PERSONAL RECOLLECTIONS OF DR. HANS SELYE AND OF HIS INSTITUT DE MèDECINE ET DE CHIRURGIE EXPèRIMENTALES (IMCE).

This article is a short personal recollection of Dr. Hans Selye (HS) and of his institute in order to show, first, why and how he influenced us; second, who he was as a person, human being, physician, scientist, professor, mentor; third, what was the structure and functioning of the Institut de Mèdecine et Chirurgie Expèrimentales (IMCE) and fourth, what HS' contributions and accomplishments were.

A randomized controlled trial of flunarizine as add-on therapy and effect on cognitive outcome in children with infantile spasms.

PURPOSE: Cognitive impairment is observed commonly in children with a history of infantile spasms (IS). The goal of this study was to prospectively examine the effect on cognitive outcome of a neuroprotective agent used as adjunctive therapy during treatment of the spasms. METHODS: In a randomized controlled trial, patients received a standardized therapy plus flunarizine or placebo. The standardized treatment consisted of vigabatrin as first-line therapy. Nonresponders were switched to intramuscular synthetic adrenocorticotropic hormone (sACTH depot) after 2 weeks and, if necessary, to topiramate after two additional weeks. The Vineland Adaptive Behavior Scale (VABS) and Bayley Scales of Infant Development (BSID) were used as outcome measures 24 months after the intervention. KEY FINDINGS: Sixty-eight of 101 children diagnosed over 3 years in seven centers in Canada received either adjunctive flunarizine or placebo. Sixty-five of the 68 children (96%) became spasm-free within 8 weeks and no late relapse occurred. Bayley and Vineland results were available at baseline and at 24 months in 45 children. There was no significant difference in the BSID developmental quotient between the flunarizine- and placebo-treated children at baseline (44.3 ± 35.5 vs. 30.9 ± 29.8; p = 0.18) or 24 months later (56.9 ± 33.3 vs. 46 ± 34.2; p = 0.29). However, the 10 flunarizine-treated children with no identified etiology had a better outcome than the eight controls at 24 months on both the Vineland Scale (84.1 ± 11.3 vs. 72.3 ± 9.8; p = 0.03) and the Bayley Scale (87.6 ± 14.7 vs. 69.9 ± 25.3; p = 0.07). SIGNIFICANCE: Our study failed to demonstrate a protective effect of flunarizine on cognitive outcome in a cohort of children with IS. An analysis of subgroups suggested that flunarizine may further improve cognitive outcome in children with no identified etiology.

Levetiracetam in children with refractory epilepsy: lack of correlation between plasma concentration and efficacy.

PURPOSE: The goals of this study are to evaluate the efficacy and tolerability of levetiracetam (LEV) as add-on therapy in children with refractory epilepsies and to determine the value of LEV blood level monitoring in this population. METHODS: Sixty-nine children (39 males and 30 females) treated with LEV between 2006 and 2007 were selected. Their medical files were reviewed for LEV efficacy and tolerability. In a subgroup of children currently taking LEV, plasma concentrations were determined by high performance liquid chromatography by ultraviolet detection (HPLC-UV) method and correlated with the given dose per kilo as well as clinical response. RESULTS: Fifty-one patients (74%) had a more than 50% reduction in seizure frequency with 16 patients (23%) becoming seizure free on LEV. Eighteen (26%) patients had a less than 50% reduction in seizure frequency. Adverse events due to LEV ranged from mild to moderate in only 18 patients (26%). The most frequently observed were drowsiness, behavioral difficulties, increase in seizure frequency and headaches. The majority (60.5%) of the responders received doses between 10 and 50mg/kg/day and had a plasma concentration (PC) between 5 and 40microg/ml. However, we found no clear correlation between PC and efficacy. CONCLUSION: Levetiracetam given twice a day in children with refractory epilepsy reduces seizure frequency in all types of epilepsy. In children, LEV is a broad spectrum anticonvulsant with a favourable safety profile.