Deep Brain Stimulation: Patient selection Halim Fadil, MD Movement Disorders Neurologist Kane Hall Barry Neurology Bedford/Keller, TX
1991: Thalamic (Vim) DBS for tremor Benabid AL, et al. Lancet. 1991;337(8738):403-406.
1993: STN DBS for PD
1998: STN DBS for PD UPDRS II UPDRS III From Limousin P., et al. NEJM, 1998
1994: GPi DBS for PD
1999: Pallidal (GPi) DBS for Dystonia
DBS Important and established treatment for movement disorders: Disorder Essential tremor DBS target Ventral Intermedius nucleus of thalamus (Vim) Year of FDA approval 1997 Parkinson s Disease Subthalamic Nucleus (STN) or Globus Pallidus Internus (GPi) 2002 Dystonia GPi or STN 2003 (Humanitarian device exemption)
Effect of DBS on Motor Fluctuations Neurostimulation Medication From Deuschl G., et al. NEJM, 2006
VA/NINDS Cooperative Study 255 PD patients randomized to BMT (n=134) or bilateral DBS (n=121; 61 to GPi and 60 to STN) DBS BMT ON time without troubling dyskinesia + 4.6 Hrs = Motor function OFF medications (UPDRS III) - 12.3 Pts - 1.7 Pts p<0.01 Minimal clinically important improvement 71% 32% p<0.01 (5-point UPDRS III) Minimal clinically important worsening 3% 21% p<0.01 Weaver, F. M. et al. JAMA 2009;301:63-73.
Deep Brain Stimulation for PD Williams et al. Lancet Neurol 2010
DBS for PD: A growing Interest 450 400 350 300 250 200 150 100 50 0 1998 2000 2002 2004 2006 2008 2010 2012 Peer-Reviewed Publications
Deep Brain Stimulation Advantages Does not involve destructive brain lesions Bilateral procedures associated with minimal risk Potential to stimulate targets that one might be hesitant to lesion Stimulation settings can be adjusted to maximize benefit and minimize adverse effects Does not preclude future therapies that depend on the integrity of the basal ganglia Olanow et al. Neurology. 2001;56(suppl 5):S1-S88.
Deep Brain Stimulation Disadvantages Mechanical and infectious adverse effects associated with implanted device Need to periodically replace battery High cost Olanow et al. Neurology. 2001;56(suppl 5):S1-S88.
DBS Failures Percentage of cases 50 45 40 35 30 25 20 15 10 5 0 Poorly selected Poorly placed lead Poor programming Poor meds adjust Okun et al., Arch Neurol 2005
Successful DBS Therapy Appropriate patient selection Reasonable expectations on the part of the patient and his family Accurate implantation of DBS leads Optimal DBS programming Medication adjustments (when indicated) Management of long-term issues
Patient selection A major determinant of successful postoperative outcome
Parkinson s Disease Conditions of success: Certainty of diagnosis: Idiopathic PD Identification of most disabling motor symptoms Response to dopaminergic therapy Cognitive status: No dementia Mood and psychotic symptoms? Upper age limit?
Predictive Effect of Levodopa Response to levodopa treatment, as measured by change in the UPDRS-III score, correlates positively with postoperative improvement from stimulation (r = 0.58, p < 0.00001) Charles et al. 2002 Levodopa challenge test: at least 30 % improvement in UPDRS III pre-operative ON/OFF evaluation
DBS target In PD STN GPi
STN vs. GPi 60 UPDRS III scores 50 40 30 20 10 0 Baseline 6 mo 24 mo STN (n=147) Gpi (n=152) From Follett et al, NEJM 2010
The Ideal PD Candidate for DBS Age: 40-75 Symptomatic PD for 5-10 years or more Initial Good Response to L-DOPA Severe dyskinesia Marked on/off phenomena Minimal on-time without dyskinesias Frequent cycles (q3h or less) Substantial disability during off-periods Freezing/Gait Disturbance Cognitively Intact Realistic expectations Adequate Social support Access to programming of stimulators
Essential Tremor Indications of surgery? Certainty of diagnosis Severe symptoms with related disability Proper trial of pharmacological treatment. DBS anatomical Target Ventral Intermedius nucleus of the thalamus
ET Candidates for DBS Moderate to severe medication-resistant ET causing functional disability Issues Adequate therapeutic trial Disability Use of tremor rating scales Age generally not a major factor very elderly need careful preoperative assessment Cognitive status
Dystonia Candidates for DBS Primary generalized dystonia - Refractory to conventional medical therapies - Progressive physical and social disability - DYT1 positive (but not only) Segmental dystonia or hemidystonia progressing to severe disability Primary focal dystonia - Cervical dystonia unresponsive to botulinum toxin 6-14% primary botulinum toxin failures 3-10% lose benefit after initial success - Complicated by cervical myelopathy
In Summary DBS is an important and established treatment for essential tremor, Parkinson s disease, and dystonia Successful DBS therapy requires accurate DBS lead placement by a functional neurosurgeon and proper patient selection with competent programming by a movement disorder neurologist DBS therapy is indicated for patients with medication-refractory ET and primary dystonia, as well as patients with moderate to severe idiopathic PD that is complicated by motor fluctuations and/or medication-induced dyskinesias