ABSTRACT
Background
Several studies examined the influence of subthalamic nucleus–deep brain stimulation (STN‐DBS) on quality of life (QoL) in patients with Parkinson's disease (PD). However, it is unclear whether this effect differs between age groups and disease durations and whether it stays consistent over time.
Objectives
We assessed the influence of stimulation duration, disease duration, and age at surgery on QoL after STN‐DBS.
Methods
We systematically searched for studies reporting the results of the Parkinson's Disease Questionnaire 39 or 8. Studies were included if they investigated the time passed since STN‐DBS or if their study cohort fell into the range of one of the following age groups: younger than 60 years or between 60 and 70 years. For each condition, a standardized mean difference meta‐analysis was performed. Furthermore, all studies were categorized into short or long disease duration at surgery using a median split.
Results
A total of 23 studies reporting the cumulative outcome of 76 to 802 PD patients were included in this analysis. The results demonstrate a substantial improvement of QoL after DBS that remains stable over 36 months. QoL falls to preoperative scores 60 months after surgery. However, only 3 studies could be included in this analysis. Both younger and older PD patients profit in QoL from STN‐DBS, independent of the disease duration.
Conclusions
The results of this analysis show an impressive improvement in QoL after STN‐DBS, with a loss of QoL 60 months after DBS surgery. This highlights the need to explore the factors influencing QoL after STN‐DBS to prevent or delay a decline in QoL.
Keywords: deep brain stimulation, Parkinson's disease, quality of life, age, follow‐up time
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well‐established treatment option for patients with Parkinson's disease (PD).1 As a result of its complex symptomatology, PD has a significantly negative impact on patients’ quality of life (QoL).2 Health‐related quality of life is the aspect of QoL that considers the physical, mental, and social factors that influence an individual's well‐being3 and is influenced by a variety of motor and nonmotor aspects in PD patients, such as depression, sleep problems, pain, motor fluctuations, and age.4, 5 Previous studies have already shown a significant improvement in QoL after 6 months following DBS.1, 6, 7 Given the invasive procedure of STN‐DBS, the longevity of QoL improvement is an important but less studied aspect of STN‐DBS. Identifying the time course of QoL after STN‐DBS may help to develop strategies to prevent or to delay the decline in QoL in the course of the disease. Furthermore, it is not clear whether there is a different susceptibility of different age groups to QoL following STN‐DBS. To our knowledge, only 2 studies have directly investigated the effect of age at surgery, including a short follow‐up after STN‐DBS6, 8 demonstrating a less pronounced effect of STN‐DBS on QoL in patients aged older than 70 years, but no significant difference between age groups. Furthermore, we are not aware of any study systematically comparing the effect of short and long disease duration on QoL following DBS. This meta‐analysis, therefore, aims to identify studies that provide information on change in QoL following STN‐DBS in patients with PD and to summarize and compare results from these studies with a specific focus on age and disease duration at intervention and time passed until the follow‐up investigation.
Methods
This review was based on the criteria of the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement.9
Eligibility Criteria
To keep the sample as homogeneous as possible, we only considered studies for this meta‐analysis in which the patients received bilateral subthalamic stimulation. QoL assessment had to be done with the Parkinson's Disease Questionnaire (PDQ)–3910 or its shorter version, the PDQ8.11 All PDQ means and standard deviations had to be provided, and the follow‐up period had to be at least 6 months after DBS surgery. Studies were categorized into at least 1 of the following 5 groups for the follow‐up analysis: 6 months, 12 months, 24 months, 36 months, or 60 months of follow‐up. The analysis of age groups was based on a categorization into at least 1 of 2 groups: age younger than 60 and an age from 60 to 70 years. Studies that fulfilled the inclusion criteria but did not fit into one of the aforementioned groups were excluded from the analysis. This review considered articles that were peer reviewed and published later than 2005 because at that time QoL became an outcome variable in DBS studies. Publications had to be written in English to be included.
Search Strategy
We performed an electronic search for relevant articles in 3 databases between July and September 2018. The search included PUBMED, ScienceDirect, and Scopus and was based on the following keyword combinations: Deep Brain Stimulation AND Quality of Life AND Parkinson's Disease; Subthalamic Stimulation AND Quality of Life AND Parkinson's Disease; Deep Brain Stimulation AND Quality of Life AND Parkinson's Disease AND PDQ. The search was performed independently by 2 investigators (C.B. and M.M.) and was completed by September 11, 2018. We excluded duplicates after the preselection process. During preselection, we screened the abstract of each article to check whether the study fits our research interest. All publications that were not excluded after the preselection were fully read to further verify their eligibility. The results were then compared by the investigators and discussed and corrected if necessary.
Main Outcome
A common tool for the assessment of quality of life in PD patients is the PDQ39, which consists of 39 items that are divided into 8 subscales. In sum, one can reach up to 100 points, with higher scores indicating worse QoL. The PDQ39 provides good reliability and validity as well as a good reproducibility.12 The sum of all PDQ items reflects the summary index that can be used for an interpretation of health‐related QoL. The summary index by itself has been found to provide high levels of reliability and validity as well.10 It has also been found to correlate positively and significantly with depression, cognitive performance, and disease severity.4, 5 However, no correlation was shown with age and disease duration. A shorter version of the PDQ39 is the PDQ8, which consists of 8 items, each of which represents 1 subscale of the PDQ39. The PDQ8 provides lower reliability and validity than the PDQ39; however, it is quicker to administer.11
Risk of Bias Assessment
To guarantee a systematic risk of bias evaluation, the authors followed the Cochrane handbook for meta‐analyses.13 For all included studies, the risk of bias was rated (Table S1).
Meta‐Analysis
All relevant information from the eligible studies was extracted. The variables that were considered in the current analysis were sample sizes, pre‐DBS PDQ mean score, pre‐DBS PDQ standard deviation, post‐DBS PDQ mean score, and post‐DBS PDQ standard deviation. In total, we conducted 9 meta‐analyses. Five meta‐analyses were performed considering the time of follow‐up (6 months, 12 months, 24 months, 36 months, and 60 months), 2 analyses were performed dividing the studies into long and short disease duration at surgery according to a median split, and 2 analyses were performed considering age (younger 60 years and 60–70 years). An investigation of an older sample was not possible because of the low availability of studies investigating such a sample. To avoid possible heterogeneity because of 2 different PDQ versions, this meta‐analysis was performed using the standardized mean difference. Analyses were performed using the meta package in R.14 Data were analyzed using a random effects analysis because we cannot assume that the variance in effect size only results from sampling errors. Furthermore, we compared the outcome of the single meta‐analyses in the condition “disease duration” and “age” using a 2‐sided Mann‐Whitney U test in R. The nonparametric test was used because of the small sample size and the heterogeneity in most of the analyses. A Mann‐Whitney U test for the condition “follow‐up period” was not performed because of the extreme difference in sample size.
Results
Literature Search and Study Inclusion
With respect to our inclusion criteria, we identified a total number of 366 articles that initially fitted the research topic. The selection process is displayed in Figure 1. After the exclusion of duplicates, a total of 169 articles were left. A further reduction was based on full text. Based on the abstracts that did not meet the inclusion criteria, we read 78 full‐text articles. A further exclusion left us with a total of 23 articles that we included in out meta‐analysis (Table 1).
Figure 1.
Flowchart describing the literature search process. Suitable studies for the meta‐analysis were selected following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement. DBS, deep brain stimulation; PDQ, Parkinson's Disease Questionnaire; STN, subthalamic nucleus.
Table 1.
Studies that were included in the meta‐analyses, providing baseline and postoperative PDQ score
| Author | Year | Sample Size | Baseline PDQ Score (mean ± SD) | Month of Follow‐Up (mean ± SD) | Follow‐up PDQ Score | Mean Age at Surgery | Disease Duration at Surgery | Gender (% Male) | Analysis |
|---|---|---|---|---|---|---|---|---|---|
| Dafsari et al.29 | 2018 | 87 | 34.5a (16.4) | 6 | 23.8a (14.4) | 61.2 | 10.5 | n.r. | 6‐month follow‐up, 60–70 years |
| Dafsari et al.26 | 2018 | 48 | 34.7a (16.1) | 6 | 24.9a (15.9) | 60.9 | 10.3 | n.r. | 6‐month follow‐up, 60–70 years |
| Chan et al.30 | 2016 | 18 | 47.1 (10.9) | 12 | 32.1 (11.4) | 55 | n.r. | 68 | 12‐month follow‐up, <60 years |
| 18 | 47.1 (10.9) | 24 | 28.3 (18.6) | 55 | n.r. | 68 | 24‐month follow‐up | ||
| Yamamoto et al.31 | 2016 | 31 | 33.63 (2.7) | 12 | 28.29 (2.72) | 66.7 | 11.6 | n.r. | 12‐month follow‐up, 60–70 years |
| 12 | 33.63 (2.7) | 36 | 28.08 (5.61) | 66.7 | 11.6 | n.r. | 36‐month follow‐up | ||
| 7 | 33.63 (2.7) | 60 | 42.05 (7.77) | 66.7 | 11.6 | n.r. | 60‐month follow‐up | ||
| Dafsari et al.32 | 2016 | 60 | 33.23 (17.96) | 6 | 24.74 (16) | 61.6 | 10.45 | 58 | 6‐month follow‐up |
| Sobstyl et al.33 | 2014 | 16 | 35.4 (6.6) | 12 | 24.7 (4.2) | 63.5 | n.r. | 69 | 12‐month follow‐up, 60–70 years |
| 16 | 35.8 (6.9) | 24 | 26 (3.9) | 63.5 | n.r. | 69 | 24‐month follow‐up | ||
| Williams et al.6 | 2010 | 162 | 37.5 (14.6) | 12 | 32.5 (15.08) | 59 | 11.5 | 68 | 12‐month follow‐up,<60 years |
| Drapier et al.34 | 2005 | 27 | 44.1 (10.9) | 12 | 34.8 (12.3) | 60.8 | 14.6 | 70 | 12‐month follow‐up, 60–70 years |
| Dafsari et al.35 | 2018 | 65 | 33.3 (17.4) | 24 | 30.6 (18.5) | 62.3 | 10.9 | 74 | 24‐month follow‐up |
| Dafsari et al.8 | 2017 | 44 | 34.9 (12.9) | 6 | 22.6 (16.2) | 53.2 | 10.5 | 59 | <60 years |
| 50 | 43.8 (17.9) | 6 | 23.7 (13.5) | 64.7 | 11.1 | 66 | 60–70 years | ||
| Lezcano et al.20 | 2016 | 64 | 41.1 (14.1) | 12 | 26.1 (14.1) | 61.3 | 13.2 | n.r. | 12‐month follow‐up, 60–70 years |
| 54 | 41.1 (14.1) | 60 | 37.5 (16.5) | 61.3 | 13.2 | n.r. | 60‐month follow‐up, | ||
| Jiang et al.21 | 2015 | 10 | 32.4 (14.1) | 12 | 19.8 (8.5) | 59.4 | 9.3 | 60 | 12‐month follow‐up, <60 years |
| 10 | 32.4 (14.1) | 36 | 13.5 (10.5) | 59.4 | 9.3 | 60 | 36‐month follow‐up | ||
| 10 | 32.4 (14.1) | 60 | 26.1 (9.7) | 59.4 | 9.3 | 60 | 60‐month follow‐up | ||
| Soulas et al.28 | 2011 | 37 | 49.89 (11.6) | 6 | 41.68 (13.67) | 62 | 14.5 | n.r. | 6‐month follow‐up, 60–70 years |
| 35 | 49.89 (11.6) | 12 | 39.12 (16.09) | 62.7 | 15.4 | n.r. | 12‐month follow‐up | ||
| Nazzoaro et al.36 | 2011 | 24 | 32.4 (14.2) | 12 | 17.2 (9.6) | 64.2 | 10.6 | 67 | 12‐month follow‐up, 60–70 years |
| Weaver et al.37 | 2009 | 121 | 44.9 (13.2) | 6 | 37.3 (16) | 62.4 | 10.8 | n.r. | 6‐month follow‐up, 60–70 years |
| Lyons et al.38 | 2005 | 59 | 41.7 (11.8) | 12 | 28.2 (13.6) | 58.5 | 11.5 | n.r. | 12‐month follow‐up, <60 years |
| 43 | 41.7 (11.8) | 24 | 32.7 (14.6) | 58.5 | 11.5 | n.r. | 24‐month follow‐up | ||
| Follett et al.39 | 2010 | 147 | 46.9 (12.6) | 24 | 42.7 (15.6) | 61.9 | 11.1 | 79 | 24‐month follow‐up |
| Tykocki et al.40 | 2012 | 74 | 64.95 (30.09) | 6 | 37.32 (16.53) | 55.6 | 12.3 | n.r. | 6‐month follow‐up, <60 years |
| 74 | 64.95 (30.09) | 12 | 39.51 (17.54) | 55.6 | 12.3 | n.r. | 12‐month follow‐up | ||
| 74 | 64.95 (30.09) | 24 | 43.15 (20.54) | 55.6 | 12.3 | n.r. | 24‐month follow‐up | ||
| Weaver et al.22 | 2012 | 67 | 48.1 (13.2) | 6 | 37.9 (17) | 60.7 | 11.3 | 80 | 6‐month follow‐up, 60–70 years |
| 66 | 48.1 (13.2) | 24 | 39.5 (15.3) | 60.7 | 11.3 | 80 | 24‐month follow‐up | ||
| 62 | 48.1 (13.2) | 36 | 44 (15.1) | 60.7 | 11.3 | 80 | 36‐month follow‐up | ||
| Schuepbach et al.7 | 2013 | 124 | 30.2 (15.59) | 24 | 22.4 (13.32) | 52 | 7.5 | 71 | 24‐month follow‐up |
| 124 | 30.2 (15.59) | 12 | 20.3 (13.32) | 52 | 7.5 | 71 | 12‐month follow‐up,<60 years | ||
| Deuschl et al.1 | 2006 | 48 | 41.8 (13.9) | 6 | 31.8 (16.3) | 60.5 | n.r. | 64 | 6‐month follow‐up, 60–70 years |
| Daniels et al.41 | 2011 | 60 | 41.1 (13.8) | 6 | 29.9 (11.9) | 59.7 | 13 | n.r. | 6‐month follow‐up, <60 years |
| Lewis et al.42 | 2014 | 28 | 36.84 (13.76) | 12 | 30.84 (14.07) | 61.2 | 12.4 | 61 | 12‐month follow‐up, 60–70 years |
PDQ8 was used to measure quality of life.
n.r., not reported; PDQ, Parkinson's Disease Questionnaire.
Results of the Meta‐Analysis: Changes in QoL at Different Time Points After STN‐DBS
6 Months
A total of 9 studies investigated the effect of DBS on QoL 6 months after surgery with a total sample size of n = 802. Across studies, the mean age was 60.7 years, and the disease duration at surgery was 11.6 years. One study did not report the mean disease duration at the time of surgery. The meta‐analysis revealed a significant improvement in QoL with a standardized mean difference (SMD) to the baseline scores of SMD = 0.70 (95% confidence interval [CI], 0.58–0.82), z = 11.34, P < 0.01.
12 Months
For the follow‐up of 12 months, we found 13 studies (n = 615) that matched our eligibility criteria. The mean age across studies was 60 years, and the disease duration was 11.8 years at surgery. A total of 2 studies did not report the mean disease duration at the time of surgery. We found a significant improvement to baseline scores of SMD = 1.03 (95% CI, 0.74–1.32), z = 6.89, P < 0.01.
24 Months
A total of 7 studies with a total sample size of 510 were included for the analysis of a 24‐month follow‐up. Across studies, the sample showed a mean age of 58.2 years and a disease duration of 10.7 years at surgery. A total of 3 studies did not report the mean disease duration of their sample. The meta‐analysis revealed a significant improvement of SMD = 0.63 (95% CI, 0.35–0.91), z = 4.47, P < 0.01 when compared with baseline scores.
36 Months
Studies investigating a follow‐up of 36 months (n = 84) showed a mean age of 62.3 years and a mean disease duration of 10.7 years at the time of surgery. The meta‐analysis showed a SMD = 0.88 (95% CI, 0.07–1.70), z = 2.13, P = 0.03, still revealing a significant result. Here, we only included 3 studies, with a high heterogeneity of I2 = 72.8%.
60 Months
A total of 3 studies were included (n = 76) in the analysis after 60 months that also were highly heterogeneous (I2 = 82.7%). The mean age across studies was 62.5 years with a mean disease duration of 11.4 years at surgery. After 60 months, the patients’ QoL decreased back to a level that is not significantly different to baseline scores and even showed a negative SMD: SMD = −0.18 (95% CI, −1.18 to 0.81), z = −0.36, P = 0.72). A forest plot showing the results of the analyses following 6 and 60 months can be found in Figure 2. A graphical description of the SMDs at each follow‐up period can be seen in Figure 3.
Figure 2.
Forest plot of the follow‐up of 6 months (A) and 60 months (B) showing SMD and weights for the fixed and random effects analysis. Experimental condition = pre‐DBS PDQ score; control condition = post‐DBS score. CI, confidence interval; DBS, deep brain stimulation; PDQ, Parkinson's Disease Questionnaire; SD, standard deviation; SMD, standardized mean difference.
Figure 3.
Standardized mean difference for each meta‐analysis over 60 months of follow‐up. The graph shows an improvement from baseline up to 36 months following deep brain stimulation. After 60 months, the Parkinson's Disease Questionnaire scores returns to baseline.
Results of the Meta‐Analysis: The Influence of Age on Changes in QoL After STN‐DBS
Both age groups showed a significant QoL improvement up to 12 months following DBS.
Age Younger Than 60 Years
A total of 7 studies (n = 552) with a sample mean age younger than 60 years were included in the analysis. The mean age across studies was 56.6 years, and patients showed a PDQ SMD = 0.85 (95% CI, 0.60–1.10), z = 7.53, P < 0.01.
Age 60 to 70 Years
A total of 13 studies with a total sample size of 718 patients that investigated patients who were operated on between the age of 60 and 70 were included. The unweighted mean age of this sample was 62 years, and this cohort showed a SMD = 0.86 (95% CI, 0.63–1.08), z = 7.53, P < 0.01. For an overview of the results, see Figure 4. Comparing the 2 age groups, the Mann‐Whitney U test revealed a P = 0.43 (W = 40.5).
Figure 4.
Forest plot of age group <60 (A) and 60 to 70 years (B) 6‐month to 12‐month after surgery showing the SMD and the weights for the fixed and random effects analysis. Experimental condition = pre‐DBS PDQ score; control condition = post‐DBS condition. CI, confidence interval; DBS, deep brain stimulation; PDQ, Parkinson's Disease Questionnaire; SD, standard deviation; SMD, standardized mean difference.
Results of the Meta‐Analysis: The Influence of Disease Duration on Changes in QoL After STN‐DBS
All studies that reported the mean duration of disease at surgery of their sample and investigated QoL prior and 6 or 12 months following DBS were included in the analysis. The distribution of the 2 groups into short and long disease duration was based on a median split at 11.5 years. Both groups showed a significant QoL improvement up to 12 months following DBS.
Disease Duration at Less Than 11.5 Years
A total of 8 studies (n = 541) with a short disease duration according to the median split at less than 11.5 years at surgery were included in this analysis. The mean age across studies was 60.3 years, and the mean disease duration was 10.09 years at intervention. The PDQ SMD = 0.64 (95% CI, 0.52–0.77), z = 10.28, P < 0.01.
Disease Duration More Than 11.5 Years
A total of 9 studies (n = 542) were included in the analysis of the impact of long disease duration at surgery on QoL after DBS. The unweighted mean age of this sample was 60.53 years, with a disease duration of 12.78 years. The standardized mean difference of this sample was the following: SMD = 0.83 (95% CI, 0.50–1.17), z = 4.89, P < 0.01. For an overview of the results of both analyses, see Figure 5. Comparing the groups with short and long disease duration, the Mann‐Whitney U test revealed a P = 0.48 (W = 44).
Figure 5.
Forest plot of short (<11.5 years; A) and long (>11.5 years; B) disease duration 6 to 12 months after surgery showing the SMD and the weights for the fixed and random effects analysis. Experimental condition = pre‐DBS PDQ score; control condition = post‐DBS condition. CI, confidence interval; DBS, deep brain stimulation; PDQ, Parkinson's Disease Questionnaire; SD, standard deviation; SMD, standardized mean difference.
Risk of Bias in the Included Studies
A detailed overview of the risk of bias assessment can be found in Table S1. This was used to rate the quality of the studies included in this meta‐analysis. We present the assessment ratings in Table S2. The risk of distortion of the results is considered to be rather low because the single assessments of each study seem to show a low risk of bias.
Conclusion
The present meta‐analyses included 3 to 23 STN‐DBS studies to analyze the QoL changes in 76 to 803 patients. First, the analysis revealed a substantial improvement in QoL up to 36 months following surgery. Second, the follow‐up analysis showed that 60 months after surgery the QoL levels returned to baseline scores. Third, patients younger than 60 years of age and those between 60 to 70 years of age equally profited from STN‐DBS in terms of QoL. The same becomes evident for patients with a disease duration less than 11.5 years and a disease duration more than 11.5 years at the time of surgery. Both patient groups demonstrated a significant improvement of QoL after STN‐DBS without a significant difference between both groups.
QoL Follow‐Up to 36 Months After STN‐DBS
In comparison with the baseline score, the meta‐analysis showed an improvement in PDQ‐39 score of −9 points after 6 months, −12.3 points after 12 months, −6.3 points after 24 months, and − 9.5 points 36 months after surgery. This improvement in QoL clearly exceeds the minimal clinically important improvement of the PDQ‐39 with a threshold of −4.72 points.15 It also exceeds the improvement in PDQ‐39 achieved by the administration of levodopa (improvements range between −1.9 to −6 points), catechol‐O‐methyltransferase inhibitors (improvements range between −0.7 to −7.1 points) and dopamine agonists (improvements range between −0.8 to −6.9 points).16 In advanced PD continuous intrajejunal infusion of levodopa–carbidopa intestinal gel improves PDQ‐39 up to −10 points.17 For subcutaneous apomorphine infusion, the PDQ changes range between −0.06 and − 13.2.18, 19 In contrast to STN‐DBS, the effect of medication was tested in a short follow‐up of between 8 weeks to 6 months, and the longevity of a positive effect on QoL is lacking. Given the invasive therapeutic approach of STN‐DBS, the longevity of QoL improvement is important.
QoL Follow‐Up 36 to 60 Months After STN‐DBS
Our results show that QoL returns back to baseline levels after 60 months following DBS. Of note, the high heterogeneity of the 36‐month follow‐up data and the 60‐month follow‐up data, respectively, may question the predictive value when exactly QoL starts to decrease after STN‐DBS. However, a return to PDQ‐39 baseline levels has consistently been observed in all studies investigating QoL 5 years after DBS.20, 21, 22 The PDQ provides an overview over the subjective well‐being of the patient and could be affected by the satisfaction paradox,23 which is known as the discrepancy between expectations derived from objective data and the subjective self‐appraisal by the patient. A patient adapts to their situation and physical disabilities and therefore rates their QoL better than it would be expected. An intervention such as DBS would drastically improve the perceived QoL before the patient's subjective perception adapts. However, the decline in QoL 5 years after DBS may not be in accordance with the time course of the subjective perceived changes in QoL.
Because motor performance is still improved when compared with baseline after 5 years24, 25 and nonmotor symptoms have a strong impact on QoL,4, 5 it can be assumed that nonmotor symptoms are relevant for the decline in QoL 60 months after STN‐DBS surgery. In this line of argumentation, it has been shown that the improvement in nonmotor signs and symptoms after STN‐DBS significantly accounts for QoL improvements even in the short‐term follow‐up.26 Identifying the time course of QoL after STN‐DBS helps to develop strategies to prevent or to delay the decline in QoL in the course of the disease. Future studies are needed to identify the factors important for the loss of the beneficial effect of STN‐DBS on QoL.
The Influence of Age at STN‐DBS Surgery on QoL Changes
The results of our analysis do not show a difference in QoL improvement between patients younger than 60 years and patients in the age range between 60 and 70 years. Because of a lack of studies investigating separate groups of younger and older patients during a longer period of time and a lack of studies investigating PD patients older than 70 at the time of surgery, we were not able to investigate these relevant questions. Of note, the mean ages of the 2 groups analyzed in the present study differed only by 5 years, which may account for the nonsignificant result. Although some studies detected a beneficial effect of STN‐DBS on both younger and older PD patients,8, 27 other studies could not replicate these findings.6 Most studies reported that a younger age at surgery was associated with a stronger benefit in QoL after surgery.8 Given the fact that age in general and specifically in PD is an influential factor on QoL, one might assume that the younger patients’ potential for an improvement in QoL can be expected as more modest that in more advanced PD. In the controlled trial of deep brain stimulation in early patients with Parkinson's disease (EARLYSTIM) study,7 patients younger than 60 years with early motor complications were enrolled. The results of this study invalidate this assumption because the study clearly showed that even younger patients with a shorter duration of disease benefit from STN‐DBS in terms of QoL.
The Influence of Disease Duration at STN‐DBS Surgery on QoL Changes
This analysis found no difference in QoL improvement between patients with a shorter disease duration and those with a longer disease duration at surgery. Both patient groups showed a significant improvement in QoL 6 to 12 months following DBS. It is important to note that a common disease duration for studies investigating QoL following DBS is 11.1 to 13.8 years7 and that the mean disease duration of at least 1 meta‐analysis falls into that range. However, Soulas and colleagues28 found that patients with a long disease duration profited from DBS in terms of improved QoL up to 12 months following surgery. The EARLYSTIM study7 further showed that even patients with a disease duration of only 7.5 years showed a benefit in QoL when compared with a medical control group. This study was only followed up until 24 months after surgery. It would be of interest to know whether this improvement further consists for a longer period of time.
Limitations
This analysis also holds a number of limitations. Apart from the 6‐month follow‐up analysis and the analysis of short disease duration at surgery, the statistical heterogeneity of the studies included may question the predictive value. Furthermore, the analysis of 36 and 60 months of follow‐up did not include enough studies to come to a confident conclusion. However, the results of these analyses show a course of QoL that returns to the preoperative status. This result highlights the necessity of further longitudinal studies. In the analysis of age groups and disease duration, it is important to note that we included both 6 and 12 months of follow‐up to increase the sample size of studies to be investigated, but we do not consider that a problem because the results of the follow‐up analyses show a similar trend in both analyses.
The results of this analysis show a significant QoL improvement up to 36 months following STN‐DBS, followed by a decrease back to preoperative QoL status 60 months after STN‐DBS. Furthermore, the analysis revealed that both age groups (younger than 60 years or 60–70 years) as well as patients with long and short disease durations benefit in QoL after STN‐DBS. This study stresses the clinician to specifically screen QoL in the time frame between 36 and 60 months to detect and to react to a loss of QoL in PD patients with STN‐DBS. Future research should identify in more detail the time course of QoL after STN‐DBS and disentangle the factors relevant for a loss of QoL. This may help to develop strategies to prevent or delay the decline in QoL in the course of the disease after STN‐DBS.
Author Roles
1. Research project: A. Conception, B. Organization, C. Execution 2. Statistical analysis: A. Design, B. Execution, C. Review and Critique 3. Manuscript preparation: A. Writing of the first draft, B. Review and Critique
C.B.: 1C, 2A, 2B, 3A
M.M.: 1C, 2A
K.J.: 2C, 3B
K.W.: 1B, 2C, 3A
Disclosures
Ethical Compliance Statement: We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. The authors confirm that the approval of an institutional review board as well as patient consent was not required for this work. Since this meta‐analysis did not deal with patient data, no informed consent was obtained.
Funding Sources and Conflicts of Interest: No specific funding was received for this work.
Financial Disclosures for the Previous 12 Months: K.W. received reimbursement of congress fees from BIAL and Desitin and received speaker honoraria from BIAL, Boston Scientific, Medtronic, and UCB. He received royalties from Thieme publishers and Elsevier. He received grants from the Federal Ministry of Education and Research and the German Research Foundation. K.J. received grants from Abbvie.
Supporting information
Figure S1. Forest plot of the follow‐up period of 12 months showing the SMD and the weights for the fixed and random effects analysis of each study. Experimental condition = pre‐DBS PDQ score; control condition = post‐DBS score after 12 months. DBS, deep brain stimulation; PDQ, Parkinson's Disease Questionnaire; SMD, standardized mean difference.
Figure S2. Forest plot of the follow‐up period of 24 months showing the SMD and the weights for the fixed and random effects analysis of each study. Experimental condition = pre‐DBS PDQ score; control condition = post‐DBS score after 24 months. DBS, deep brain stimulation; PDQ, Parkinson's Disease Questionnaire; SMD, standardized mean difference.
Figure S3. Forest plot of the follow‐up period of 36 months showing the SMD and the weights for the fixed and random effects analysis of each study. Experimental condition = pre‐DBS PDQ score; control condition = post‐DBS score after 36 months. DBS, deep brain stimulation; PDQ, Parkinson's Disease Questionnaire; SMD, standardized mean difference.
Table S1. Risk of bias assessment.
Table S2. Ratings of the risk of bias assessment.
Acknowledgments
We thank Adam Caraballo for proofreading English grammar and spelling.
Relevant disclosures and conflicts of interest are listed at the end of this article.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Figure S1. Forest plot of the follow‐up period of 12 months showing the SMD and the weights for the fixed and random effects analysis of each study. Experimental condition = pre‐DBS PDQ score; control condition = post‐DBS score after 12 months. DBS, deep brain stimulation; PDQ, Parkinson's Disease Questionnaire; SMD, standardized mean difference.
Figure S2. Forest plot of the follow‐up period of 24 months showing the SMD and the weights for the fixed and random effects analysis of each study. Experimental condition = pre‐DBS PDQ score; control condition = post‐DBS score after 24 months. DBS, deep brain stimulation; PDQ, Parkinson's Disease Questionnaire; SMD, standardized mean difference.
Figure S3. Forest plot of the follow‐up period of 36 months showing the SMD and the weights for the fixed and random effects analysis of each study. Experimental condition = pre‐DBS PDQ score; control condition = post‐DBS score after 36 months. DBS, deep brain stimulation; PDQ, Parkinson's Disease Questionnaire; SMD, standardized mean difference.
Table S1. Risk of bias assessment.
Table S2. Ratings of the risk of bias assessment.