TY - JOUR
T1 - Radiologically isolated syndrome
T2 - 5-year risk for an initial clinical event
AU - Okuda, Darin T.
AU - Siva, Aksel
AU - Kantarci, Orhun
AU - Inglese, Matilde
AU - Katz, Ilana
AU - Tutuncu, Melih
AU - Keegan, B. Mark
AU - Donlon, Stacy
AU - Hua, Le H.
AU - Vidal-Jordana, Angela
AU - Montalban, Xavier
AU - Rovira, Alex
AU - Tintoré, Mar
AU - Amato, Maria Pia
AU - Brochet, Bruno
AU - De Seze, Jérôme
AU - Brassat, David
AU - Vermersch, Patrick
AU - De Stefano, Nicola
AU - Sormani, Maria Pia
AU - Pelletier, Daniel
AU - Lebrun, Christine
N1 - Funding Information:
Dr. Okuda reports personal fees for consulting, advisory board, and speaking activities from Acorda Therapeutics, Biogen IDEC, Genzyme, Ipsen Pharmaceuticals, and Teva Neuroscience, outside the submitted work. Professor Siva reports personal fees for consulting and serving on a scientific advisory board from Bayer-Schering AG, Novartis, Biogen IDEC and Allergan within the last year, and travel and registration coverage for congresses or symposia from Bayer-Schering AG, Merck-Serono, Gen Ilac, and Allergan. Professor Siva received research support from Bayer-Schering AG, outside the submitted work. Dr. Kantarci has nothing to disclose. Dr. Inglese reports personal fees from Celgene, and Vaccinex. Dr. Katz reports grants from Acorda Therapeutics and from the National MS Society, outside the submitted work. Dr. Tutuncu has nothing to disclose. Dr. Keegan reports personal fees from eMedicine, Bristol Meyers Squibb, Novartis, Bionest, and grants from Terumo BCT, outside the submitted work. Dr. Donlon has nothing to disclose. Dr. Hua has nothing to disclose. Dr. Vidal-Jordana reports personal fees from EMD Serono, outside the submitted work. Dr. Montalban reports personal fees from Almirall, Bayer, Biogen IDEC, EMD Serono, Merck, Genentech, GeNeuro, Genzyme, Neurotec, Novartis, Sanofi-Aventis, and Teva Neuroscience, outside the submitted work. Dr. Rovira reports personal fees from AdvanceCell Bayer-Schering Pharma, Novartis, OLEA Medical, Sanofi-Aventis, Teva Neuroscience, Biogen IDEC, grants from Siemens AG, outside the submitted work. Dr. Tintoré reports personal fees from Genzyme, Biogen IDEC, Teva Neuroscience, Novartis, Sanofi-Aventis, Bayer, and Merck Serono, outside the submitted work. Dr. Amato reports grants and personal fees from Biogen IDEC, Merck Serono, Bayer-Schering, Teva Neuroscience, Sanofi-Aventis, and Novartis, outside the submitted work. Dr. Brochet reports personal fees from Novartis, Genzyme, and Bayer, grants from Bayer and Teva Neuroscience, Merck-Serono, and Caridian, outside the submitted work. Dr. de Seze has nothing to disclose. Dr. Brassat reports personal fees from Bayer-Schering, Biogen IDEC, Merck-Serono, Novartis, Sanofi-Aventis, and Teva Neuroscience, outside the submitted work. Dr. Vermersch reports grants and personal fees from Biogen IDEC, Sanofi-Aventis, Bayer, Merck-Serono, personal fees from Novartis, GSK, and Almirall, outside the submitted work. Dr. De Stefano reports personal fees from Merck-Serono, Novartis Pharma AG, Teva Neuroscience, Sanofi-Aventis, Bayer-Schering AG, and Biogen IDEC, outside the submitted work. Dr. Sormani reports personal fees from Biogen IDEC, Merck-Serono, Actelion, Synthon, and Allozyne, outside the submitted work. Dr. Pelletier reports personal fees from Teva Neuroscience, Biogen IDEC, and Roche, grants from Biogen IDEC, outside the submitted work. Dr. Lebrun has nothing to disclose. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
PY - 2014/3/5
Y1 - 2014/3/5
N2 - Objective: To report the 5-year risk and to identify risk factors for the development of a seminal acute or progressive clinical event in a multi-national cohort of asymptomatic subjects meeting 2009 RIS Criteria. Methods: Retrospectively identified RIS subjects from 22 databases within 5 countries were evaluated. Time to the first clinical event related to demyelination (acute or 12-month progression of neurological deficits) was compared across different groups by univariate and multivariate analyses utilizing a Cox regression model. Results: Data were available in 451 RIS subjects (F: 354 (78.5%)). The mean age at from the time of the first brain MRI revealing anomalies suggestive of MS was 37.2 years (y) (median: 37.1 y, range: 11-74 y) with mean clinical follow-up time of 4.4 y (median: 2.8 y, range: 0.01-21.1 y). Clinical events were identified in 34% (standard error = 3%) of individuals within a 5-year period from the first brain MRI study. Of those who developed symptoms, 9.6% fulfilled criteria for primary progressive MS. In the multivariate model, age [hazard ratio (HR): 0.98 (95% CI: 0.96-0.99); p = 0.03], sex (male) [HR: 1.93 (1.24-2.99); p = 0.004], and lesions within the cervical or thoracic spinal cord [HR: 3.08 (2.06-4.62); p = <0.001] were identified as significant predictors for the development of a first clinical event. Interpretation: These data provide supportive evidence that ameaningful number of RIS subjects evolve to a first clinical symptom. An age <37 y, male sex, and spinal cord involvement appear to be the most important independent predictors of symptom onset.
AB - Objective: To report the 5-year risk and to identify risk factors for the development of a seminal acute or progressive clinical event in a multi-national cohort of asymptomatic subjects meeting 2009 RIS Criteria. Methods: Retrospectively identified RIS subjects from 22 databases within 5 countries were evaluated. Time to the first clinical event related to demyelination (acute or 12-month progression of neurological deficits) was compared across different groups by univariate and multivariate analyses utilizing a Cox regression model. Results: Data were available in 451 RIS subjects (F: 354 (78.5%)). The mean age at from the time of the first brain MRI revealing anomalies suggestive of MS was 37.2 years (y) (median: 37.1 y, range: 11-74 y) with mean clinical follow-up time of 4.4 y (median: 2.8 y, range: 0.01-21.1 y). Clinical events were identified in 34% (standard error = 3%) of individuals within a 5-year period from the first brain MRI study. Of those who developed symptoms, 9.6% fulfilled criteria for primary progressive MS. In the multivariate model, age [hazard ratio (HR): 0.98 (95% CI: 0.96-0.99); p = 0.03], sex (male) [HR: 1.93 (1.24-2.99); p = 0.004], and lesions within the cervical or thoracic spinal cord [HR: 3.08 (2.06-4.62); p = <0.001] were identified as significant predictors for the development of a first clinical event. Interpretation: These data provide supportive evidence that ameaningful number of RIS subjects evolve to a first clinical symptom. An age <37 y, male sex, and spinal cord involvement appear to be the most important independent predictors of symptom onset.
UR - http://www.scopus.com/inward/record.url?scp=84897134823&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0090509
DO - 10.1371/journal.pone.0090509
M3 - Article
C2 - 24598783
AN - SCOPUS:84897134823
SN - 1932-6203
VL - 9
JO - PloS one
JF - PloS one
IS - 3
M1 - e90509
ER -