Validation of the hotspot for dorsolateral subthalamic nucleus targeting in deep brain stimulation surgery for Parkinson's disease: a post hoc analysis of a randomised controlled trial.

BACKGROUND: Visualisation of the dorsolateral subthalamic nucleus (STN) remains challenging on 1.5 and 3Tesla T2-weighted MRI. Our previously defined hotspot, relative to the well-visualised medial STN border, serves as an MRI landmark for dorsolateral STN identification in deep brain stimulation (DBS). We aimed to validate this hotspot in a separate trial cohort of Parkinson's disease (PD) patients and refine its location. METHODS: In this post hoc analysis of a randomised controlled trial, in which the hotspot was taken into account during target planning, responses to DBS were evaluated using hemibody improvement on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor examination and compared with our historical cohort, as well as dopaminergic medication reduction. Then, a refined hotspot was calculated and the Euclidean distance from individual active contacts to the refined hotspot was correlated with motor improvement. RESULTS: The first quartile of the hemibodies (poor responders) showed an average improvement of 13%, which was higher than the -8% in the historical control group (p=0.044). Dopaminergic medication reduction was greater in the current cohort compared with the historical cohort (p=0.020). Overall variability of hemibody motor improvement was reduced in the current cohort compared with the historical control group (p=0.003). Motor improvement correlated to the Euclidean distance from active contact to the refined hotspot (2.8 mm lateral, 1.1 mm anterior and 2.2 mm superior to the medial STN border) (p=0.001). CONCLUSION: We validated the hotspot for dorsolateral STN targeting in DBS for patients with PD and showed an improved motor response in poor responders, a reduced variability in motor improvement and a greater dopaminergic medication reduction. We then refined the hotspot at 2.8 mm lateral, 1.1 mm anterior and 2.2 mm superior relative to the medial STN border, which visualises a readily implementable target within the dorsolateral STN on lower field strength MRI.

Surgical Complications in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease: Experience in 800 Patients.

INTRODUCTION: We present our surgical complications resulting in neurological deficit or additional surgery during 25 years of DBS of the subthalamic nucleus (STN) for Parkinson's disease (PD). METHODS: We conducted a retrospective chart review of all PD patients that received STN DBS in our DBS center between 1998 and 2023. Outcomes were complications resulting in neurological deficit or additional surgery. Potential risk factors (number of microelectrode recording tracks, age, anesthesia method, hypertension, and sex) for symptomatic intracerebral hemorrhage (ICH) were analyzed. Furthermore, lead fixation techniques were compared. RESULTS: Eight hundred PD patients (507 men, 293 women) received unilateral (n = 11) or bilateral (n = 789) implantation of STN electrodes. Neurological deficit due to ICH, edema, delirium, or infarction was seen in 8.4% of the patients (7.4% transient, 1.0% permanent). Twenty-two patients (2.8%) had a symptomatic ICH following STN DBS, for which we did not find any risk factors, and five had permanent sequelae due to ICH (0.6%). Of all patients, 18.4% required additional surgery; the proportion was reduced from 27% in the first 300 cases to 13% in the last 500 cases (p < 0.001). The infection rate was 3.5%, which decreased from 5.3% in the first 300 cases to 2.2% in the last 500 cases. The use of a lead anchoring device led to significantly less lead migrations than miniplate fixation. CONCLUSION: STN DBS leads to permanent neurological deficit in a small number of patients (1.0%), but a substantial proportion needs some additional surgical procedure after the first DBS system implantation. The risk of revision surgery was reduced over time but remained significant. These findings need to be discussed with the patient in the preoperative informed consent process in addition to the expected health benefit.

Cognitive and psychiatric outcomes in the GALAXY trial: effect of anaesthesia in deep brain stimulation.

BACKGROUND: This study aims: (1) To compare cognitive and psychiatric outcomes after bilateral awake versus asleep subthalamic nucleus (STN) deep brain stimulation (DBS) surgery for Parkinson's disease (PD). (2) To explore the occurrence of psychiatric diagnoses, cognitive impairment and quality of life after surgery in our whole sample. (3) To validate whether we can predict postoperative cognitive decline. METHODS: 110 patients with PD were randomised to receive awake (n=56) or asleep (n=54) STN DBS surgery. At baseline and 6-month follow-up, all patients underwent standardised assessments testing several cognitive domains, psychiatric symptoms and quality of life. RESULTS: There were no differences on neuropsychological composite scores and psychiatric symptoms between the groups, but we found small differences on individual tests and cognitive domains. The asleep group performed better on the Rey Auditory Verbal Learning Test delayed memory test (f=4.2, p=0.04), while the awake group improved on the Rivermead Behavioural Memory Test delayed memory test. (f=4.4, p=0.04). The Stroop III score was worse for the awake group (f=5.5, p=0.02). Worse scores were present for Stroop I (Stroop word card) (f=6.3, p=0.01), Stroop II (Stroop color card) (f=46.4, p<0.001), Stroop III (Stroop color-word card) (f=10.8, p=0.001) and Trailmaking B/A (f=4.5, p=0.04). Improvements were seen on quality of life: Parkinson's Disease Questionnaire-39 (f=24.8, p<0.001), and psychiatric scales: Hamilton Depression Rating Scale (f=6.2, p=0.01), and Hamilton Anxiety Rating Scale (f=5.5, p=0.02). CONCLUSIONS: This study suggests that the choice between awake and asleep STN DBS does not affect cognitive, mood and behavioural adverse effects, despite a minor difference in memory. STN DBS has a beneficial effect on quality of life, mood and anxiety symptoms. TRIAL REGISTRATION NUMBER: NTR5809.

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.

Implementation of Intraoperative Cone-Beam Computed Tomography (O-arm) for Stereotactic Imaging During Deep Brain Stimulation Procedures.

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.

A piece of the human heart: variance of protein phosphorylation in left ventricular samples from end-stage primary cardiomyopathy patients.

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.