Short- and long-term antidepressant effects of deep brain stimulation (DBS) in treatment-resistant depression (TRD) have been demonstrated for several brain targets in open-label studies. For two stimulation targets, pivotal randomized trials have been conducted; both failed a futility analysis. We assessed efficacy and safety of DBS of the supero-lateral branch of the medial forebrain bundle (slMFB) in a small Phase I clinical study with a randomized-controlled onset of stimulation in order to obtain data for the planning of a large RCT. Sixteen patients suffering from TRD received DBS of the slMFB and were randomized to sham or real stimulation for the duration of 2 months after implantation. Primary outcome measure was mean reduction in Montgomery–Åsberg Depression Rating Scale (MADRS) during 12 months of DBS (timeline analysis). Secondary outcomes were the difference in several clinical measures between sham and real stimulation at 8 weeks and during stimulation phases. MADRS ratings decreased significantly from 29.6 (SD +/− 4) at baseline to 12.9 (SD +/− 9) during 12 months of DBS (mean MADRS, n = 16). All patients reached the response criterion, most patients (n = 10) responded within a week; 50% of patients were classified as remitters after 1 year of stimulation. The most frequent side effect was transient strabismus. Both groups (active/sham) demonstrated an antidepressant micro-lesioning effect but patients had an additional antidepressant effect after initiation of stimulation. Both rapid onset and stability of the antidepressant effects of slMFB-DBS were demonstrated as in our previous pilot study. Given recent experiences from pivotal trials in DBS for MDD, we believe that slow, careful, and adaptive study development is germane. After our exploratory study and a large-scale study, we conducted this gateway trial in order to better inform planning of the latter. Important aspects for the planning of RCTs in the field of DBS for severe and chronic diseases are discussed including meaningful phases of intra-individual and between-group comparisons and timeline instead of single endpoint analyses.
The observed alterations are consistent with a state-related affective processing bias during the expectation of gains and losses which may contribute to clinical features of mania, such as the enhanced motivation for seeking rewards and the underestimation of risks and potential punishments.
Introduction Deep brain stimulation alleviates tremor of various origins. The dentato-rubro-thalamic tract (DRT) has been suspected as a common tremor-reducing structure. Statistical evidence has not been obtained. We here report the results of an uncontrolled case series of patients with refractory tremor who underwent deep brain stimulation under tractographic assistance. Methods A total of 36 patients were enrolled (essential tremor (17), Parkinson's tremor (8), multiple sclerosis (7), dystonic head tremor (3), tardive dystonia (1)) and received 62 DBS electrodes (26 bilateral; 10 unilateral). Preoperatively, diffusion tensor magnetic resonance imaging sequences were acquired together with high-resolution anatomical T1W and T2W sequences. The DRT was individually tracked and used as a direct thalamic or subthalamic target. Intraoperative tremor reduction was graded on a 4-point scale (0 = no tremor reduction to 3 = full tremor control) and recorded together with the current amplitude, respectively. Stimulation point coordinates were recorded and compared to DRT. The relation of the current amplitude needed to reduce tremor was expressed as TiCR (tremor improvement per current ratio). Results Stimulation points of 241 were available for analysis. A total of 68 trajectories were tested (62 dB leads, 1.1 trajectories tested per implanted lead). Tremor improvement was significantly decreasing (p < 0.01) if the distance to both the border and the center of the DRT was increasing. On the initial trajectory, 56 leads (90.3%) were finally placed. Long-term outcomes were not part of this analysis. Discussion Tremor of various origins was acutely alleviated at different points along the DRT fiber tract (above and below the MCP plane) despite different tremor diseases. DRT is potentially a common tremor-reducing structure. Individual targeting helps to reduce brain penetrating tracts. TiCR characterizes stimulation efficacy and might help to identify an optimal stimulation point.Keywords Deep brain stimulation . DRT . DRTT . Brain . Diffusion tensor magnetic resonance imaging . MRI . Parkinson's disease . Tremor Bastian Sajonz contributed equally to this work.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.