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Abstract
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective neurosurgical treatment for Parkinson’s disease. Surgical accuracy is a critical determinant to achieve an adequate DBS effect on motor performance. A two-millimetre surgical accuracy is commonly accepted, but scientific evidence is lacking. A systematic review and meta-analysis of study-level and individual patient data (IPD) was performed by a comprehensive search in MEDLINE, EMBASE and Cochrane Library. Primary outcome measures were (1) radial error between the implanted electrode and target; (2) DBS motor improvement on the Unified Parkinson’s Disease Rating Scale part III (motor examination). On a study level, meta-regression analysis was performed. Also, publication bias was assessed. For IPD meta-analysis, a linear mixed effects model was used. Forty studies (1391 patients) were included, reporting radial errors of 0.45–1.86 mm. Errors within this range did not significantly influence the DBS effect on motor improvement. Additional IPD analysis (206 patients) revealed that a mean radial error of 1.13±0.75 mm did not significantly change the extent of DBS motor improvement. Our meta-analysis showed a huge publication bias on accuracy data in DBS. Therefore, the current literature does not provide an unequivocal upper threshold for acceptable accuracy of STN-DBS surgery. Based on the current literature, DBS-electrodes placed within a 2 mm range of the intended target do not have to be repositioned to enhance motor improvement after STN-DBS for Parkinson’s disease. However, an indisputable upper cut-off value for surgical accuracy remains to be established. PROSPERO registration number is CRD42018089539.
- META-ANALYSIS
- PARKINSON'S DISEASE
- ELECTRICAL STIMULATION
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Introduction
Parkinson’s disease (PD) is a progressive neurodegenerative disorder, affecting more than 6 million people worldwide.1 2 Dopaminergic medication is the cornerstone of PD treatment. However, after several years of treatment, invalidating response-fluctuations may occur.3 In such cases, deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well recognised and effective treatment.4 In particular, stimulation of the dorsolateral STN is considered a sweet spot to establish a beneficial effect on Parkinsonian motor symptoms.5–9 Although DBS has been successfully performed in PD patients for the last three decades,10 11 a variability remains in individual patient outcome.12 13 The management of PD patients with insufficient clinical benefit is challenging due to the many underlying causes. Some failures may be attributed to inappropriate patient selection, while in other cases DBS programming is suboptimal.14 Misplaced DBS electrodes account for 46% of treatment failures14 and revision surgery has shown valuable results.15–17 As such, surgical accuracy is a critical determinant to achieve an adequate DBS effect on motor performance in PD.
In the past, it has been suggested that DBS-electrode placement within a 3 mm radius from the intended target overall provides a beneficial clinical effect.18 19 However, Herzog et al reported that DBS-electrodes placed more than 1.5 mm dorsal of the STN had a suboptimal outcome.20 Therefore, an accuracy of max. 2 mm from the intended target is commonly accepted.21–26 Since scientific evidence for this surgical threshold is lacking, this study aims to assess the correlation between accuracy of DBS-electrode placement and motor improvement by conducting a systematic review, including a meta-analysis of study-level data and individual patient data (IPD).
Methods
A systematic review and meta-analysis of study-level data and of IPD was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Individual Patient Data guidelines.27 The protocol of this systematic review was specified in advance and published in the PROSPERO database.
Search strategy
A systematic search in MEDLINE (PubMed), EMBASE and Cochrane Database of Systematic Reviews was performed (until 17 February 2022). The search strategy was developed using the PICO method. Participants (P): patients with medically refractory PD. Intervention (I): STN-DBS surgery. Comparison (C): postoperative versus preoperative situation. Outcomes (O): DBS-electrode placement accuracy and motor improvement.
The peer-reviewed search strategy was designed with the indexing terms: ‘Deep Brain Stimulation’, ‘Parkinson Disease’, ‘Surveys and Questionnaires’; supplemented by the free text terms: ‘outcome’, ‘UPDRS’, ‘quality of life’, ‘accuracy’, ‘precision’, ‘placement’ and ‘error’.
An additional search was conducted in www.clinicaltrials.gov. References of all included studies and relevant reviews on this topic were screened for potentially eligible studies. Forward citation searching was performed to identify studies that cite the studies included in this systematic review.
Eligibility criteria and study selection
Eligible articles consisted of clinical studies that met the following criteria: (1) involved humans; (2) reported on original data (no review articles); (3) included PD patients treated with STN-DBS; (4) investigated accuracy of DBS-electrode placement relative to the intended STN-target on imaging; (5) clearly reported how the intended target was established and (6) included a measure of motor improvement after DBS. Studies using ventriculography for targeting purposes were excluded. Only full-text, peer-reviewed papers were included in the systematic review. No restrictions regarding study design were made. Publications written in languages other than English were excluded. If studies included multiple cohorts, these cohorts were considered separately.
Study selection was independently performed by two reviewers. Disagreements were resolved by consensus. All retrieved titles and abstracts were screened for eligibility. The final selection was made based on full-text papers. If suspected that papers were based on the same study population (ie, same study, same study centre or same authors), the paper with the most complete patient data was included. Other overlapping studies were excluded.
Data extraction
A predesigned form was used to extract data from the included studies. Data extraction was performed independently by two reviewers. Disagreements were resolved by cross-checking. The following data were extracted both on study level and individual patient level (if available): (1) patient characteristics (age, gender, disease duration); (2) inclusion criteria; (3) duration of follow-up and (4) surgical technique: local versus general anaesthesia, frame-based versus frameless, unilateral versus bilateral implantation, use of microelectrode recording (MER), test stimulation; (5) imaging modality and software used to assess DBS-electrode location; (6) outcome measures: DBS-electrode placement accuracy, motor improvement after DBS. If no IPD were reported, the corresponding author of the study was contacted by email. If necessary, a reminder was sent after 2 weeks.
Methodological quality assessment
The methodological quality of all included studies was assessed independently by two reviewers, using the Methodological Index for Non-Randomised Studies (MINORS).28 The MINORS instrument contains eight items for non-comparative studies and an additional four items for comparative studies. Each item is scored 0 (not reported); 1 (reported but inadequate); or 2 (reported and adequate). Item 9 (adequate control group) was not used, since none of the studies reported a control group. Thus, comparative studies (studies comparing two or more groups) could obtain a maximum score of 22, while non-comparative studies had a maximum score of 16. The MINORS’ item on appropriate endpoints was deemed adequate if both method of accuracy measurement (used imaging modality and method of accuracy calculation) and DBS motor improvement (Unified Parkinson’s Disease Rating scale motor examination (UPDRS III) scores, timing of measurement, medication- and stimulation-state) were clearly described. The item related to blinded evaluation was considered adequate if the assessor of DBS motor improvement was blinded to the accuracy results. Follow-up duration of at least 6 months was considered adequate. Disagreements between reviewers were resolved by consensus. An intraclass correlation coefficient (ICC) was calculated to evaluate inter-rater agreement on the methodological quality of the included studies.
Statistical analysis
DBS-electrode placement accuracy
The primary outcome measure regarding DBS-electrode placement accuracy was radial error. Radial error was defined as the distance between the intended DBS target and the actual DBS-electrode measured on the axial plane of the intended DBS target (figure 1). Thus, errors in X (mediolateral axis) and Y (anteroposterior axis) were considered (formula 1).
Accuracy outcome measures. Radial error (R) is defined as the perpendicular distance from target to DBS electrode in the axial plane used for targeting (
). 3D error is defined as the linear distance between target and target contact on the DBS-electrode (
) (adapted from Burchiel et al
19 with permission from Oregon Health & Science University). 3D, three dimensions; DBS, deep brain stimulation.
Secondary outcome measures were (1) three-dimensional (3D) error (or Euclidean error) and (2) separate X - Y - Z errors. 3D error was defined as the distance between the intended DBS-target and the actual location of the DBS electrode, considering the errors in X, Y and Z (superoinferior) axis (figure 1, formula 2).
DBS motor improvement
The change (%) in UPDRS III score comparing off-stimulation state with on-stimulation state (in off-medication state), was considered the primary outcome to measure DBS motor improvement, since this measure is reflecting true DBS effectiveness. Most studies that reported on DBS motor improvement used this measure (formula 3).
Secondary outcome measures were (1) change (%) in UPDRS III comparing on-medication state with on-medication/on-stimulation state, referred to as on-medication DBS motor improvement; (2) change (%) in Levodopa Equivalent Daily Dose (LEDD) (postoperative dosage compared with preoperative dosage) and (3) postoperative stimulation amplitude.
Aggregate data analysis
Mean data on study level (aggregate data) were presented using descriptive statistics. If multiple follow-up moments were described in the included study, the follow-up moment closest to 6 months was used for the analysis. If accuracy measures or amplitudes were reported per hemisphere separately, these were pooled using formula 4:
If UPDRS III scores were reported per body side, these were also pooled using formula 4. In addition, if available, IPD were used to calculate mean values that could be used in the aggregate data analysis.
To combine results from different studies into single summarised statistics, we used meta-regression analysis to relate the DBS-electrode placement accuracy outcome measures (radial error, 3D error and separate X - Y - Z errors) as covariates to (1) DBS motor improvement; (2) on-medication DBS motor improvement; (3) change (%) in LEDD and (4) postoperative stimulation amplitude (response variables).
This allowed us to investigate whether these covariates explained any of the heterogeneity of the response variables between studies. Since residual heterogeneity was expected to remain after the model was adjusted for the covariates, a random-effects meta-regression analysis was performed and restricted maximum likelihood estimation was used, hence estimating the mean of the distribution of effects across studies. Heterogeneity was expressed in I² (percentage variability caused by heterogeneity rather than chance; >75% denoting high heterogeneity) and in τ² (variability among the true effects not accounted for by the covariates included in the model). In addition, to identify potential publication bias, funnel plots were created and Egger’s test was used.
IPD meta-analysis
The characteristics of the IPD cohort were presented using descriptive statistics. Continuous variables were described using means with SD for normal distributed data and median with IQR for skewed distributed data. If separate X - Y - Z errors were available, radial errors and 3D errors were calculated using formula 1 and 2, respectively.
IPD meta-analyses were conducted using mixed-effects models with maximum likelihood estimation. Clustering of patients within studies was accounted for by incorporating random intercepts for the studies. We related DBS-electrode placement accuracy outcome measures (radial error, 3D error, separate X - Y - Z errors) as covariates to (1) DBS motor improvement; (2) on-medication DBS motor improvement; (3) change (%) in LEDD; (4) postoperative stimulation amplitude.
All statistical analyses were performed with the metafor (aggregate analyses) and nlme (IPD analyses) libraries in R V.3.6.3 (2020-02-29). The level of significance was set at p<0.05.
Results
Study selection
The search in MEDLINE, EMBASE and Cochrane Database retrieved 1061 articles. In addition, 1694 articles were obtained through reference screening and other sources, resulting in a total of 2755 screened articles. Duplicates were removed. The review of 1837 titles and abstracts, and 408 full-text articles resulted in inclusion of 40 articles,8 21 23–25 29–63 of which 33 articles were eligible to be included in the meta-analysis (figure 2). Seven articles did not report means and/or SD and were excluded from the meta-analysis.
PRISMA-IPD flow diagram. PRISMA-IPD, Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Individual Patient Data.
Methodological quality assessment
Twelve comparative and 28 non-comparative studies were included. Mean total MINORS score was 8.4±2.1 for non-comparative studies (max. score 16) and 13.0±3.5 for comparative studies (max. score 22). Overall, 90% of studies had a clearly stated aim; 73% had appropriate follow-up of at least 6 months. However, only 58% had appropriate endpoints (ie, both method of accuracy measurement and DBS motor improvement were clearly described); 40% had under 5% loss of follow-up; 15% of studies had prospective collection of data; just one study had unbiased assessment of study endpoints. There was substantial inter-rater agreement among quality assessment scores using MINORS (ICC 0.73, 95% CI 0.68 to 0.78). Results of the methodological quality assessment are presented in online supplemental table 1.
Supplemental material
Characteristics of 40 studies comprising total population of review
Forty studies included in this review were published between 2002 and 2021, from various countries. Enrolled patients per study varied from 2 to 101. In total, 1391 patients (2734 DBS-electrodes) were included in this review; 556 patients (40%) were female (3 studies did not report gender and were counted 50% women). The mean age was 61.0±7.5 years. Disease duration was 10.4±4.4 years on average, while mean follow-up was 8.8 months. Nearly all studies (78%) described their STN-target to be situated in the dorsolateral part of the nucleus. Others targeted the central STN (8%) or did not specify the target location within the STN (15%). Average intended target coordinates in relation to the mid-commissural line were available for 10 studies and are reported in online supplemental table 2. Awake surgery was applied in 65% of studies; 28% reported general anaesthesia. Most studies (80%) used a frame-based technique (74% Leksell, 7% Riechert-Mundinger, 7% Cosman-Roberts-Wells (CRW), 7% Inomed and 5% CRW/Leksell combination). Frameless surgeries were performed using Smartframe, Nexframe or Clearpoint. MER was used in 69% of studies, while test-stimulation was carried out in 72%. DBS-electrode placement accuracy was assessed with CT (49%) or MRI (42%), 8% used both CT and MRI, and 2% used intraoperative fluorescence. Further details are presented in online supplemental table 3.
Aggregate data analysis
Random effects meta-analysis showed an estimated mean radial error of 1.21 mm (95% CI 1.01 mm to 1.41 mm) and an estimated mean DBS motor improvement of 49.6% (95% CI 45.6% to 53.6%), both showing high heterogeneity (figure 3A,C). Potential publication bias was identified for radial error (figure 3B).
(A) Forest plot showing averages (black boxes) and CIs for radial error for all studies contributing mean and SD. The dotted line represents the prediction interval for the mean estimate from the random effects model. (B) Asymmetric funnel plot for radial error, indicating possible publication bias. Each point represents the mean and SE for a single study’s radial error. In the absence of publication bias, it would be expected that the white, triangular region would include 95% of the studies. The vertical line represents the average mean radial error (1.21 mm) found in the meta-analysis. (C) Forest plot showing averages (black boxes) and confidence intervals for DBS motor improvement for all studies contributing mean and SD. The dotted line represents the prediction interval for the mean estimate from the random effects model. (D) Bubble plot showing mean DBS motor improvement of the individual studies plotted against their mean radial error. The symbol sizes are related to the weights of the studies in the analysis (symbols are proportional to the inverse of the sum of within study variance and the variance between the studies, larger and more precise studies correspond to larger diamonds). Based on the meta-regression random-effects model, the predicted average mean DBS motor improvement as a function of the covariate radial error is added to the plot (line) with corresponding 95% CI bounds (dotted line). DBS, deep brain stimulation.
With an estimated effect of −6.1%, meta-regression analysis showed that the reported range in radial error (0.45–1.86 mm) was not significantly related to the magnitude of motor improvement (95% CI −16.6 to 4.3, p=0.25) (figure 3D). Considerable heterogeneity remained after the model was adjusted for radial error (τ² = 32.9; p=0.0004; I² = 65.41%).
Meta-regression analyses on the secondary outcome measures are described in online supplemental data. Z-error showed a positive effect on DBS motor improvement (p<0.001; only nine studies included in this model), while radial error showed a negative effect on both change in LEDD (p<0.001) and postoperative stimulation amplitude (p<0.001; only seven studies included in this model). No other covariate affected any response variable. All secondary variables showed high heterogeneity, but none had signs of potential publication bias.
IPD meta-analysis
IPD were adequately reported in seven studies.25 29 35 38 40 53 56 On our request, five authors shared their IPD.23 39 43 48 51 As such, IPD from 206 patients were available in 12 studies (marked with an asterisk in online supplemental table 3). In table 1, characteristics are presented.
Characteristics of the 206 patients included in the IPD meta-analysis
According to the random intercept model, mean radial error was estimated 1.15 mm for the right hemisphere (95% CI 0.91 mm to 1.39 mm) and 1.10 mm for the left hemisphere (95% CI 0.81 mm to 1.39 mm). Mean DBS motor improvement was estimated to be 46.2% (95% CI 41.2% to 51.1%). The mixed effects model showed that radial errors within this very small range were not significantly related to the magnitude of DBS motor improvement (95% CI −12.2 to 0.3 right hemisphere; 95% CI −7.2 to 5.1 left hemisphere) (figure 4). IPD meta-analyses on secondary outcome measures are shown in online supplemental data. Radial errors in the right hemisphere were negatively correlated to on-medication motor improvement (p=0.037). Radial error had no effect on any other response variable.
(A) Relationship between DBS motor improvement and radial error of the right hemisphere. (B) Relationship between DBS motor improvement and radial error of the left hemisphere. DBS, deep brain stimulation.
Discussion
This systematic review and meta-analysis studied the correlation between accuracy of DBS-electrode placement and motor improvement in STN-DBS surgery for PD. We confirmed that the surgical accuracy of DBS-electrodes within a 2 mm range of the intended target does not affect the extent of DBS motor improvement. Therefore, repositioning within this radial margin does not yield extra motor benefit. Our results are concordant with previous studies. With average radial errors of 0.2–2.2 mm, these studies failed to show a significant correlation between DBS-electrode placement accuracy and motor improvement.18 32 64 Also, a previous meta-regression analysis with radial errors of 0.50–1.52 mm was unable to show a significant correlation between accuracy of DBS-electrode placement and motor improvement.65 Thus, motor improvement is not affected by radial errors within these small ranges. However, an upper cut-off value remains to be established, as radial errors above 2 mm are scarcely reported in smaller studies that did not fulfil the criteria for this meta-analysis.
DBS outside of the dorsolateral part of the STN has been associated with limited or absent clinical benefit15–17 26 66 and severe adverse effects, including effects on mood and other neuropsychological functions.67–71 Therapeutic effect was hindered by low stimulation thresholds for stimulation-induced side effects.15–17 26 Repositioning of DBS-electrode misplacements (>2 to 3 mm off target in any direction17 26 66 72 73) by 2.7 to 5.5 mm on average resulted in better clinical results,15–18 26 66 74–76 higher stimulation thresholds,15 17 disappearance of stimulation-induced adverse events71 and decrease in LEDD.15 In addition, unwanted stimulation-induced side effects, such as dysarthria or involuntary muscle contractions, may also necessitate DBS-electrode repositioning. In these cases, direction of error relative to the intended target is especially important, as stimulation of critical brain structures, including the pyramidal tract, must to be avoided. When, for example, the dorsolateral STN is targeted, a two mm error in the anteromedial or posterolateral direction could still result in a DBS-electrode located in the STN with corresponding good clinical effect. However, an anterolateral error of this magnitude will inevitably result in stimulation-induced side effects due to pyramidal tract stimulation.
Although adequate positioning of DBS-electrodes is a key success factor for DBS outcome,5–7 9 20 77 a broad range of parameters coaffect the clinical effect of DBS. Predictors of success are appropriate patient selection, age, response to levodopa therapy prior to surgery, disease severity and disease subtype.78 79 Also, proper programming has avoided DBS-electrode repositioning, but no amount of programming can compensate for a sub-optimally placed DBS-electrode.14
Most included studies assessed motor improvement as difference in UPDRS III score of postoperative off-medication/on-stimulation versus preoperative off-medication state. Although this is the most reported clinical outcome measure in DBS surgery for PD, it does not include disease progression, which can only be based on the comparison relative to off-medication/off-stimulation scores. It is possible that the off-medication state has progressed over time, causing a shift in baseline scores. This may also have a role in the lacking correlation between accuracy and motor improvement.
Finally, the lack of standardised methods in DBS-surgery might have influenced our analysis of DBS-accuracy and its influence on clinical outcome. All variables included in the meta-analysis showed high heterogeneity. Targeting and surgical techniques differed greatly between studies, as well as imaging modalities to verify the electrode position (online supplemental table 3). The part of the DBS electrode used for comparison with the intended target varied between studies reporting on 3D error. Some studies compared the intended target with the tip of the electrode, others used the active contact of the electrode or the contact closest to target, again emphasising the high variability of STN-DBS procedures. Likewise, studies that used MER or test stimulation to adjust the imaging-based target either used the adjusted or the original (imaging-based) target for accuracy calculations. In our meta-regression analysis, 63% of the studies using MER adjusted their initial target according to MER findings, while the other 38% did not report on target correction due to MER. In our IPD, targets were adjusted for 62% of the patients operated with MER, while for the other 38% target correction due to MER was not reported. Target corrections based on electrophysiology during surgery should be clearly reported in future studies, enabling more thorough exploration of the value of MER in STN-DBS.
Additional exploratory analysis
Additional explorative sets of meta-regression analyses were performed to explore potential differences in DBS motor improvement between subgroups of patients distinguished by (1) MER versus no MER, (2) local versus general anaesthesia and (3) frame-based versus frameless surgery (stereotactic method). The meta-regression models including radial error and the study level characteristics revealed neither MER, nor anaesthesia, nor stereotactic method to be a moderator. Considerable heterogeneity remained; τ²=39.4, p=0.002, I²=67.1% for the model including MER, τ²=41.4, p=0.001, I²=62.9% for the model including anaesthesia and τ²=29.0, p=0.001, I²=63.8% for the model including stereotactic method; reaffirming the lack of standardisation in STN-DBS procedures.
Target selection and trajectory
Appropriate target selection for DBS-electrode implantation is the mainstay of DBS-success.80 It is evident that targets should be positioned in the dorsolateral part of the STN, while a save margin around the target is established to prevent stimulation-induced side effects, such as dysarthria.81 Optimal targeting is considered to be the first of many other factors that determine DBS outcome. One argument for the lack of association between radial error and DBS motor improvement found in this study may be target selection error, as only a small portion of heterogeneity was explained by radial error. Conceivably, if the initial target was to be poorly selected, but successfully hit during surgery, one could achieve great accuracy, but DBS outcome would be deficient. Research on the direct influence of STN target selection on DBS motor improvement is currently lacking and should be addressed in the future. Alternatively, accuracy could be low at target level, but the selected trajectory might be such that the DBS-electrode does pass through the dorsal STN.82 Thus, although accuracy is considered to be the main determinant of DBS-outcome, target selection and trajectory are also major determinants of DBS outcome.
Limitations
The main factor limiting our meta-analysis was the lack of variation in radial error in the studies included. None of the studies included in the meta-regression analysis reported radial errors beyond 1.86 mm. Some of the studies explicitly considered electrode misplacement as exclusion criterium. Moreover, it is possible that errors of higher magnitudes are less likely to be published in the literature, as we identified publication bias for radial error. Likewise, our estimated DBS motor improvement falls within a narrow range, which is unlikely to be representative of the population. This creates another source of reporting bias that needs to be considered when interpreting our results.
Second, we assessed bivariate correlation between accuracy of DBS-electrode placement and motor improvement. However, DBS outcome depends on many other variables that ideally would have been included as cofounders in the analysis. This was not possible due to insufficient reporting of these parameters. Future studies should report on other factors influencing clinical DBS outcome, such as patient selection (age, disease duration, disease severity and response to levodopa therapy prior to surgery) and programming strategies.
Third, we assumed that postoperative imaging is sufficient to determine DBS-electrode accuracy. However, image distortion, brain shift and image fusion errors may have influenced our accuracy assessment.
Finally, our sample size is a limitation. Due to high heterogeneity of included studies, only small sample sizes were available for meta-regression and IPD mixed model analyses. Also, only studies with low evidence (level 4) were found eligible to assess our questions. Nevertheless, these are currently the best available evidence.
Future directions and recommendations
Based on our meta-analysis, the future evaluation of DBS-accuracy and clinical outcome should be based on more harmonised and standardised protocols. More factors influencing DBS outcome, like disease progression, should be included. In addition to reporting total UPDRS III scores (including limb and axial motor functioning), hemibody improvements should be included as well, since DBS mainly affects the contralateral body side. Another relevant DBS-outcome measure is the ratio between stimulation and levodopa response.17 Since the response to levodopa is considered the benchmark for the best achievable motor improvement, the ratio between response to DBS and levodopa might be more informative than difference in UPDRS III score. Also, clinicians need to be aware of a possible microlesion effect that may mask the true stimulation effect up to 6 months after surgery.83 The assessment of DBS effects should not be based solely on UPDRS III scores, but should also include functional outcome scales, like quality of life and activities of daily living, for example, by using the Parkinson’s Disease Questionnaire (PDQ-39).84 85 We recommend transparent publication of DBS-electrode placement accuracy data. Accuracy should be reported in either radial error or 3D (Euclidean) error per hemisphere (figure 1). Besides, when reporting 3D error, it should be clearly described which part of the implanted DBS electrode is compared with the intended target. Also, data sharing via a research data repository is highly recommended.
Conclusions
Based on the current literature, DBS electrodes placed within a 2 mm range of the intended target do not have to be repositioned to enhance motor improvement after STN-DBS for PD. However, an indisputable upper cut-off value for surgical accuracy remains to be established.
Ethics statements
Patient consent for publication
Acknowledgments
We are indebted to Dr. J.L. Ostrem, Dr. W.H. Polanski, Dr. H. Toda, Dr. P. Mazzone and Dr. A. Nowacki for sharing individual patient data of their patients. In addition, we would like to thank Dr. L. Zrinzo and Dr. P. Mazzone for their thoughts and considerations on this topic. Thanks to Lilian Mennink for creating figure 1.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors NIK, TvL, SSM, GD and JMCvD conceptualised the study. NIK, SFL, SSM and SlB-vG conducted the study, including data collection and data analysis. NIK prepared the initial manuscript draft with important intellectual input from TvL, SlBvG, DLMO, GD and JMCvD. All authors approved the final version of the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.