Deep Brain Stimulation-Induced Mania in Parkinson's Disease

NCT ID: NCT05444907

Last Updated: 2025-02-26

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-05-25
• Study Completion Date: 2025-12-31

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.

Conditions

Mania; Parkinson Disease

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: RETROSPECTIVE

Study Groups

DBS-induced Mania Cohort

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.

No Intervention / Exposure

Intervention Type: OTHER

No intervention / exposure since this is an observational study

DBS Control Cohort

Patients diagnosed with PD who were submitted to DBS surgery irrespective of its target and who did not develop DBS-induced mania.

No Intervention / Exposure

Intervention Type: OTHER

No intervention / exposure since this is an observational study

Interventions

No Intervention / Exposure

No intervention / exposure since this is an observational study

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age≥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.

Exclusion Criteria

• 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:

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centro Hospitalar Lisboa Ocidental

OTHER_GOV

Sponsor Role: collaborator

Centro Hospitalar De São João, E.P.E.

OTHER

Sponsor Role: collaborator

Unidade Local de Saúde de Coimbra, EPE

OTHER

Sponsor Role: collaborator

Centro Hospitalar de Lisboa Central

OTHER

Sponsor Role: collaborator

Albino Maia

OTHER

Sponsor Role: lead

Responsible Party

Albino Maia

Director of Neuropsychiatry Unit, Champalimaud Foundation

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Albino J. Oliveira-Maia, MD, MPH, PhD

Role: PRINCIPAL_INVESTIGATOR

Champalimaud Foundation

Locations

Champalimaud Foundation

Lisbon, , Portugal

Site Status: RECRUITING

Countries

Portugal

Central Contacts

Sofia Marques

Role: CONTACT

sofia.marques@research.fchampalimaud.org

+351 210 480 048 ext. 4153

Facility Contacts

Sofia Marques

Role: primary

sofia.marques@research.fchampalimaud.org

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Other Identifiers

BPD_DBS

Identifier Type: -

Identifier Source: org_study_id