Efficacy and Tolerability of Lacosamide in Pediatric and Young Adult Epilepsy Patients with Severe Motor and Intellectual Disabilities

Abstract

Objective Epilepsy is common among patients with severe motor and intellectual disabilities (SMID) patients, often taking a prolonged and intractable course. Lacosamide (LCM) is widely used to treat epilepsy in both adults and children. We assess the efficacy and tolerability of LCM among pediatric and young adult epilepsy patients with SMID who suffer from intractable seizures.

Methods This retrospective analysis reviewed the medical records of SMID patients undergoing LCM treatment for more than a year. The study included 24 patients (14 males) aged 3 to 29 years. Epilepsy was classified as focal in 17 patients, generalized in 4 patients, and combined generalized and focal in 3 patients.

Results The retention rates were 70.8%, 65%, and 52.9% at 1, 2, and 3 years after LCM initiation, respectively. The 50% responder rate (achieving >50% seizure reduction) for LCM treatment was 50%, with two patients experiencing complete seizure control (absence of seizures for 6 months before the follow-up visit). The 50% responders included a higher proportion of patients with focal epilepsy (58.8%) compared to those with generalized epilepsy (25.0%). Treatment-emergent adverse events (TEAEs) included somnolence in five patients and nausea in two patients. TEAEs, particularly nausea, developed within 1 month after treatment initiation in two patients, leading to LCM discontinuation.

Conclusion LCM demonstrated good efficacy for intractable epilepsy in pediatric and young adult SMID patients. It was generally well-tolerated, resulting in a favorable retention rate. LCM emerged as a useful antiseizure medication for epilepsy treatment in pediatric and young adult SMID patients.

Keywords

lacosamide - severe motor and intellectual disabilities - pediatric and young adult - efficacy and tolerability

Publikationsverlauf

Eingereicht: 09. Mai 2024

Angenommen: 26. Dezember 2024

Accepted Manuscript online:
30. Dezember 2024

Artikel online veröffentlicht:
14. Januar 2025

• References

• 1 Fiest KM, Sauro KM, Wiebe S. et al. Prevalence and incidence of epilepsy: a systematic review and meta-analysis of international studies. Neurology 2017; 88 (03) 296-303
• 2 Arima M. Future perspective in the study of developmental disabilities [in Japanese]. Hattatsu Shogai Kenkyu (Tokyo) 1996; 17: 264-266
• 3 Matsumoto A, Miyazaki S, Hayakawa C, Komori T, Nakamura M. Epilepsy in severe motor and intellectual disabilities syndrome (SMIDS)–a clinical and electroencephalographic study of epileptic syndromes. Epilepsy Res 2007; 77 (2–3): 120-127
• 4 Ben-Menachem E, Biton V, Jatuzis D, Abou-Khalil B, Doty P, Rudd GD. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia 2007; 48 (07) 1308-1317
• 5 Hillenbrand B, Wisniewski I, Jürges U, Steinhoff BJ. Add-on lacosamide: a retrospective study on the relationship between serum concentration, dosage, and adverse events. Epilepsy Behav 2011; 22 (03) 548-551
• 6 Welsh SS, Lin N, Topjian AA, Abend NS. Safety of intravenous lacosamide in critically ill children. Seizure 2017; 52: 76-80
• 7 Hasegawa N, Fukuda M. The effect of lacosamide on psychiatric comorbidities in patients with epilepsy. Epilepsy Behav Rep 2020; 14: 100402
• 8 Ortiz de la Rosa JS, Ladino LD, Rodríguez PJ, Rueda MC, Polanía JP, Castañeda AC. Efficacy of lacosamide in children and adolescents with drug-resistant epilepsy and refractory status epilepticus: a systematic review. Seizure 2018; 56: 34-40
• 9 Ishikawa N, Eguchi Y, Izumo H. et al. Clinical impact of the dose and blood concentration of lacosamide in Japanese pediatric patients with epilepsy: a cohort study. Epilepsy Behav 2022; 129: 108614
• 10 Allard J, Henley W, Mclean B. et al. Lacosamide in the general population and in people with intellectual disability: similar responses?. Seizure 2020; 76: 161-166
• 11 Grosso S, Parisi P, Spalice A, Verrotti A, Balestri P. Efficacy and safety of lacosamide in infants and young children with refractory focal epilepsy. Eur J Paediatr Neurol 2014; 18 (01) 55-59
• 12 Casas-Fernández C, Martínez-Bermejo A, Rufo-Campos M. et al. Efficacy and tolerability of lacosamide in the concomitant treatment of 130 patients under 16 years of age with refractory epilepsy: a prospective, open-label, observational, multicenter study in Spain. Drugs R D 2012; 12 (04) 187-197
• 13 Toupin JF, Lortie A, Major P. et al. Efficacy and safety of lacosamide as an adjunctive therapy for refractory focal epilepsy in paediatric patients: a retrospective single-centre study. Epileptic Disord 2015; 17 (04) 436-443
• 14 Pozzi M, Zanotta N, Epifanio R. et al. Lacosamide effectiveness and tolerability in patients with drug-resistant epilepsy and severe disability under polytherapy: Therapy optimization as emerging from an observational study. Epilepsy Behav 2022; 128: 108598
• 15 Kleist A, Kerling F, Hamer H, Winterholler M. Lacosamide in patients with intellectual disability and refractory epilepsy. Acta Neurol Belg 2019; 119 (03) 423-430
• 16 Wechsler RT, Yates SL, Messenheimer J, Leroy R, Beller C, Doty P. Lacosamide for uncontrolled primary generalized tonic-clonic seizures: an open-label pilot study with 59-week extension. Epilepsy Res 2017; 130: 13-20
• 17 Vossler DG, Knake S, O'Brien TJ. et al; SP0982 co-investigators. Efficacy and safety of adjunctive lacosamide in the treatment of primary generalised tonic-clonic seizures: a double-blind, randomised, placebo-controlled trial. J Neurol Neurosurg Psychiatry 2020; 91 (10) 1067-1075
• 18 Verrotti A, Loiacono G, Pizzolorusso A. et al. Lacosamide in pediatric and adult patients: comparison of efficacy and safety. Seizure 2013; 22 (03) 210-216
• 19 Miskin C, Khurana DS, Valencia I, Legido A, Hasbani DM, Carvalho KS. Efficacy and tolerability of lacosamide in the treatment of children with refractory generalized epilepsy. J Child Neurol 2016; 31 (07) 925-928
• 20 Ferreira JA, Le Pichon JB, Abdelmoity AT. et al. Safety and tolerability of adjunctive lacosamide in a pediatric population with focal seizures - an open-label trial. Seizure 2019; 71: 166-173
• 21 Villanueva V, López-Gomáriz E, López-Trigo J. et al. Rational polytherapy with lacosamide in clinical practice: results of a Spanish cohort analysis RELACOVA. Epilepsy Behav 2012; 23 (03) 298-304
• 22 Rosati A, Ilvento L, Rizzi R. et al. Long-term efficacy of add-on lacosamide treatment in children and adolescents with refractory epilepsies: a single-center observational study. Epilepsia 2018; 59 (05) 1004-1010
• 23 Böttcher S, Lutz MT, Mayer T. Lacosamide in the treatment of patients with epilepsy and intellectual disabilities: a long-term study of 136 patients. Epilepsia 2017; 58 (10) 1749-1754
• 24 Enjoji M, Yanai N. Analytic test for development in infancy and childhood. Pediatr Int (Roma) 1961; 4 (01) 2-6
• 25 Society for the Kyoto Scale of Psychological Development Test. Shinpan K Shiki Hattatsu Kensahou 2001 Nenban [The Kyoto Scale of Psychological Development Test 2001]. Nakanishiya Shuppan, Kyoto, 2008 (in Japanese) .
• 26 Motegi M, Inagaki A, Minakata T. et al. Developmental delays assessed using the Enjoji Scale in children with cochlear implants who have intellectual disability with or without autism spectrum disorder. Auris Nasus Larynx 2019; 46 (04) 498-506
• 27 Koyama T, Osada H, Tsujii H, Kurita H. Utility of the Kyoto Scale of Psychological Development in cognitive assessment of children with pervasive developmental disorders. Psychiatry Clin Neurosci 2009; 63 (02) 241-243