A BS TRACT: Objective: Real-life observational report of clinical efficacy of bilateral subthalamic stimulation (STN-DBS), apomorphine (APO), and intrajejunal levodopa infusion (IJLI) on quality of life, motor, and nonmotor symptoms (NMS) in Parkinson's disease (PD). Methods: In this prospective, multicenter, international, reallife cohort observation study of 173 PD patients undergoing STN-DBS (n = 101), IJLI (n = 33), or APO (n = 39) were followed-up using PDQuestionnaire-8, NMSScale (NMSS), Unified PD Rating Scale (UPDRS)-III, UPDRS-IV, and levodopa equivalent daily dose (LEDD) before and 6 months after intervention. Outcome changes were analyzed with Wilcoxon signed-rank or paired t test when parametric tests were applicable. Multiple comparisons were corrected (multiple treatments/scales). Effect strengths were quantified with relative changes, effect size, and number needed to treat. Analyses were computed before and after propensity score matching, balancing demographic and clinical characteristics. Results: In all groups, PDQuestionnaire-8, UPDRS-IV, and NMSS total scores improved significantly at follow-up. ---Levodopa equivalent daily dose was significantly reduced after STN-DBS. Explorative NMSS domain analyses resulted in distinct profiles: STN-DBS improved urinary/ sexual functions, mood/cognition, sleep/fatigue, and the miscellaneous domain. IJLI improved the 3 latter domains and gastrointestinal symptoms. APO improved mood/ cognition, perceptual problems/hallucinations, attention/ memory, and the miscellaneous domain. Overall, STN-DBS and IJLI seemed favorable for NMSS total score, and APO favorable for neuropsychological/neuropsychiatric NMS and PDQuestionnaire-8 outcome.Conclusions: This is the first comparison of quality of life, nonmotor. and motor outcomes in PD patients undergoing STN-DBS, IJLI, and APO in a real-life cohort. Distinct effect profiles were identified for each treatment option. Our results highlight the importance of holistic nonmotor and motor symptoms assessments to personalize treatment choices.

BACKGROUND STN-DBS is well established to improve motor symptoms and quality of life in patients with PD. While non-motor symptoms are crucial for quality of life in these patients, only neuropsychiatric and neuropsychological symptoms have been systematically studied in a longitudinal design thus far. However, these are only a part of the spectrum of non-motor symptoms in PD. We hypothesized that STN-DBS is associated with a beneficial effect on a range of non-motor symptoms. METHODSIn this multicenter, open, prospective, international study we investigated non-motor effects of STN-DBS in "real-life" use. We evaluated Non-motor Symptom Scale, and Questionnaire, PD Questionnaire-8, Scales for Outcomes of PD motor examination and complications, and activities of daily living preoperatively and at 6 months follow-up in 60 consecutive patients (35 male, mean age: 61.64 ±7.84 years, mean disease duration: 10.45 ±4.22 years) undergoing STN-DBS. RESULTSAll outcomes improved significantly at 6 months follow-up (PD Questionaire-8, p=0.006; activities of daily living, p=0.012; all others, p<0.001; Wilcoxon signedrank, respectively paired t-test; Bonferroni-correction). Post-hoc analyses of Nonmotor Symptom Scale domains showed a significant reduction of sleep/fatigue and miscellaneous domains (p≤0.001), perceptual problems/hallucinations (p=0.036), and urinary (p=0.018) scores. Effect sizes were "moderate" effect for Non-motor Non-motor effects of subthalamic DBS -5 -Symptom Scale, and motor complications, "large" for motor examination, and "small" for other outcomes. CONCLUSIONSThis study provides first evidence that bilateral STN-DBS improves non-motor burden in patients with PD and opens the door to a more balanced evaluation of DBS outcomes. Further randomized studies are needed to confirm these findings and compare DBS non-motor effects to other therapies such as infusion based treatments of advanced PD.

Deep brain stimulation of the subthalamic nucleus improves non-motor symptoms in Parkinson’s disease, but with considerable inter-individual variability. Petry-Schmelzer et al. show that neurostimulation in specific subregions of the subthalamic nucleus has differential effects on mood/apathy, attention/memory and sleep-related outcomes. Neurostimulation could thus be tailored to patients’ individual non-motor profiles.

No abstract

Objective: Subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) not only stimulates focal target structures but also affects distributed brain networks. The impact this network modulation has on non-motor DBS effects is not well-characterized. By focusing on the affective domain, we systematically investigate the impact of electrode placement and associated structural connectivity on changes in depressive symptoms following STN-DBS, which have been reported to improve, worsen, or remain unchanged. Methods: Depressive symptoms before and after STN-DBS surgery were documented in 116 patients with PD from 3 DBS centers (Berlin, Queensland, and Cologne). Based on individual electrode reconstructions, the volumes of tissue activated (VTAs) were estimated and combined with normative connectome data to identify structural connections passing through VTAs. Berlin and Queensland cohorts formed a training and cross-validation dataset used to identify structural connectivity explaining change in depressive symptoms. The Cologne data served as the test-set for which depressive symptom change was predicted. Results: Structural connectivity was linked to depressive symptom change under STN-DBS. An optimal connectivity map trained on the Berlin cohort could predict changes in depressive symptoms in Queensland patients and vice versa. Furthermore, the joint training-set map predicted changes in depressive symptoms in the independent test-set. Worsening of depressive symptoms was associated with left prefrontal connectivity. Interpretation: Fibers connecting the electrode with left prefrontal areas were associated with worsening of depressive symptoms. Our results suggest that for the left STN-DBS lead, placement impacting fibers to left prefrontal areas should be avoided to maximize improvement of depressive symptoms.

No abstract

Our study provides evidence that more anterior, medial, and ventral STN-DBS is significantly related to more beneficial non-motor outcomes.

Our results provide evidence that QoL improvement after STN-DBS depends on preoperative NMS characteristics. These findings are important in the advising and selection of individuals for DBS therapy. Future studies investigating motor and non-motor PD clusters may enable stratifying QoL outcomes and help predict patients' individual prospects of benefiting from DBS.