Tim Spelman1, Claire Meyniel1,2, Juan Ignacio Rojas3, Alessandra Lugaresi4, Guillermo Izquierdo5, Francois Grand'Maison6, Cavit Boz7, Raed Alroughani8, Eva Havrdova9, Dana Horakova9, Gerardo Iuliano10, Pierre Duquette11, Murat Terzi12, Pierre Grammond13, Raymond Hupperts14, Jeannette Lechner-Scott15, Celia Oreja-Guevara16, Eugenio Pucci17, Freek Verheul18, Marcela Fiol19, Vincent Van Pesch20, Edgardo Cristiano3, Thor Petersen21, Fraser Moore22, Tomas Kalincik1, Vilija Jokubaitis1, Maria Trojano23, Helmut Butzkueven24. 1. Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia. 2. Department of Neurophysiologie, Pitié-Salpêtrière Hospital, Paris, France. 3. Hospital Italiano de Buenos Aires, Buenos Aires, Argentina. 4. MS Center, Department of Neuroscience and Imaging, University 'G. d'Annunzio', Chieti, Italy. 5. Hospital Universitario Virgen Macarena, Sevilla, Spain. 6. Neuro Rive-Sud, Hôpital Charles LeMoyne, Greenfield Park, QC, Canada. 7. Karadeniz Technical University, Trabzon, Turkey. 8. Amiri Hospital, Kuwait City, Kuwait. 9. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, General University Hospital and Charles University in Prague, Prague, Czech Republic. 10. Ospedali Riuniti di Salerno, Salerno, Italy. 11. Hôpital Notre-Dame, Montreal, QC, Canada. 12. Ondokuz Mayis University, Samsun, Turkey. 13. Centre de réadaptation en déficience physique Chaudière-Appalaches, Levis, QC, Canada. 14. Maaslandziekenhuis, Sittard, The Netherlands. 15. John Hunter Hospital, Newcastle, NSW, Australia. 16. Hospital Clínico San Carlos, Madrid, Spain. 17. Neurology Unit, ASUR Marche - AV3, Macerata, Italy. 18. Groene Hart Ziekenhuis, Gouda, The Netherlands. 19. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia, Buenos Aires, Argentina. 20. Cliniques Universitaires Saint-Luc, Brussels, Belgium. 21. Kommunehospitalet, Aarhus, Denmark. 22. Jewish General Hospital, Montreal, QC, Canada. 23. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy. 24. Department of Neurology, Box Hill hospital, Monash University, Box Hill, VIC, Australia.
Abstract
BACKGROUND: Characteristics at clinically isolated syndrome (CIS) examination assist in identification of patient at highest risk of early second attack and could benefit the most from early disease-modifying drugs (DMDs). OBJECTIVE: To examine determinants of second attack and validate a prognostic nomogram for individualised risk assessment of clinical conversion. METHODS: Patients with CIS were prospectively followed up in the MSBase Incident Study. Predictors of clinical conversion were analysed using Cox proportional hazards regression. Prognostic nomograms were derived to calculate conversion probability and validated using concordance indices. RESULTS: A total of 3296 patients from 50 clinics in 22 countries were followed up for a median (inter-quartile range (IQR)) of 1.92 years (0.90, 3.71). In all, 1953 (59.3%) patients recorded a second attack. Higher Expanded Disability Status Scale (EDSS) at baseline, first symptom location, oligoclonal bands and various brain and spinal magnetic resonance imaging (MRI) metrics were all predictors of conversion. Conversely, older age and DMD exposure post-CIS were associated with reduced rates. Prognostic nomograms demonstrated high concordance between estimated and observed conversion probabilities. CONCLUSION: This multinational study shows that age at CIS onset, DMD exposure, EDSS, multiple brain and spinal MRI criteria and oligoclonal bands are associated with shorter time to relapse. Nomogram assessment may be useful in clinical practice for estimating future clinical conversion.
BACKGROUND: Characteristics at clinically isolated syndrome (CIS) examination assist in identification of patient at highest risk of early second attack and could benefit the most from early disease-modifying drugs (DMDs). OBJECTIVE: To examine determinants of second attack and validate a prognostic nomogram for individualised risk assessment of clinical conversion. METHODS:Patients with CIS were prospectively followed up in the MSBase Incident Study. Predictors of clinical conversion were analysed using Cox proportional hazards regression. Prognostic nomograms were derived to calculate conversion probability and validated using concordance indices. RESULTS: A total of 3296 patients from 50 clinics in 22 countries were followed up for a median (inter-quartile range (IQR)) of 1.92 years (0.90, 3.71). In all, 1953 (59.3%) patients recorded a second attack. Higher Expanded Disability Status Scale (EDSS) at baseline, first symptom location, oligoclonal bands and various brain and spinal magnetic resonance imaging (MRI) metrics were all predictors of conversion. Conversely, older age and DMD exposure post-CIS were associated with reduced rates. Prognostic nomograms demonstrated high concordance between estimated and observed conversion probabilities. CONCLUSION: This multinational study shows that age at CIS onset, DMD exposure, EDSS, multiple brain and spinal MRI criteria and oligoclonal bands are associated with shorter time to relapse. Nomogram assessment may be useful in clinical practice for estimating future clinical conversion.
Authors: T K Banerjee; M Saha; E Ghosh; A Hazra; A Das; D Choudhury; S Ojha; A Haldar; A Mukherjee; S S Nandi; A Ghosh; A Mukherjee; A Chatterjee; A Datta; S Purakayastha Journal: Mult Scler J Exp Transl Clin Date: 2019-05-13