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Background and purpose: Sodium channel blockers (SCBs) have traditionally been utilized as anti‐seizure medications by primarily targeting the inactivation process. In a drug discovery project aiming at finding potential anticonvulsants, we have identified arbidol, originally an antiviral drug, as a potent SCB. In order to evaluate its anticonvulsant potential, we have thoroughly examined its biophysical properties as well as its effects on animal seizure models. Experimental approach: Patch clamp recording was used to investigate the electrophysiological properties of arbidol, as well as the binding and unbinding kinetics of arbidol, carbamazepine and lacosamide. Furthermore, we evaluated the anticonvulsant effects of arbidol using three different seizure models in male mice. Key results: Arbidol effectively suppressed neuronal epileptiform activity by blocking sodium channels. Arbidol demonstrated a distinct mode of action by interacting with both the fast and slow inactivation of Nav1.2 channels compared with carbamazepine and lacosamide. A kinetic study suggested that the binding and unbinding rates might be associated with the specific characteristics of these three drugs. Arbidol targeted the classical binding site of local anaesthetics, effectively inhibited the gain‐of‐function effects of Nav1.2 epileptic mutations and exhibited varying degrees of anticonvulsant effects in the maximal electroshock model and subcutaneous pentylenetetrazol model but had no effect in the pilocarpine‐induced status epilepticus model. Conclusions and implications: Arbidol shows promising potential as an anticonvulsant agent, providing a unique mode of action that sets it apart from existing SCBs. [ABSTRACT FROM AUTHOR]

Carbamazepine (CBZ) use has been limited by multiple adverse reactions. Lacosamide (LCM) is a functional amino acid anti‐seizure medication (ASM), approved for focal seizure patients more than 4 years old. It is non‐inferior in terms of efficacy to controlled release CBZ and was proven to have better tolerability. This study examines the effect of abruptly changing CBZ to LCM in epilepsy patients with elevated gamma‐glutamyl transpeptidase (GGT). Consenting adult patients aged 18 years old and above, with controlled focal seizure disorder for more than 2 years, who were consistently taking CBZ and who had elevated GGT were included in this study. Out of 1526 patients screened, only 12 satisfied the inclusion criteria. After abruptly changing CBZ to LCM, the GGT level significantly dropped from a median of 141.5 to 63.5 IU/L (z = 3.06, p = 0.0005). Moreover, there was significantly lower proportion of patients with abnormal GGT levels after the switch in medications was done (100% vs. 66.7%, McNemar χ2 = 8, p = 0.008). Moderate to high levels of GGT in patients with focal epilepsy can be decreased by changing CBZ to LCM. Moreover, abruptly changing CBZ to LCM without cross‐titration may be safe and effective in preventing seizure incidence within a 1‐month period. Plain Language Summary: Although carbamazepine (CBZ) is the standard drug for focal seizures, its numerous side effects, especially in the liver, limits its use in a lot of patients with epilepsy. Gamma‐glutamyl transferase (GGT), which is elevated in liver disease of whatever cause including intake of CBZ, is associated with increased mortality. In this study, we found that abruptly changing CBZ to Lacosamide (LCM) can significantly decrease the GGT level in 1 month without apparent increase in seizure recurrence and side effects. Therefore, we conclude that high levels of GGT may be decreased by abruptly changing CBZ to LCM. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is a chronic neurological condition requiring effective management with minimal adverse effects. Lacosamide (LCM) and Perampanel (PER), two promising treatments, have distinct profiles that merit comparative analysis to guide clinical decision-making. Methods: This study utilizes a pharmacovigilance analysis of adverse events reported in the FDA Adverse Event Reporting System database from Q1 2009 to Q3 2023. Employing disproportionality and Bayesian analyses, we assessed and compared the AE signals associated with LCM and PER to elucidate their safety profiles in epilepsy treatment. Results: The analysis included 12,576 AE reports for LCM and 2,703 for PER, highlighting a higher incidence of psychiatric disorders, including aggression with LCM, and a notable association of PER with psychiatric disorders such as psychotic disorders and dizziness. LCM showed a relatively safe profile during pregnancy, whereas PER's data suggested caution due to reported cases of suicidal ideation and attempts. Conclusion: This comprehensive evaluation underscores the importance of understanding the distinct AE profiles of LCM and PER in clinical practice, providing valuable insights for personalized epilepsy management. Future research with rigorous prospective designs is recommended to validate these findings and explore the mechanisms underlying the reported adverse events. [ABSTRACT FROM AUTHOR]

Background: The widespread clinical use of lacosamide (LCM) has revealed significant individual differences in clinical response, with various reported influencing factors. However, it remains unclear how genetic factors related to the disposition and clinical response of LCM, as well as drug–drug interactions (DDIs), exert their influence on pediatric patients with epilepsy. Objectives: To evaluate the impact of genetic variations and DDIs on plasma LCM concentrations and clinical response. Design: Patients with epilepsy treated with LCM from June 2021 to March 2023 in the Children's Hospital of Nanjing Medical University were included in the analysis. Methods: The demographic information and laboratory examination data were obtained from the hospital information system. For the pharmacogenetic study, the left-over blood specimens, collected for routine plasma LCM concentration monitoring, were used to perform genotyping analysis for the selected 26 single nucleotide polymorphisms from 14 genes. The trough concentration/daily dose (C 0/D) ratio and efficacy outcomes were compared. Results: Patients achieved 90.1% and 68.9% responder rates in LCM mono- and add-on therapy, respectively. The genetic variant in the CYP2C19 *2 (rs4244285) was associated with a better responsive treatment outcome (odds ratio: 1.82; 95% confidence interval: 1.05–3.15; p = 0.031). In monotherapy, 36% of patients were CYP2C19 normal metabolizers (NMs), 49% were intermediate metabolizers (IMs), and 15% were poor metabolizers (PMs) carrying CYP2C19 *2 or *3. Of note, the C 0/D ratios of IMs and PMs were 9.1% and 39.6% higher than those of NMs, respectively. Similar results were in the add-on therapy group, and we also observed a substantial decrease in the C 0/D ratio when patients were concomitant with sodium channel blockers (SCBs). Conclusion: This study was the first to confirm that CYP2C19 *2 or *3 variants impact the disposition and treatment response of LCM in children with epilepsy. Moreover, concomitant with SCBs, particularly oxcarbazepine, also decreased plasma LCM concentration. Plain language summary: CYP2C19 genotype and sodium channel blockers in lacosamide-treated children with epilepsy: two major determinants of plasma lacosamide concentration or treatment efficacy This study examined the impact of genetic factors and drug combinations on the effectiveness and plasma concentrations of lacosamide, an antiseizure medication, in patients under 18. Analyzing blood samples from 316 patients at the Children's Hospital of Nanjing Medical University, researchers discovered that genetic variations in the CYP2C19 (i.e. *2 and *3), along with metabolic capacity, and co-medication with sodium channel blockers, all influence plasma lacosamide concentration. Understanding these genetic influences could inform personalized dosing strategies, improving the medication's management for pediatric epilepsy patients. [ABSTRACT FROM AUTHOR]

Background: The goal of this study was to develop and validate a UPLC-MS/MS method for simultaneous measurement of 13 AEDs, including carbamazepine, oxcarbazepine, lamotrigine, levetiracetam, topiramate, primidone, zonisamide, gabapentin, lacosamide, perampanel, pregabalin, rufinamide, and vigabatrin, in whole blood samples. Methods: A UPLC-MS/MS method for simultaneous determination of 13 AEDs in whole blood was developed, and validation was conducted for accuracy, precision, limit of quantification (LOQ), matrix effect, and stability. Our method was compared to two different hospitals using UPLC-MS/MS. Results: All AEDs exhibited linearity across the AMR (analytical measurement range), with R² values ranging from 0.994 to 1.000. The imprecision and inaccuracy for low and high quality control (QC) levels were within an acceptable range, with the coefficient of variation (CV) < 15%. The LOQ was 0.62 μg/mL for carbamazepine, 1.61 μg/mL for oxcarbazepine, 1.30 μg/mL for lamotrigine, 13.20 μg/mL for levetiracetam, 1.26 μg/mL for topiramate, 1.01 μg/mL for primidone, 1.59 μg/mL for zonisamide, 1.09 μg/mL for lacosamide, 1.61 μg/mL for gabapentin, 0.50 μg/mL for pregabalin, 0.07 ng/mL for perampanel, 3.00 μg/mL for rufinamide, and 2.06 μg/mL for vigabatrin. All AEDs demonstrated acceptable assay parameters for carryover, stability, and matrix effects. Moreover, the assay showed satisfactory results compared to two different hospitals with a bias of less than 15%. Conclusions: We successfully developed and validated a fast and robust UPLC-MS/MS method for routine therapeutic drug monitoring of thirteen antiepileptic drugs simultaneously. [ABSTRACT FROM AUTHOR]

Abstract Carbamazepine (CBZ) use has been limited by multiple adverse reactions. Lacosamide (LCM) is a functional amino acid anti‐seizure medication (ASM), approved for focal seizure patients more than 4 years old. It is non‐inferior in terms of efficacy to controlled release CBZ and was proven to have better tolerability. This study examines the effect of abruptly changing CBZ to LCM in epilepsy patients with elevated gamma‐glutamyl transpeptidase (GGT). Consenting adult patients aged 18 years old and above, with controlled focal seizure disorder for more than 2 years, who were consistently taking CBZ and who had elevated GGT were included in this study. Out of 1526 patients screened, only 12 satisfied the inclusion criteria. After abruptly changing CBZ to LCM, the GGT level significantly dropped from a median of 141.5 to 63.5 IU/L (z = 3.06, p = 0.0005). Moreover, there was significantly lower proportion of patients with abnormal GGT levels after the switch in medications was done (100% vs. 66.7%, McNemar χ2 = 8, p = 0.008). Moderate to high levels of GGT in patients with focal epilepsy can be decreased by changing CBZ to LCM. Moreover, abruptly changing CBZ to LCM without cross‐titration may be safe and effective in preventing seizure incidence within a 1‐month period. Plain Language Summary Although carbamazepine (CBZ) is the standard drug for focal seizures, its numerous side effects, especially in the liver, limits its use in a lot of patients with epilepsy. Gamma‐glutamyl transferase (GGT), which is elevated in liver disease of whatever cause including intake of CBZ, is associated with increased mortality. In this study, we found that abruptly changing CBZ to Lacosamide (LCM) can significantly decrease the GGT level in 1 month without apparent increase in seizure recurrence and side effects. Therefore, we conclude that high levels of GGT may be decreased by abruptly changing CBZ to LCM.

Abstract Lacosamide was the first approved third-generation antiepileptic drug. However, real-world data regarding its adverse cardiac reactions in large samples still need to be completed. We evaluated the cardiac safety profile of lacosamide using the Food and Drug Administration Adverse Event Reporting System (FAERS). We performed disproportionality analysis computing reporting odds ratio (ROR) as a quantitative metric to assess the signal of lacosamide-related cardiac adverse events (AEs) from 2013 Q1 to 2022 Q4. The signal was considered significant when the lower limit of the 95% confidence interval (CI) of the ROR exceeded 1, and ≥ 5 AEs were reported. Serious and nonserious cases were compared by statistical analysis, and signals were further prioritized using a rating scale. A total of 812 cardiac AEs associated with lacosamide were identified, and 92 signals were detected, of which 17 AEs were significantly associated signals. The median time-to-onset (TTO) for moderate priority signals was 10 days, whereas for weak priority signals, it was 54 days. Notably, all cardiac AEs exhibited an early failing pattern, indicating the risk gradually decreasing. Based on the comprehensive analysis of the FAERS database and prioritization of cardiac AE signals, our research enhances the awareness among healthcare professionals regarding cardiac AEs associated with lacosamide.

Lacosamide (LCM) is a third-generation antiseizure medication (ASM) currently approved for the treatment of focal seizures in children aged greater than one month. There are limited data on its efficacy in the neonatal age group. We describe our experience with LCM as an adjunct ASM for the treatment of neonatal seizures. A retrospective chart review over a five-year period (2018 to 2022) was conducted at Le Bonheur Children's Hospital to identify neonates with electroencephalography (EEG)-proven seizures who were treated with LCM. Data were collected on electroclinical seizure characteristics, underlying etiology, ASMs, treatment response, and any adverse effects. A total of 15 neonates with EEG-confirmed seizures who were treated with LCM were included. Ten neonates achieved seizure cessation after LCM was added to their ASM regimen consisting of phenobarbital, levetiracetam, or both. No new treatment-related adverse effects were noted. LCM is effective as an adjunct treatment for neonatal seizures. Randomized controlled studies are needed to establish its effectiveness and adequate dosing regimen in this population. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the efficacy, safety, and tolerability of adjunctive lacosamide therapy against focal seizures in young children (1 month – 4 years). Methods: This non‐randomized, open‐label, and self‐controlled real‐world study included 105 children (1 month–4 years) with focal seizures treated with adjunctive lacosamide therapy at Children's Hospital of Chongqing Medical University. Results: (1) The 50% response rates at 3, 6, 9, and 12 months of follow‐up were 58.1%, 61.0%, 57.1%, and 56.2%, while the seizure‐free rates were 27.6%, 34.3%, 32.4%, and 37.1%, respectively. The 50% response rate of the first addition of lacosamide for focal seizures was much higher than the second and later added treatment at 3 months (p = 0.038). After 1 year of follow‐up, these children showed an improvement in neurodevelopmental levels (p < 0.05). (2) Lacosamide retention rate was 72.7% (64/88) after 1 year of follow‐up. Lack of efficacy and serious adverse events were independent risk factors for the lacosamide retention rate. (3) During adjunctive lacosamide therapy, 13 (12.4%) patients reported adverse events and five (4.7%) patients withdrew due to adverse events, including vomiting drowsiness, ataxia (0.94%), neck itching with eczema (0.94%), irritability (1.88%), and gastrointestinal discomfort (0.94%). Conclusion: Adjunctive lacosamide therapy was effective, safe, and well‐tolerated in young Chinese children with focal seizures in this study. [ABSTRACT FROM AUTHOR]

Trigeminal neuralgia is a rare condition that can be effectively treated by carbamazepine or oxcarbazepine but these older drugs are associated with dose-dependent and potentially treatment-limiting adverse effects. Third-generation anticonvulsants, new calcitonin gene-related peptide blockers for migraine, and older drugs such as ketamine and cannabinoids may be promising adjuvants or monotherapeutic options. The new drugs, their presumed mechanisms of action, safety and efficacy are discussed herein. There is a paucity of robust clinical evidence in support of these drugs for trigeminal neuralgia. New migraine agents are considered as well although migraines and trigeminal neuralgia are distinct, albeit similar, conditions. No new drugs have been released to market in recent years with the specific indication of trigeminal neuralgia. In real-world clinical practice, about half of trigeminal neuralgia patients take more than one agent for prevention and combination therapy may be the optimal approach. Combination therapy might allow for lower doses of carbamazepine or oxcarbazepine, thus reducing the number and severity of potential adverse events but the potential for pharmacokinetic drug-drug interactions must be considered. Drug therapy for trigeminal neuralgia involves acute or abortive treatments, often administered in hospital versus long-term preventive therapy, usually involving oral agents. Trigeminal neuralgia is a relatively rare condition that usually affects one side of the face below the eye around the cheekbone. The cause of trigeminal neuralgia is sometimes a damaged nerve or a nerve that has lost part of its outer protective sheath (myelin). However, trigeminal neuralgia may have other neurological causes as well. Pain can be triggered by touch, pressure, or chewing and it tends to occur in very painful brief attacks followed by pauses with little or no pain. There are two types of drug treatment for trigeminal neuralgia: drugs to stop an ongoing attack (which are often administered in an emergency room or hospital intravenously) and drugs that are taken orally over the long term to reduce or prevent attacks. The two most effective drugs for trigeminal neuralgia are carbamazepine and oxcarbazepine, which are actually drugs to prevent seizures. They are effective in reducing the pain intensity and number of attacks of trigeminal neuralgia but they have side effects. In fact, these side effects can be so severe that people stop taking the drugs. Many new drugs have come to market recently that may work for trigeminal neuralgia, although none was specifically developed for this use. The newest generation of anti-seizure medications including eslicarbazepine, lacosamide, levetiracetam, and retigabine, may be just as effective as the older carbamazepine and oxcarbazepine drugs with fewer side effects. Clinical studies are needed to test them in trigeminal neuralgia patients but their mechanisms of action suggest that they might work well. There are some new drugs developed for migraine headache that inhibit a substance in the body called CGRP. Migraine headaches and trigeminal neuralgia have some of the same symptoms but they are different conditions but both involve too much CGRP. Other new drugs include lasmiditan, pimozide (used for Tourette syndrome), tizanidine (muscle relaxant), lamotrigine and vixotrigine (anti-seizure drugs) may also be beneficial. It may be that people with trigeminal neuralgia will have to take combination therapy, the use of two or more drugs with different mechanisms of action. Older drugs like ketamine and cannabinoids are also being considered as possible add-on agents for therapy for trigeminal neuralgia. [ABSTRACT FROM AUTHOR]

Lacosamide was the first approved third-generation antiepileptic drug. However, real-world data regarding its adverse cardiac reactions in large samples still need to be completed. We evaluated the cardiac safety profile of lacosamide using the Food and Drug Administration Adverse Event Reporting System (FAERS). We performed disproportionality analysis computing reporting odds ratio (ROR) as a quantitative metric to assess the signal of lacosamide-related cardiac adverse events (AEs) from 2013 Q1 to 2022 Q4. The signal was considered significant when the lower limit of the 95% confidence interval (CI) of the ROR exceeded 1, and ≥ 5 AEs were reported. Serious and nonserious cases were compared by statistical analysis, and signals were further prioritized using a rating scale. A total of 812 cardiac AEs associated with lacosamide were identified, and 92 signals were detected, of which 17 AEs were significantly associated signals. The median time-to-onset (TTO) for moderate priority signals was 10 days, whereas for weak priority signals, it was 54 days. Notably, all cardiac AEs exhibited an early failing pattern, indicating the risk gradually decreasing. Based on the comprehensive analysis of the FAERS database and prioritization of cardiac AE signals, our research enhances the awareness among healthcare professionals regarding cardiac AEs associated with lacosamide. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate age, adjunctive antiseizure medication (ASM), and specific ASMs on lacosamide (LCM) weight normalized dose-to-concentration ratio (DCR) and US Food and Drug Administration (FDA) dosing guidelines in pediatric patients. METHODS Patients 1 mo to ≤18 years with a LCM serum concentration between October 2009 and June 2017 were considered. Demographics, LCM DCR, and adjunctive ASM were recorded. LCM DCR/hr was used as a surrogate for clearance. Data were stratified by age (1 mo-< 2 yr; ≥ 2–6 yr; ≥ 6–12 yr; and ≥12–≤18 yr), FDA dosing weights, and ASM potential to interaction with LCM. RESULTS There were 646 sera (380 patients) with median dose 8.36 mg/kg/day (IQR, 5.92–11.16). 50.2% of doses were within FDA-weight guidelines; however, 40.4% exceeded recommendations. Most (81.3%) LCM concentrations were between 2 and 12 mg/L. A difference existed in DCR between ages, with those <2 years having the highest DCR (p < 0.001). Moving across age groups, the DCR decreases by 30.7%, 50.5%, and 63.4%. There was a weak (r2 = 0.073) but significant (p < 0.001) negative correlation between DCR and age. 84.8% received adjunctive ASM consisting of at least one of 31 different ASMs. DCR was higher with adjunctive ASMs compared with monotherapy [0.061 (0.039–0.095) vs 0.043 (0.030–0.062)], respectively (p < 0.001) and was greatest with inducers. Phenobarbital increased DCR by 2.6-fold, topiramate by 72.1%, and clobazam by 32.6%. Inhibitors had no effect. CONCLUSIONS The correlation between age and DCR was weak, accounting for 6% of variability. Strong inducers significantly increased DCR. Synergy may exist when multiple inducers are given. Weak inhibitors did not affect DCR. Those ≥6 to 11 kg, ≥30 to 50 kg, and those given strong inducers may require larger initial LCM doses. Serum concentrations should be used to individualize dosing, especially in those receiving strong inducers. [ABSTRACT FROM AUTHOR]

There is growing evidence supporting the safety and effectiveness of lacosamide in older children. However, minimal data are available for neonates. We aimed to determine the incidence of adverse events associated with lacosamide use and explore the electroencephalographic seizure response to lacosamide in neonates. A retrospective cohort study was conducted using data from seven pediatric hospitals from January 2009 to February 2020. For safety outcomes, neonates were followed for ≤30 days from index date. Electroencephalographic response of lacosamide was evaluated based on electroencephalographic reports for ≤3 days. Among 47 neonates, 98% received the first lacosamide dose in the intensive care units. During the median follow-up of 12 days, 19% of neonates died, and the crude incidence rate per 1000 patient-days (95% confidence interval) of the adverse events by diagnostic categories ranged from 2.8 (0.3, 10.2) for blood or lymphatic system disorders and nervous system disorders to 10.5 (4.2, 21.6) for cardiac disorders. Electroencephalographic seizures were observed in 31 of 34 patients with available electroencephalographic data on the index date. There was seizure improvement in 29% of neonates on day 1 and also in 29% of neonates on day 2. On day 3, there was no change in 50% of neonates and unknown change in 50% of neonates. The results are reassuring regarding the safety of lacosamide in neonates. Although some neonates had fewer seizures after lacosamide administration, the lack of a comparator arm and reliance on qualitative statements in electroencephalographic reports limit the preliminary efficacy results. [ABSTRACT FROM AUTHOR]

Lacosamide, a voltage‐gated sodium channel inhibitor, is an anti‐seizure medication (ASM) from the age of 4. We report on the case of a woman treated with lacosamide for pharmacoresistant epilepsy who breastfed her infant for more than 6 months after birth. The infant's blood concentrations of lacosamide were 2.4 mg/L on Day 1 and less than 1 mg/L on Day 10 (reference values are 1–10 mg/L). No adverse drug reactions (ADRs) were reported for the infant. Eight cases of breastfeeding by mothers receiving lacosamide are described in the literature. These data confirm that a significant amount of lacosamide seems to pass into breast milk, with a relative infant dose (RID) above 20% in two cases but a low RID (1.8%) in another case. Nevertheless, blood tests, performed in two breastfed infants, revealed low concentrations of lacosamide. No ADRs were reported in eight of the breastfed infants; however, one infant, whose mother was also treated with levetiracetam, presented poor feeding and sleepiness at Day 15 of life. Given the well‐known benefits of breastfeeding for both mothers and their infants, as well as the above reassuring data, breastfeeding of healthy full‐term infants could be possible for mothers on lacosamide monotherapy. Nonetheless, relatives should be warned that data concerning the safety of lacosamide during breastfeeding are scarce and that long‐term neurodevelopment outcomes in breastfed children are unknown. Clinical monitoring of breastfed infants for drowsiness, adequate weight gain, or cutaneous rash is recommended. Additionally, the infants' serum levels should be measured in case of an unexplained adverse reaction. [ABSTRACT FROM AUTHOR]

Ring chromosome 20 syndrome is a rare genetic disorder characterized by non-convulsive status epilepticus (NCSE) attacks, leading to prolonged confusional states of varying intensity. It is often accompanied by electroencephalography (EEG) changes, such as long-lasting slow waves and occasional spikes, primarily over the frontal lobes, as well as focal seizures with visual hallucinations, cognitive impairment, and behavioral problems. Although clinical suspicion, typical EEG abnormalities, and network disorders revealed by functional neuroimaging method aid in diagnosis, karyotyping remains essential. Seizures are typically drug-resistant although some limited success has been reported with certain anti-seizure drugs. In this report, we present the case of a patient with previously frequent drug-resistant NCSE periods characterized by prolonged confusional states and frightening visual hallucinations. Treatment with lacosamide partially decreased the frequency of seizures. In addition, positron emission tomography/computed tomography (PET/CT) imaging revealed hypometabolism in the frontal and parietal regions of the brain. In patients with drug-resistant and early frightening hallucinations, consideration of the ring 20 chromosome anomaly is crucial. PET/CT imaging may demonstrate hypometabolism in the parietal and frontal lobes, potentially associated with the hallucinations and epileptogenesis of the syndrome. Lacosamide may be a viable option for reducing seizures in Ring chromosome 20 syndrome.

Jun Feng, Liya Zhang, Jihong Tang, Bingbing Zhang, Xiao Xiao, Xiaoyan Shi Department of Neurology, Children’s Hospital of Soochow University, Suzhou, Jiangsu, 215025, People’s Republic of ChinaCorrespondence: Liya Zhang; Jihong Tang, Email zhliyasz@163.com; tjhsuzhou@163.comObjective: To evaluate the efficacy and safety of lacosamide (LCM) monotherapy in the treatment of self-limited epilepsy with centrotemporal spikes (SeLECTS).Methods: In this study, 89 children with SeLECTS who were treated with LCM monotherapy in the Children’s Hospital Affiliated to Soochow University from June 2019 to June 2021 were included. Clinical seizures and spike wave index (SWI) on video EEG during slow-wave sleep were evaluated before and after treatment. The role of LCM monotherapy in improving SWI, controlling clinical seizures and improving cognition was analyzed, and corresponding adverse reactions were documented.Results: There were 52 males and 37 females in this group, with an average age of 7.6 ± 2.1 years. The total effective rate was 93.83% and at 18 months of treatment, the cumulative control rate was 85.19%, the retention rate was 91.01% and the effective rate in terms of EEG spike index was 72.92%, all of which showed a high rate; there was no statistically significant difference in intelligence quotient before and after treatment (P > 0.05). In addition, it was found in the study that the earlier the age of onset, the less obvious the improvement in SWI after LCM treatment; the lower the baseline seizure frequency, the more significant the improvement in SWI after LCM treatment.Conclusion: LCM monotherapy had curative effect and adverse reactions for SeLECTS, with no negative impact on cognition. These significant findings indicate that LCM is likely to become a widely prescribed ASM for the treatment of SeLECTS. Meanwhile, the onset age and baseline seizure frequency had certain value in judging prognosis and predicting curative effect.Keywords: lacosamide, epilepsy, self-limited epilepsy with centrotemporal spikes, efficacy, safety

• Lacosamide was effective in patients with epilepsy aged 1 month to 4 years. • There were no unexpected safety concerns. • A lower baseline seizure frequency was associated with a higher retention rate. • Younger age group in monotherapy group was associated with a higher retention rate. Lacosamide (LCM) has shown promising efficacy and safety outcomes in clinical trials. However, the evidence is limited among pediatric patients especially under four years in real-world. The study investigated the treatment outcomes and safety of LCM in patients under four years based on the data of the epilepsy registry of Children in China. A prospective cohort study was conducted among patients under 4 years who newly received LCM as monotherapy or adjunctive therapy. The treatment outcomes were measured by retention rate of LCM, 50 % response rates and seizure-free rates during follow-up. The retention rate of LCM was assessed using the Kaplan-Meier survival model. Adverse events were reported as a percentage of all participants. Of 109 participants (mean follow-up: 18.6 months), 59 received LCM as monotherapy and 50 as adjunctive therapy. Sixty patients had focal epilepsy, 44 had generalized epilepsy and 5 had combined generalized and focal epilepsy. 70 % of patients in the monotherapy group and 41 % in the adjunctive therapy group remained on LCM treatment without additional treatments for at least one year. In patients with monotherapy, 50 % response rate and seizure-free rate were 75 % and 56 % at 12 months, respectively. In adjunctive therapy group, these rates were 51 % and 36 %, respectively. Lower baseline seizure frequency in both treatment groups (monotherapy: p < 0.001; adjunctive therapy: p = 0.02) and younger age groups within the monotherapy group (P = 0.04) correlated with a higher LCM retention rate. Adverse events were reported by 15 patients (13.8 %), with somnolence being the most common (7 of 15 patients). With a comprehensive information and high-quality of data, the study demonstrates the effective treatment outcome and safety of LCM. The study adds reliable evidence to exiting real-word evidence of LCM in the specific age group of patients with epilepsy to fill the evidence gap. [ABSTRACT FROM AUTHOR]

• This is the first study that assessed rash induced by lacosamide in children. • This is the first report of lacosamide-induced rash in Mainland China. • Lacosamide-induced rashes are potentially serious. • We reviewed the 13 cases of lacosamide-induced rash that have been reported to date. To draw clinical attention to rashes caused by lacosamide. This retrospective analysis included patients admitted to the Department of Pediatrics, Second Affiliated Hospital of Xi'an Jiaotong University between January 2021 and September 2023. We focused on patients who developed rashes after lacosamide treatment and analyzed all patients who exhibited rashes after lacosamide treatment to analyze the risk factors. In total, 190 patients received lacosamide, of whom four developed allergies (2.1 %). Three patients had severe rashes, and two patients had high fever. All of these adverse events improved after the withdrawal of lacosamide. Of the 13 patients reported to date, including the four patients in this study, eight used various antiseizure medicines, including seven patients who used four or more antiseizure medicines. Four patients underwent testing for HLA-B*1502, and two patients were positive. Patients developed rashes within 1–10 days after treatment initiation, and the duration of the rash ranged 2–37 days. Lacosamide-induced rash was detected in 2.1 % of patients in our cohort. Rashes are potentially serious, and prompt evaluation is required. Rashes are more likely to occur when multiple antiseizure medicines are used simultaneously, typically within 10 days of treatment initiation. [ABSTRACT FROM AUTHOR]

Objective: This meta-analysis aimed to assess the effectiveness and safety of novel antiepileptic drugs (AEDs) in treating epilepsy in patients with brain tumors (BTRE). Methods: A search was conducted on PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to February 2023, with English language restriction. Results: In this meta-analysis, 18 clinical trials involving 755 BTRE patients were included to assess the efficacy and safety of novel AEDs in BTRE treatment. At the last follow-up, a =50% reduction in seizure frequency was experienced by 72% of patients (random-effects model, 95% CI = 0.64-0.78) using novel AEDs. At the last follow-up, seizure freedom was experienced by 34% of patients (random-effects model, 95% CI = 0.28-0.41) using novel AEDs. The pooled incidence of AEs was found to be 19% (95% CI: 13%-26%), with a withdrawal rate due to adverse effects of only 3%. Comparable efficacy and incidence of adverse effects were observed between lacosamide and perampanel. Conclusion: This meta-analysis suggests that novel antiepileptic drugs are deemed effective for seizure control in brain tumor patients, particularly when used as adjunctive therapy. Although lacosamide and perampanel received more focus in studies, no significant difference was observed in the efficacy and adverse reactions of these two drugs in seizure control. Further randomized controlled trials are deemed necessary to validate our findings. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine whether clinical efficacy and reported adverse effects (AEs) of the newer antiseizure medications (ASMs) brivaracetam (BRV), lacosamide (LCM), and perampanel (PER) have been associated with plasma levels of these ASMs. We also investigated whether plasma levels outside the reference range has led to dose adjustments. Methods: Plasma levels of 300 people with epilepsy (PWE) seen at our tertiary epilepsy center were determined by liquid chromatography–tandem mass spectrometry. PWE received BRV (n = 100), LCM (n = 100), or PER (n = 100), in most cases in polytherapy. Demographic and clinical data were retrospectively analyzed and related to plasma levels. Clinical efficacy of BRV, LCM, or PER was assessed retrospectively by comparing seizure frequency at the time of current blood draw with seizure frequency at the time of first administration. AEs were also recorded and, if reported, compared retrospectively with the time of first administration. Results: No significant associations were found between plasma levels of BRV, LCM, or PER and seizure freedom (BRV, p = 1.000; LCM, p =.243; PER, p =.113) or responder status (BRV, p =.118; LCM, p =.478; PER, p =.069) at presentation. There was also no pattern between plasma levels and the occurrence of AEs. In the majority of cases, drug levels outside the reference ranges have not led to adjustments in the daily doses of BRV (93.5%), LCM (93.9%), or PER (89.1%). Significance: Plasma levels at a given time point did not allow conclusions to be drawn about seizure control or the occurrence of AEs. Our findings indicate that efficacy and tolerability cannot be predicted based on averaged data from a single plasma measurement due to high interindividual variability. Instead, individual reference values should be established when sufficient clinical data are available, in line with the 2008 International League Against Epilepsy position paper on therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

Opinion statement: Seizure activity is common in patients with primary and metastatic brain tumors, affecting more than 50% of cases over the course of their disease. Several mechanisms contribute to brain tumor–related epilepsy (BTRE), including a pro-inflammatory environment, excessive secretion of glutamate and an increase in neuronal excitatory tone, reduction of GABAergic inhibitory activity, and an increase in 2-hydroxygluturate production in isocitrate dehydrogenase mutant tumors. After a verified seizure in a brain tumor patient, the consensus is that BTRE has developed, and it is necessary to initiate an antiepileptic drug (AED). It is not recommended to initiate AED prophylaxis. Second- and third-generation AEDs are the preferred options for initiation, due to a lack of hepatic enzyme induction and reduced likelihood for drug-drug interactions, especially in regard to neoplastic treatment. The efficacy of appropriate AEDs for patients with BTRE is fairly equivalent, although some data suggests that levetiracetam may be slightly more active in suppressing seizures than other AEDs. The consensus among most Neuro-Oncology providers is to initiate levetiracetam monotherapy after a first seizure in a brain tumor patient, as long as the patient does not have any psychiatric co-morbidities. If levetiracetam is not tolerated well or is ineffective, other appropriate initial AED options for monotherapy or as an add-on anticonvulsant include lacosamide, valproic acid, briviracetam, lamotrigine, and perampanel. [ABSTRACT FROM AUTHOR]

Aim of the study. To evaluate the safety of lacosamide (LCM) monotherapy during pregnancy and breastfeeding. Material and methods. Patients taking LCM monotherapy treated at the university epilepsy clinic were prospectively followed up during pregnancy, delivery, and breastfeeding. Data on seizure frequency, LCM dosage, pregnancy course, delivery and breastfeeding, birth outcome, congenital malformation, and development of newborns was collected. Material and methods. Patients taking LCM monotherapy treated at the university epilepsy clinic were prospectively followed up during pregnancy, delivery, and breastfeeding. Data on seizure frequency, LCM dosage, pregnancy course, delivery and breastfeeding, birth outcome, congenital malformation, and development of newborns was collected. Conclusions and clinical implications. This case series adds to a growing body of evidence suggesting the relative safety of LCM monotherapy throughout pregnancy and breastfeeding. [ABSTRACT FROM AUTHOR]

Rasmussen's encephalitis (RE) is a rare inflammatory neurological disease, characterized by frequent and severe seizures, loss of motor skills and speech, hemiparesis (weakness on one side of the body), encephalitis (inflammation of the brain), and dementia. It is characterized by refractory epilepsy and progressive atrophy of one cerebral hemisphere. Here, we report a successful anesthetic management of a child with RE scheduled for functional hemispherectomy. Keywords: Functional hemispherectomy, Rasmussen's encephalitis, refractory epilepsy, Author(s): Shalvi Mahajan [1]; Aparna Depuru [1]; Vinitha Narayan [1]; Kirandeep Kaur [1] Introduction Theodore Rasmussen, a neurosurgeon, and his co-workers in the late 1950s described bizarre seizure disorder with [...]