Deep Brain Stimulation: A Proven Treatment for Movement Disorders Wendell Lake MD, MS Assistant Professor Director of Functional Neurosurgery/Epilepsy surgery

Financial Disclosures None At This Time Received Fellowship Support From Medtronic July 2014 to July 2015

Outline A brief History of Deep Brain Stimulation (DBS) Parkinson’s Disease Essential Tremor Dystonia Surgical Technique Future Technologies Conclusions

History Surgical Treatment began in the Mid-twentieth century with ablative procedures Introduction of levodopa therapy diminished interest in Surgery thectr.org

Basic Science of Parkinson’s Disease In the 1980s and 1990s Delong and Bergman study PD with the MPTP primate model Benabid discovers that high frequency electrical stimulation creates a temporary reversible lesion A working model of PD helped to usher in the DBS era Direct pathway Indirect pathway E. Eskandar, G. Cosgrove, L. Shinobu. neurosurgery.mgh.harvard.edu

Parkinson’s Disease FDA Approved in 2002 Usual targets are the subthalamic nucleus or the Globus Pallidus Interna Ideal candidates are Levodopa (Sinemet) responsive and have classic Parkinson’s disease Machado A et al. CCJM Vol 79, No. 2, Feb. 2012

Parkinson’s Disease: What DBS Doesn’t Help Gait or balance Cognitive problems Depression (unless situational) Studyblue.com

Parkinson’s Disease: What DBS Does Help Increases “On” time Decreases Bradykinesia and Rigidity Reduces Medication Dose Improves dyskinesia Effectively treats tremor

Parkinson’s Disease Outcomes 6 Randomized controlled trials support DBS for Parkinson’s Disease DBS Statistically improves motor function and Quality of Life Average increase of 4.6 hours per day of “On” time

Essential Tremor FDA approved in 1997 Familial or Essential tremor responds well Improves tremor that is medication refractory Target is the ventral intermediate (Vim) Nucleus of the thalamus Costa J et al. Journal of Neurophysiology Published 1 September 2008 Vol. 100 no. 3, 1610-1621 Movementdisorders.florida.edu

Essential Tremor: What DBS Doesn’t Help DBS doesn’t “Cure” tremor May not eliminate all tremor Sometimes tremor worsens with aging Vocal and head tremor may be difficult to eliminate Some DBS settings may cause dysarthria

Essential Tremor Outcomes Randomized controlled trials demonstrated improved Activities of Daily Living and Improved tremor 80% improvement in tremor 70% improvement in handwriting Zhang K et al. J Neurosurg. 2010 Jun;112(6):1271-6. doi: 10.3171/2009.10.JNS09371.

Dystonia FDA Humanitarian Device exemption 2003 Patients with medically resistant symptoms More commonly used for primary dystonias (DYT-1, DYT-6) and torticollis Target is globus pallidus (Rarely subthalamic nucleus) Machado A et al. CCJM Vol 79, No. 2, Feb. 2012

Dystonia: What DBS Doesn’t Help DBS doesn’t Cure dystonia Sometimes symptoms progress despite therapy May be less effective for secondary generalized dystonias May not improve speech or swallowing

Dystonia: What DBS Does Help/Outcomes 3 randomized controlled trials demonstrated Improved Activities of daily living/quality of life Effects of stimulation are not immediate May improve pain in Cervical dystonia Younger patients may have better outcomes

DBS Preoperative Evaluation Evaluation in the Neurology Movement Disorders Clinic Neuropsychological testing Physical Therapy Evaluation Discussion in Movement Disorders Conference Neurosurgery Clinic Visit

DBS Placement Usually done awake IV pain medications, local anesthesia and intermittent sedation Placement of small recording microelectrodes Above photo Courtesy of Leland Albright

Neurophysiology and Intraop Testing Final lead position is determined from information obtained during microelectrode recording and test stimulation. Z Williams, J Neimat, G. Cosgrove, E. Eskandar. Timing and direction selectivity of subthalamic and pallidal neurons in patients with Parkinson disease Exp Brain Res (2005) 162: 407–416

3D Printed Stereotactic Frames Allow fast, accurate placement of DBS Leads for Awake Cases Improve Patient Comfort

Initial Postoperative Care Usually stay in the hospital one night following Cranial lead placement Battery is placed in the outpatient setting under general anesthesia Light activity for 2 weeks following the operation Activation of the DBS system 1 month after placement of the Cranial leads

Programming and Maintenance Programming and maintenance of the system is key Initially the patient has frequent programming visits until they feel that the system is optimized Batteries are replaced every 3-5 years Rechargeable options are available

Risks of DBS Surgery Brain hemorrhage: ~3%, most are asymptomatic but some can cause weakness or deficits Infection: ~5%. Usually treated with removal of the battery and antibiotics. Slurring of speech in Tremor patients (dysarthria) Cognitive difficulties (risk increases with age) Balance Problems

Options for Asleep MRI Guided DBS UW-Madison is a pioneer in this field Currently Emphasizing Parkinson’s disease patients Generally reserved for patients unable or unwilling to tolerate awake surgery

Future Technologies Expansion of MRI Guidance techniques for DBS placement Treating other diseases with DBS: Depression, Alzheimer’s disease, Obsessive-Compulsive disorder Implants that sense brain activity and adjust stimulation accordingly Use prior Implantation data for computer modeling Pierre-Francoise, D et. al. Stereotact Funct Neurosurg 2013; 91 (3): 148-152.

Conclusions DBS is a proven therapy for select patients suffering from Parkinson’s Disease, Essential Tremor and Dystonia This exciting technology is undergoing continual improvement and may allow the treatment of many other diseases in the future