Perspectives thérapeutiques dans l’AVC Dr Assia Jaillard Unité neurovasculaire CHU Grenoble 9 mai 2006

Facteur VII activé recombinant Les hématomes: NOVOSEVENR Indication = hématome intracérébral intraparenchymateux Délai <4h 1 seule injection IV de 4 M UI/kg Risque thromboembolique (7% vs 2%) => ECG et troponine prix élevé: 3000-4000 Euros Etude de référence: Mayer et al. NEJM 2005 : 399 patients répartis en 4 groupes décès 29% vs 18% (p=0.02) lié à la réduction significative du volume de l’hématome Effet dose

CLOTBUST : Recanalisation artérielle Doppler transcranien continu Indication = occlusion artérielel dans la thrombolyse Favorise la recanalisation Étude phase II nécessitant confirmation: 126 patients sans effet significatif sur l’outcome Suivi TCD en routine

Ce qui est en cours d’étude FLAME Les IRS dans la récupération motrice PHRC multicentrique (300 patients) étudiant la fluoxétine (20 mg) versus Placébo 5-10 jours après l’AVC

Ce à quoi vous avez échappé: le valium pour tous Cerebrovasc Dis. 2006;21(1-2):120-7. Epub 2005 Dec 9.   Diazepam to improve acute stroke outcome: results of the early GABA-Ergic activation study in stroke trial. a randomized double-blind placebo-controlled trial. Lodder J, van Raak L, Hilton A, Hardy E, Kessels A; EGASIS Study Group. Department of Neurology, University Hospital Maastricht, Maastricht, The Netherlands. BACKGROUND: We tested whether diazepam, a GABA-ergic drug that also inhibits brain nitric monoxide formation, improves acute stroke prognosis. METHODS: 880 patients, randomized within 12 h of acute stroke, received diazepam 10 mg or placebo by rectiole, as soon as possible, followed by 10-mg tablets twice daily for 3 days. Primary outcome was independence (Rankin score <3) at 3 months; secondary outcome was complete recovery (Barthel index >or=95 or Rankin score <or=1). RESULTS: Intention-to-treat analyses on all 849 patients with full follow-up (50.4% on diazepam): odds ratio (OR) 1.14, 95% CI 0.87-1.49 for primary endpoint, and an OR of 1.26 (0.90-1.76) for complete recovery, both favoring diazepam.

Thérapie cellulaire Intracerebral transplantation of human mesenchymal stem cells after cerebral ischemia in rats: functional recovery, in vivo MRI and histology   Detante O., MD1,2; Barbier E., PhD2; de Fraipont F., PharmD-PhD3; Grillon E., MSc2; Meo J., BSc3; Valable S., PhD2; Moriscot C., PhD3; Garambois K., MD1; Richard MJ., PharmD-PhD3; Favrot MC., MD-PhD3; Segebarth C., PhD2; Hommel M., MD-PhD1,2; Jaillard A., MD-PhD1,2; Rémy C., PhD2 1. Stroke Unit, Department of Neurology, University Hospital, Grenoble, Fr 2. UMR INSERM U 594 / Joseph Fourier University (Functional and Metabolic Imaging), Grenoble, Fr 3.Cell and Tissue Therapy Unit, University Hospital, Grenoble, Fr Stroke is the leading cause of adult disability. Stem cells transplantation in animal models leading to functional improvement following stroke, might be a promising therapy. Despite clinical trials appeared to improve clinical outcome, limited data are available regarding safety and efficacy. The best cell type, the delivery technique, and the graft timing are still debated. Among the various cell sources, human bone marrow mesenchymal stem cells (hMSC) offer the advantage of not providing from a tumoral or modified source. The aim of the present study is to assess the functional effects of hMSC graft after a experimental cerebral ischemia, in the context of a longitudinal multiparametric study comprising behavioural tests, in vivo magnetic resonance imaging (MRI), and histology.