1. TECHNOLOGY IN REHABILITATION
Neuromodulation
Deep Brain Stimulation Overview
Elena Draznin, MD
Medical Director ,
Swedish Rehabilitation Unit.

2. Neuromodulation is a therapeutic alteration of activity in central, peripheral or autonomic nervous systems, electrically or pharmacologically, by means of implanted devices
Spasticity
Parkinson’s disease, other movement disorders
Cortical stimulation for stroke
Pain
Epilepsy
Intractable nausea
Cochlear implants

3. Idiopathic Parkinson’s disease
Progressive neurodegenerative disorder
1.5 million in US
Slowly progressive
Asymmetric onset
Affecting mostly people over 60
Etiology is unknown.

4. Two advocates for research who developed Parkinson's early: Muhammad Ali at age 42 and Michael J. Fox at age 30.

5. What Causes PD?
A small area in the brain stem called the substantia nigra controls movement. In PD, cells in the substantia nigra stop producing dopamine, a chemical that helps nerve cells communicate. As dopamine-producing cells die, the brain does not receive the necessary messages about how and when to move.

6. Parkinson's Disease
Brain disorder with a gradual loss of movement control.
Cardinal signs : Tremors,
Stiffness, rigidity
Akinesia or bradykinesia.
Postural instability, impaired balance.

7. Symptom: Tremor
Tremor is an early symptom for about 70% of people with Parkinson's. It occurs in a finger or hand at rest, rhythmically, usually four to six beats per second, or in a "pill-rolling" manner, as if rolling a pill between the thumb and index finger.

8. TYPES OF TREMOR
*Essential Tremor- 50% familial
*Parkinsonism
*Dystonia
*Secondary tremor
medicine
stroke MS
*Peripheral Nerve damage
*Psychological

9. The early signs of Parkinson's disease include
Stiffness or difficulty walking
Difficulty getting out of a chair

10. The early signs of Parkinson's disease:
Stooped posture
A 'masked' face, frozen in a serious expression

11. Symptom: Rigidity
Rigidity occurs when the muscles stay stiff and don't relax. The arms may not swing when a person is walking. There may be cramping or pain in the muscles.

12. Parkinson's disease: Small, crowded handwriting

13. Parkinson’s disease
Cost of drug therapy $1,000- $6,000 per year
Health care cost $2,000- $20,000 per year
Risk of death doubles
Referral to neurologist associated with decreased morbidity/ mortality and SNF placement.

14. Moderate to Advance Disease
* On-off fluctuations
random or EOD wearing off
* Dose failures
* Dyskenesias
* Non dopamine responsive symptoms:
postural flexion and instability
falls
retropulsion and propulsion
freezing, motor initiation
speech and swallowing

15. Parkinson’s Disease Treatment: Continuum of Interventions
Signs of levodopa “wearing-off”
Dyskinesia, “On-Off” Motor Fluctuations
Postural Instability, Freezing, Falls, Dementia
DBS
Mild Moderate Severe
Levodopa, COMT inhibitors, others
Treatment
Patient Symptoms
Disease Severity
Agonists
Modified from Giroux, ML and Farris, SF. Cleveland Clinic Foundation 2005
Cleveland Clinic Foundation
Center for Neurological Restoration

16. When Should DBS be Considered?
When, despite optimized pharmacotherapy, your patient experiences troubling motor symptoms, which may include:
Wearing off – Off periods that contain troubling bradykinesia, rigidity, tremor, and/or gait difficulty
Troubling dyskinesia
Motor fluctuations
Refractory tremor

17. Optimal candidate for DBS
Presence of on-off fluctuations
Dyskenesia impairing quality of life
Medication resistant tremor
Reasonable cognitive function
Adequate response to dopaminergic therapy

18. DBS: When Pharmacotherapy isn’t Enough
As Parkinson’s disease progresses, medications may fail to provide consistent and adequate symptom control
Medications used at levels required for symptom control may produce adverse effects
Motor complications, such as dyskinesia
Cognitive and psychiatric problems
Nausea, hypotension, and other systemic effects

19. Approved Indications
DBS Therapy is approved for the treatment of symptoms due to:
Essential Tremor
FDA approved in 1997
Parkinson’s disease
FDA approved in 2002
Dystonia
FDA approved (HDE*) in 2003
Over 100,000 patients implanted worldwide
*Humanitarian Device: Authorized by Federal Law for the use as an aid in the management of chronic, intractable (drug refractory) primary dystonia, including generalized and segmental dystonia, hemidystonia, and cervical dystonia, for individuals 7 years of age and older.

20. Team Screening for DBS Neurologist Neurosurgeon Neuropsychologist
Physiatrist
Cost DBS $28, $50,000
Programming cost $3,000

21. Dopamine dysregulation syndrome
Impulse control disorder: gambling, shopping, hypersexuality,
Behavior disturbances: aggressive tendencies, fights, psychosis, compulsive eating
Punding: repetition of complex motor behaviors
Hypomania, mania, dysphoria

22. Surgery: Deep Brain Stimulation
Uses an implanted electrode to deliver high-frequency electrical stimulation to structures involved in the control of movement
This electrical stimulation overrides abnormal neuronal activity within brain regions to bring motor controlling circuits into a more normal state of function, thereby reducing movement disorder symptoms

23. DBS Therapy
Acts on cells and fibers closest to the electrode, changing firing pattern of individual neurons in BG
Triggers neighboring astrocytes to release Ca2+ and neurotransmitters
Increases blood flow, stimulates neurogenesis
Click screen to play

24. Target Sites for DBS Ventral Intermediate Thalamus: Essential Tremor
Subthalamic Nucleus: Parkinson’s disease and Dystonia
Globus Pallidus: Parkinson’s disease and Dystonia

25. DBS for Parkinson Disease
GPi
STN

26. Lesion therapy DBS Thalamotomy Subthalamotomy Pallidotomy
High risk with bilateral lesion
Programmable
Bilateral placement
Reversible effect

27. DBS Therapy Steps Inpatient admission for lead implant
Inpatient or outpatient admission for placement of implantable pulse generator.
Follow-up programming of IPG(s)
Rehabilitation

28. Inpatient Rehab Admission Criteria DBS Therapy
Patients may meet IRF admission criteria due to the change in clinical status:
Deep Brain Stimulation changes clinical status through symptom relief2
Presence of ADL deficits is a patient selection criteria for DBS Therapy
Intensive rehabilitation contributes to the success of DBS therapy by improving ADL deficits
2 Rehncrona S;Johnels B;Widner H;Tornqvist AL;Hariz M;Sydow O. Long-term efficacy of thalamic deep brain stimulation for tremor: Double-blind assessments.Mov Disord 2003 Feb;18 (2):

29. American Academy of Neurology - PD Guidelines
DBS is included in the AAN PD Guidelines (released in April 2006) with the following key points:
“Ten to 20% of people with Parkinson disease may be eligible for surgical treatment.”1
“Talk to your neurologist early in your disease to discuss the potential for future surgical treatment.”1
1AAN Guideline Summary for Patients and their Families: Medical and Surgical Treatment for
Motor Fluctuations and Dyskinesia in Parkinson Disease, 2006

30. 6 Months After Surgery Bilateral STN Activa® Implant
“ON” Time Without Dyskinesias Improves from 27% to 74% of a Patient’s Waking Day*
27%
19%
49% 7%
74%*
23%
In the prospective, randomised, double-bind, crossover multi-center study conducted by the Deep-Brain Stimulation for Parkinson's Disease Study Group, 96 patients with advanced, drug-refractory PD underwent bilateral stimulation of the STN with Activa® Therapy.
Patients completed a home diary documenting their motor status during the 2 days before each visit. Three motor states were identified: poor mobility (‘Off’), good mobility without dyskinesia (‘On’ without dyskinesia), and good mobility with dyskinesia (‘On’ with dyskinesia).
Assessments of the percentage of time with good mobility and without dyskinesia (‘On’ without dyskinesia) during the waking time increased from 27% at baseline to 74% at six months, a 3-fold gain. This was paralleled by a decrease in the percentage of time with poor mobility (‘Off’ state), from 49% to 19%.
Deep-Brain Stimulation for Parkinson's Disease Study Group. “Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson's disease.” N Engl J Med 2001; 345: 956–63.
PD = Parkinson’s disease; STN = subthalamic nucleus; DBS = deep-brain stimulation
Before Surgery
(n=96)
6 Months After Surgery Bilateral STN Activa® Implant
(n=91)
‘ON’ with Dyskinesia
‘ON’ without Dyskinesia
‘OFF’
* The Deep-Brain Stimulation for Parkinson’s Disease Study Group. Deep-brain stimulation of the subthalamic nucleus for the pars interna of the globus pallidus in Parkinson’s disease. N Eng J Med. 2001;345:

31. Motor Symptoms Improvements Maintained After 5 Years
In a 5-year study, DBS significantly improved OFF-medication assessments of tremor, rigidity, and akinesia/bradykinesia
OFF-Medication Motor Score Improvements*
6-month
1-year
3 years
5 years
Tremor
79%
75%
83%
Rigidity
58%
73%
74%
71%
Akinesia
42%
63%
52%
49%
*Results for STN

32. DBS efficacy for ET
69% of Essential Tremor patients experience total or significant suppression of disabling tremor *
This results in significant reduction in disability
Stimulation-induced adverse effects include transient paresthesia, dysarthria, and disequilibrium
Many of the side effects were temporary or improved with adjustment of electrical parameters
* Data on File. Medtronic, Inc.

33. “Conclusions: In this randomized controlled trial, deep brain stimulation was more effective than best medical therapy in alleviating disability in patients with moderate to severe PD with motor complications responsive to levodopa and no significant cognitive impairment.”
255 randomized patients
Follow-up at 6 months 33