Deep Brain Stimulation-Induced Mania in Parkinson's Disease

NCT05444907 | Recruiting

• 1 other identifier: BPD_DBS
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Mania; Parkinson Disease

Keywords

Parkinson's Disease; Deep Brain Stimulation; Mania

Outcome Measures

Primary Outcomes (1)

• Topographic localization of volume of tissue activation (VTA) in DBS-induced mania

  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.

  From DBS parametres change until the date of first documented manic symptoms, assessed up to 24 months

Secondary Outcomes (2)

• 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

• 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

Study Arms (2)

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.

Other: No Intervention / Exposure

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.

Other: No Intervention / Exposure

Interventions

No Intervention / Exposure OTHER

No intervention / exposure since this is an observational study

DBS Control Cohort; DBS-induced Mania Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study cohort will be collected retrospectively from DBS surgery databases from different Movement Disorders and Functional Surgery Groups and further analyzed at the Champalimaud Neuropsychiatry Unit. Data collection will be conducted by each center independently under the approval of their respective Ethics Committees. The data that will be analyzed in this project, including neuroimages, has been collected according to the usual clinical practice of the Movement Disorders and Functional Surgery Groups.

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• Albino Maia: lead
• Centro Hospitalar Lisboa Ocidental: collaborator
• Centro Hospitalar De São João, E.P.E.: collaborator
• Unidade Local de Saúde de Coimbra, EPE: collaborator
• Centro Hospitalar de Lisboa Central: collaborator

Study Sites (1)

Champalimaud Foundation

Lisbon, 1400-038, Portugal

RECRUITING

Related Publications (22)

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• Accolla EA, Pollo C. Mood Effects After Deep Brain Stimulation for Parkinson's Disease: An Update. Front Neurol. 2019 Jun 14;10:617. doi: 10.3389/fneur.2019.00617. eCollection 2019.

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• Mosley PE, Smith D, Coyne T, Silburn P, Breakspear M, Perry A. The site of stimulation moderates neuropsychiatric symptoms after subthalamic deep brain stimulation for Parkinson's disease. Neuroimage Clin. 2018 Mar 13;18:996-1006. doi: 10.1016/j.nicl.2018.03.009. eCollection 2018.

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• Cotovio G, Talmasov D, Barahona-Correa JB, Hsu J, Senova S, Ribeiro R, Soussand L, Velosa A, Silva VCE, Rost N, Wu O, Cohen AL, Oliveira-Maia AJ, Fox MD. Mapping mania symptoms based on focal brain damage. J Clin Invest. 2020 Oct 1;130(10):5209-5222. doi: 10.1172/JCI136096.

  PMID: 32831292 BACKGROUND

• Barahona-Correa JB, Cotovio G, Costa RM, Ribeiro R, Velosa A, Silva VCE, Sperber C, Karnath HO, Senova S, Oliveira-Maia AJ. Right-sided brain lesions predominate among patients with lesional mania: evidence from a systematic review and pooled lesion analysis. Transl Psychiatry. 2020 May 12;10(1):139. doi: 10.1038/s41398-020-0811-0.

  PMID: 32398699 BACKGROUND

• van den Heuvel MP, Hulshoff Pol HE. Exploring the brain network: a review on resting-state fMRI functional connectivity. Eur Neuropsychopharmacol. 2010 Aug;20(8):519-34. doi: 10.1016/j.euroneuro.2010.03.008. Epub 2010 May 14.

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  BACKGROUND

• Darby RR, Laganiere S, Pascual-Leone A, Prasad S, Fox MD. Finding the imposter: brain connectivity of lesions causing delusional misidentifications. Brain. 2017 Feb;140(2):497-507. doi: 10.1093/brain/aww288. Epub 2017 Jan 12.

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MeSH Terms

Conditions

Mania; Parkinson Disease

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

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

  Champalimaud Foundation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sofia Marques

CONTACT

+351 210 480 048; sofia.marques@research.fchampalimaud.org

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Neuropsychiatry Unit, Champalimaud Foundation

Study Record Dates

• First Submitted: June 28, 2022
• First Posted: July 6, 2022
• Study Start: May 25, 2021
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: February 26, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

PT (1)