1. Erwin B. Montgomery Jr. MDMedical Director, Greenville Neuromodulation CenterThe Greenville Neuromodulation Scholar in Neuroscience and Philosophy,Thiel College, Greenville PA 2014 Greenville Neuromodulation Center

2. A nonprofit corporation for the advancementof neuromodulation, particularly Deep BrainStimulation (DBS) through patient care,research, development, education and training 3. Medical Director, evaluates and treatspatients with dystonia Inventor of devices and software for DBS Author of three textbooks on DBS Consultant to FHC, Inc. who makes devicesand software for DBS surgery. 4. Any mention of devices or drugs used in anoff-label, experimental or investigationalwill be identified. Any suggestion for off-label use will besupported by appropriate evidence publishedin peer-review journals. Spelling Dr. Montgomery does not vouch for anyspelling 5. In a review of over 200 patients the degreeof improvement in symptom or physicalsignbased assessments, such as the Burke-Fahn-Marsden Rating Scales, on the order of50% to 60% for primary generalized torsiondystonia. (Vidailhet M, Vercueil L, Houeto JL, et al.Bilateral deep-brain stimulation of the globus pallidus inprimary generalized dystonia. N Engl J Med.2005;352(5):459467.) 6. Related to surgery Bleeding in the brain with serious orpersistent problems Approximately 1-2 out of 100 surgeries Infection Approximately 5-6 out of 100 surgeries Approximately 2-3 out of 100 surgeriesrequire removal of the DBS system 7. Related to stimulation Depends on DBS electrode placement Typically in the globus pallidus interna (Gpi) Typically reversible with change in stimulation 8. Need to avoid strong electro-magnetic fields MRI Can be safely done under specific conditions Metal detectors Large electric motors Hybrid cars 9. ElectrodeQuarter 10. External ComponentsClinicianProgrammerPatientController 11. How is the Surgery Done? U.S. FDA regulates the interstatecommerce in drugs and devices. Doesnot regulate how surgeries are done. Not all surgeons do the surgery the sameway. Critical to use microelectrode recordingsto find the right target 12. Stage 1 - Placement of DBS Local anesthesia Placement of stereotactic head frame Localization MRI Case planning Placement of DBS Survey MRI Stage 2 Implantable pulse generator (IPG) General anesthesia Same day surgery 13. Local Anesthesia 14. Frameless system not bolted to OR table, patient wears a hard cervicalcollar allows some patient movement which is more comfortable. 15. Diagnosis A condition that will respond to DBS Exhaustion of all reasonable alternatives Able to tolerate surgery Availability of post-operative managementand programming 16. Primary dystonia Approved by the FDA Secondary dystonia FDA has no position Considered appropriate and accepted useof an FDA approved drug and device for anindication on which the FDA does not havea position 17. Anatomical or fixed dystonia Often related to musculoskeletal changes froma variety of causes, including primary dystonias Not likely to respond to treatment Physiological dystonia Result of brain driving the muscles to produceabnormal postures Differentiating anatomical or fixed versusphysiological Limited passive range of motion Presence during sleep or sedation 18. Spontaneous remission rate of 20%(Jahanshahi et al., Marion and Marsden, 1990) Median remission duration of three years wasobserved in nine of the participating patients. 87% of the spontaneous remissions occurredin the first five years. 19. Issue of spontaneous remission A larger retrospective study of 107patients, spontaneous remission rate ofapproximately 14%(Kiriakakis, Bhatia, Quinn et al. 1998) Mean number of years for remission was5.2 years following diagnosis and 2.6 yearsfollowing discontinuation of theneuroleptic. 20. 27% of participating patients experiencedremissions Median span from onset to remission beingthree years (Castelbuono and Miller 1998) The range was from 3 months to 22 years A mean duration of 4.85 years indicated thatthe distribution was heavily weighted towardsshorter durations 21. Agents anticholinergics dopamine agonists (levodopa particularly) dopamine antagonists dopamine-depleting agents gamma-aminobutyric acid (GABA)related agents baclofen benzodiazepines Within each class are multiple agents. The possiblenumber of combinations is thus 31 among the fiveclasses and 1,023 combinations if two agents fromeach class are considered. 22. Maximum tolerated dosage, for exampletrihexyphenidyl (Artane) 50 mg per day, oradverse effect that cannot be circumvented Approximately 20% of patients who failed toachieve satisfactory benefit fromanticholinergics improved with baclofen 23. Titrated up to 80 mg per day or the patientexperiences a dose limiting adverse effectthat cannot be circumvented. 24. Converted to dopamine in the brain Usually given in combination with carbidopato improve effectiveness of levodopa andreduce adverse effects. Typically up to at least 2000 mg as levodopaor until a dose-limiting adverse effect thatcannot be circumvented 25. Tetrabenazine and similar dopamine-depletingagents have been reported effectivein treating dystonia (Chen et al. 2012) Titrated up to 150 mg per day or theappearance of a dose-limiting side effect thatcannot be circumvented Approved by the FDA for the treatment ofHuntingtons disease. Most experts considerit safe and effective for off-label use indystonia 26. Demonstrated failure At least 6 attempts by expert and usingelectromyographic (EMG) targeting Especially for anterocollis and laterocollis Demonstration of neutralizing antibodies toall available serotypes Forehead test 27. 20 patients underwent selective peripheralnerve denervation 15 underwent GPi DBS Outcomes were considerably better inpatients undergoing DBS 28. marked improvement, 60% with DBS and 5%with selective peripheral nerve denervation bad outcomes - 13.3% with DBS and 65%with selective denervation Eleven of 20 (55%) of patients who hadinitially undergone selective peripheral nervedenervation required a second surgery 1 of 15 patients who were undergoing DBSrequired second attempt 29. Adverse effects - 75% of patients whounderwent selective peripheral nervedenervation, compared to 60% of thoseunderwent DBS Changes in sensation experienced by patientswith selective peripheral nerve denervation Problems with hardware and altered speechwith DBS 30. Mean follow-up was 32.8 months gatheredfollow-up results on 140 patients 18 (13%) complete relief of their symptoms 50 (36%) significant relief 34 (24%) moderate relief 19 (14%) minor relief 19 (14%) no improvement Recurrence rate 11% 31. By comparison, the long-term follow-up(typically on the order of 30 months) ofpatients with cervical dystonia undergoingDBS found that, of 20 patients combined intwo studies, only 1 patient failed toexperience sustained benefit 32. Most important decider not the physician orhealthcare provider Only patient can determine how bothersomeare the symptoms and how much the patientis willing to risk for benefit 33. Benefit comes from turning the stimulationon and adjusting to optimal benefit Unethical to proceed with DBS surgery unlessdefinitive plans are made for post-operativecare Complicated 34. Questions, comments and suggestions areappreciated and can be sent by e-mail to toinfo@grnneuromod.com If you want to help in our mission you cancontact GNC via U.S. telephone 724-588-1324 or by e-mail to info@grnneuromod.com 35. Erwin B. Montgomery Jr. MDMedical Director, Greenville Neuromodulation CenterThe Greenville Neuromodulation Scholar in Neuroscience and Philosophy,Thiel College, Greenville PAErwinMontgomery@GRNNeuroMod.com724-588-1324 2014 Greenville Neuromodulation Center