Parkinson disease: Parkinson Disease

Transcription

1 Surgical Surgical treatment treatment for for Parkinson disease: Parkinson Disease the Present and the Future the Present and the Future Olga Klepitskaya, MD Associate Professor of Neurology Co-Director, Deep Brain Stimulation Center Olga Klepitskaya, MD University of Colorado Associate Professor University of Neurology of Colorado at Denver Denver Assistant Center Director, for Movement disorders and Movement Neurorestoration disorders Deep Brain Stimulation Center

2 Neurosurgery for Parkinson disease n 1890s - Lesions in basal ganglia n Pallidotomy n Thalamotomy n 1960s - Levodopa era n Late 1990s Deep Brain Stimulation n FDA approved in USA since 2002 n Standard of care in advanced PD n More then 100 thousand patients impanted

3 Deep Brain Stimulation Implanted electrode delivers continuous high frequency electrical stimulation to structures involved in the control of movements. n Reversible n Adjustable

4 DBS system components DBS electrode Programmer

5 Targets for DBS in PD STN Subthalamic Nucleus Gpi Globus Pallidus

6 Deep Brain Stimulation: surgery overview

7 Stereotactic frame

8 Surgical targeting Anatomical targeting MRI CT

9 Microelectrode Recording DBS lead = 5x thicker than a microelectrode! Model 3387: Four contacts over 10.5 mm Model 3389: Four contacts over 7.5 mm 1.27mm 10.5mm 0.25mm Recording signal from individual single neurons in basal ganglia

10 Mapping of the basal ganglia structures by single neuron microelectrode recording Border cells Sagittal Section STN SNr

11 Precision of placement of a DBS electrode in the subthalamic nucleus (STN) 3 DBS electrode Cognitive/ associative functions F a c e Complex movements A r m L e g L e g 1 2 A r m Simple voluntary movements F a c e Complex Forelimb Movement 0 Medial Voluntary eye movements Lateral MER is performed to identify the sensorimotor region of the STN

12 Test stimulation

13 Deep Brain Stimulation Programming parameters n Electrode configuration n Choice of active electrode n Monopolar vs bipolar n Pulse Width n Frequency n Amplitude Amplitude (V) [intensity of stimulation] Pulse width (µs) [duration of each stimulus] Frequency (Hz) [number of pulses per second]

14 Therapeutic effects of DBS in PD

15 B-STN DBS vs Medications

16 Therapeutic effects of DBS in PD Decrease dyskinesia Longer periods and better quality of mobility Improvement of quality of life Decrease medication intake

17 The expert consensus In carefully selected patients neurostimulation is a powerful treatment that alleviates the burden of advanced PD. The prospect of the improved quality of life should be weighted against the surgical risks.

18 Potential complications and risks n Surgery-related - uncommon n Stroke n Bleeding n Seizure n Transient confusion n Infection (more common and typically occurs at the site of generator) n Stimulation-related: n Usually can be minimized or eliminated by adjusting stimulation settings n Typically reversible tingling, muscle pulling, speech problems, balance imparement

19 Long- term effects of DBS on motor symptoms of PD

20 5 year follow up after B-STN DBS OFF-Medication Motor Score Improvements 6 m 1 y 3 y 5 y Tremor 79% 75% 83% 75% Rigidity 58% 73% 74% 71% Slowness 42% 63% 52% 49%

21 Review and meta-analysis of published literature, reporting long-term outcomes of STN DBS on motor function in PD patients

22 Review of published outcomes of STN DBS in PD n Analyze the long-term effects of STN DBS on the progression of motor disability, measured by UPDRS# n Compare the rate of progression with estimated expected natural progression. # n Results:# n 38 articles were included in the analysis. The total number of subjects was 1,341. # n The maximum follow-up time was 11.7 years. #

23 Long term effect of DBS on motor scores Expected score, based on natural progression Reported mean score

24 DBS in earlier stages of PD n n n n Controlled Clinical trial of DBStimulation for Early Patients with Parkinson disease. German Parkinson Study Group Prospective study to compare results of STN DBS between early-treated and late-treated PD patients. Italian Parkinson Association DBS for Early Stage Parkinson disease: prospective clinical trial. Vanderbilt University, USA Prospective, randomized, double-blind, placebocontrolled clinical trial evaluating safety and efficacy of DBS in early PD. Multicenter clinical trial, USA, approved, study initiation pending (UCD is participating)

25 Future of the DBS technology n On-demand stimulation System automatically adjusts stimulation based on ongoing changes in brain activity n More advanced electrodes n steering of electrical current n Surgical targeting technique n Implantation under direct MRI guidance n Clear Point technique available at UCH n Computerized programming process

26 Experimental surgical treatments n Fetal dopamine transplant n Spheramine n Human retinal pigment epithelial cells implantation n Trophic factor infusion n Gene therapy n Neurturin n GAD n Stem cells

27 Gene Therapy n Uses harmless virus as vehicle for gene delivery (viral vector) Brian Evans/Science Photo Library n Genetically engineered gene of a neurotransmitter or enzyme critical in pathological pathway causing PD symptoms n Surgically delivered to the part of the brain responsible for motor control n Virus replicates, increasing amount of neurotransmitter, leading to improvement of the PD symptoms

28 AAV2-GAD gene therapy for advanced Parkinson s disease: a double-blind, sham-surgery controlled, randomised trial Peter A LeWitt, Ali R Rezai, Maureen A Leehey, Steven G Ojemann, Alice W Flaherty, Emad N Eskandar, Sandra K Kostyk, Karen Thomas, Atom Sarkar, Mustafa S Siddiqui, Stephen B Tatter, Jason M Schwalb, Kathleen L Poston, Jaimie M Henderson, Roger M Kurlan, Irene H Richard, Lori Van Meter, Christine V Sapan, Matthew J During*, Michael G Kaplitt*, Andrew Feigin Lancet Neurol 2011; 10: Conclusion The efficacy and safety of bilateral infusion of AAV2-GAD in the STN supports its further development for PD and shows the promise for gene therapy for neurological disorders.

29 Questions Questions?