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Journal Articles Brain - A Journal of Neurology Year : 2023

The radiologically isolated syndrome: revised diagnostic criteria

Christine Lebrun-Frénay (1, 2, 3) , Darin Okuda (4) , Aksel Siva (5) , Cassandre Landes-Chateau (1, 2, 3) , Christina Azevedo (6) , Lydiane Mondot (1, 2, 3) , Clarisse Carra-Dallière (7) , Helene Zephir (8, 9) , Celine Louapre (10, 11) , Françoise Durand-Dubief (12) , Emmanuelle Le Page (13, 14) , Caroline Bensa (15) , Aurélie Ruet (16, 17) , Jonathan Ciron (18, 19) , David Laplaud (20, 21, 22) , Olivier Casez (23, 24, 25) , Guillaume Mathey (26, 27) , Jerome de Seze (28, 29) , Burcu Zeydan (30) , Naila Makhani (31) , Melih Tutuncu (5) , Michael Levraut (1, 2, 3) , Mikael Cohen (1, 2, 3) , Eric Thouvenot (32, 33) , Daniel Pelletier (6) , Orhun Kantarci (30) , Sabrina Sehaki , Nathalie Devys-Meyer , Mathieu Bereau , Chrystelle Cappe , Bruno Brochet , Jean-Christophe Ouallet , Katy-Kim Kounkou , Gilles Defer , Pierre Branger , Frédéric Taithe , Emilie Dumont , Edwige Lescieux , Agnès Fromont , Alexia Protin , Maty Diop Kane , Patrick Hautecoeur , Olivier Outteryck , Patrick Vermersch , Julie Boucher , Julie Petit , Irène Tabellah Kasonde , Aymeric de Vilmarrest , Laurent Magy , Marie Nicol , Muriel Malbezin , Javier Olaiz , Claire Rigaud-Bully , Nadine Debard , Sandra Vukusic François Cotton , Iuliana Ionescu , Amalle Abdelalli , Jean Pelletier , Bertrand Audoin , Adil Maarouf , Bernadette Di Lelio , Xavier Ayrignac , Pierre Labauge , Frédéric Pinna , Francis Guillemin , Marc Debouverie , Amandine Ziegler , Sandrine Wiertlevski , Saskia Bresch , Céline Callier , Elodie David , Giovanni Castelnovo , Caroline Papeix , Elisabeth Maillart , Catherine Lubetzki , Karima Zehrouni , Bertrand Fontaine , Claire Giannesini , Jérôme Hodel , Abir Wahab , Mickaël Zedet , Ombeline Fagniez , Clémence Laage , Corinne Pottier , Iuliana Slesari , Mathilde Sampaio , Emilie Rabois , Cédric Castex , Benjamin Hebant , Maxime Guillaume , Christine Vimont , Olivier Gout , Antoine Guegen , Laure Michel , Romain Muraz , Damien Le Port , Emmanuelle Leray , Carole Henry , Thomas de Broucker , Nicolas Collongues , Carole Berthe , Damien Biotti , Noellie Freitas , Vincent Visneux , Mélanie Forestier , Stéphane Beltran , Géraldine Meunier , Jérôme Servan , Fernando Pico , Virginie Chatagner , Fatai Radji , Nathalie Morel , Deborah Grosset-Jeannin , Aurelian Ungureanu , Latine Boyer , Laurent Suchet , Christine Lebrun-Frenay , Orhun Kantarci , Aksel Siva , Daniel Pelletier , Christina Azevedo , Naila Makhani , Darin Okuda
1 CHU Nice - Centre Hospitalier Universitaire de Nice
2 UniCA - Université Côte d'Azur
3 URRIS UR2CA - Unité de Recherche Clinique de la Côte d’Azur
4 University of Texas Southwestern Medical Center [Dallas]
5 Cerrahpasa Faculty of Medicine
6 USC - University of Southern California
7 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
8 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
9 LilNCog - Lille Neurosciences & Cognition - U 1172
10 CHU Pitié-Salpêtrière [AP-HP]
11 SU - Sorbonne Université
12 Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
13 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
14 CIC - Centre d'Investigation Clinique [Rennes]
15 Fondation Ophtalmologique Adolphe de Rothschild [Paris]
16 U1215 Inserm - UB - Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale
17 CHU Bordeaux
18 Infinity - Institut Toulousain des Maladies Infectieuses et Inflammatoires
19 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
20 CIC Plurithématique de Nantes
21 CHU Nantes - Centre hospitalier universitaire de Nantes
22 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
23 TIMC-GREPI - Groupe de Recherche et d’Étude du Processus Inflammatoire
24 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
25 TIMC - Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525
26 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
27 APEMAC - Adaptation, mesure et évaluation en santé. Approches interdisciplinaires
28 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
29 Centre d’Investigation Clinique Plurithématique (CIC - P) - CIC Strasbourg
30 Mayo Clinic [Rochester]
31 YSM - Yale School of Medicine [New Haven, Connecticut]
32 Pôle NIRR - Service de Neurologie [CHU Nimes]
33 IGF - Institut de Génomique Fonctionnelle
Burcu Zeydan
Sabrina Sehaki
  • Function : Author
Nathalie Devys-Meyer
  • Function : Author
Mathieu Bereau
  • Function : Author
Chrystelle Cappe
  • Function : Author
Bruno Brochet
  • Function : Author
Jean-Christophe Ouallet
  • Function : Author
Katy-Kim Kounkou
  • Function : Author
Gilles Defer
  • Function : Author
Pierre Branger
  • Function : Author
Frédéric Taithe
  • Function : Author
Emilie Dumont
  • Function : Author
Edwige Lescieux
  • Function : Author
Agnès Fromont
  • Function : Author
Alexia Protin
  • Function : Author
Maty Diop Kane
  • Function : Author
Patrick Hautecoeur
  • Function : Author
Olivier Outteryck
  • Function : Author
Patrick Vermersch
  • Function : Author
Julie Boucher
  • Function : Author
Julie Petit
  • Function : Author
Irène Tabellah Kasonde
  • Function : Author
Aymeric de Vilmarrest
  • Function : Author
Laurent Magy
  • Function : Author
Marie Nicol
  • Function : Author
Muriel Malbezin
  • Function : Author
Javier Olaiz
  • Function : Author
Claire Rigaud-Bully
  • Function : Author
Nadine Debard
  • Function : Author
Iuliana Ionescu
  • Function : Author
Amalle Abdelalli
  • Function : Author
Jean Pelletier
  • Function : Author
Bertrand Audoin
  • Function : Author
Adil Maarouf
  • Function : Author
Bernadette Di Lelio
  • Function : Author
Xavier Ayrignac
  • Function : Author
Pierre Labauge
  • Function : Author
Frédéric Pinna
  • Function : Author
Francis Guillemin
  • Function : Author
Marc Debouverie
  • Function : Author
Amandine Ziegler
  • Function : Author
Sandrine Wiertlevski
  • Function : Author
Saskia Bresch
  • Function : Author
Céline Callier
  • Function : Author
Elodie David
  • Function : Author
Giovanni Castelnovo
  • Function : Author
Caroline Papeix
  • Function : Author
Elisabeth Maillart
  • Function : Author
Catherine Lubetzki
  • Function : Author
Karima Zehrouni
  • Function : Author
Bertrand Fontaine
  • Function : Author
Claire Giannesini
  • Function : Author
Jérôme Hodel
  • Function : Author
Abir Wahab
  • Function : Author
Mickaël Zedet
  • Function : Author
Ombeline Fagniez
  • Function : Author
Clémence Laage
  • Function : Author
Corinne Pottier
  • Function : Author
Iuliana Slesari
  • Function : Author
Mathilde Sampaio
  • Function : Author
Emilie Rabois
  • Function : Author
Cédric Castex
  • Function : Author
Benjamin Hebant
  • Function : Author
Maxime Guillaume
  • Function : Author
Christine Vimont
  • Function : Author
Olivier Gout
  • Function : Author
Antoine Guegen
  • Function : Author
Laure Michel
  • Function : Author
Romain Muraz
  • Function : Author
Damien Le Port
  • Function : Author
Emmanuelle Leray
Carole Henry
  • Function : Author
Thomas de Broucker
  • Function : Author
Nicolas Collongues
  • Function : Author
Carole Berthe
  • Function : Author
Damien Biotti
  • Function : Author
Noellie Freitas
  • Function : Author
Vincent Visneux
  • Function : Author
Mélanie Forestier
  • Function : Author
Stéphane Beltran
  • Function : Author
Géraldine Meunier
  • Function : Author
Jérôme Servan
  • Function : Author
Fernando Pico
  • Function : Author
Virginie Chatagner
  • Function : Author
Fatai Radji
  • Function : Author
Nathalie Morel
  • Function : Author
Deborah Grosset-Jeannin
  • Function : Author
Aurelian Ungureanu
  • Function : Author
Latine Boyer
  • Function : Author
Laurent Suchet
  • Function : Author
Christine Lebrun-Frenay
  • Function : Author
Orhun Kantarci
  • Function : Author
Aksel Siva
  • Function : Author
Daniel Pelletier
  • Function : Author
Christina Azevedo
  • Function : Author
Naila Makhani
  • Function : Author
Darin Okuda
  • Function : Author

Abstract

The radiologically isolated syndrome (RIS) was defined in 2009 as the presence of asymptomatic, incidentally identified demyelinating-appearing white matter lesions in the CNS within individuals lacking symptoms typical of multiple sclerosis (MS). The RIS criteria have been validated and predict the transition to symptomatic MS reliably. The performance of RIS criteria that require fewer MRI lesions is unknown. 2009-RIS subjects, by definition, fulfil three to four of four criteria for 2005 dissemination in space (DIS) and subjects fulfilling only one or two lesions in at least one 2017 DIS location were identified within 37 prospective databases. Univariate and multivariate Cox regression models were used to identify predictors of a first clinical event. Performances of different groups were calculated. Seven hundred and forty-seven subjects (72.2% female, mean age 37.7 ± 12.3 years at the index MRI) were included. The mean clinical follow-up time was 46.8 ± 45.4 months. All subjects had focal T2 hyperintensities suggestive of inflammatory demyelination on MRI; 251 (33.6%) fulfilled one or two 2017 DIS criteria (designated as Groups 1 and 2, respectively), and 496 (66.4%) fulfilled three or four 2005 DIS criteria representing 2009-RIS subjects. Group 1 and 2 subjects were younger than the 2009-RIS group and were more likely to develop new T2 lesions over time (P < 0.001). Groups 1 and 2 were similar regarding survival distribution and risk factors for transition to MS. At 5 years, the cumulative probability for a clinical event was 29.0% for Groups 1 and 2 compared to 38.7% for 2009-RIS (P = 0.0241). The presence of spinal cord lesions on the index scan and CSF-restricted oligoclonal bands in Groups 1-2 increased the risk of symptomatic MS evolution at 5 years to 38%, comparable to the risk of development in the 2009-RIS group. The presence of new T2 or gadolinium-enhancing lesions on follow-up scans independently increased the risk of presenting with a clinical event (P < 0.001). The 2009-RIS subjects or Groups 1 and 2 with at least two of the risk factors for a clinical event demonstrated better sensitivity (86.0%), negative predictive value (73.1%), accuracy (59.8%) and area under the curve (60.7%) compared to other criteria studied. This large prospective cohort brings Class I evidence that subjects with fewer lesions than required in the 2009 RIS criteria evolve directly to a first clinical event at a similar rate when additional risk factors are present. Our results provide a rationale for revisions to existing RIS diagnostic criteria.
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Dates and versions

hal-04020134 , version 1 (30-03-2023)

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Attribution - NonCommercial

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Christine Lebrun-Frénay, Darin Okuda, Aksel Siva, Cassandre Landes-Chateau, Christina Azevedo, et al.. The radiologically isolated syndrome: revised diagnostic criteria. Brain - A Journal of Neurology , 2023, 146 (8), pp.3431-3443. ⟨10.1093/brain/awad073⟩. ⟨hal-04020134⟩
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