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

Department of Neurosurgery, Massachusetts General HospitalGrand Rounds

Vivek P. BuchMD Candidate, Brown Alpert Medical School

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

Brief Case Presentation: JR

Starr et al, JNS 2006

BFMDRS scores

Open circle: > 70% improvement

Open square: 50%-70% improvementAided by: Josh Aronson

Dystonia: How bad can it actually be?

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

http://www.leidenuniv.nl

Sanger, JNNP 2003

Neurosurgical management of Dystonia: The “Past”

Pallidotomy/Thalamotomy

Cervical rhizotomy/Bertrand procedure

Weetman and Anderson, JNNP 2007

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 Kondziolka et al, Surg

Neurol Int 2012

Friedman et al, JNS 1993 Anderson et al, JNS 2008 in reference to: Bertrand, Surg Neurol 1993

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)

Neurosurgical management of Dystonia: The “Present”

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

Thank you!