Effects of deep brain stimulation on non motor fluctuations in Parkinson's disease (assessed with the NMF severity scale)

Christian Matta¹, Camille Comet², Corentin Gaillard², Florent Faggianelli², Stephan Grimaldi², Tatiana Witjas², Solène Ansquer³, Cécile Hubsch⁴, Mathieu Anheim^{5

6

7

8}, Caroline Moreau⁹, Elodie Hainque¹⁰, Sophie Drapier¹¹, Béchir Jarraya¹², Chloé Laurencin^{13

14}, Dominique Guehl^{15

16}, Lucie Hopes¹⁷, Christine Brefel-Courbon¹⁸, Melissa Tir¹⁹, Ana Marques^{20

21}, Tiphaine Rouaud²², David Maltete²³, Caroline Giordana²⁴, Karine Baumstarck^{25

26}, Olivier Rascol²⁷, Jean-Christophe Corvol²⁸, Fabienne Ory-Magne^{5

29}, Anne-Sophie Rolland³⁰, David Devos^{31

32}, J-P Azulay², Alexandre Eusebio²; PREDISTIM Study Group

Affiliations

¹ Department of Neurology, Saint Joseph University, Beirut, Lebanon.
² Department of Neurology, University Hospital Timone, Marseille, France.
³ Centre Hospitalier Universitaire de Poitiers, France - Centre d'investigation clinique CIC INSERM 1402, France.
⁴ Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.
⁵ French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS-PARK), France.
⁶ Department of Neurology, Parkinson Expert Centre, U964/UMR7104, France.
⁷ Strasbourg University Hospital, University of Strasbourg, INSERM, CNRS, Strasbourg, France.
⁸ Strasbourg Institute of Neuroscience, Strasbourg, France.
⁹ DD and ASR Department of Medical Pharmacology, Neurology and Movement Disorders Department, Referent Center of Parkinson's Disease, CHU of Lille, Univ. Lille Neuroscience & Cognition, Inserm, UMR-S1172, NS-Park Network France, Lille, France.
¹⁰ Département de Neurologie, APHP, Paris, France.
¹¹ Neurologie, CHU Pontchaillou, Rennes, France.
¹² Neuroscience, Hospital Foch, Suresnes, Île-de-France, France.
¹³ CNRS UMR 5229, Bron, France.
¹⁴ Centre Expert Parkinson, Bron, France.
¹⁵ Pôle de Neurosciences Cliniques, CHU de Bordeaux, Bordeaux, France.
¹⁶ CNRS UMR 5293, Institut des Maladies Neurodégénératives, Bordeaux, France.
¹⁷ Neurology, Centre Hospitalier Universitaire de Nancy, Nancy, Lorraine, France.
¹⁸ Department of Clinical Pharmacology and Neurosciences, Parkinson Expert Centre, Centre d'Investigation Clinique CIC1436, University Hospital of Toulouse, NeuroToul COEN Centre Inserm UMR-1214, NS-PARK Network, Toulouse, France.
¹⁹ Neurology, CHU Amiens-Picardie, Amiens, Hauts-de-France, France.
²⁰ Department of Neurology, Clermont-Ferrand University Hospital, Université Clermont Auvergne, Clermont-Ferrand, France.
²¹ Neurology, University Hospital Centre Clermont-Ferrand, Clermont-Ferrand, France.
²² Department of Neurology, Nantes University Hospital, Nantes, France.
²³ Department of Neurology, Rouen University Hospital and University of Rouen, France.
²⁴ Neurology Department, Centre, Nice, France.
²⁵ Aix Marseille Université, EA 3279 Self-Perceived Health Assessment Research Unit, Marseille, France.
²⁶ Department of Neurosciences and Clinical Pharmacology, Parkinson Expert Centre, Centre d'Investigation Clinique CIC1436, NeuroToul COEN Centre, NS-PARK/FCRIN Network, France.
²⁷ University Hospital of Toulouse, INSERM, University of Toulouse 3, Toulouse, France.
²⁸ Département de Neurologie, CIC Neurosciences, Sorbonne Université, Assistance Publique Hôpitaux de Paris, Paris Brain Institute (ICM), Inserm, CNRS, Hôpital Pitié-Salpêtrière, NS-PARK/FCRIN Network, Paris, France.
²⁹ Departments of Neurosciences, Parkinson Expert Centre, Clinical Investigation Center CIC1436, Toulouse University Hospital, INSERM, University of Toulouse 3, Toulouse, France.
³⁰ Department of Medical Pharmacology, Neurology and Movement Disorders Department, Referent Center of Parkinson's Disease, CHU of Lille, Univ. Lille Neuroscience & Cognition, Inserm, UMR-S1172, Lille, France.
³¹ Medical Pharmacology, Lille University Medical Center, Lille, France University of Lille, Inserm, CHU Lille, UMR-S1172 Lille Neuroscience & Cognition (LilNCog), Lille, France.
³² Department of Medical Pharmacology, CHU de Lille, France.

PMID: 41716855
PMCID: PMC12915265
DOI: 10.1016/j.prdoa.2026.100426

Effects of deep brain stimulation on non motor fluctuations in Parkinson's disease (assessed with the NMF severity scale)

Christian Matta et al. Clin Park Relat Disord. 2026.

. 2026 Feb 8:14:100426.

doi: 10.1016/j.prdoa.2026.100426. eCollection 2026.

Authors

Affiliations

¹ Department of Neurology, Saint Joseph University, Beirut, Lebanon.
² Department of Neurology, University Hospital Timone, Marseille, France.
³ Centre Hospitalier Universitaire de Poitiers, France - Centre d'investigation clinique CIC INSERM 1402, France.
⁴ Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.
⁵ French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS-PARK), France.
⁶ Department of Neurology, Parkinson Expert Centre, U964/UMR7104, France.
⁷ Strasbourg University Hospital, University of Strasbourg, INSERM, CNRS, Strasbourg, France.
⁸ Strasbourg Institute of Neuroscience, Strasbourg, France.
⁹ DD and ASR Department of Medical Pharmacology, Neurology and Movement Disorders Department, Referent Center of Parkinson's Disease, CHU of Lille, Univ. Lille Neuroscience & Cognition, Inserm, UMR-S1172, NS-Park Network France, Lille, France.
¹⁰ Département de Neurologie, APHP, Paris, France.
¹¹ Neurologie, CHU Pontchaillou, Rennes, France.
¹² Neuroscience, Hospital Foch, Suresnes, Île-de-France, France.
¹³ CNRS UMR 5229, Bron, France.
¹⁴ Centre Expert Parkinson, Bron, France.
¹⁵ Pôle de Neurosciences Cliniques, CHU de Bordeaux, Bordeaux, France.
¹⁶ CNRS UMR 5293, Institut des Maladies Neurodégénératives, Bordeaux, France.
¹⁷ Neurology, Centre Hospitalier Universitaire de Nancy, Nancy, Lorraine, France.
¹⁸ Department of Clinical Pharmacology and Neurosciences, Parkinson Expert Centre, Centre d'Investigation Clinique CIC1436, University Hospital of Toulouse, NeuroToul COEN Centre Inserm UMR-1214, NS-PARK Network, Toulouse, France.
¹⁹ Neurology, CHU Amiens-Picardie, Amiens, Hauts-de-France, France.
²⁰ Department of Neurology, Clermont-Ferrand University Hospital, Université Clermont Auvergne, Clermont-Ferrand, France.
²¹ Neurology, University Hospital Centre Clermont-Ferrand, Clermont-Ferrand, France.
²² Department of Neurology, Nantes University Hospital, Nantes, France.
²³ Department of Neurology, Rouen University Hospital and University of Rouen, France.
²⁴ Neurology Department, Centre, Nice, France.
²⁵ Aix Marseille Université, EA 3279 Self-Perceived Health Assessment Research Unit, Marseille, France.
²⁶ Department of Neurosciences and Clinical Pharmacology, Parkinson Expert Centre, Centre d'Investigation Clinique CIC1436, NeuroToul COEN Centre, NS-PARK/FCRIN Network, France.
²⁷ University Hospital of Toulouse, INSERM, University of Toulouse 3, Toulouse, France.
²⁸ Département de Neurologie, CIC Neurosciences, Sorbonne Université, Assistance Publique Hôpitaux de Paris, Paris Brain Institute (ICM), Inserm, CNRS, Hôpital Pitié-Salpêtrière, NS-PARK/FCRIN Network, Paris, France.
²⁹ Departments of Neurosciences, Parkinson Expert Centre, Clinical Investigation Center CIC1436, Toulouse University Hospital, INSERM, University of Toulouse 3, Toulouse, France.
³⁰ Department of Medical Pharmacology, Neurology and Movement Disorders Department, Referent Center of Parkinson's Disease, CHU of Lille, Univ. Lille Neuroscience & Cognition, Inserm, UMR-S1172, Lille, France.
³¹ Medical Pharmacology, Lille University Medical Center, Lille, France University of Lille, Inserm, CHU Lille, UMR-S1172 Lille Neuroscience & Cognition (LilNCog), Lille, France.
³² Department of Medical Pharmacology, CHU de Lille, France.

PMID: 41716855
PMCID: PMC12915265
DOI: 10.1016/j.prdoa.2026.100426

Abstract

Background: Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for motor fluctuations (MF) in Parkinson's disease (PD), but its impact on non-motor fluctuations (NMF) remains unclear. As NMFs are frequent, disabling, and affect quality of life, understanding their response to DBS is critical.

Objectives: To assess the presence of NMF after STN-DBS, identify preoperative factors of improvement, and compare NMF responses to DBS and levodopa.

Methods: This project is an ancillary study of the French multicenter PREDISTIM cohort. We used the validated Non-Motor Fluctuation Severity Scale (NMF2S) to evaluate NMFs one year after STN-DBS and before surgery when data were available. Evaluations were performed under standardized conditions (OFF-Dopa/OFF-Stim vs. OFF-Dopa/ON-Stim).

Results: We included 284 PD patients assessed one year after STN-DBS using the NMF2S scale. Preoperative data were available for 153 patients. Evaluations were performed under standardized stimulation conditions (OFF-Dopa/OFF-Stim vs. OFF-Dopa/ON-Stim).STN-DBS led to a 41.1% reduction in NMF severity, with anxiety, concentration difficulties, and pain showing the most improvement. However, DBS effects were less pronounced than those of levodopa, especially for psychiatric symptoms. NMF improvement did not correlate with motor improvement. Among all preoperative variables, only the levodopa response in the cognitive domain was associated with post-DBS NMF benefit.

Conclusions: STN-DBS significantly improves NMFs, although to a lesser extent than levodopa. The dissociation between motor and non-motor responses underscores the need for specific markers to predict NMF outcomes. These findings support the integration of NMF assessment into DBS indications and patient selection.

Keywords: Deep brain stimulation; Non-motor fluctuations; Parkinson’s disease; Predictive factors of DBS response; Subthalamic nucleus.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Fig. 1**
NMF2S scores in the OFF-Dopa/OFF-Stim and OFF-Dopa/ON-Stim conditions.

See this image and copyright information in PMC

References

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1. Borgohain R., Kandadai R.M., Jabeen A., Kannikannan M.A. Nonmotor outcomes in Parkinson’s disease: is deep brain stimulation better than dopamine replacement therapy? Ther. Adv. Neurol. Disord. 2012;5(1):23–41. - PMC - PubMed
1. Georgiev D., Mencinger M., Rajnar R., Mušič P., Benedičič M., Flisar D., et al. Long-term effect of STN-DBS on non-motor symptoms: a four-year prospective study. Parkinsonism Relat. Disord. 2021;89:13–16. - PubMed
1. Witjas T., Kaphan E., Régis J., Jouve E., Chérif A.A., et al. Effects of chronic STN stimulation on NMFs. Mov. Disord. 2007;22(12):1729–1734. - PubMed

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Effects of deep brain stimulation on non motor fluctuations in Parkinson's disease (assessed with the NMF severity scale)

Affiliations

Effects of deep brain stimulation on non motor fluctuations in Parkinson's disease (assessed with the NMF severity scale)

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous