Can Dopamine Responsiveness Be Predicted in Parkinson's Disease Without an Acute Administration Test?


Journal

Journal of Parkinson's disease
ISSN: 1877-718X
Titre abrégé: J Parkinsons Dis
Pays: Netherlands
ID NLM: 101567362

Informations de publication

Date de publication:
2022
Historique:
pubmed: 25 7 2022
medline: 19 10 2022
entrez: 24 7 2022
Statut: ppublish

Résumé

Dopamine responsiveness (dopa-sensitivity) is an important parameter in the management of patients with Parkinson's disease (PD). For quantification of this parameter, patients undergo a challenge test with acute Levodopa administration after drug withdrawal, which may lead to patient discomfort and use of significant resources. Our objective was to develop a predictive model combining clinical scores and imaging. 350 patients, recruited by 13 specialist French centers and considered for deep brain stimulation, underwent an acute L-dopa challenge (dopa-sensitivity > 30%), full assessment, and MRI investigations, including T1w and R2* images. Data were randomly divided into a learning base from 10 centers and data from the remaining centers for testing. A machine selection approach was applied to choose the optimal variables and these were then used in regression modeling. Complexity of the modelling was incremental, while the first model considered only clinical variables, the subsequent included imaging features. The performances were evaluated by comparing the estimated values and actual valuesResults:Whatever the model, the variables age, sex, disease duration, and motor scores were selected as contributors. The first model used them and the coefficients of determination (R2) was 0.60 for the testing set and 0.69 in the learning set (p < 0.001). The models that added imaging features enhanced the performances: with T1w (R2 = 0.65 and 0.76, p < 0.001) and with R2* (R2 = 0.60 and 0.72, p < 0.001). These results suggest that modeling is potentially a simple way to estimate dopa-sensitivity, but requires confirmation in a larger population, including patients with dopa-sensitivity < 30.

Sections du résumé

BACKGROUND
Dopamine responsiveness (dopa-sensitivity) is an important parameter in the management of patients with Parkinson's disease (PD). For quantification of this parameter, patients undergo a challenge test with acute Levodopa administration after drug withdrawal, which may lead to patient discomfort and use of significant resources.
OBJECTIVE
Our objective was to develop a predictive model combining clinical scores and imaging.
METHODS
350 patients, recruited by 13 specialist French centers and considered for deep brain stimulation, underwent an acute L-dopa challenge (dopa-sensitivity > 30%), full assessment, and MRI investigations, including T1w and R2* images. Data were randomly divided into a learning base from 10 centers and data from the remaining centers for testing. A machine selection approach was applied to choose the optimal variables and these were then used in regression modeling. Complexity of the modelling was incremental, while the first model considered only clinical variables, the subsequent included imaging features. The performances were evaluated by comparing the estimated values and actual valuesResults:Whatever the model, the variables age, sex, disease duration, and motor scores were selected as contributors. The first model used them and the coefficients of determination (R2) was 0.60 for the testing set and 0.69 in the learning set (p < 0.001). The models that added imaging features enhanced the performances: with T1w (R2 = 0.65 and 0.76, p < 0.001) and with R2* (R2 = 0.60 and 0.72, p < 0.001).
CONCLUSION
These results suggest that modeling is potentially a simple way to estimate dopa-sensitivity, but requires confirmation in a larger population, including patients with dopa-sensitivity < 30.

Identifiants

pubmed: 35871363
pii: JPD223334
doi: 10.3233/JPD-223334
doi:

Substances chimiques

Antiparkinson Agents 0
Levodopa 46627O600J
Dopamine VTD58H1Z2X

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2179-2190

Auteurs

Nacim Betrouni (N)

University Lille, INSERM, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, LICEND, Lille, France.

Caroline Moreau (C)

University Lille, INSERM, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, LICEND, Lille, France.
CHU Lille, Neurology and Movement Disorders Department, Reference Center for Parkinson's Disease, Lille, France; NS-Park French Network.

Anne-Sophie Rolland (AS)

University Lille, INSERM, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, LICEND, Lille, France.

Nicolas Carrière (N)

University Lille, INSERM, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, LICEND, Lille, France.
CHU Lille, Neurology and Movement Disorders Department, Reference Center for Parkinson's Disease, Lille, France; NS-Park French Network.
University Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, US 41 - UMS 2014 - PLBS, Lille, France; NS-Park French Network.

Romain Viard (R)

University Lille, INSERM, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, LICEND, Lille, France.
University Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, US 41 - UMS 2014 - PLBS, Lille, France; NS-Park French Network.

Renaud Lopes (R)

University Lille, INSERM, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, LICEND, Lille, France.
University Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, US 41 - UMS 2014 - PLBS, Lille, France; NS-Park French Network.

Gregory Kuchcinski (G)

University Lille, INSERM, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, LICEND, Lille, France.
CHU Lille, Neuroradioloy Department, Lille, France.

Alexandre Eusebio (A)

Aix Marseille Universitë, AP-HM, Hôpital de La Timone, Service de Neurologie et Pathologie du Mouvement, UMR CNRS 7289, Institut de Neuroscience de La Timone, Marseille, France; NS-Park French Network.

Stephane Thobois (S)

Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Neurologie C, Bron, France.

Elodie Hainque (E)

Dëpartement de Neurologie, Hôpital Pitië-Salpêtrière, AP-HP, Paris, France; NS-Park French Network.

Cecile Hubsch (C)

Fondation Ophtalmologique A de Rothschild, Unitë James Parkinson, Paris, France; NS-Park French Network.

Olivier Rascol (O)

University of Toulouse 3, University Hospital of Toulouse, INSERM, Departments of Neuroscience and Clinical Pharmacology, Clinical Investigation Center CIC 1436, Toulouse Parkinson Expert Center, NS-NeuroToul Center of Excellence for Neurodegenerative Disorders (COEN), Toulouse, France; NS-Park French Network.

Christine Brefel (C)

University of Toulouse 3, University Hospital of Toulouse, INSERM, Departments of Neuroscience and Clinical Pharmacology, Clinical Investigation Center CIC 1436, Toulouse Parkinson Expert Center, NS-NeuroToul Center of Excellence for Neurodegenerative Disorders (COEN), Toulouse, France; NS-Park French Network.

Sophie Drapier (S)

Service de Neurologie, CHU Pont Chaillou, 2 rue Henri le Guilloux, Rennes cedex, France; NS-Park French Network.

Caroline Giordana (C)

Universitë Clermont Auvergne, EA7280, Clermont-Ferrand University Hospital, Neurology Department, Clermont-Ferrand, France; NS-Park French Network.

Franck Durif (F)

Universitë Clermont Auvergne, EA7280, Clermont-Ferrand University Hospital, Neurology Department, Clermont-Ferrand, France; NS-Park French Network.

David Maltête (D)

Department of Neurology, Rouen University Hospital and University of Rouen, France; INSERM U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Mont-Saint-Aignan, France; NS-Park French Network.

Dominique Guehl (D)

Service d'Explorations Fonctionnelles du Système Nerveux, Institut des Maladies Neurodëgënëratives Cliniques, CHU de Bordeaux, Bordeaux, France; NS-Park French Network.

Lucie Hopes (L)

Neurology Department, Nancy University Hospital, Nancy, France; NS-Park French Network.

Tiphaine Rouaud (T)

Clinique Neurologique, Hôpital Guillaume et Renë Laennec, Boulevard Jacques Monod, Nantes Cedex, France; NS-Park French Network.

Bechir Jarraya (B)

Movement Disorders Unit, Foch Hospital, Universitë Paris-Saclay (UVSQ), INSERM U992, NeuroSpin, CEA Paris-Saclay, Suresnes, France; NS-Park French Network.

Isabelle Benatru (I)

Service de Neurologie, Centre Expert Parkinson, CIC-INSERM 1402, CHU Poitiers, Poitiers, France; NS-Park French Network.

Christine Tranchant (C)

Service de Neurologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; Institut de Gënëtique et de Biologie Molëculaire et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Universitë de Strasbourg, Illkirch, France; Fëdëration de Mëdecine Translationnelle de Strasbourg (FMTS), Universitë de Strasbourg, Strasbourg, France; NS-Park French Network.

Melissa Tir (M)

Department of Neurosurgery, Amiens University Hospital, Amiens, France; Medical Imaging Unit, Amiens University Hospital, Amiens, France; BioFlowImage Research Group, Jules Verne University of Picardie, Amiens, France; NS-Park French Network.

Marie Chupin (M)

CATI, Institut du Cerveau et de le Moelle Epinière, ICM, INSERM U1127, CNRS UMR7225, Sorbonne Universitë, Paris, France.

Eric Bardinet (E)

Institut du Cerveau et de le Moelle Epinière, ICM, INSERM U1127, CNRS UMR7225, Sorbonne Universitë, Paris, France.

Luc Defebvre (L)

University Lille, INSERM, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, LICEND, Lille, France.
CHU Lille, Neurology and Movement Disorders Department, Reference Center for Parkinson's Disease, Lille, France; NS-Park French Network.

Jean-Christophe Corvol (JC)

Dëpartement de Neurologie, Hôpital Pitië-Salpêtrière, AP-HP, Paris, France; NS-Park French Network.
Facultë de Mëdecine de Sorbonne Universitë, UMR S 1127, INSERM U 1127, and CNRS UMR 7225, and Institut du Cerveau et de la Moëlle Epinière, Paris, France; NS-Park French Network.

David Devos (D)

University Lille, INSERM, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, LICEND, Lille, France.
CHU Lille, Neurology and Movement Disorders Department, Reference Center for Parkinson's Disease, Lille, France; NS-Park French Network.

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