Indications. DBS for Tremor. What is the PSA? 6/08/2014. Tremor. 1. Tremor. 2. Gait freezing/postural instability. 3. Motor fluctuations

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1 Indications Deep brain stimulation for Parkinson s disease A Tailored Approach 1. Tremor 2. Gait freezing/postural instability Wesley Thevathasan FRACP DPhil.Oxf 3. Motor fluctuations Consultant Neurologist, Melbourne University Hospitals NHMRC Research Fellow, Melbourne Brain Centre, University of Melbourne DBS for Tremor Tremor Subthalamic Nucleus (STN) Thalamus (VIM/VOP) Posterior Subthalamic Area (PSA) STN stimulation Also improves akinesia Most patients with tremor dominant PD Thalamic/PSA stimulation No impact on akinesia Old patients with tremor dominant PD What is the PSA? VIM/VOP (Thalamus) PSA (Posterior Subthalamic Area) 2 Components: 1. Caudal Zona Incerta 2. Prelemniscal Radiation Plaha et al, Brain

2 Where is the PSA? Trajectory through VIM/VOP PSA DBS for tremor Why PSA for tremor? Off On Lower stimulation amplitudes Less side effects? Easy to find! Nothing to lose! Can explore PSA under VIM/VOP Can span both with a 3387 electrode Herzog, Brain 2007 Sandvik et al, Neurosurgery 2012 Pedunculopontine nucleus (PPN) Gait freezing: Subthalamic Nucleus (STN) Pedunculopontine Nucleus (PPN) Substantia Nigra pars reticulata (SNr) PPN: Improves off and on freezing - No impact on akinesia, rigidity, tremor 2

3 Pedunculopontine nucleus (PPN) PPN: Improves off and on freezing - No impact on akinesia, rigidity, tremor The rare patient with gait freezing the main issue Off Stimulation PPN DBS: Gait Freezing On Stimulation Thevathasan et al, Neurosurgery 2011 PPN DBS: How much benefit? PPN DBS: How much benefit? Thevathasan et al, Brain 2012a Thevathasan et al, Brain 2012a PPN Where? Caudal PPN sweet-spot? Rostral PPN: Zrinzo et al, Brain 2008 Caudal PPN: Thevathasan et al, Brain 2012a Thevathasan et al, Brain 2012b 3

4 PPN DBS for postural instability? Stimulation off Stimulation on STN Improves off freezing and gait akinesia - Can worsen on freezing Evidence pending. Faist et al, Brain 2001 Moreau et al, Neurology 2008 STN + SNr DBS? (single 3387 electrode) Impact on gait freezing Weiss et al, Brain 2013 STN + SNr DBS (single 3387 electrode) STN + SNr DBS (single 3387 electrode) STN + SNr STN + SNr 4

5 Motor fluctuations: STN and GPi Who? When? Where? Who? Who? 1. Good on state Who? 1. Good on state 2. Low burden of non-motor issues Charles et al, Neurology 2002 Conventional timing: When? Severe fluctuations causing functional impairment e.g. Activities timed around good on-times Deuschl et al, NEJM

6 Early timing: A Revolution Early motor fluctuations in younger patients See writing on the wall Operate before lose too much quality of life The EARLY-STIM Cohort 1) Young: 60 years old 2) Mild fluctuations and/or dyskinesias - 1/3 had no dyskinesias - the observed off may be incomplete or even very mild - Average LDopa equivalent dose < 1000 mg 3) Mild impairment: - Social and occupational functioning or - Activities of daily living in the worst condition Schuepbach et al, NEJM 2013 Schuepbach et al, NEJM 2013 PD-MED PD-MED Initial treatment: LDopa Dopamine agonist/maob inhibitor PD-MED group, Lancet 2014 PD-MED group, Lancet 2014 PD-MED LDopa: Earlier dyskinesias Initial treatment: LDopa = better QOL PD-MED group, Lancet 2014 PD-MED group, Lancet

7 New Paradigm: 2 Honeymoons Early LDopa Early DBS (PD-MED) (EARLY-STIM) Where? STN. GPi STN or GPi? Postop titration: Medication and Stimulation Follett et al, NEJM 2010 Odekerken et al, Lancet Neurol 2013 My method My method Stun effect: Motor decay Low threshold for SE s Start low level DBS day 1, then slowly increase Stun effect: Motor decay Low threshold for SE s Start low level DBS day 1, then slowly increase Medication reduction: Affective issues Dopamine agonist withdrawal syndrome Restless legs Gradual taper of meds Leave on some agonist Leave on some LDopa 7

8 Compromise, compromise, compromise Insufficient stimulation Motor fluctuations Tremor Off Gait freezing Pain Excessive stimulation Motor Dyskinesia and On-Dystonia On Gait Freezing Postural instability Dysarthria Psychiatric Apathy Impulsivity Cognitive Dual tasking impairment Reduced verbal fluency The Future: Closed Loop Stimulation Patterned stimulation Current DBS: Open loop Continuous, unchanging Future DBS: Closed loop Feedback: Stimulation varies with biomarker of motor control What should that biomarker be? LFP Oscillations as Biomarkers STN Biomarker: Beta Oscillations STN/GPi: Beta PPN: Alpha Thalamus: Tremor frequency/harmonic Eusebio, Thevathasan et al, JNNP

9 Closed loop DBS with Beta biomarker Finely patterned stimulation Little et al, Annals of Neurology 2014 Tass et al, Annals of Neurology