Neural Correlates of Movement Disorders Associated With PRRT2 Related Paroxysmal Kinesigenic Dyskinesia - an Ancillary Study of AMEDYST Research (TRIGGER)

Corrélats Neuronaux Des Accès de Mouvements Anormaux Paroxystiques Liées Aux Dyskinésies Paroxystiques kinésigéniques Secondaires à Une Mutation du Gene PRRT2 - Recherche Ancillaire de L'étude AMEDYST " Dont Vous êtes l'Investigateur Principal

The main objective of this study is to investigate in real-time the neuronal correlates of paroxysmal dyskinesia episodes related to the PRRT2 mutation within this subgroup of patients (who can control paroxysmal dyskinesia episodes), and more specifically, the pathological role of the reciprocal influence between the striatum and the cerebellum in paroxysmal dyskinesia episodes.

Study Overview

• Status: Recruiting
• Conditions: Paroxysmal Dyskinesia
• Intervention / Treatment: Behavioral: Voluntary and involuntary conditions

Detailed Description

We propose to conduct a study using functional MRI and EEG in this subgroup of patients with the PRRT2 mutation capable of triggering paroxysmal dyskinesia episodes. For both modalities, we aim to perform an analysis of the activation of regions involved in the occurrence of abnormal movements during the prodromal phase when the acquisition is not affected by movements. Using these techniques, we will also investigate the regions involved in judging control over action during phases where abnormal movements may occur before the episode (when the system is excitable) and when it is no longer possible during the refractory period (when the system is no longer excitable). Additionally, we plan to conduct a targeted analysis of functional connectivity in the striato-cerebellar pathway before the episodes (when the system is excitable) and after the episodes during the refractory period (when it is no longer excitable).

Our hypotheses are as follows: 1) there is a relationship between the cerebellum, the basal ganglia and the cortex implicated in the abnormal movements associated with the PRRT2 mutation; 2) the frontal or prefrontal cortex, the cerebellum and basal ganglia are involved in the inhibition of unwanted movements; 3) there is a distortion in the sense of control over action related to paroxysmal dyskinesia episodes.

• Study Type: Interventional
• Enrollment (Estimated): 1
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Emmanuel Roze, MD, PhD; Phone Number: +33142162748; Email: emmanuel.flamand-roze@psl.aphp.fr

Study Locations

• France
  • Paris, France, 75651 PARIS cedex 13
    • Recruiting
    • Institut du Cerveau de la Moelle Epinière ICM, Hôpital Pitié Salpêtrière,
    • Contact: Emmanuel FLAMAND ROZE; Phone Number: +33 1 42 16 27 48; Email: emmanuel.flamand-roze@psl.aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Male or female Individuals with dystonic disease carrying a PRRT2 mutation and demonstrating the ability to control paroxysmal dyskinesia episodes.

Affiliated with a health insurance system or a beneficiary of such a system. Individuals aged 18 to 75 years. Signature of informed consent

Exclusion Criteria:

Individuals under guardianship. Individuals not residing in France. Individuals unable to comply with protocol constraints (compliance with visit schedules and ability to perform required tasks).

Individuals undergoing an exclusion period for another research study. Contraindications to MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients; We will conduct a study using functional MRI and EEG in this subgroup of at least 1 patient(s) with a PRRT2 mutation capable of triggering paroxysmal dyskinesia episodes. We will analyze of the activation of regions involved in the occurrence of abnormal movements during the prodromal phase, during which the acquisition is not affected by movements. We will also investigate the regions involved in judging control over action during phases where abnormal movements may occur before and after the dyskinetic episode. Thus, each subject will serve as their own control across different conditions of the experimental paradigm.

Behavioral: Voluntary and involuntary conditions; An task fMRI/EEG acquisition during the prodromal phase preceding the episode of abnormal movements. A task fMRI/EEG acquisition the episode of abnormal movements A task fMRI/EEG acquisition when the subject voluntary mimics the sequence of events (prdrosomal phase + episode of dyskinesia)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
BOLD signal amplitude	Visit 1 to 5
EEG signal amplitude	Visit 6 to 10

Secondary Outcome Measures

Outcome Measure	Time Frame
Perception of control over an movement	Visit 11 to Visit 14 (optional)

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: November 20, 2024
• First Submitted That Met QC Criteria: November 21, 2024
• First Posted (Actual): November 22, 2024

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: fMRI; EEG; dyskinesia; cerebellum; cortex; basal ganglia; voluntary movements
• Additional Relevant MeSH Terms: Neurologic Manifestations; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Dyskinesias; Chorea
• Other Study ID Numbers: C22-09; 022-A02824-39 (Registry Identifier: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Due to ethical policies

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No