Nonmotor symptoms evolution during 24 months of bilateral subthalamic stimulation in Parkinson's disease.

The objective of this study was to investigate 24-month of effects of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on nonmotor symptoms in Parkinson's disease (PD). In this prospective, observational, multicenter, international study including 67 PD patients undergoing bilateral STN-DBS, we examined the Non-motor Symptom Scale, Non-Motor Symptoms Questionnaire, Parkinson's Disease Questionnaire-8, Scales for Outcomes in Parkinson's Disease-motor examination, -activities of daily living, and -complications, and levodopa-equivalent daily dose preoperatively and at 5 and 24-month of follow-up. After checking distribution normality, longitudinal outcome changes were investigated with Friedman tests or repeated-measures analysis of variance and Bonferroni correction for multiple comparisons using multiple tests. Post hoc, Wilcoxon signed rank t tests were computed to compare visits. The strength of clinical responses was analyzed using effect size. Explorative Spearman correlations of change scores from baseline to 24-month follow-up were calculated for all outcomes. The Non-motor Symptom Scale and all other outcome parameters significantly improved from baseline to the 5-month follow-up. From 5 to 24-month, partial decrements in these gains were found. Nonetheless, comparing baseline with 24-month follow-up, significant improvements were observed for the Non-motor Symptom Scale (small effect), Scales for Outcomes in PD-motor examination showed a moderate effect, and Scales for Outcomes in Parkinson's Disease-complications and levodopa-equivalent daily dose showed large effects. Non-motor Symptom Scale change scores from baseline to 24-month follow-up correlated significantly with Parkinson's Disease Questionnaire-8, Scales for Outcomes in Parkinson's Disease-activities of daily living, and -motor complications change scores. This study provides evidence of beneficial effects of bilateral STN-DBS on nonmotor symptoms at 24-month follow-up. The extent of nonmotor symptom improvement was directly proportionate to improvements in quality of life, activities of daily living, and motor complications. This study underlines the importance of nonmotor symptoms for holistic assessments of DBS outcomes. © 2018 International Parkinson and Movement Disorder Society.

Dafsari HS ，Silverdale M ，Strack M ，Rizos A ，Ashkan K ，Mahlstedt P ，Sachse L ，Steffen J ，Dembek TA ，Visser-Vandewalle V ，Evans J ，Antonini A ，Martinez-Martin P ，Ray-Chaudhuri K ，Timmermann L ，EUROPAR and the IPMDS Non Motor PD Study Group ... -  《-》

Beneficial effect of 24-month bilateral subthalamic stimulation on quality of sleep in Parkinson's disease.

Dafsari HS ，Ray-Chaudhuri K ，Ashkan K ，Sachse L ，Mahlstedt P ，Silverdale M ，Rizos A ，Strack M ，Jost ST ，Reker P ，Samuel M ，Visser-Vandewalle V ，Evans J ，Antonini A ，Martinez-Martin P ，Timmermann L ，EUROPAR, the IPMDS Non Motor P.D. Study Group ... -  《-》

Beneficial nonmotor effects of subthalamic and pallidal neurostimulation in Parkinson's disease.

Subthalamic (STN) and pallidal (GPi) deep brain stimulation (DBS) improve quality of life, motor, and nonmotor symptoms (NMS) in advanced Parkinson's disease (PD). However, few studies have compared their nonmotor effects. To compare nonmotor effects of STN-DBS and GPi-DBS. In this prospective, observational, multicenter study including 60 PD patients undergoing bilateral STN-DBS (n = 40) or GPi-DBS (n = 20), we examined PDQuestionnaire (PDQ), NMSScale (NMSS), Unified PD Rating Scale-activities of daily living, -motor impairment, -complications (UPDRS-II, -III, -IV), Hoehn&Yahr, Schwab&England Scale, and levodopa-equivalent daily dose (LEDD) preoperatively and at 6-month follow-up. Intra-group changes at follow-up were analyzed with Wilcoxon signed-rank or paired t-test, if parametric tests were applicable, and corrected for multiple comparisons. Inter-group differences were explored with Mann-Whitney-U/unpaired t-tests. Analyses were performed before and after propensity score matching which balanced out demographic and preoperative clinical characteristics. Strength of clinical changes was assessed with effect size. In both groups, PDQ, UPDRS-II, -IV, Schwab&England Scale, and NMSS improved significantly at follow-up. STN-DBS was significantly better for LEDD reduction, GPi-DBS for UPDRS-IV. While NMSS total score outcomes were similar, explorative NMSS domain analyses revealed distinct profiles: Both targets improved sleep/fatigue and mood/cognition, but only STN-DBS the miscellaneous (pain/olfaction) and attention/memory and only GPi-DBS cardiovascular and sexual function domains. To our knowledge, this is the first study to report distinct patterns of beneficial nonmotor effects of STN-DBS and GPi-DBS in PD. This study highlights the importance of NMS assessments to tailor DBS target choices to patients' individual motor and nonmotor profiles.

Dafsari HS ，Dos Santos Ghilardi MG ，Visser-Vandewalle V ，Rizos A ，Ashkan K ，Silverdale M ，Evans J ，Martinez RCR ，Cury RG ，Jost ST ，Barbe MT ，Fink GR ，Antonini A ，Ray-Chaudhuri K ，Martinez-Martin P ，Fonoff ET ，Timmermann L ，EUROPAR and the IPMDS Non Motor PD Study Group ... -  《-》

EuroInf 2: Subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson's disease.

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). In this prospective, multicenter, international, real-life 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. 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. 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. © 2019 International Parkinson and Movement Disorder Society.

Dafsari HS ，Martinez-Martin P ，Rizos A ，Trost M ，Dos Santos Ghilardi MG ，Reddy P ，Sauerbier A ，Petry-Schmelzer JN ，Kramberger M ，Borgemeester RWK ，Barbe MT ，Ashkan K ，Silverdale M ，Evans J ，Odin P ，Fonoff ET ，Fink GR ，Henriksen T ，Ebersbach G ，Pirtošek Z ，Visser-Vandewalle V ，Antonini A ，Timmermann L ，Ray Chaudhuri K ，EUROPAR and the International Parkinson and Movement Disorders Society Non-Motor Parkinson's Disease Study Group ... -  《-》

Quality of life outcome after subthalamic stimulation in Parkinson's disease depends on age.

The purpose of this study was to investigate how quality of life outcome after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) depends on age. In this prospective, open-label, multicenter study including 120 PD patients undergoing bilateral STN-DBS, we investigated the PDQuestionnaire-8 (PDQ-8), Unified PD Rating Scale-III, Scales for Outcomes in PD-motor examination, complications, activities of daily living, and levodopa equivalent daily dose preoperatively and at 5 months follow-up. Significant changes at follow-up were analyzed with Wilcoxon signed-rank test and Bonferroni correction for multiple comparisons. To explore the influence of age post hoc, the patients were classified into 3 age groups (≤59, 60-69, ≥70 years). Intragroup changes were analyzed with Wilcoxon signed-rank and intergroup differences with Kruskal-Wallis tests. The strength of clinical responses was evaluated using effect size. The PDQuestionnaire-8, Scales for Outcomes in PD-motor complications, activities of daily living, and levodopa equivalent daily dose significantly improved in the overall cohort and all age groups with no significant intergroup differences. However, PDQuestionnaire-8 effect sizes for age groups ≤59, 60 to 69, and ≥70 years, respectively, were strong, moderate, and small. Furthermore, PDQuestionnaire-8 domain analyses revealed that all domains except cognition and emotional well-being significantly improved in patients aged ≤59 years, whereas only communication, activities of daily living, and stigma improved in patients aged 60-69 years, and activities of daily living and stigma in patients aged ≥70 years. Although quality of life, motor complications, and activities of daily living significantly improved in all age groups after bilateral STN-DBS, the beneficial effect on overall quality of life was more pronounced and affected a wider range of quality of life domains in younger patients. © 2017 International Parkinson and Movement Disorder Society.

Dafsari HS ，Reker P ，Stalinski L ，Silverdale M ，Rizos A ，Ashkan K ，Barbe MT ，Fink GR ，Evans J ，Steffen J ，Samuel M ，Dembek TA ，Visser-Vandewalle V ，Antonini A ，Ray-Chaudhuri K ，Martinez-Martin P ，Timmermann L ，EUROPAR and the IPMDS (International Parkinson's and Movement Disorders Society) Non-Motor Parkinson's Disease Study Group ... -  《-》