.68, CI [1.61, 20.10], p = 0.0060) were significant risk factors for inability to discontinue ASMs by last follow up. Preoperative seizures (OR: 4.33, 95% CI [1.59, 11.85], p = 0.0050) and modified STAMPE score of 3-5 (OR: 6.09, 95% CI [2.16, 17.20], p = 0.0007) were significant risk factors for postoperative seizures. Preoperative seizures, modified STAMPE2 score of 3-5, non-skull base tumor location, intratumoral calcifications, and Ki67 > 7% were significant risk factors for inability to achieve seizure freedom without ASMs. In addition, the modified STAMPE2 score successfully predicted increased seizure risk following meningioma resection for patients with a score of 3 or higher.

Sinus vein thrombosis and epileptic seizures: outcomes of long term follow-up

Purpose: In the acute phase of Cerebral Venous Sinus Thrombosis (CVST), approximately 35-50 % of patients diagnosed epileptic seizures. This study aimed to investigate the demographic and clinical characteristics, frequency of seizures, prognosis of patients during a one-year follow-up period.&#x0D; Materials and Methods: The files of patients who were followed up with the diagnosis of acute ischemic stroke between January 1, 2018 and January 1, 2022 were evaluated in this retrospective study. Demographic features, presence of seizure history and seizure frequency, neuroimaging findings, affected cerebral venous sinuses, and anti-seizure medication use were recorded.&#x0D; Results: A total of 701 patients with acute stroke had their medical records reviewed. Thirty-two of 701 patients (4.56 %) were diagnosed with CVST; 37.5 % of patients experienced early-onset seizures. Seizure control was achieved with monotherapy in 88.8 % (n:8) of patients with seizures. Involved sinuses in patients with seizures; 50 % (n=6) superior sagittal sinus was the most commonly involved sinus and inferior sagittal sinus and sinus rectus were not involved. In terms of sinus involvement, there was no statistically significant difference between patients with and without seizures. On cerebral magnetic resonance imaging, venous infarcts were detected in 66.7 % (n=8) of patients with seizures, compared to 35 % of patients without seizures.&#x0D; Conclusion: This retrospective study revealed that seizures typically occur early in the disease, have a favorable prognosis over the long term, and can be managed with monotherapy.

An audit of prescribing pattern of anti-epileptic drugs with its effect on therapeutic drug levels and seizure control at a tertiary care public hospital.

The study objective was to evaluate the prescription pattern and use of anti-seizure medications (ASMs) in patients with a seizure disorder and to evaluate if a change in the ASM dose had a beneficial effect on seizure control, observed through Therapeutic Drug Monitoring [TDM] level of ASMs. Details of anti-seizure medications with their therapeutic levels in the blood of patients with seizure disorder were analysed. Hospital-based retrospective analysis of patient case records. Therapeutic Drug Monitoring OPD of a tertiary care public teaching hospital. Case records of 918 patients with seizure disorder from 2016-2021. Data of men (53%) and women (47%) aged between 18-75 years was assessed About 62% (566/918) of patients were on levetiracetam, the most frequently prescribed anti-seizure medication. Whenever the ASMs dose was increased or decreased based on TDM levels, it was associated with a significant increase in the frequency of break-through seizures [OR- 5 (95% CI: 1.28-19.46)]. However, significant seizure control was observed when the patients were on the same maintenance dose of the anti-seizure medication [OR- 0.2 (95% CI: 0.06-0.63)]. Whenever an additional new anti-epileptic drug was prescribed or removed from the pre-existing anti-epileptic medications, it did not significantly impact seizure control. Individualising drug therapy and therapeutic drug monitoring for each patient, along with patient factors such as medication compliance, concomitant drug and disease history, and pharmacogenetic assessment, should be the ideal practice in patients with seizures for better seizure control. None declared.

Prognosis and management of acute symptomatic seizures: a prospective, multicenter, observational study

BackgroundAcute symptomatic epileptic seizures are frequently seen in neurocritical care. To prevent subsequent unprovoked seizures, long-term treatments with antiseizure medications are often initiated although supporting evidence is lacking. This study aimed at prospectively assessing the risk of unprovoked seizure relapse with respect to the use of antiseizure medications. It was hypothesized that after a first acute symptomatic seizure of structural etiology, the cumulative 12-month risk of unprovoked seizure relapse is ≤ 25%.MethodsInclusion criteria were age ≥ 18 and acute symptomatic first-ever epileptic seizure; patients with status epilepticus were excluded. Using telephone and mail interviews, participants were followed for 12 months after the acute symptomatic first seizure. Primary endpoint was the occurrence and timing of a first unprovoked seizure relapse. In addition, neuro-intensivists in Germany were interviewed about their antiseizure treatment strategies through an anonymous online survey.ResultsEleven of 122 participants with structural etiology had an unprovoked seizure relapse, resulting in a cumulative 12-month risk of 10.7% (95%CI, 4.7%–16.7%). None of 19 participants with a non-structural etiology had a subsequent unprovoked seizure. Compared to structural etiology alone, combined infectious and structural etiology was independently associated with unprovoked seizure relapse (OR 11.1; 95%CI, 1.8–69.7). Median duration of antiseizure treatment was 3.4 months (IQR 0–9.3). Seven out of 11 participants had their unprovoked seizure relapse while taking antiseizure medication; longer treatment durations were not associated with decreased risk of unprovoked seizure relapse. Following the non-representative online survey, most neuro-intensivists consider 3 months or less of antiseizure medication to be adequate.ConclusionsEven in case of structural etiology, acute symptomatic seizures bear a low risk of subsequent unprovoked seizures. There is still no evidence favoring long-term treatments with antiseizure medications. Hence, individual constellations with an increased risk of unprovoked seizure relapse should be identified, such as central nervous system infections causing structural brain damage. However, in the absence of high-risk features, antiseizure medications should be discontinued early to avoid overtreatment.