OBJECTIVE: Acute repetitive seizures and convulsive status epilepticus are common neurological emergencies in critically ill children. The aim of the study was to evaluate the effectiveness and safety of intravenous lacosamide in critically ill children with acute repetitive seizures and convulsive status epilepticus.
METHODS: This retrospective study included children who received intravenous lacosamide for acute repetitive seizures or convulsive status epilepticus from October 2017 to September 2022 and were admitted to the pediatric intensive care unit at a tertiary medical center. Children who were newly started on intravenous lacosamide were included and divided into two groups: (a) previously healthy, and (b) history of epilepsy and receiving antiseizure medications. Efficacy was defined as the cessation of seizures within 72 h of administering lacosamide. Adverse effects were defined using predefined criteria, and most were evaluated during the first 7 days.
RESULTS: Sixty-seven children were enrolled, including 25 (37.3%) girls and 42 (62.7%) boys with a mean age of 7.20 ± 5.66 years. Among them, 30 (44.8%) had acute repetitive seizures, and 37 (55.2%) had convulsive status epilepticus. The seizure types were focal onset (n = 34, 50.7%), generalized onset (n = 27, 40.3%), and mixed type (n = 6, 9.0%). In the previously healthy group, 9 patients had acute repetitive seizures and 23 had convulsive status epilepticus, and the rates of seizure cessation when lacosamide was used as the first to fourth choice of antiseizure medication were 100.0%, 85.7%, 40.0%, and 50.0%, respectively, compared to 73.7%, 54.5%, 100.0%, and 0.0% in the patients with epilepsy (21 had acute repetitive seizures and 14 had convulsive status epilepticus). Sixteen (23.9%) patients developed bradycardia and 1 (1.5%) patient developed a rash.
CONCLUSIONS: The early use of intravenous lacosamide was effective with acceptable side effects in treating acute repetitive seizures and convulsive status epilepticus in critically ill children, including young infants and children less than 4 years old and those with different etiologies.
CONCLUSIONS: Acute repetitive seizures and convulsive status epilepticus are common neurological emergencies in pediatric intensive care units (PICUs), traditional intravenous antiseizure medications (ASMs) include phenytoin, valproic acid, levetiracetam, and phenobarbital. In this study, we categorized patients based on their epilepsy history and different etiologies. We observed that early use of lacosamide, even in young infants, demonstrated good efficacy and safety.

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.

OBJECTIVE: 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%).
CONCLUSIONS: Adjunctive lacosamide therapy was effective, safe, and well-tolerated in young Chinese children with focal seizures in this study.

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CONCLUSIONS: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.
OBJECTIVE: Intravenous administration of the antiseizure medication lacosamide can be delayed given operational challenges related to short beyond-use-dating and controlled substance requirements. The purpose of this study was to describe the steps required to successfully transition from intravenous piggyback administration to intravenous push administration and demonstrate that workflow changes improved time to administration without compromising patient safety.
METHODS: This multicenter study had 2 components; the first portion was a prospective description of the implementation and operationalization process, while the second was a retrospective cohort analysis comparing patients who received intravenous piggyback and intravenous push lacosamide. After the transition, the default administration route for adult patients for lacosamide doses of 400 mg or less was intravenous push. While the primary objective was to describe the implementation process, secondary objectives included comparison of time to administration and safety, using a composite and incidence of PR prolongation.
RESULTS: Success in implementation and operationalization across a large health system was achieved by following a 6-month timeline. A total of 102 patients were included in the cohort study, with 869 individual administrations analyzed (519 intravenous piggyback and 350 intravenous push). Time from verification to administration was significantly decreased when comparing intravenous piggyback (median, 159 minutes) to intravenous push (median, 88 minutes) administrations (P = 0.008). No significant difference was found in the safety composite or PR prolongation.
CONCLUSIONS: Transitioning intravenous lacosamide administration from piggyback to push administration is feasible and decreases time from verification to administration without increased incidence of adverse effects.

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.

OBJECTIVE: 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.
METHODS: 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.
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: Arbidol shows promising potential as an anticonvulsant agent, providing a unique mode of action that sets it apart from existing SCBs.

The lithium-pilocarpine model is commonly used to recapitulate characteristics of human intractable focal epilepsy. In the current study, we explored the impact of topiramate (TPM) alone and in combination with pregabalin and lacosamide administration for 6 weeks on the evolution of spontaneous recurrent seizures (SRS) and disease-modifying potential on associated neuropsychiatric comorbidities. In addition, redox impairments and neurodegeneration in hippocampus regions vulnerable to temporal lobe epilepsy (TLE) were assessed by cresyl violet staining. Results revealed that acute electrophysiological (EEG) profiling of the ASD cocktail markedly halted sharp ictogenic spikes as well as altered dynamics of brain wave oscillations thus validating the need for polytherapy vs. monotherapy. In TLE animals, pharmacological intervention for 6 weeks with topiramate 10 mg/kg in combination with PREG and LAC at the dose of 20 mg/kg exhibited marked protection from SRS incidence, improved body weight, offensive aggression, anxiety-like behavior, cognitive impairments, and depressive-like behavior (p < 0.05). Moreover, combination therapy impeded redox impairments as evidenced by decreased MDA and AchE levels and increased activity of antioxidant SOD, GSH enzymes. Furthermore, polytherapy rescued animals from SE-induced neurodegeneration with increased neuronal density in CA1, CA3c, CA3ab, hilus, and granular cell layer (GCL) of the dentate gyrus. In conclusion, early polytherapy with topiramate in combination with pregabalin and lacosamide prompted synergy and prevented epileptogenesis with associated psychological and neuropathologic alterations.

BACKGROUND: Status epilepticus (SE) is potentially life-threatening, however, it is unclear which antiepileptic drugs (AEDs) should be used as second-line AEDs.
OBJECTIVE: We conducted a network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing multiple second-line AEDs for SE to investigate the efficacy of AEDs.
METHODS: We searched MEDLINE, CENTRAL, ClinicalTrials.gov, and World Health Organization International Clinical Trials Platform Search Portal and included RCTs for patients aged ≥15 years with SE on December 31, 2023. We compared multiple second-line AEDs for SE including fosphenytoin (fPHT), lacosamide (LCM), levetiracetam (LEV), phenytoin (PHT), phenobarbital (PHB), and valproate (VPA). The primary and secondly outcomes were termination of seizures integrating the absence of seizure recurrence at 30 min and 60 min, and adverse events associated with AEDs, respectively, with expressing as relative risk (RR) with a 95% confidence interval (CI). We conducted a NMA using frequentist-based approach with multivariate random effects, and assessed the certainty based on the Grading of Recommendations, Assessment, Development, and Evaluations framework.
RESULTS: Seven RCTs (n = 780) were included, and statistically significant difference was detected between VPA vs. PHB (RR, 0.67; 95% CI, 0.53-0.85; very low certainty), fPHT vs. PHB (RR, 0.66; 95% CI, 0.48-0.90; very low certainty), LCM vs. PHB (RR, 0.62; 95% CI, 0.41-0.93; very low certainty), and LEV vs. PHB (RR, 0.69; 95% CI, 0.51-0.94; very low certainty). Moreover, PHB was the highest in the ranking for termination of seizures. For adverse events, no significant reduction was observed owing to the selection of AEDs, although the ranking of PHB was the lowest.
CONCLUSIONS: PHB may have been the most effective for seizure termination as second-line AEDs in adult patients with SE. However, the certainty of almost all comparisons was \"very low\", and careful interpretation is essential.