Cognitive, adaptive, and behavioral effects of adjunctive rufinamide in Lennox-Gastaut syndrome: A prospective observational clinical study

Francesca Felicia Operto; Alberto Verrotti; Alfonso Marrelli; Roberta Ciuffini; Giangennaro Coppola; Grazia Maria Giovanna Pastorino; Pasquale Striano; Michela Sole; Claudio Zucca; Valentina Manfredi; Santina Città; Maurizio Elia

doi:10.1016/j.yebeh.2020.107445

Cognitive, adaptive, and behavioral effects of adjunctive rufinamide in Lennox-Gastaut syndrome: A prospective observational clinical study

Epilepsy Behav. 2020 Nov:112:107445. doi: 10.1016/j.yebeh.2020.107445. Epub 2020 Sep 10.

Affiliations

¹ Child and Adolescent Neuropsychiatry Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Salerno, Italy. Electronic address: opertofrancesca@gmail.com.
² Department of Pediatrics, University of L'Aquila, L'Aquila, Italy.
³ Child and Adolescent Neuropsychiatry Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Salerno, Italy.
⁴ Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 'G. Gaslini' Institute, Genova, Italy.
⁵ Clinical Neurophysiology Unit, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy.
⁶ Oasi Research Institute (IRCCS), Unit of Neurology and Clinical Neurophysiopathology, Troina, Italy.

PMID: 32920379
DOI: 10.1016/j.yebeh.2020.107445

Abstract

Introduction: Lennox-Gastaut syndrome (LGS) is a severe pediatric epilepsy syndrome characterized by multiple drug-resistant seizure types. Children with LGS usually experience cognitive regression, and LGS is almost always associated with moderate to severe cognitive impairment. Rufinamide (RFM) was approved by the European Medicines Agency in 2007 for the adjunctive treatment of seizures associated with LGS in patients ≥4 years of age. The primary objective of our study was to assess cognitive, adaptive, and behavior functioning of patients with LGS after 12 months of RFM therapy.

Methods: This was an observational, multicenter, prospective study involving 16 patients diagnosed with LGS aged between 7 and 58 years (mean = 22 ± 16.3). Fourteen of 16 patients were already on therapy with 3 antiseizure drugs and 2/16 with 4 antiseizure drugs; RFM has been added with 100 mg/week increments up to a dose of 300-2400 mg/day. The participants and their parents underwent a neuropsychological evaluation for the assessment of intellectual, adaptive, and emotional/behavioral functioning (Leiter International Performance Scale-Revised (LEITER-R), Vineland, and Child Behavior CheckList (CBCL), respectively) before the RFM introduction (baseline) and 12 months after the RFM therapy (T2). Physical and neurological examination, electroencephalography (EEG) recording, seizure type and frequency, and adverse reactions were also considered.

Results: After 12 months, the total intelligence quotient (IQ) assessed by LEITER-R did not show statistical significant changes, such as there were no statistically significant changes in adaptive functions, assessed by Vineland. Furthermore, there were no statistically significant changes in internalizing and externalizing problems assessed by CBCL.

Conclusion: Adjunctive treatment with RFM did not negatively affect cognitive, adaptive function, and emotional profile in patients with LGS after 1 year of follow-up.

Keywords: Cognitive profile; Lennox–Gastaut syndrome; Rufinamide.

Publication types

Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Anticonvulsants / therapeutic use
Child
Cognition
Humans
Lennox Gastaut Syndrome* / drug therapy
Middle Aged
Prospective Studies
Triazoles
Young Adult

Substances

Anticonvulsants
Triazoles
rufinamide