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 MEASURESThe 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], points; asleep group: mean [SD], 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 RELEVANCEThere 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 microelectrodeguided procedures.

BackgroundThe aim of the study is to investigate if deep brain stimulation (DBS) in the subthalamic nucleus (STN) for Parkinson’s disease (PD) under general anesthesia further improves outcome by lessening postoperative cognitive, mood, and behavioral adverse effects; shorten surgical time and hospital admittance; and produce comparable symptomatic and functional improvement to surgery under local anesthesia.Methods/designThe study will be a single-center, prospective, randomized, open-label, blinded endpoint trial comparing DBS under general anesthesia with DBS under local anesthesia. The primary outcome measure is a composite score of the postoperative cognitive, mood, and behavioral adverse effects and will be measured 6 months after surgery. The secondary outcome measures consist of changes in motor symptoms, adverse effects of stimulation and surgical complications, surgical time, functional health, quality of life, patient satisfaction with the outcome of treatment, patient evaluation of the burden of therapy, and medication. A total of 110 patients with advanced PD who are candidates for DBS will be randomized during a 2.5-year period.DiscussionThe aim of this trial is to further enhance the effectiveness of DBS treatment in PD while reducing the burden of DBS surgery by studying if DBS surgery under general anesthesia results in less cognitive, mood, and behavioral adverse effects compared with surgery under local anesthesia.Trial registrationNetherlands Trial Register, NTR5809. Registered on 23 April 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2136-8) contains supplementary material, which is available to authorized users.

Cardiomyocyte contraction is regulated by phosphorylation of sarcomeric proteins. Throughout the heart regional and transmural differences may exist in protein phosphorylation. In addition, phosphorylation of sarcomeric proteins is altered in cardiac disease. Heterogeneity in protein phosphorylation may be larger in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) as it may be caused by multiple mutations in genes encoding different sarcomeric proteins. Moreover, HCM is characterized by asymmetric remodelling of the heart. In the present study we assessed if local differences in sarcomeric protein phosphorylation are more evident in primary HCM or DCM than in non-failing donors. Thereto, phosphorylation of the two main target proteins of the beta-adrenergic receptor pathway, troponin I (cTnI) and myosin binding protein C (cMyBP-C) was analysed in different parts in the free left ventricular wall of end–stage failing HCM and DCM patients and donors obtained during transplant surgery. Intra-patient variability in protein phosphorylation within tissue samples of approximately 2 g wet weight was comparable between donor, HCM and DCM samples and could partly be attributed to the precision of the technique. Thus, our data indicate that within the precision of the measurements small, biopsy-sized cardiac tissue samples are representative for the region of the free left ventricular wall from which they were obtained.

BACKGROUND Intraoperative cone-beam computed tomography (iCBCT) allows for rapid 3-dimensional imaging. However, it is currently unknown whether this imaging technique offers sufficient accuracy for stereotactic registration during deep brain stimulation (DBS) procedures. OBJECTIVE To determine the accuracy of iCBCT, with the O-arm O2 (Medtronic), for stereotactic registration by comparing this modality to stereotactic magnetic resonance imaging (MRI). METHODS All DBS patients underwent a preoperative non-stereotactic 3 Tesla MRI, stereotactic 1.5 Tesla MRI, stereotactic O-arm iCBCT, postimplantation O-arm iCBCT, and postoperative conventional multidetector computed tomography (CT) scan. We compared stereotactic (X, Y, and Z) coordinates of the anterior commissure (AC), the posterior commissure (PC), and midline reference (MR) between stereotactic MRI and iCBCT. For localisation comparison of electrode contacts, stereotactic coordinates of electrode tips were compared between the postoperative multidetector CT and iCBCT. RESULTS A total of 20 patients were evaluated. The average absolute difference in stereotactic coordinates of AC, PC, and MR was 0.4 ± 0.4 mm for X, 0.4 ± 0.4 mm for Y, and 0.7 ± 0.5 mm for Z. The average absolute difference in X-, Y-, and Z-coordinates for electrode localisation (N = 34) was 0.3 ± 0.3 mm, 0.6 ± 0.3 mm, and 0.6 ± 0.6 mm. These differences were small enough not to be considered clinically relevant. CONCLUSION Stereotactic MRI and O-arm iCBCT yield comparable coordinates in pre- and postoperative imaging. Differences found are below the threshold of clinical relevance. Intraoperative O-arm CBCT offers rapid stereotactic registration and evaluation of electrode placement. This increases patient comfort and neurosurgical workflow efficiency.