Long-Term Follow-Up of the LEAP Study: Early Versus Delayed Levodopa in Early Parkinson's Disease.

BACKGROUND AND OBJECTIVE: The Levodopa in EArly Parkinson's disease study showed no effect of earlier versus later levodopa initiation on Parkinson's disease (PD) progression over 80 weeks. We now report the effects over 5 years. METHODS: The Levodopa in EArly Parkinson's disease study randomly assigned patients to levodopa/carbidopa 300/75 mg daily for 80 weeks (early start) or to placebo for 40 weeks followed by levodopa/carbidopa 300/75 mg daily for 40 weeks (delayed start). Follow-up visits were performed 3 and 5 years after baseline. We assessed the between-group differences in terms of square root transformed total Unified Parkinson's Disease Rating Scale score at 3 and 5 years with linear regression. We compared the prevalence of dyskinesia, prevalence of wearing off, and the levodopa equivalent daily dose. RESULTS: A total of 321 patients completed the 5-year visit. The adjusted square root transformed total Unified Parkinson's Disease Rating Scale did not differ between treatment groups at 3 (estimated difference, 0.17; standard error, 0.13; P = 0.18) and 5 years (estimated difference, 0.24; standard error, 0.13; P = 0.07). At 5 years, 46 of 160 patients in the early-start group and 62 of 161 patients in the delayed-start group experienced dyskinesia (P = 0.06). The prevalence of wearing off and the levodopa equivalent daily dose were not significantly different between groups. CONCLUSIONS: We did not find a difference in disease progression or in prevalence of motor complications between patients with early PD starting treatment with a low dose of levodopa 40 weeks earlier versus 40 weeks later over the subsequent 5 years. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Efficacy and safety of adjunctive oral therapy in Parkinson's disease with motor complications: a systematic review and network meta-analysis.

Background: The aim of this manuscript is to review the evidence and compare the efficacy and safety of catechol-O-methyltransferase inhibitors (COMT-Is), dopamine receptor agonists (DRAs) and monoamine-oxidase B inhibitors (MAOB-Is) as adjunctive treatment to levodopa in patients with Parkinson's disease (PD) experiencing motor complications. Methods: In this systematic review and network meta-analysis, literature searches were performed in MEDLINE and Embase to identify eligible randomised controlled trials (RCTs) with a minimal follow-up of at least 4 weeks published in English between 1980 and 2021. RCTs were included if either a COMT-I, DRA or MAOB-I was evaluated as an adjunctive therapy to levodopa in patients with PD experiencing motor complications and dyskinesia. The main outcomes included daily off-medication time, motor and non-motor examination scales, and adverse events including dyskinesia. Results: 74 RCTs reporting on 18 693 patients were included. All three studied drug classes decreased daily off-medication time compared with placebo (COMT-Is mean -0.8 hours (95% CI -1.0 to -0.6), DRAs -1.1 hours (95% CI -1.4 to -0.8), MAOB-Is -0.9 hours (95% CI -1.2 to -0.6)). Safety analysis showed an increased risk of dyskinesia for all three drug classes (COMT-Is OR 3.3 (95% CI 2.7 to 4.0), DRAs 3.0 (95% CI 2.5 to 3.5), MAOB-Is 1.6 (95% CI 1.2 to 2.2)). According to surface under the cumulative ranking curve scores, pramipexole IR was associated with the most favourable benefit-risk profile. Conclusions: COMT-Is, DRAs and MAOB-Is effectively reduce motor complications and increase incidence of dyskinesia. In the network meta-analysis, adjunctive use of DRAs appeared most effective.

Programming Algorithm for the Management of Speech Impairment in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVES: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) has an ambiguous relation to speech. Speech impairment can be a stimulation-induced side effect, and parkinsonian dysarthria can improve with STN-DBS. Owing to the lack of an up-to-date and evidence-based approach, DBS reprogramming for speech impairment is largely blind and greatly relies on the physician's experience. In this study, we aimed to establish an evidence- and experience-based algorithm for managing speech impairment in patients with PD treated with STN-DBS. MATERIALS AND METHODS: We performed a single-center retrospective study to identify patients with STN-DBS and speech impairment. Onset of speech impairment, lead localization, and assessment of DBS-induced nature of speech impairment were collected. When DBS settings were adjusted for improving speech, the magnitude and duration of effect were collected. We also performed a systematic literature review to identify studies describing the effects of parameter adjustments aimed at improving speech impairment in patients with PD receiving STN-DBS. RESULTS: In the retrospective study, 245 of 631 patients (38.8%) with STN-DBS had significant speech impairment. The probability of sustained marked improvement upon reprogramming was generally low (27.9%). In the systematic review, 23 of 662 identified studies were included. Only two randomized controlled trials have been performed, providing evidence for interleaving-interlink stimulation only. Considerable methodologic heterogeneity precluded the conduction of a meta-analysis. CONCLUSIONS: Speech impairment in STN-DBS for PD is frequent, but high-quality evidence regarding DBS parameter adjustments is scarce, and the probability of sustained improvement is low. To improve this outcome, we propose an evidence- and experience-based approach to address speech impairment in STN-DBS that can be used in clinical practice.

Directional versus ring-mode deep brain stimulation for Parkinson's disease: protocol of a multi-centre double-blind randomised crossover trial.

BACKGROUND: The effectiveness of Deep Brain Stimulation (DBS) therapy for Parkinson's disease can be limited by side-effects caused by electrical current spillover into structures adjacent to the target area. The objective of the STEEred versus RING-mode DBS for Parkinson's disease (STEERING) study is to investigate if directional DBS for Parkinson's disease results in a better clinical outcome when compared to ring-mode DBS. METHODS: The STEERING study is a prospective multi-centre double-blind randomised crossover trial. Inclusion criteria are Parkinson's disease, subthalamic nucleus DBS in a 'classic' ring-mode setting for a minimum of six months, and optimal ring-mode settings have been established. Participants are categorised into one of two subgroups according to their clinical response to the ring-mode settings as 'responders' (i.e., patient with a satisfactory effect of ring-mode DBS) or 'non-responder' (i.e., patient with a non-satisfactory effect of ring-mode DBS). A total of 64 responders and 38 non-responders will be included (total 102 patients). After an optimisation period in which an optimal directional setting is found, participants are randomised to first receive ring-mode DBS for 56 days (range 28-66) followed by directional DBS for 56 days (28-66) or vice-versa. The primary outcome is the difference between ring-mode DBS and directional DBS settings on the Movement Disorders Society Unified Parkinson's Disease Rating Scale - Motor Evaluation (MDS-UPDRS-ME) in the off-medication state. Secondary outcome measures consist of MDS-UPDRS-ME in the on-medication state, MDS-UPDRS Activities of Daily Living, MDS-UPDRS Motor Complications-Dyskinesia, disease related quality of life measured with the Parkinson's Disease Questionnaire 39, stimulation-induced side-effects, antiparkinsonian medication use, and DBS-parameters. Participants' therapy preference is measured at the end of the study. Outcomes will be analysed for both responder and non-responder groups, as well as for both groups pooled together. DISCUSSION: The STEERING trial will provide insights into whether or not directional DBS should be standardly used in all Parkinson's disease DBS patients or if directional DBS should only be used in a case-based approach. TRIAL REGISTRATION: This trial was registered on the Netherlands Trial Register, as trial NL6508 ( NTR6696 ) on June 23, 2017.

Levodopa Response in Patients With Early Parkinson Disease: Further Observations of the LEAP Study.

BACKGROUND AND OBJECTIVES: The Levodopa in EArly Parkinson's Disease (LEAP) study enabled us to conduct post hoc analyses concerning the effects of levodopa in patients with early Parkinson disease. METHODS: The LEAP study was a double-blind, placebo-controlled, randomized, delayed-start trial in which patients with early Parkinson disease were randomized to receive levodopa/carbidopa 300/75 mg daily for 80 weeks (early-start group) or to placebo for 40 weeks followed by levodopa/carbidopa 300/75 mg daily for 40 weeks (delayed-start group). We analyzed the effect of levodopa with the Unified Parkinson's Disease Rating Scale on bradykinesia, rigidity, and tremor. At week 80, participants answered 3 questions regarding motor response fluctuations. RESULTS: A total of 222 patients were randomized to the early-start group (mean ± SD age at baseline 64.8 ± 8.7 years; 71% male) and 223 to the delayed-start group (mean ± SD age at baseline 65.5 ± 8.8 years; 69% male). The difference between the early- and delayed-start groups in mean change from baseline to week 4, expressed as Hedges g effect size, was -0.33 for bradykinesia, -0.29 for rigidity, and -0.25 for tremor (for all symptoms indicating a small effect in favor of the early-start group); from baseline to week 22, respectively, -0.49, -0.36, and -0.44 (small to medium effect); and from baseline to week 40, respectively, -0.32, -0.19, and -0.27 (small effect). At 80 weeks, fewer patients in the early-start group (46 of 205 patients, 23%) experienced motor response fluctuations than patients in the delayed-start group (81 of 211, 38%; p < 0.01). DISCUSSION: In patients with early Parkinson disease, levodopa improves bradykinesia, rigidity, and tremor to the same order of magnitude. For all 3 symptoms, effects were larger at 22 weeks compared with 4 weeks. At 80 weeks, there were fewer patients with motor response fluctuations in the group that had started levodopa earlier. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the effect of levodopa on bradykinesia, rigidity, and tremor is larger after 22 weeks compared with 4 weeks of treatment. TRIAL REGISTRATION INFORMATION: ISRCTN30518857, EudraCT number 2011-000678-72.

General Anesthesia vs Local Anesthesia in Microelectrode Recording-Guided Deep-Brain Stimulation for Parkinson Disease: The GALAXY Randomized Clinical Trial.

Importance: It is unknown if there is a difference in outcome in asleep vs awake deep brain stimulation (DBS) of the subthalamic nucleus for advanced Parkinson disease. Objective: To determine the difference in adverse effects concerning cognition, mood, and behavior between awake and asleep DBS favoring the asleep arm of the study. Design, Setting, and Participants: This study was a single-center prospective randomized open-label blinded end point clinical trial. A total of 187 persons with Parkinson disease were referred for DBS between May 2015 to March 2019. Analysis took place from January 2016 to January 2020. The primary outcome follow-up visit was conducted 6 months after DBS. Interventions: Bilateral subthalamic nucleus DBS was performed while the patient was asleep (under general anesthesia) in 1 study arm and awake in the other study arm. Both arms of the study used a frame-based intraoperative microelectrode recording technique to refine final target placement of the DBS lead. Main Outcomes and Measures: The primary outcome variable was the between-group difference in cognitive, mood, and behavioral adverse effects as measured by a composite score. The secondary outcomes included the Movement Disorders Society Unified Parkinson's Disease Rating Scale, the patient assessment of surgical burden and operative time. Results: A total of 110 patients were randomized to awake (local anesthesia; n = 56; mean [SD] age, 60.0 (7.4) years; 40 [71%] male) or to asleep (general anesthesia; n = 54; mean [SD] age, 61.3 [7.9] years; 38 [70%] male) DBS surgery. The 6-month follow-up visit was completed by 103 participants. The proportion of patients with adverse cognitive, mood, and behavioral effects on the composite score was 15 of 52 (29%) after awake and 11 of 51 (22%) after asleep DBS (odds ratio, 0.7 [95% CI, 0.3-1.7]). There was no difference in improvement in the off-medication Movement Disorders Society Unified Parkinson's Disease Rating Scale Motor Examination scores between groups (awake group: mean [SD], -27.3 [17.5] points; asleep group: mean [SD], -25.3 [14.3] points; mean difference, -2.0 [95% CI, -8.1 to 4.2]). Asleep surgery was experienced as less burdensome by patients and was 26 minutes shorter than awake surgery. Conclusions and Relevance: There was no difference in the primary outcome of asleep vs awake DBS. Future large randomized clinical trials should examine some of the newer asleep based DBS technologies because this study was limited to frame-based microelectrode-guided procedures. Trial Registration: trialregister.nl Identifier: NTR5809.

Advanced Care Planning in Parkinson's Disease: In-depth Interviews With Patients on Experiences and Needs.

Introduction: Advance care planning (ACP) is an iterative process of discussing the needs, wishes, and preferences of patients regarding disease-specific and end-of-life issues. There is ample evidence that ACP improves the quality of life and promotes the autonomy of patients with cancer and motor neuron disease who have a high disease burden and shortened life expectancy. In Parkinson's disease (PD) though, knowledge about the experiences and preferences of patients regarding ACP is scarce, despite the major disease burden associated with PD. Aim: This study aims to explore the experiences, needs, and preferences of PD patients regarding the content and timing of ACP. Methods: In-depth interviews were conducted with a purposively selected sample of patients diagnosed with PD. Using a semi-structured topic list, the participants were asked about their prospects for a future living with PD and with whom they wanted to discuss this. Qualitative analysis was performed in parallel with data collection using a data-driven constant comparative approach. The transcribed interviews were coded and analyzed by two researchers using MAXQDA software. Results: Of all 20 patients (13 males; age 47-82; disease duration 1-27 years), most expressed a wish to talk about ACP with a healthcare provider, enabling them to anticipate the uncertain future. The majority of patients preferred their healthcare provider to initiate the discussion on ACP, preferably at an early stage of the disease. Nearly all patients expressed the wish to receive more information regarding the long-term impact of PD, although, the preferred timing varied between patients. They also perceived that their neurologist was primarily focused on medication and had little time to address their need for a more holistic approach toward living with PD. Conclusion: Our results suggest that PD patients are in need of discussing ACP with their healthcare provider (HCP), even in the early stages of the disease. In addition, PD patients perceive a lack of information on their disease course and miss guidance on available supportive care. We recommend HCPs to inquire the information requirements and preferences of patients regarding ACP regularly, starting soon after diagnosis.

Combined and Sequential Treatment with Deep Brain Stimulation and Continuous Intrajejunal Levodopa Infusion for Parkinson's Disease.

(1) Background: Deep brain stimulation (DBS) and continuous intrajejunal levodopa infusion (CLI) are efficacious treatments of medication related motor response fluctuations in advanced Parkinson's disease (PD). Literature regarding the use of both advanced treatments within one patient is scarce. (2) Methods: We present a retrospective single center case series and a review of the literature. Patients with PD who were treated with both DBS and CLI in our tertiary referral center between 2005 and 2020 were identified and medical records were assessed. Additionally, literature on patients treated with both therapies was systematically searched for in Medline and Embase. (3) Results: Nineteen patients were included. Medication related motor response fluctuations were a major indication for the second therapy in all but one. Of nine patients initially treated with DBS, five reported improvement with CLI. Seven of ten patients initially treated with CLI experienced benefits from DBS. The systematic literature search resulted in fifteen previous publications comprising 66 patients. Of the 59 patients, for whom the effect of the second treatment was known, 57 improved. (4) Conclusions: PD patients, who have persisting medication related motor response fluctuations, despite DBS or CLI treatment, may benefit from an additional or alternative treatment with either CLI or DBS.

The Choice Between Advanced Therapies for Parkinson's Disease Patients: Why, What, and When?

When oral dopaminergic medication falls short in the treatment of Parkinson's disease, patients are left with motor response fluctuations and dyskinesias that may have a large impact on functioning in daily life. They may benefit from one of the currently available advanced treatments, namely deep brain stimulation, continuous levodopa-carbidopa intestinal gel, and continuous subcutaneous apomorphine infusion. The indication, choice between the separate advanced treatments and the timing can be challenging and will be discussed against the background of the progressive nature of the disease, the heterogeneity of disease manifestation and variable patient characteristics.

Internet-based self-help randomized trial for motor functional neurologic disorder (SHIFT).

OBJECTIVE: To determine whether self-rated health of patients with motor functional neurologic disorder (FND) can be improved by unguided Internet-based self-help and education. METHODS: In this nonblinded randomized controlled trial, patients were allocated 1:1 unbiased to an unguided education and self-help website in addition to usual care or usual care only. Patients over 17 years of age with a functional motor symptom that caused distress or disability were included. The primary outcome was self-rated health on the Clinical Global Improvement scale at 3 and 6 months. Secondary outcomes were severity of motor symptoms, other physical and psychiatric symptoms, physical functioning, quality of life, work and social adjustment, illness beliefs, and satisfaction with care. RESULTS: A total of 186 patients were randomized, with a follow-up rate of 87% at 6 months. There was no difference in improvement of self-rated health at 3 months (44% vs 40%, p = 0.899) or 6 months (42% vs 43%, p = 0.435). Secondary outcomes did not differ between groups, with a threshold of p < 0.01. Satisfaction was high, with 86% of patients recommending the website to other patients. CONCLUSION: We found no significant effect of the intervention added to usual care on self-rated health or secondary outcome measures, despite high patient satisfaction with the intervention. These results suggest that online education and nonguided self-help could be valuable additions to stepped care for motor FND, but are not effective treatments as interventions in their own right. CLINICALTRIALSGOV IDENTIFIER: NCT02589886. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with motor FND, online education and self-help intervention does not significantly improve self-rated health.

Value of Clinical Signs in Identifying Patients with Scans without Evidence of Dopaminergic Deficit (SWEDD).

BACKGROUND: In clinical trials that recruited patients with early Parkinson's disease (PD), 4-15% of the participants with a clinical diagnosis of PD had normal dopamine transporter single photon emission computed tomography (DAT SPECT) scans, also called "scans without evidence of dopaminergic deficit" (SWEDD). OBJECTIVE: To investigate in patients with a clinical diagnosis of PD, if specific clinical features are useful to distinguish patients with nigrostriatal degeneration from those that have no nigrostriatal degeneration. METHODS: We performed a diagnostic test accuracy study. Patients that participated in the Levodopa in Early Parkinson's disease trial, a clinical trial in patients with early PD, were asked to participate if they had not undergone DAT SPECT imaging earlier. The index tests were specific clinical features that were videotaped. A panel of six neurologists in training (NT), six general neurologists (GN), and six movement disorders experts (MDE) received a batch of ten videos consisting of all SWEDD subjects and a random sample of patients with abnormal DAT SPECT scans. The raters analyzed the videos for presence of specific signs and if they suspected the patient to have SWEDD. The reference test was visually assessed DAT SPECT imaging. RESULTS: Of a total of 87 participants, three subjects were SWEDDs (3.4%). The overall intraclass correlation coefficient (ICC) of the Parkinsonian signs was poor to moderate with ICCs ranging from 0.14 to 0.67. NT correctly identified 50.0% of the SWEDD subjects, GN 33.3%, and MDE 66.7%. CONCLUSION: Our study suggests that the selected videotaped clinical features cannot reliably distinguish patients with a clinical diagnosis of PD and an abnormal DAT SPECT from patients with clinical PD and a SWEDD.

Defining the Dorsal STN Border Using 7.0-T MRI: A Comparison to Microelectrode Recordings and Lower Field Strength MRI.

BACKGROUND: 7.0-T T2-weighted MRI offers excellent visibility of the subthalamic nucleus (STN), which is used as a target for deep brain stimulation (DBS) in Parkinson's disease (PD). A comparison of 7.0-T MRI to microelectrode recordings (MER) for STN border identification has not been performed. OBJECTIVE: To compare representation of STN borders on 7.0-T T2 MRI with the borders identified during MER in patients undergoing DBS for PD and to evaluate whether STN identification on 7.0-T T2 MRI leads to alterations in stereotactic target planning. DESIGN/METHODS: STN border identification was done using volumetric 7.0-T T2 MRI acquisitions. This was compared to the STN borders identified by MER. STN target planning was independently performed by 3 DBS surgeons on T2 imaging using 1.5-, 3.0-, and 7.0-T MRI. RESULTS: A total of 102 microelectrode tracks were evaluated in 19 patients. Identification of the dorsal STN border was well feasible on 7-T T2, whereas the ventral STN was un-distinguishable from the substantia nigra. The dorsal STN border on MRI was located more dorsal than MER in 73% of trajectories. The average distance from MRI to MER border was 0.9 mm (range -4.4 to +3.5 mm). STN target planning showed high correspondence between the 3 field strengths. CONCLUSION: 7.0-T T2 MRI offers the possibility of easy identification of the dorsal border of the STN. However, higher field strength MRI does not change the planning of the target. Compared to MER, the dorsal border on MRI was located more dorsal in the majority of cases, situating MER activity within STN representation.

Botulinum neurotoxin treatment in jerky and tremulous functional movement disorders: a double-blind, randomised placebo-controlled trial with an open-label extension.

OBJECTIVE: To study the effect of botulinum neurotoxin (BoNT) treatment in jerky and tremulous functional movement disorders (FMD). METHODS: Patients with invalidating, chronic (>1 year) symptoms were randomly assigned to two subsequent treatments with BoNT or placebo every 3 months with stratification according to symptom localisation. Improvement on the dichotomised Clinical Global Impression-Improvement scale (CGI-I) (improvement vs no change or worsening) at 4 months, assessed by investigators blinded to the allocated treatment was the primary outcome. Subsequently all patients were treated with BoNT in a ten month open-label phase. RESULTS: Between January 2011 and February 2015 a total of 239 patients were screened for eligibility of whom 48 patients were included. No difference was found on the primary outcome (BoNT 16 of 25 (64.0%) vs Placebo 13 of 23 patients (56.5%); proportional difference 0.075 (95% CI -0.189 to 0.327; p=0.77). Secondary outcomes (symptom severity, disease burden, disability, quality of life and psychiatric symptoms) showed no between-group differences. The open-label phase showed improvement on the CGI-I in 19/43 (44.2%) of remaining patients, with a total of 35/43 (81.4%) improvement compared with baseline. CONCLUSIONS: In this double-blind randomised controlled trial of BoNT for chronic jerky and tremulous FMD, we found no evidence of improved outcomes compared with placebo. Motor symptoms improved in a large proportion in both groups which was sustained in the open-label phase. This study underlines the substantial potential of chronic jerky and tremulous FMD patients to recover and may stimulate further exploration of placebo-therapies in these patients. TRIAL REGISTRATION NUMBER: NTR2478.

Randomised controlled trial of escitalopram for cervical dystonia with dystonic jerks/tremor.

OBJECTIVE: Trials for additional or alternative treatments for cervical dystonia (CD) are scarce since the introduction of botulinum neurotoxin (BoNT). We performed the first trial to investigate whether dystonic jerks/tremor in patients with CD respond to the selective serotonin reuptake inhibitor (SSRI) escitalopram. METHODS: In a randomised, double-blind, crossover trial, patients with CD received escitalopram and placebo for 6 weeks. Treatment with BoNT was continued, and scores on rating scales regarding dystonia, psychiatric symptoms and quality of life (QoL) were compared. Primary endpoint was the proportion of patients that improved at least one point on the Clinical Global Impression Scale for jerks/tremor scored by independent physicians with experience in movement disorders. RESULTS: Fifty-threepatients were included. In the escitalopram period, 14/49 patients (29%) improved on severity of jerks/tremor versus 11/48 patients (23%) in the placebo period (P=0.77). There were no significant differences between baseline and after treatment with escitalopram or placebo on severity of dystonia or jerks/tremor. Psychiatric symptoms and QoL improved significantly in both periods compared with baseline. There were no significant differences between treatment with escitalopram and placebo for dystonia, psychiatric or QoL rating scales. During treatment with escitalopram, patients experienced slightly more adverse events, but no serious adverse events occurred. CONCLUSION: In this innovative trial, no add-on effect of escitalopram for treatment of CD with jerks was found on motor or psychiatric symptoms. However, we also did not find a reason to withhold patients treatment with SSRIs for depression and anxiety, which are common in dystonia. TRIAL REGISTRATION NUMBER: NTR2178.

Substituting the Target After Unsatisfactory Outcome of Deep Brain Stimulation in Advanced Parkinson's Disease: Cases From the NSTAPS Trial and Systematic Review of the Literature.

BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and the subthalamic nucleus (STN) are established treatment option in Parkinson's disease (PD). If DBS does not provide the desired effect, re-operation to the alternative target is a treatment option, but data on the effect of re-operation are scarce. OBJECTIVES: The objective of this study is to evaluate the clinical effect of re-operation the alternative target after failure of initial STN or GPi DBS for Parkinson's disease. MATERIALS AND METHODS: We descriptively analyzed the baseline characteristics, the effect of initial surgery and re-operation of eight NSTAPS (Netherlands SubThalamic and Pallidal Stimulation) patients and six previously published cases that underwent re-operation to a different target. RESULTS: In the NSTAPS cohort, two of the eight patients showed more than 30% improvement of off-drug motor symptoms after re-operation. The initial DBS leads of these patients were off target. In the cases from the literature, 30% off-drug motor improvement was seen in all three patients re-operated from GPi to STN and none of the three patients re-operated from STN to GPi. Only one of the three cases from the literature where any improvement was seen with the operation had a confirmed on target lead location after the first surgery, while the other two patients did not undergo post-operative imaging after the first surgery. CONCLUSIONS: Re-operation to a different target due to lack of effect appears to have a limited chance of leading to objective improvement if the leads were correctly placed during initial surgery.