Although deep brain stimulation surgery (DBS) has been established as a superior treatment option for advanced Parkinson’s disease (PD) [
We performed a retrospective review of consecutive PD patients who underwent DBS implantation (subthalamic or internal globus pallidus) at our center from 2006 to 2011 and had near-complete charting. We collected two health status measures (HSM), the European Quality of Life 5-Dimension Questionnaire (EQ-5D) and the Unified Parkinson’s Disease Rating Scale, part 2: activities of daily living (UPDRS II) [the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale or MDS-UPDRS II was used for visits after 2008], for the following time points when available: latest preoperatively (within one month prior to surgery), 6 months postoperatively (range: 3–9 months), and 12 months postoperatively (range: 9–15 months). The EQ-5D is a standardized instrument for measuring health-related QOL in terms of five dimensions (5D), mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, producing a single index value for overall health status. In addition, we also conducted a one-item Patient Global Impression of Change Scale (PGIS) via phone/email survey using an IRB-approved phone/email script for all study subjects to provide additional long-term global outcome specific for this study. The PGIS aims at determining the patient’s global impression of his/her current state compared to the state prior to DBS surgery with the following possible answers: very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. The PGIS survey was distributed in mid-2011 (1 to 5 years from date of first surgery). To match our patient-perceived outcomes to clinicians’ perception of overall outcome after surgery, we also conducted a one-item Clinician’s Global Impression of Change Scale (CGIS) survey for study subjects. The CGIS aims at determining the clinician’s impression of the overall clinical change in each patient after surgery using the same 7-point anchor as the PGIS. The CGIS scores were retrospectively determined based on the full information derived from patients’ medical records and postoperative office visits during the same time periods when the PGIS was obtained.
The following potential clinical predictors were collected for all patients from their preoperative visits and operative reports: Disease factors: disease duration, dopaminergic burden (based on levodopa equivalent daily dose [LEDD] conversion), preoperative UPDRS part III motor subscale (MDS-UPDRS part III after 2008) in the ON state, presence of tremors, dyskinesia, freezing of gait (FOG), and falls/balance dysfunction. Clinical symptoms were based on the patients’ major complaints when presenting for DBS evaluation. Although these complaints were matched to their UPDRS III/MDS-UPDRS III subscores on exam, no formal score cutoffs were used for quantification. This was based, in part, on the difficulty of developing unified cutoff scores for the two different versions of the motor scale. More importantly, since this study was geared towards patients’ experience, we meant to put more emphasis on patient-reported symptoms rather than motor subscores as potential predictors of QOL and functional outcomes Patient factors: age, marital status, and body mass index (BMI) Surgical factors: surgery type (i.e., unilateral, staged bilateral, or simultaneous bilateral) and number of intraoperative microelectrode passes
To determine short-term and intermediate predictors of improved functional state and QOL, we created simple linear regression models where the 6-month and 12-month postoperative UPDRS II/MDS-UPDRS II score or EQ-5D index was the dependent variable. For each of these models, we adjusted for the preoperative score by including it in the model as a covariate. For each of the clinical predictors listed in Methods, we created a separate model where that predictor was the independent variable. The effect of each predictor on outcome is provided through estimated beta coefficients and associated 95% confidence intervals. Patients with missing data for certain time point were not included in the analysis for that time point.
To determine predictors of global outcomes based on patient’s and clinician’s perceptions, we dichotomized the responses in the PGIS and CGIS into “much improved” or “very much improved” versus all other responses. For categorical predictors, we computed the proportion and percent of patients with PGIS or CGIS of “much improved” or “very much improved.” Fisher’s exact tests were used to determine statistical significance. For continuous predictors, we created logistic regression models. We estimated odds ratios and computed 95% confidence intervals for each. Due to the exploratory nature of this study, we did not correct for multiple comparisons.
All analyses were conducted using R, version 3.0.1, and
There were 130 patients in the dataset. Overall, patients had an average age at time of surgery of 63.0 (±9.1) years, had PD for 10.7 (±5.1) years, had an average BMI of 27.5 (±5.2) kg/m2, and had an average LEDD of 1190 (±666). The cohort was more predominantly male (70.8%), white (86.9%), and married (66.9%). Of the 130 patients, 55 (42.3%) had unilateral surgery, 50 (38.4%) had bilateral staged surgery, and 25 (19.2%) had bilateral unstaged surgery. Most patients were implanted in the STN, 124 (95.3%).
Forty-five patients had both preoperative and postoperative data at 6 months and at 12 months. This group had mostly similar characteristics to the group with incomplete data except for having a younger average age (60.4 years,
There were 116 patients for which the CGIS could be completed from the available records. Of these, 19 (16.4%) were rated as “very much improved,” 63 (54.3%) as “much improved,” 23 (19.8%) as “minimally improved,” 6 (5.2%) as “no change,” 3 (2.6%) as “minimally worsened,” and 2 (1.7%) as “much worsened.”
There were 67 patients that completed the PGIS. Of these 67 patients, 29 (43.3%) reported “very much improved,” 25 (37.3%) reported “much improved,” 10 (14.9%) reported “minimally improved,” 2 (3.0%) reported “much worse,” and 1 (1.5%) reported “very much worse.”
Table
Beta estimates for health status measures collected at 2 follow-ups.
6 months postop. | 1 year postop. | ||||||
---|---|---|---|---|---|---|---|
|
Estimate (95% CI) |
|
|
Estimate (95% CI) |
|
||
UPDRS II | Age | 39 | −0.05 (−0.34, 0.23) | 0.7058 | 32 | 0.03 (−0.3, 0.36) | 0.8438 |
Disease duration | 38 | −0.45 (−1.00, 0.11) | 0.1127 | 31 | 0.21 (−0.56, 0.97) | 0.5859 | |
BMI | 37 | 0.49 (0.04, 0.94) |
|
32 | 0.68 (−0.002, 1.37) | 0.0507 | |
Laterality (versus unilateral) | |||||||
Staged bilateral | 39 | 1.16 (−4.58, 6.89) | 0.6849 | 32 | 0.53 (−6.75, 7.82) | 0.8819 | |
Simultaneous bilateral | 39 | −3.68 (−12.69, 5.32) | 0.4118 | 32 | −5.46 (−14.34, 3.42) | 0.2179 | |
Electrode passes (right) | 29 | 2.09 (−0.41, 4.60) | 0.0978 | 24 | 1.96 (−1.77, 5.69) | 0.2876 | |
Electrode passes (left) | 35 | −1.21 (−4.29, 1.87) | 0.4300 | 30 | −2.18 (−6.14, 1.78) | 0.2681 | |
Electrode passes (total) | 36 | 0.31 (−1.15, 1.76) | 0.6731 | 30 | 0.00 (−1.96, 1.97) | 0.9963 | |
% equivalent levodopa dose | 37 | 1.83 (−3.93, 7.58) | 0.5233 | 30 | 0.89 (−6.15, 7.94) | 0.7967 | |
On UPDRS III | 39 | 0.09 (−0.21, 0.38) | 0.5535 | 31 | 0.22 (−0.10, 0.54) | 0.1709 | |
Tremor | 39 | −0.95 (−5.78, 3.88) | 0.6909 | 32 | 1.35 (−4.41, 7.12) | 0.6345 | |
Dyskinesia | 39 | −2.46 (−7.28, 2.36) | 0.3072 | 32 | −2.06 (−7.86, 3.74) | 0.4736 | |
Freezing | 39 | 2.32 (−2.97, 7.62) | 0.3792 | 32 | 3.85 (−2.55, 10.26) | 0.2284 | |
Falls/balance | 39 | 6.48 (1.11, 11.84) |
|
32 | 6.45 (−0.38, 13.28) | 0.0634 | |
Marital status | 38 | −1.86 (−7.35, 3.63) | 0.4958 | 31 | 2.74 (−3.88, 9.36) | 0.4041 | |
|
|||||||
EQ-5D index | Age | 45 | 0.00 (−0.01, 0.00) | 0.3403 | 36 | 0.00 (−0.01, 0.01) | 0.9897 |
Disease duration | 43 | 0.01 (0.00, 0.02) | 0.1810 | 35 | −0.01 (−0.02, 0.00) | 0.0696 | |
BMI | 45 | 0.001 (−0.009, 0.011) | 0.8450 | 36 | −0.002 (−0.014, 0.011) | 0.7983 | |
Laterality (versus unilateral) | |||||||
Staged bilateral | 44 | 0.08 (−0.02, 0.19) | 0.1252 | 36 | −0.01 (−0.14, 0.12) | 0.9127 | |
Simultaneous bilateral | 44 | 0.13 (−0.04, 0.29) | 0.1351 | 36 | 0.003 (−0.15, 0.16) | 0.9654 | |
Electrode passes (right) | 33 | −0.02 (−0.06, 0.02) | 0.3494 | 28 | −0.03 (−0.09, 0.04) | 0.3837 | |
Electrode passes (left) | 38 | 0.04 (−0.02, 0.11) | 0.2006 | 32 | 0.07 (0.00, 0.14) | 0.0508 | |
Electrode passes (total) | 41 | 0.02 (−0.01, 0.05) | 0.2458 | 34 | 0.01 (−0.03, 0.04) | 0.6988 | |
Equivalent levodopa dose | 42 | −0.07 (−0.19, 0.04) | 0.2000 | 34 | 0.06 (−0.06, 0.19) | 0.3138 | |
On UPDRS III | 44 | −0.01 (−0.01, 0.00) |
|
35 | 0.00 (−0.01, 0.00) | 0.6310 | |
Tremor | 44 | 0.03 (−0.07, 0.13) | 0.5516 | 36 | 0.07 (−0.03, 0.17) | 0.1602 | |
Dyskinesia | 44 | −0.01 (−0.11, 0.09) | 0.8448 | 36 | 0.02 (−0.09, 0.12) | 0.7197 | |
Freezing | 44 | −0.03 (−0.13, 0.08) | 0.5955 | 36 | −0.09 (−0.19, 0.01) | 0.0762 | |
Falls/balance | 44 | −0.06 (−0.17, 0.05) | 0.269 | 36 | −0.12 (−0.23, −0.02) |
|
|
Marital status | 44 | −0.04 (−0.15, 0.08) | 0.4992 | 35 | −0.04 (−0.16, 0.07) | 0.4668 |
The BMI distribution in the patient group was as follows: underweight, 0 patients; normal weight, 12 patients; overweight, 16 patients; and obese, 15 patients. After excluding 2 outliers, the estimated effect of BMI on 6-month UPDRS II/MDS-UPDRS II score was significant (
Table
Patient Global Impression of Change Scale (PGIS) and Clinician’s Global Impression of Change Scale (CGIS) results by various categorical predictors.
% PGIS much improved or very much improved (proportion) |
|
% CGIS much improved or very much improved (proportion) |
|
|
---|---|---|---|---|
Tremor | 76.9% (20/26) | 0.7566 | 84.0% (42/50) |
|
No tremor | 82.1% (32/39) | 60.0% (42/70) | ||
|
||||
Dyskinesia | 83.7% (36/43) | 0.5167 | 64.2% (52/81) |
|
No dyskinesia | 75.0% (18/24) | 83.7% (36/43) | ||
|
||||
Freezing | 78.8% (26/33) | 0.7591 | 61.9% (39/63) |
|
No freezing | 82.4% (28/34) | 80.3% (49/61) | ||
|
||||
Falls/balance | 75.0% (21/28) | 0.3688 | 66.1% (41/62) | 0.3218 |
No falls/balance | 84.6% (33/39) | 75.8% (47/62) | ||
|
||||
Left unilateral | 75.0% (6/8) | 1.0000 | 63.6% (7/11) | 1.0000 |
Right unilateral | 77.8% (14/18) | 67.6% (23/34) | ||
|
||||
Unilateral | 76.9% (20/26) | 0.7906 | 66.7% (30/45) | 0.7741 |
Two-stage bilateral | 81.5% (22/27) | 73.1% (38/52) | ||
Unstaged bilateral | 85.7% (12/14) | 73.1% (19/26) |
There was no significant association between QOL, functional, or global outcomes and patients’ age, disease duration, laterality of surgery (unilateral versus bilateral), number of intraoperative electrode passes, LEDD, or marital status. However, some interesting trends were observed including a trend between shorter disease duration and more improvement in EQ-5D index at 1 year (
In this study, we looked at predictors of functional and QOL outcomes of DBS in a cohort of PD patients who underwent DBS under a standardized protocol. We explored a large number of potential predictors including several disease, patient, and surgical factors. We have previously reported the socioeconomic and cognitive data of the same cohort [
The presence of dyskinesia preoperatively was associated with somewhat poorer long-term global outcome in our study as represented by the CGIS. In 2011, Daniels and colleagues reported similar findings showing that patients with lower preoperative dyskinesia scores did better on QOL measures after surgery as represented by the Parkinson’s Disease Questionnaire-39 (PD-Q39) and the 36-Item Short Form Health Survey (SF-36) [
Our results agreed with both Welter’s and Daniels’ studies in confirming a role for preoperative UPDRS III motor score in predicting functional/QOL outcomes following DBS, with higher scores indicating worse outcomes, perhaps as a general indication of more advanced disease [
Studies of functional, QOL, and global impression outcomes after DBS in PD.
Study | Functional, QOL, or global impression scale | Significant predictors | Number of patients | Time lapse since surgery |
---|---|---|---|---|
Welter et al., 2002 | UPDRS II | (i) Age |
41 | 6 months |
|
||||
Daniels et al., 2011 | PD-Q39 |
(i) Daily off time (+ve) |
61 | 6 months |
|
||||
Soulas et al., 2011 | PD-Q39 |
(i) Age |
41 | 6 months and 12 months |
|
||||
Smeding et al., 2011 | PDQL | (i) L-dopa response at baseline (+ve) | 105 | 12 months |
|
||||
Maier et al., 2013 | Subjective perceived outcome | (i) Depression |
30 | 3 months |
|
||||
Floden et al., 2014 | PD-Q39 | (i) Depression |
85 | 8 months (average) |
|
||||
Genc et al., 2016 | MDS-UPDRS II |
(i) Household median income | 125 (43 for MDS-UPDRS II and EQ-5D) | 6 months and 12 months |
|
||||
Maier et al., 2016 | Subjective perceived outcome | (i) Apathy |
28 | 12 months |
|
||||
Abboud et al. | MDS-UPDRS II |
(i) Falls/balance dysfunction |
130 (45 FOR MDS-UPDRS II and EQ-5D) | 6 months and 12 months |
UPDRS II: Unified Parkinson’s Disease Rating Scale, part 2: activities of daily living; LED: L-dopa equivalent dose; PD-Q39: Parkinson’s Disease Questionnaire-39; SF-36: 36-Item Short Form Health Survey; PDQL: Parkinson’s Disease Quality of Life Questionnaire; MDS-UPDRS II: Movement Disorders Society-Unified Parkinson’s Disease Rating Scale, part 2: motor experience of daily living; EQ-5D: European Quality of Life 5-dimension Questionnaire; CGIS: Clinician’s Global Impression of Change Scale; PGIS: Patient Global Impression of Change Scale.
In addition to disease characteristics, our study suggests that certain patient characteristics, regardless of disease severity, may also influence functional and QOL outcomes after DBS. In addition to the impact of socioeconomic status, which we previously reported [
There are several limitations to our study. In addition to the retrospective nature of the study, the sample size was fairly small for the number of comparisons and the study may have been underpowered, especially for the functional and QOL outcomes. Nonetheless, the demographic features of the subset of patients with complete data versus the entire cohort showed largely similar demographics; therefore, we believe that this subset still represented the PD population who underwent DBS surgery. The slight difference in age between the two groups is probably attributed to the fact that younger patients are more familiar with technology and therefore more likely to complete computer-based surveys and assessment scales. Further studies utilizing larger patient cohorts are needed to better study predictors of functional and QOL outcomes following DBS. We did not look into other QOL measures that are more specific for PD such as the PDQ-39 due to limited availability of data in this cohort; however, PDQ-39 data were available in a more recent patient cohort and were recently published by our group in a separate paper as discussed earlier [
In conclusion, our study suggests that certain disease characteristics may influence outcomes after DBS. While the majority of the patients in our cohort were globally rated as significantly improved on global scales, falls and balance dysfunction, absence of tremors, presence of dyskinesia, freezing of gait, and preoperative motor severity as represented by UPDRS III/MDS-UPDRS III were the most influential predictors of poorer outcome. In addition, some previously underrecognized patient characteristics may also influence DBS outcomes such as higher preoperative BMI and lower socioeconomic status. By confirming known DBS outcome predictors and identifying new factors, we hope to provide new insights into the process of patient selection and risk stratification prior to DBS. Further prospective studies utilizing higher number of patients and combining both objective and subjective outcome measures should be performed to confirm or refute the results of our study.
This study was presented as an abstract at the 2015 International Parkinson’s and Movement Disorders Congress and at the 2016 American Academy of Neurology Annual Meeting.
Gencer Genc, Nicolas R. Thompson, Srivadee Oravivattanakul, Faisal Alsallom, Dennys Reyes, Kathy Wilson, Russell Cerejo, Xin Xin Yu, Darlene Floden, Ayman Ezzeldin, Hazem Marouf, Ossama Y. Mansour, Anwar Ahmed, and Michal Gostkowski report no conflicts of interest. Dr. Hesham Abboud is a consultant for Biogen, Genentech, and Genzyme. Dr. Andre Machado received personal compensation from IntElect Medical/Boston Scientific, ATI, Cardionomics, and Monteris for consulting services and is a consultant for Functional Neuromodulation, Spinal Modulation, and Icahn. He holds distribution rights from intellectual property in ATI, Cardionomic, and Enspire; fellowship support from Medtronic; and research funding from the National Institutes of Health. Dr. Hubert H. Fernandez has received honoraria from Advanced Health Media, Cleveland Clinic CME, Medical Communications Media, Movement Disorders Society, and Vindico Medical Education, as a speaker in CME events. Hubert H. Fernandez has received honoraria from Ipsen, Merz Pharmaceuticals, Pfizer, Teva Neuroscience, and Zambon Pharmaceuticals, as a speaker and/or consultant. Hubert H. Fernandez has received personal compensation for serving as Co-Medical Editor of the Movement Disorders Society Website. Hubert H. Fernandez has received royalty payments from Demos Publishing and Manson Ltd. for serving as a book author/editor. Hubert H. Fernandez has received research support from Abbott, Acadia, Biotie Therapies, EMD Serono, Huntington Study Group, Merck, Michael J. Fox Foundation, Movement Disorders Society, National Parkinson Foundation, NIH/NINDS, Novartis, Parkinson Study Group, Synosia, and Teva but has no owner interest in any pharmaceutical company.
Dr. Hesham Abboud was responsible for conception and design of the study, acquisition of data, interpretation of data, literature search, writing of the first draft, and revising the manuscript. Dr. Gencer Genc was responsible for acquisition of data, interpretation of data, literature search, and reviewing/revising the manuscript. Mr. Nicolas R. Thompson performed the statistical analysis and contributed to writing of the statistical methods and results. Drs. Srivadee Oravivattanakul, Faisal Alsallom, and Xin Xin Yu were responsible for acquisition and interpretation of data. Drs Dennys Reyes, Russell Cerejo, and Kathy Wilson designed the body mass index analysis and analyzed and interpreted the data. Drs. Darlene Floden, Michal Gostkowski, Anwar Ahmed, Ayman Ezzeldin, Hazem Marouf, Ossama Y. Mansour, and Andre Machado critiqued, reviewed, and revised the manuscript. Dr. Hubert H. Fernandez was responsible for the conception and design of the study and review, revision, and final approval of the manuscript. All persons who meet authorship criteria are listed as authors, and all authors certify that they have participated sufficiently in the work to take public responsibility for the content. Each author confirms that all authors have read the manuscript.