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12-1020-Nuttin-Hall #42873B.PPT Electrical brain stimulation for treatment-refractory OCD from rat work to FDA and CE approval Bart Nuttin, Loes Gabriëls, Kris van Kuyck, Marleen Welkenhuysen, Laura Luyten, Dimiter Prodanov, Paul Cosyns Electrical brain stimulation in OCD K.U. Leuven : Gabriëls, van Kuyck, Welkenhuysen, Van Huffel, Gligorijevi_, Luyten, Prodanov, Ahmed, Van Laere, Dupont, Sunaert, Demeulemeester, Gybels, Tousseyn, Dewil, Vandenbroeck, Brak, Das, Arckens, Nuttin. Universiteit Antwerpen : Cosyns, Neefs, Vankerckhoven, Cluydts, … Karolinska : Meyerson, Linderoth, Andréewitch, Mindus, Rück, … IMEC : Bartic, Eberle, Musa, Borghs, Verstreken, … Brown University : Friehs, Rasmussen, Greenberg, … Cleveland Clinic : Rezai, Malone, … Köln : Sturm, Klosterkötter, … University of Michigan : Curtis, Abelson, … Orlando : Goodman, Okun, Foot, … Amsterdam – Utrecht : Bosch, Schuurman, … Grenoble : Benabid, … Medtronic Inc. : Mullett, Gielen, Rise, Stypulkowski, Langevin, … Disclosure • Medtronic is providing grants for research, education and traveling • Patent : DBS in OCD • Grants : OT, FWO, IWT, SBO No stimulation With stimulation Surgery medio-dorsal nucleus bed nucleus of stria terminalis (BST) of the thalamus (MD) • v nucleus accumbens (NACC) DESIGN ! ! ! ! ! ! NACC BST MD SHAM 0.1, 0.2, 0.3, 0.4, 0.5mA 2, 100Hz + stimulation off Kris van Kuyck et al. Kris van Kuyck et al. Electrical stimulation • Study protocol – Approved by the local hospital ethics committees – In accordance with Helsinki Declaration of 1975 (revision 1983) • Committee for neurosurgery for psychiatric disorders. • Bilateral electrode implant in 21 very severely ill treatment-refractory OCD-patients. • World-wide probably 100 implanted patients. Electrodes : Pisces quad compact Model 3887 DBS electrode Model 3387 DBS for treatment-refractory OCD was investigational in Europe The electrodes used for this kind of surgery are not labeled for this indication Electrodes : Pisces quad compact Model 3887 DBS electrode Model 3387 Indication Reduce drugs On Off Operation Off On 3m 3m 6m E v a l u a t i o n s Patient + evaluators blind Blind for parameters Nuttin B., Cosyns P., Demeulemeester H., Gybels J., Meyerson B. Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder, The Lancet, 354:1526, 1999. 26 patients : - Leuven/Antwerp - Brown University, Providence - Cleveland Clinic, Ohio - Orlando T2 BEFORE IMPLANT T1 AFTER IMPLANT Bed nucleus of stria terminalis Electrodes Fornix Anterior limb of internal capsule Anterior commissure Bed nucleus of stria terminalis anterior posterior 20 Atlas of Mai anterior posterior 21 Atlas of Mai anterior posterior 22 Wired recording with Leadpoint + Medtronic electrodes (n=44) Three clusters (different neurons) observed Analysis tools included modified Wave_clus algorithm developed by Rodrigo Quian Quiroga (Carltech) and Eytan Domany (Weizman institute of science) and autonomously developed code for handling and analysis of large data sets (Ivan Gligorijevi_ and Sabine Van Huffel, K.U.Leuven) Bleeding 2 • Treatment of psychiatric patients with DBS remains investigational and is NOT considered standard therapy. In Europe : CE-mark (3991 and Kinetra) • Treatment of psychiatric patients with DBS remains investigational and is NOT considered standard therapy. FDA 2009 : Humanitarian device exemption (HDE) for DBS in OCD Conclusions DBS in OCD : – Some evidence : randomized controlled cross-over study and reports from other groups – Major problems : haemorrhage, battery life, different targets (cf. other research groups !!), ... – It has not been shown that it is better than anterior capsulotomy – From rats to a therapy with HDE and CD Thank you.
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