Abstracts

Rationale: Lennox-Gastaut syndrome (LGS) is a severe pediatric epilepsy syndrome characterized by multiple seizure types including tonic, atonic, atypical absence, and generalized tonic-clonic seizures (1).Children with LGS usually experience cognitive regression around the time of diagnosis and established LGS is almost always associated with moderate to severe cognitive impairment. Cognitive impairment seems linked to the age of onset and persistence of seizures (2). Moreover, a follow-up study of 72 patients for a mean duration of 17 years has suggested progressive cognitive impairment, with a 15 point decrease in IQ from diagnosis to the end of the follow-up period (3).Rufinamide was approved by the EMA in 2007 for the adjunctive treatment of seizures associated with LGS in patients >=4 years of age. Although the precise mechanism of action of rufinamide in controlling seizures is not known, the mode of action appears to be by prolonging the inactive state of sodium channels.  Methods: The present study is an observational, prospective study with the aim at assessing in clinical practice the cognitive impact of rufinamide in patients with Lennox-Gastaut Syndrome by the evaluation of adaptive behavior, measured by Vineland scales, and the cognitive Leiter scale which offers a completely non-verbal measure of intelligence that is ideal for use with those who are cognitively delayed, hearing impaired, and speech impaired. After the informed consent is signed by Parents/Tutors, eligible patients will undergo the baseline visit. Patients fulfilling all of the inclusion criteria and none of the exclusion criteria will be included in the study and will complete the baseline visit. Patients will then be seen during normal clinical visits at intervals which are appropriate to the typical practice of the treating clinician, i.e., after 6, and 12 months of treatment with rufinamide. Therefore, each patient will be observed for a maximum of 12 months. The 12-month visit will be the final visit of the study. In case of premature discontinuation, patients will undergo the early termination visit. Our sample includes 13 patients aged between 8-58 years, with Lennox Gastaut Syndrome (3) or Lennox-like Syndrome (10). 10/13 patients were already on therapy with 3 AEDs and 3/13 with 2 AEDs; Rufinamide has been added with 100mg/week increments up to a dose of 300-2400mg/day.Changes in Cognitive function, adaptive function and emotional behavioral profile were assessed by respectively by Leiter-R, Vineland-I, CBCL that were performed before taking Rufinamide and after 6 and 12 months of follow-up.  Results: After 12 months the total intelligence quotient assessed by Leiter-R did not show statistical significant changes (p=0.068), such as there were not statistical significant changes in adaptive functions assessed by Vineland-I represented by communication (p=0.276), daily skills (p=0.775) and socialization (p=0.708). Furthermore there were not statistical significant changes in internalizing problems (p=0.258) and externalizing problems (p=0.297) assessed by CBCL. Conclusions: Adjunctive treatment with RUF did not negatively affect cognitive and adaptive function and emotional profile.References 1.Gastaut HEpilepsia1966;2Arzimanoglou, et al 2009.3Oguni, et al 1996  Funding: No funding