Clinical Outcomes of Deep Brain Stimulator Electrodes Placed Using Intraoperative Computed Tomography and Frameless Stereotaxis Versus Microelectrode Recording and Frame-based Stereotaxis
Phase: NA
Conditions: Parkinson's Disease
Sponsor: Oregon Health and Science University

IRB Document Approval Date: 10/6/2016 
 
NCT Number: NCT01703598 
 
Title: Clinical Outcomes of deep brain stimulator electrodes placed using intraoperative computed 
tomography and frameless stereotaxis versus microelectrode recording and frame-based 
stereotaxis 
 
Principle Investigator: Matthew Brodsky, M.D. 
Department of Neurology         
 
Co-Investigators: 
Kim J. Burchiel, M.D., FACS. Department of Neurological Surgery 
 
 
 
Shannon Donovan, MPAS, P.A.-C Department of Neurology 
 
 
 
 
Joanna O’Leary, M.D.  
Department of Neurology 
 
 
 
Marvin Smith, DPT   
 
Department of Neurology 
Kitty Leelaamornvichet, DPT 
Department of Neurology 
Mara Seier, M.D. 
 
Department of Neurology 
 
 

Title: Clinical Outcomes of deep brain stimulator electrodes placed using intraoperative computed 
tomography and frameless stereotaxis versus microelectrode recording and frame-based 
stereotaxis 
 
Principle Investigator: Matthew Brodsky, M.D. 
Department of Neurology         
 
Co-Investigators: 
Kim J. Burchiel, M.D., FACS. Department of Neurological Surgery 
 
 
 
Shannon Donovan, MPAS, P.A.-C Department of Neurology 
 
 
 
 
Joanna O’Leary, M.D.  
Department of Neurology 
 
 
 
Marvin Smith, DPT   
 
Department of Neurology 
Kitty Leelaamornvichet, DPT 
Department of Neurology 
Mara Seier, M.D. 
 
Department of Neurology 
 
 
 
 
 
 
ABSTRACT 
 
Background: Frame-based stereotaxis and microelectrode recording (MER) with mapping of target 
structures has been the gold standard for deep brain stimulator (DBS) implantation.  Though supported 
by historical considerations, no Class I or II evidence exists that MER adds significant value to the DBS 
implant procedure. With the advent of advanced magnetic resonance imaging (MRI) and computed 
tomography (CT) imaging, particularly intra-operative imaging, the argument for the continued use of 
MER during DBS implantation has been substantially weakened.  One rationale for pursuing CT-guided 
intraoperative imaging is due to presumed increase in patient comfort with this method.  DBS 
implantation with MER requires that the patient remain awake during the entire procedure.  MER with 
frame-based stereotaxis requires the patient to keep their head in a fixed position for a prolonged period 
of time during which time they remain awake, causing significant patient discomfort. Furthermore, 
Parkinson’s disease patients must withhold their PD meds for a minimum of 12 hours prior to the 
procedure adding a sometimes significant degree of discomfort and anxiety to the procedure.  
 
Objective: The goal of this study is to compare the clinical outcomes of DBS electrodes placed using 
intraoperative CT and frameless stereotaxis with those placed using MER and frame-based stereotaxis. 
 
Design: The proposed study will be a prospective non-interventional data collection study. 
   
Setting and Subjects: Subjects for this study will be idiopathic Parkinson’s disease patients identified 
from the Oregon Health & Science University movement disorder clinic as candidates for deep brain 
stimulation therapy.  We will also enroll patients referred by community neurologists to OHSU for deep 
brain stimulation therapy for idiopathic Parkinson’s disease.  These patients will be recruited in the 
OHSU movement disorder clinic during their evaluation for the deep brain stimulation procedure.   
Enrollment will continue until fifty subjects meeting inclusion and exclusion criteria have been 
implanted with electrodes using frameless stereotaxis and intraoperative CT. Data regarding quality of 
life, motor control, and amount of time during the day without levodopa-associated side effects will be 
collected pre-operatively and post-operatively. This data will be compared to historical controls who 
have been implanted with DBS electrodes using MER and frame-based stereotaxis. This data will be 
obtained from consulting the Veterans Affairs cooperative study entitled, “Bilateral Deep Brain 
Stimulation vs Best Medical Therapy for Patients with Advanced Parkinson Disease” published in 
JAMA in 2009 (5). 
 
All surgical procedures will involve only Federal Drug Administration (FDA) approved stereotactic 
equipment, used in the manner for which they have been approved.  All clinic procedures are standard 
of care for movement disorders patients in the deep brain stimulation program.  

 
Intervention: This study will be a non-interventional data collection study. 
 
Measurements: Data regarding patient age, diagnosis, intracranial target, complications, Unified 
Parkinson’s Disease Rating Scale (UPDRS) Part 2 (activities of daily living), UPDRS Part 3 (motor 
examination), Parkinson’s Disease Quality of life (PDQ-39), 3 day motor diary, and neuropsychological 
evaluation. 
 
Analysis:   The patients will be examined prior to DBS placement both on and off dopaminergic 
medications.  All patients will receive their initial programming optimization visit approximately 30 
days after electrode implant.  The timing of further clinic visits for continued stimulator optimization 
will be up to the discretion of the DBS neurology provider and the patient.   All patients will present for 
a 6 month visit following electrode placement. This visit will include the following procedures:   
 
UPDRS Part 2 
 
UPDRS Part 3 
 
PDQ-39 
 
Review of motor symptom diary 
 
neuropsychiatric evaluation, including: 
· 
Beck Depression Inventory-II (BDI-II)  
· 
Mattis Dementia Rating Scale-Second Edition (DRS-2)  
· 
Wechsler Abbreviated Scale of Intelligence (WASI)  
We will also obtain information regarding adverse events directly related to surgery, falls and length of 
hospital stay. 
 
A. Specific Aims 
The objective is to compare the clinical outcomes of patients who receive placement of DBS electrodes 
by intraoperative CT scanning and frameless stereotaxis with those placed using frame-based 
stereotaxis and MER mapping for target verification The primary outcome measure is change in the 
motor section of the UPDRS in the OFF-levodopa state from pre-operative baseline to 6-month 
followup. 
 
B. Background  
Deep Brain Stimulation has become standard therapy for medically intractable Parkinson’s disease, 
Essential Tremor, congenital and acquired dystonias, and is currently being investigated in the 
treatment of other common disorders.  Class I evidence now supports its use in patients with advanced 
Parkinson’s disease, in comparison to best medical therapy (1).   
 
OHSU has been a pioneer in the development and use of DBS, and was the first center after Grenoble, 
France to perform DBS implantation.  The original FDA Investigational Device Exemption studies 
supporting DBS were conducted at OHSU in 1990-91.  Since then, OHSU was the first center to 
conduct a randomized prospective comparison study of subthalamic nucleus (STN) DBS v. globus 
Pallidus pars interna (GPi) DBS, the results of which have now largely been replicated in a multi-center 
protocol conducted by the US Department of Veterans Affairs  and the National Institutes of Health (2).   
 
Throughout the history of DBS implant procedures at OHSU, MER and mapping of target structures 
has been the gold standard.  However, it is highly unlikely that any future study will ever provide Class 
I evidence that MER adds significant value to the DBS implant procedure (3).  On the other hand, the 
best available evidence would indicate that MER does add risk to the DBS procedure; approximately 
1% chance of hemorrhage per MER pass.   
 

Prior to the routine use of advanced imaging in movement disorder surgery, MER provided the required 
degree of localization and verification of stereotactic target centers for movement disorder surgery.  
With the advent of advanced MRI and CT imaging, particularly intra-operative imaging, the argument 
for the continued use of MER during DBS implantation has been substantially weakened.  (4) 
 
In addition to the added risk of hemorrhage with MER there is also a presumed increase in discomfort 
for the patients during this procedure.  With MER, the patient must remain awake for the entire 
procedure, including frame-placement, magnetic resonance imaging, surgical incision and drilling of 
the site of insertion, MER, and closure of the site. Patients must also withhold dopaminergic 
medications for a minimum of twelve hours prior to the procedure creating a significant degree of 
discomfort and anxiety.   
 
With placement of DBS electrodes by intraoperative CT scanning and frameless stereotaxis, MRI is 
obtained prior to the procedure.  The patient is then taken to the operating room for anesthesia, the head 
is placed in a frame, CT scan is obtained, pre-operative MRI and intra-operative CT images are merged, 
the navigation site is determined, and DBS is placed surgically.   
 
Because the surgical targets have not changed, it is hypothesized that patient outcomes will be 
comparable to those seen using the traditional MER and frame-based surgery. Furthermore, it is 
believed that this procedure will prove to be the preferred technique both from a clinician stand point as 
well as the patient’s as it addresses many concerns patients have regarding deep brain stimulation 
surgery. 
 
 
C. Methods  
1. Subjects 
Fifty appropriate surgical candidates (Group 2), with Parkinson’s disease implanted using an 
intraoperative CereTom 8-slice CT scanner (NeuroLogica Corporation, Danvers, MA), StealthStation® 
treatment guidance system, (Medtronic Surgical Navigation Technologies Minneapolis, MN), and using 
the NeXframe frameless system (Medtronic, Minneapolis, MN) will form the study group.  Subjects 
will be identified through clinic visits and review of medical records.  Informed consent will be 
conducted in person or through a recruitment cover letter for telephone consent.  For telephone 
consenting, subjects will be given the opportunity to review the consent and discuss the study with the 
study team before they sign the consent or complete any study procedures.  The information collected 
from these patients will be compared to the published data on 121 DBS patients who underwent 
implantation of electrodes via frame based stereotaxis and MER for the treatment of Parkinson’s 
disease (Group 1). We will obtained de-identified data from theVA Cooperative study, “Bilateral Deep 
Brain Stimulation vs Best Medical Therapy for Patients With Advanced Parkinson Disease.”(5)  No 
medical records, source documents, or case report forms will need to be accessed to obtain the 
necessary values needed to compare the two groups. All procedures will involve only FDA approved 
stereotactic equipment, used in the manner for which they have been approved. Medtronic lead # 3387 
will be used for all DBS implants. 
 
a. Inclusion criteria  
1. Idiopathic Parkinson’s disease patients identified by OHSU movement disorders 
neurologists and community neurologists as deep brain stimulation surgical candidates 
who choose to undergo implantation of DBS electrodes using intraoperative computed 
tomography and frameless sterotaxis in the treatment of Parkinson’s disease  
a. Hoehn and Yahr stage 2 or greater while not taking medication 
b. Responsive to levodopa 

c. Persistent disabling symptoms (eg motor fluctuations, dyskinesia) 
despite medication 
d. Experienced 3 or more hours per 24-hour period with poor motor 
function or symptom control 
2. Surgical sites include subthalamic nucleus and globus Pallidus pars interna 
3. Age > 18 years 
 
b. Exclusion criteria 
1. Subjects with atypical parkinsonism or parkinsons-plus syndrome 
2. Subjects who have undergone implantation of DBS electrodes using MER and frame-
based stereotaxis or computed tomography and frameless stereotaxis in the treatment of 
other movement disorders.  
3. Other previous surgeries for Parkinson’s disease 
4. Age < 18 years 
5. Surgical target site other than subthalamic nucleus or globus Pallidus pars interna 
6. Subjects who choose to undergo MER and frame-based stereotaxis for the placement of 
electrodes. 
 
2. Study procedures 
As this is a non-interventional data collection study, we will obtain patient consent.  We will then 
compare the study group of 50 patients with the historical cohorts in the following measures:  UPDRS 
Parts 2, 3 and 4, change in PDQ-39, change in amount of time patient is experiencing Parkinson’s 
Disease symptoms and/or side effects of treatment, and neuropsychiatric evaluation. 
DBS settings will be optimized 30 (+/-3) days after electrode implantation.  Further DBS programming 
optimization will be performed at 60 (+/-3) and 90 (+/-3) days post-implantation. 
 
Studies 
Screening 
Baseline 
DBS 
Implant 
30 day 
post-
implant 
60 day 
post-
implant 
90 day 
post-
implant 
6 month 
follow-
up 
Informed consent 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
History & 
Physical 
 
X 
 
X 
X 
X 
X 
UPDRS Part 2 
 
X 
 
 
 
 
X 
UPDRS Part 3 
(ON and OFF) 
 
X 
 
 
 
 
X 
UPDRS Part 4 
 
X 
 
 
 
 
X 
DBS 
programming 
 
 
 
X 
X 
X 
 
PDQ-39 
 
X 
 
 
 
 
X 
Motor Diary 
 
X 
 
 
 
 
X 
Neuropsychiatric 
evaluation 
 
X 
 
 
 
 
X 
Adverse Events 
 
 
X 
X 
X 
X 
X 
Medications 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 

 
D. Data Analysis and Interpretation 
(1) Experimental design.  
The proposed study is a prospective data analysis to compare the clinical outcomes of DBS electrode 
placement using intraoperative CT and frameless stereotaxis versus an historical control of DBS 
electrode placement using MER with frame-based stereotaxis (5). 
  
(2) Analysis. 
The primary outcome will be a comparison of change in motor UPDRS (part 3) in the OFF 
medication/ON stimulation state at 6 months postoperatively between groups 1 and 2.  Analysis will be 
based on the intent-to-treat principle.  For patients without baseline data, follow-up data or both, the 
change score will be set to zero. The mean group change will be compared between treatment groups 
using a 2-sample t test.   
 
Secondary outcomes will be a comparison between groups 1 and 2 in the change from baseline to 6 
months in ON time without dyskinesia, PDQ-39, and UPDRS part 2.  In addition, a comparison will be 
made between groups 1 and 2 in the change from baseline to 6 months in the Beck Depression 
Inventory-II (BDI-II), Mattis Dementia Rating Scale-Second Edition (DRS-2), and the Wechsler 
Abbreviated Scale of Intelligence (WASI) , using a 2-sample t test.  The sample size and power 
calculations are 2-tailed with an α level of 0.05.   
 
 (3) Sample Size Calculations.  
Data from historical control patients using MER and frame-based stereotaxy (5) will be compared with 
50 patients who undergo DBS placement using frameless stereotaxis and intraoperative CT. 
 
E. Human Subjects 
1. Risks to Subjects:  As this is a non-interventional data collection study, no additional risks will 
be posed to the patients involved in this study.  The patients will be treated using accepted 
surgical techniques, such as planning and surgical execution and all steps will be carried out in 
the usual fashion of performing such procedures in the Department of Neurological Surgery at 
OHSU. All clinical outcome measures are standard of care in the movement disorders center 
for patients in the deep brain stimulation program. Patient confidentiality will be respected 
during information retrieval. 
 
2. Potential Benefits of the Proposed Research to the Subjects and Others: This research project 
proposed here aims to drive a paradigm shift, from MER verification of stereotactic targets, to 
an entirely image-based anatomic targeting methodology.  We would like to demonstrate non-
inferiority of the image-based anatomic targeting method in terms of treatment of Parkinson’s 
disease symptoms. 
 
The implications of this shift are: 
A. Increased patient comfort 
B. Operative procedures will be faster. 
C. Operative procedures will be easier, absent the requirement for MER equipment, 
macroelectrodes and electrophysiologic expertise.   
D. Most operative procedures can be performed entirely under general anesthesia. 
E. If intraoperative imaging is used, anatomic verification of the electrode position can be 
established prior to the patient leaving the operating room.   
F. Intraoperative images are provided to the neurologist which can be used to help guide 
selection of optimal programming configurations. 
 

3. Importance of Knowledge to be Gained: We project that this paradigm shift will simplify and 
enhance the patient experience, which will promote the use of DBS technology for an 
expanding list of indications and applications. Data collected and shared with neurosurgical 
colleagues will provide increased knowledge regarding accuracy of functional stereotactic 
procedures and help to improve outcome. 
 
F. References 
1. Deuschl G, Schade-Brittinger C, Krack P, et al. A randomized trial of deep-brain stimulation 
for Parkinson’s Disease. N Engl J Med. 355(9):896-908, 2006 
2. Burchiel KJ, Anderson VC, Favre J, Hammerstad JP. Comparison of pallidal and subthalamic 
nucleus deep brain stimulation for advanced Parkinson’s disease: results of a randomized, 
blinded pilot study. Neurosurgery. 45(6):1375-82, 1999. 
3. Burchiel KJ. The future of microelectrode recording. In: Microelectrode Recording in 
Movement Disorder Surgery. Eds: Israel Z and Burchiel KJ. New York: 2004. 
4. Ostrem et al.  Clinical outcomes of PD patients after bilateral STN DBS using high-field 
interventional MR-imaging for lead placement. Movement Disorders. 26 (Suppl 2): S77, 2011. 
5. Weaver FM et al. Bilateral Deep Brain Stimulation vs Best medical Therapy for Patients With 
Advanced Parkinson Disease JAMA 2009; 301(1): 63-73.