Neurosurgical Management of Dystonia: The Past, Present, and Future

1. Neurosurgical Management of Dystonia: The Past, Present, and Future Department of Neurosurgery, Massachusetts General Hospital Grand Rounds Vivek P. Buch MD Candidate, Brown Alpert Medical School

2. Brief Case Presentation: JR CC: Progressive, abnormal posturing HPI: JR is a 12 year old right-handed male who was completely healthy until June 2010 when he began noticing his right arm stiffening and internally rotating. This progressed over the next several months to one year to involve “twitching” movements of his neck and then stiffening of his left arm and trunk. By June 2011 his trunkal posturing caused him to be bent forward at rest. He was diagnosed with generalized dystonia, with genetic testing revealing a DYT1 mutation. Exam: Persistent left neck rotation between 60-90 degrees. Mild trunkal arching. Stiffening of BUE. Inversion of left foot to 15 degrees. Treatment course: Trihexyphenidyl 12mg 3XD, Botulinum toxin injections Surgical plan: Bilateral GPi DBS implantation

3. Brief Case Presentation: JR BFMDRS scores Open circle: > 70% improvement Open square: 50%-70% improvement Aided by: Josh Aronson Starr et al, JNS 2006

4. Dystonia: How bad can it actually be?

5. http://www.leidenuniv.nl Sanger, JNNP 2003 Dystonia • Definition • Sustained, involuntary muscle contractions causing repetitive movements or abnormal postures (Dystonia Fact Sheet: NINDS) • Epidemiology • 30 per 100,000(Nutt et al, Mov Dis 1998) • 3-5x increased frequency in Ashkenazi Jewish population • Focal ↔ Generalized • Primary vs. Secondary

6. Neurosurgical management of Dystonia: The “Past” Pallidotomy/Thalamotomy Cervical rhizotomy/ Bertrand procedure Leksell’s coordinates for PVP (AC-PC): 2-3 mm anterior; 18-22 mm lateral; 4-6 mm below VIM nucleus target (AC-PC): 4 mm posterior; 13 mm lateral; 1 mm above Weetman and Anderson, JNNP 2007 Kondziolka et al, Surg Neurol Int 2012 Anderson et al, JNS 2008 in reference to: Bertrand, Surg Neurol 1993 Friedman et al, JNS 1993

7. Neurosurgical management of Dystonia: The “Present” • Bilateral GPi DBS has emerged as treatment of choice for refractory generalized dystonia, cervical dystonia, and childhood-onset dystonia (Coubes et al, Lancet 2000; Vidailhet et al, NEJM 2005; Zorzi et al, Mov Disord 2005; Parr et al, Arch Dis Child 2007; Alterman et al, Neurology 2007; Kiss et al, Brain 2007) • Kupsch et al, NEJM 2006 • RCT, double-blinded, 40 patients randomly assigned to GPi DBS vs. sham • Significant improvements in BFMDRS at 3 months (~ 15 points  1 point) • When sham group turned on, similar improvements seen • Improvements in motor symptoms and quality of life measures evident 3-6 years after implantation (Vidailhet et al, Lancet Neurol 2007; Isaias et al, Arch Neurol 2009; Cif et al, Mov Disord 2010)

8. Neurosurgical management of Dystonia: The “Present”

9. Neurosurgical management of Dystonia: The “Future?” Convection-enhanced delivery of viral vectors: 1. Gene therapy – DYT1 RNAi 2. Optogenetics – Light-induced modulation of targeted neuronal pathways via ChR

10. Thank you!