Deep Brain Stimulation-Induced Mania in Parkinson's Disease
- Conditions
- ManiaParkinson Disease
- Interventions
- Other: No Intervention / Exposure
- Registration Number
- NCT05444907
- Lead Sponsor
- Albino Maia
- Brief Summary
Parkinson's Disease (PD) is a common and debilitating neurodegenerative disease. While medication can alleviate its symptoms, not all patients will adequately respond to medical therapy. For these cases, deep brain stimulation (DBS) has been used to improve symptoms and quality of life. Nevertheless, this approach is, in some cases, associated with incapacitating neuropsychiatric side-effects, including mood disturbances, such as DBS-induced mania. While this condition has important functional short- and long-term consequences for quality of life and prognosis, its pathophysiology is still poorly understood. In this project the investigators propose to conduct a retrospective and naturalistic study in PD patients in whom DBS stimulation resulted in mania or mixed state episode, to clarify if specific sociodemographic and clinical predictors, namely stimulation parameters and target locations, might be associated to the occurrence of this neuropsychiatric adverse event. Additionally, the investigators aim to clarify if the occurrence of DBS-induced mania results from the impact of specific stimulation parameters and/or target locations in functional connectivity networks. To explore this question, the investigators will use different neuroimaging analysis methods termed lesion topography analysis and lesion network mapping, in order to compute maps of the stimulated regions topography and the functional networks that are associated with DBS-mania, respectively. The data that will be analyzed in this project, including neuroimages, will be obtained retrospectively, by different Movement Disorders and Functional Surgery Groups in the context of Deep Brain Stimulation, and that has been collected according to their usual clinical practice.
- Detailed Description
Parkinson's Disease is the second most common neurodegenerative disorder, characterized by very debilitating motor and non-motor symptoms. While medication can alleviate the impact of this disease in patient's daily life, not all patients will respond adequately to treatment, its benefits may not be long-lasting and/or incapacitating side-effects may result. For these cases, DBS has been used to improve symptoms and quality of life. Nevertheless, this approach may have clinically significant side-effects. In fact, important neuropsychiatric adverse events can occur as a result of DBS stimulation, including DBS-induced mania. This is a debilitating mood disorder, frequently associated to a decrease in DBS efficacy due to the need to change/alter stimulation parameters or switch off the device entirely with the patient losing the benefits and the improving quality of life associated with the amelioration of his motor (but also non-motor) symptoms provided by DBS-stimulation. However, reliable predictors for its occurrence are lacking and its pathophysiology is still poorly understood. In this project, the investigators aim to clarify if there are specific DBS electrode locations and/or stimulation parameters associated to development of DBS-induced Mania while additionally determining other potential sociodemographic and clinical predictors. The investigators also aim to further explore if DBS-induced mania results from the impact of specific stimulation parameters and/or target locations in functional connectivity networks.
The investigators hypothesize that specific stimulation parameters and treatment targets associated with DBS-induced mania stimulation will impact particular subcortical brain regions, alongside other clinical and sociodemographic predictors. Additionally, the investigators hypothesize that such specific pattern of stimulation will be associated to specific dysfunctional brain connectivity networks. To address these hypotheses, the investigators propose three specific aims:
1. To determine if there are specific DBS electrode location and/or stimulation parameters associated to development of DBS-induced Mania;
2. To determine if there are specific sociodemographic and/or clinical predictors for the emergence of DBS-induced Mania;
3. To explore if specific functional connectivity networks are associated to the DBS target location and/or stimulation parameters associated with Mania.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
- Ageā„18-years-old;
- Patients diagnosed with PD who were submitted to DBS surgery irrespective of its target;
- Manic episode or mixed affective state diagnosed after surgery and associated to DBS modulation, i.e., after switching on the device or changing modulation parameters.
- Patients diagnosed with bipolar disorder, or manic episode, or mixed affective state before the age of 18
- Patients diagnosed with bipolar disorder, or manic episode, or mixed affective state, before DBS surgery.
DBS Control Cohort:
A control cohort will also be collected. These patients will also meet the aforementioned inclusion and exclusion criteria with the exception of not having presented a manic episode or mixed affective state diagnosed after surgery and associated to DBS modulation.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description DBS-induced Mania Cohort No Intervention / Exposure Patients diagnosed with Parkinson's Disease (PD) who were submitted to deep brain stimulation (DBS) surgery irrespective of its target and who developed a manic episode or mixed affective state diagnosed after surgery and associated to DBS modulation, i.e., after switching on the device or changing modulation parameters. DBS Control Cohort No Intervention / Exposure Patients diagnosed with PD who were submitted to DBS surgery irrespective of its target and who did not develop DBS-induced mania.
- Primary Outcome Measures
Name Time Method Topographic localization of volume of tissue activation (VTA) in DBS-induced mania From DBS parametres change until the date of first documented manic symptoms, assessed up to 24 months Differences in voxel-wise topographic localization of VTAs between DBS-induced mania in Parkinson's Disease (PD) and DBS PD controls. VTAs will be obtained using DBS electrodes locations and stimulation parameters.
- Secondary Outcome Measures
Name Time Method Sociodemographic and/or clinical predictors of DBS-induced mania From DBS parametres change until the date of first documented manic symptoms, assessed up to 24 months Level of prediction of different models for DBS-induced mania in PD, when compared to DBS PD controls. Such models will explore different sociodemographic and/or clinical variables.
Connectivity profile of volume of tissue activation (VTA) in DBS-induced mania From DBS parametres change until the date of first documented manic symptoms, assessed up to 24 months Differences in voxel-wise connectivity profile of VTAs between DBS-induced mania in PD and DBS PD controls.
Trial Locations
- Locations (1)
Champalimaud Foundation
šµš¹Lisbon, Portugal