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Article Dans Une Revue Brain - A Journal of Neurology Année : 2021

Dopaminergic imaging and clinical predictors for phenoconversion of REM sleep behaviour disorder

Dario Arnaldi
  • Fonction : Auteur
Andrea Chincarini
  • Fonction : Auteur
Michele Hu
  • Fonction : Auteur
Karel Sonka
Bradley Boeve
  • Fonction : Auteur
Tomoyuki Miyamoto
  • Fonction : Auteur
Monica Puligheddu
Michele Terzaghi
  • Fonction : Auteur
Giuseppe Plazzi
Naoko Tachibana
  • Fonction : Auteur
Silvia Morbelli
  • Fonction : Auteur
Michal Rolinski
  • Fonction : Auteur
Petr Dusek
  • Fonction : Auteur
Val Lowe
  • Fonction : Auteur
Masayuki Miyamoto
  • Fonction : Auteur
Michela Figorilli
Delphine De Verbizier
  • Fonction : Auteur
Irene Bossert
  • Fonction : Auteur
Elena Antelmi
Riccardo Meli
  • Fonction : Auteur
Thomas Barber
Jiří Trnka
  • Fonction : Auteur
Toji Miyagawa
  • Fonction : Auteur
Alessandra Serra
  • Fonction : Auteur
Fabio Pizza
  • Fonction : Auteur
Matteo Bauckneht
Kevin Bradley
  • Fonction : Auteur
David Zogala
Daniel Mcgowan
  • Fonction : Auteur
Lennon Jordan
  • Fonction : Auteur
Raffaele Manni
  • Fonction : Auteur
Flavio Nobili

Résumé

Abstract This is an international multicentre study aimed at evaluating the combined value of dopaminergic neuroimaging and clinical features in predicting future phenoconversion of idiopathic REM sleep behaviour (iRBD) subjects to overt synucleinopathy. Nine centres sent 123I-FP-CIT-SPECT data of 344 iRBD patients and 256 controls for centralized analysis. 123I-FP-CIT-SPECT images were semiquantified using DaTQUANTTM, obtaining putamen and caudate specific to non-displaceable binding ratios (SBRs). The following clinical variables were also analysed: (i) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale, motor section score; (ii) Mini-Mental State Examination score; (iii) constipation; and (iv) hyposmia. Kaplan-Meier survival analysis was performed to estimate conversion risk. Hazard ratios for each variable were calculated with Cox regression. A generalized logistic regression model was applied to identify the best combination of risk factors. Bayesian classifier was used to identify the baseline features predicting phenoconversion to parkinsonism or dementia. After quality check of the data, 263 iRBD patients (67.6 ± 7.3 years, 229 males) and 243 control subjects (67.2 ± 10.1 years, 110 males) were analysed. Fifty-two (20%) patients developed a synucleinopathy after average follow-up of 2 years. The best combination of risk factors was putamen dopaminergic dysfunction of the most affected hemisphere on imaging, defined as the lower value between either putamina (P < 0.000001), constipation, (P < 0.000001) and age over 70 years (P = 0.0002). Combined features obtained from the generalized logistic regression achieved a hazard ratio of 5.71 (95% confidence interval 2.85–11.43). Bayesian classifier suggested that patients with higher Mini-Mental State Examination score and lower caudate SBR asymmetry were more likely to develop parkinsonism, while patients with the opposite pattern were more likely to develop dementia. This study shows that iRBD patients older than 70 with constipation and reduced nigro-putaminal dopaminergic function are at high risk of short-term phenoconversion to an overt synucleinopathy, providing an effective stratification approach for future neuroprotective trials. Moreover, we provide cut-off values for the significant predictors of phenoconversion to be used in single subjects.

Dates et versions

hal-03584080 , version 1 (22-02-2022)

Identifiants

Citer

Dario Arnaldi, Andrea Chincarini, Michele Hu, Karel Sonka, Bradley Boeve, et al.. Dopaminergic imaging and clinical predictors for phenoconversion of REM sleep behaviour disorder. Brain - A Journal of Neurology , 2021, 144 (1), pp.278-287. ⟨10.1093/brain/awaa365⟩. ⟨hal-03584080⟩
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