Runamide, an ASM, is prescribed for treating epilepsy linked with Lennox– Gastaut syndrome and possesses a distinct structural composition compared with traditional ASDs. A presentation by Junaid Humayun etal. offered a succinct and illustrative overview of FDA-approved indications, pharmacodynamics, and phar­macokinetic properties. Additionally, this study shed light on the side effects, con­traindications, and dosing regimens of this drug while elucidating the practical aspects of the American Academy of Neurology guidelines regarding its efca­cious utilization in clinical settings [778]. Lennox–Gastaut syndrome (LGS) is a type of developmental and epileptic encephalopathy in which the initial symp­toms typically manifest in early childhood. Due to its highly variable underlying causes, LGS cannot be categorized as a singular disease; rather, it is considered an electroclinical entity often posing challenges in early diagnosis and tailored treat­ment. Runamide, an antiepileptic medication, is recommended as an adjunctive therapy for LGS patients aged ≥1year. Alexis Arzimanoglou etal. conducted a post hoc analysis to assess the safety and efcacy of adjuvant runamide treat­ment in the 022 study for total seizures and tetano-atonic seizures in children (<16years) and adults (≥16years). The randomized, placebo-controlled phase III 022 studies included LGS diagnosis and various seizure types (including tetano­atonic or standing inability seizures and atypical absence seizures; with ≥90 epi­sodes in the month preceding baseline). The evaluation criteria included monitoring adverse events during treatment (TEAEs), percentage change in tonic­atonic seizure frequency over 28days of the double-blind phase relative to base­line (primary endpoint), and the proportion of patients experiencing seizure frequency reduction of ≥25%, ≥50%, or ≥75% from baseline. Among the 138 enrolled patients, 74 received runamide (<16 years, n = 49 [66%]), and 64 received placebo (<16years, n=43 [67%]). The incidence of TEAEs was compa­rable across age groups. Both younger and older patients exhibited reduced

Lennox–Gastaut syndrome (LGS) poses a signicant challenge as a severe, chronic, and intricate form of early childhood epilepsy characterized by diverse seizure types, generalized slow (≤2.5Hz) spike-and-wave and other EEG abnor­malities, and cognitive impairments. Early seizure control is a pivotal therapeutic objective, and several ASMs are available. Given the limited success of monother­apy in achieving seizure control and the absence of conclusive efcacy data sup­porting specic ASM combinations for LGS, a judicious selection of combination therapy is imperative to optimize patient outcomes. This approach, termed “rational combination treatment,” involves evaluating factors such as safety (including black box warnings), potential drug interactions, and synergistic mechanisms of action. Drawing from the clinical insights of Raman Sankar etal., runamide has emerged as the preferred adjuvant therapy for LGS, particularly when combined with cloba­zam and other newer LGS medications, offering promise in reducing tetano-atonic seizures associated with LGS [780].

A review encompassing 1759 participants in six trials, four of which focused on patients with uncontrolled focal epilepsy (1563 participants) and two of which specically targeted individuals with identied Lennox–Gastaut syndrome (196 participants). The ndings indicated that in patients with refractory focal epilepsy, runamide treatment in combination with a conventional ASM (adjunctive to a conventional ASM) signicantly outperformed the placebo (adjunctive to a con­ventional ASM) in reducing seizure frequency by at least 50%. However, the runamide treatment group exhibited a greater likelihood of experiencing adverse reactions. Adverse events signicantly associated with runamide included head­ache, dizziness, drowsiness, vomiting, nausea, fatigue, and double vision. While runamide adjunctive therapy effectively diminishes seizure frequency in patients with drug- resistant focal epilepsy, the reviewed trials were relatively brief in dura­tion and did not provide evidence regarding the long-term utilization of run­amide [781].

Children with epilepsy represent a unique subset within the epilepsy population, necessitating careful consideration of both the efcacy and safety of ASMs and their impact on growth and development.

To assess the efcacy and safety of ASMs in patients with Lennox–Gastaut syn­drome (LGS), Zhang etal. conducted a systematic review of randomized controlled trials (RCTs) comparing ASM efcacy against placebo or each other for LGS.Efcacy and safety outcomes included seizure reduction, dropout rates, and serious adverse events with at least a 50% reduction in monthly seizure frequency. The results were ranked by the area under the cumulative ranking curve (SUCRA). The review included 1171 patients from eight RCTs involving six ASM types: lamotrigine, runamide, cannabidiol, topiramate, clobazam, and felbamate. SUCRA analysis indicated that runamide, cannabidiol, and topiramate were most likely to

Concerning the safety of novel ASMs in children and the risk of movement dis­orders, Peacock DJSJ etal. conducted a systematic review and meta-analysis. They searched randomized controlled trials on novel antiseizure agents, including lacos­amide, perampanel, eslicarbazepine, runamide, fenuramine, cannabidiol, and bri­varacetam, in pediatric populations up to October 2020. Among the 1690 nonredundant manuscripts, 23 studies were selected (total studies, n=1912). The analysis revealed a signicantly increased risk of movement disorders associated with perampanel use (RD 0.07, 95% CI 0.01–0.13; N=133), albeit based on only one relevant clinical trial. Other ASMs did not increase the risk of movement disor­ders. This suggests that most new ASMs are generally safe for children with move­ment disorders, although the quality of evidence is limited by adverse event reporting [783].

Furthermore, investigations into the effects of runamide include morpho­logical and histological evaluations in animal studies. Pınar Ozkan Kart etal. sought to ascertain the morphological and histological impacts of runamide alongside other ASMs on follicular genesis in rats. Sixty female Wistar rats were divided into experimental groups and treated with zonisamide, sulthiame, lacos­amide, clobazam, runamide, or a control regimen via intragastric administra­tion for 90days. Ovaries were extracted and xed based on daily vaginal smears indicating the oestrus cycle stage. Immunohistochemistry and apoptosis staining were also performed. The results indicated a signicant increase in the healthy follicular count in the control group compared with the ASM group (p<0.001), with a notable decrease in luteinized follicles in the latter group (p<0.001). Additionally, there was a signicant difference in the number of TUNEL-positive apoptotic follicles between the control and drug groups (p < 0.001). Immunohistochemical analysis revealed stronger immune responses in the con­trol group, suggesting that long-term treatment with ASMs such as runamide suppressed ovarian follicle development and increased apoptosis [534].