Stridor Is an Independent Risk Factor for Mortality and Disease Progression in Patients with Multiple System Atrophy

Pauline Dodet^{1

2}, Cecile Proust-Lima^{3

4}, Federico Sirna^{3

4

5

6}, David Bendetowicz^{5

6}, Giulia Lazzeri^{7

8}, Rachel Debs⁹, Anna Delamarre^{5

6}, Margaux Dunoyer^{10

11}, Margherita Fabbri^{12

13}, Claire Georges¹², Imad Ghorayeb^{14

15}, David Grabli^{1

10

11}, Cécile Londner², Anne Pavy-Le Traon^{12

13}, Maxime Patout^{2

16}, Olivier Rascol^{12

13}, Isabelle Arnulf^{1

2}, Alexandra Foubert-Samier^{3

4

5

6}, Wassilios G Meissner^{5

6

17

18}

Affiliations

¹ Sorbonne Université, Paris Brain Institute, Inserm, CNRS, Paris, France.
² Sleep Unit, National Reference Centre for Orphan Diseases, Narcolepsy and Rare Hypersomnias, Pitié-Salpêtrière hospital, AP-HP, Paris, France.
³ Inserm, Bordeaux Population Health Research Center, U1219, University of Bordeaux, Bordeaux, France.
⁴ CIC1401-EC, Inserm, Bordeaux, France.
⁵ CHU Bordeaux, Service de Neurologie des Maladies Neurodégénératives, IMNc, CRMR AMS, NS-Park/FCRIN Network, Toulouse, France.
⁶ CNRS, IMN UMR 5293, University of Bordeaux, Bordeaux, France.
⁷ Centro Parkinson e Parkinsonismi, ASST G. Pini-CTO, Milan, Italy.
⁸ Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
⁹ Sleep Unit, Department of Neurology, National Competence Centre for Orphan Diseases, Narcolepsy-Rare Hypersomnias, Pierre-Paul Riquet/Purpan University Hospital, Toulouse, France.
¹⁰ MSA French Reference Center, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.
¹¹ Department of Neurology, Pitié-Salpêtrière Hospital, APHP, Paris, France.
¹² MSA French Reference Center, University Hospital Toulouse, Toulouse, France.
¹³ Department of Clinical Pharmacology and Neurosciences, University of Toulouse, CIC-1436, NeuroToul COEN Center, NS-Park/FCRIN Network, Toulouse University Hospital, Inserm U1048/1214, Toulouse, France.
¹⁴ Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, UMR 5287, Université de Bordeaux, Bordeaux, France.
¹⁵ Département de Neurophysiologie Clinique, Pôle Neurosciences Cliniques, CHU de Bordeaux, Bordeaux, France.
¹⁶ FHU HUMANHYS, Inserm UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Sorbonne Université, Paris, France.
¹⁷ Department Medicine, University of Otago, Christchurch, New Zealand.
¹⁸ New Zealand Brain Research Institute, Christchurch, New Zealand.

PMID: 41054890
DOI: 10.1002/mds.70080

Stridor Is an Independent Risk Factor for Mortality and Disease Progression in Patients with Multiple System Atrophy

Pauline Dodet et al. Mov Disord. 2025.

. 2025 Oct 7.

doi: 10.1002/mds.70080. Online ahead of print.

Authors

Affiliations

¹ Sorbonne Université, Paris Brain Institute, Inserm, CNRS, Paris, France.
² Sleep Unit, National Reference Centre for Orphan Diseases, Narcolepsy and Rare Hypersomnias, Pitié-Salpêtrière hospital, AP-HP, Paris, France.
³ Inserm, Bordeaux Population Health Research Center, U1219, University of Bordeaux, Bordeaux, France.
⁴ CIC1401-EC, Inserm, Bordeaux, France.
⁵ CHU Bordeaux, Service de Neurologie des Maladies Neurodégénératives, IMNc, CRMR AMS, NS-Park/FCRIN Network, Toulouse, France.
⁶ CNRS, IMN UMR 5293, University of Bordeaux, Bordeaux, France.
⁷ Centro Parkinson e Parkinsonismi, ASST G. Pini-CTO, Milan, Italy.
⁸ Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
⁹ Sleep Unit, Department of Neurology, National Competence Centre for Orphan Diseases, Narcolepsy-Rare Hypersomnias, Pierre-Paul Riquet/Purpan University Hospital, Toulouse, France.
¹⁰ MSA French Reference Center, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.
¹¹ Department of Neurology, Pitié-Salpêtrière Hospital, APHP, Paris, France.
¹² MSA French Reference Center, University Hospital Toulouse, Toulouse, France.
¹³ Department of Clinical Pharmacology and Neurosciences, University of Toulouse, CIC-1436, NeuroToul COEN Center, NS-Park/FCRIN Network, Toulouse University Hospital, Inserm U1048/1214, Toulouse, France.
¹⁴ Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, UMR 5287, Université de Bordeaux, Bordeaux, France.
¹⁵ Département de Neurophysiologie Clinique, Pôle Neurosciences Cliniques, CHU de Bordeaux, Bordeaux, France.
¹⁶ FHU HUMANHYS, Inserm UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Sorbonne Université, Paris, France.
¹⁷ Department Medicine, University of Otago, Christchurch, New Zealand.
¹⁸ New Zealand Brain Research Institute, Christchurch, New Zealand.

PMID: 41054890
DOI: 10.1002/mds.70080

Abstract

Background and aim: Stridor and sleep apnea syndrome (SAS) are common in multiple system atrophy (MSA). Retrospective cohort studies have yielded conflicting results regarding the consequences of stridor and SAS on the disease course. This study aimed to assess the prognostic significance of stridor and SAS, as well as the potential survival benefits of continuous positive airway pressure (CPAP) therapy.

Method: Retrospective data from 232 participants with MSA (mean age 65 years old, 51% male) from the three sites of the French Reference Center for MSA were analyzed. Patients underwent video-polysomnography to confirm the presence of stridor and SAS (AHI >15). Survival analyses adjusted for disease progression, age, sex, MSA subtype, and time since symptom onset were conducted using a joint modeling approach. Disease progression was quantified by the repeated assessments of a six-item composite score and the total Unified MSA Rating Scale I + II.

Results: Stridor was independently associated with an increased risk of mortality (hazard ratio [HR] = 2.44 [1.41;4.22]), even after adjusting for disease progression. Stridor was also linked to more severe disease progression over time. In contrast, SAS did not independently predict mortality or disease progression. CPAP therapy initiation was associated with a substantial reduction in mortality risk after adjusting for center and AHI (HR = 0.40 [0.19;0.85], P = 0.017).

Discussion: Stridor is a critical prognostic factor in MSA, associated with higher mortality and worse disease progression, whereas SAS alone is not associated with a change in mortality. Patients undergoing CPAP therapy have a much better survival among those with stridor. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: multiple system atrophy; sleep; stridor.

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References

1. Vetrugno R, Provini F, Cortelli P, et al. Sleep disorders in multiple system atrophy: a correlative video‐polysomnographic study. Sleep Med 2004;5(1):21–30. https://doi.org/10.1016/j.sleep.2003.07.002
1. Shimohata T, Shinoda H, Nakayama H, et al. Daytime hypoxemia, sleep‐disordered breathing, and laryngopharyngeal findings in multiple system atrophy. Arch Neurol 2007;64(6):856–861. https://doi.org/10.1001/archneur.64.6.856
1. Rekik S, Martin F, Dodet P, et al. Stridor combined with other sleep breathing disorders in multiple system atrophy: a tailored treatment? Sleep Med 2018;42:53–60. https://doi.org/10.1016/j.sleep.2017.12.008
1. Wenning GK, Ben Shlomo Y, Magalhães M, Daniel SE, Quinn NP. Clinical features and natural history of multiple system atrophy. An analysis of 100 cases. Brain 1994;117(Pt 4):835–845. https://doi.org/10.1093/brain/117.4.835
1. Cortelli P, Calandra‐Buonaura G, Benarroch EE, et al. Stridor in multiple system atrophy: consensus statement on diagnosis, prognosis, and treatment. Neurology 2019;93(14):630–639. https://doi.org/10.1212/wnl.0000000000008208

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Stridor Is an Independent Risk Factor for Mortality and Disease Progression in Patients with Multiple System Atrophy

Affiliations

Stridor Is an Independent Risk Factor for Mortality and Disease Progression in Patients with Multiple System Atrophy

Authors

Affiliations

Abstract

References

LinkOut - more resources

Full Text Sources