Pietro Iaffaldano1, Marta Simone2, Giuseppe Lucisano1,3, Angelo Ghezzi4, Gabriella Coniglio5, Vincenzo Brescia Morra6, Giuseppe Salemi7, Francesco Patti8, Alessandra Lugaresi9,10, Guillermo Izquierdo11, Roberto Bergamaschi12, Jose Antonio Cabrera-Gomez13, Carlo Pozzilli14, Enrico Millefiorini15, Raed Alroughani16, Cavit Boz17, Eugenio Pucci18, Giovanni Bosco Zimatore19, Patrizia Sola20, Giacomo Lus21, Davide Maimone22, Carlo Avolio23, Eleonora Cocco24, Seyed Aidin Sajedi25, Gianfranco Costantino26, Pierre Duquette27, Vahid Shaygannejad28, Thor Petersen29, Ricardo Fernández Bolaños30, Damiano Paolicelli1, Carla Tortorella1, Tim Spelman31,32, Lucia Margari2, Maria Pia Amato33, Giancarlo Comi34, Helmut Butzkueven31,32, Maria Trojano1. 1. Department of Basic Medical Sciences, Neurosciences, and Sense Organs, University of Bari Aldo Moro, Bari, Italy. 2. Child Neuropsychiatry Unit, Department of Basic Medical Sciences, Neurosciences, and Sense Organs, University of Bari Aldo Moro, Bari, Italy. 3. Center for Outcomes Research and Clinical Epidemiology, CORESEARCH, Pescara, Italy. 4. Multiple Sclerosis Center, Sant'Antonio Abate Hospital, Gallarate, Italy. 5. Neurology Unit, Madonna delle Grazie Hospital, Matera, Italy. 6. Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy. 7. Department of Clinical Neuroscience, University of Palermo, Palermo, Italy. 8. Department of Advanced Medical and Surgical Sciences and Technologies, Multiple Sclerosis Center, University of Catania, Catania, Italy. 9. Department of Biomedical and Neuro Motor Sciences, University of Bologna, Bologna, Italy. 10. IRCCS Institute of Neurological Science and Bellaria Hospital, Bologna, Italy. 11. Department of Neurology, Virgin of Hope of Macarena University Hospital, Seville, Spain. 12. Interdepartment Multiple Sclerosis Research Center, C. Mondino National Institute of Neurology Foundation, Pavia, Italy. 13. International Center for Neurological Restoration, Havana, Cuba. 14. Multiple Sclerosis Center, Sant'Andrea Hospital, Department of Neurology and Psychiatry, Sapienza University, Rome, Italy. 15. Multiple Sclerosis Center, Umberto I Hospital, Sapienza University, Rome, Italy. 16. Division of Neurology, Department of Medicine, Amiri Hospital, Kuwait City, Kuwait. 17. Karadeniz Technical University, Trabzon, Turkey. 18. Neurology Unit, ASUR Marche Hospital, Macerata, Italy. 19. Operative Unit of Neurology, Dimiccoli General Hospital, Barletta, Italy. 20. Department of Neurosciences, Neurology Unit, University of Modena and Reggio Emilia, Sant'Agostino-Estense Hospital, Modena, Italy. 21. Multiple Sclerosis Center, II Division of Neurology, Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy. 22. Multiple Sclerosis Center, Garibaldi-Nesima Hospital, Catania, Italy. 23. Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy. 24. Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Cagliari, Italy. 25. Multiple Sclerosis Center, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 26. Multiple Sclerosis Center, Ospedali Riuniti, Foggia, Italy. 27. Department of Neurology, Notre Dame Hospital, Montreal, Quebec, Canada. 28. Neurosciences Research Center and Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran. 29. Aarhus University Hospital, Aarhus, Denmark. 30. Virgin of Valme University Hospital, Seville, Spain. 31. Department of Neurology, Box Hill Hospital, Monash University, Melbourne, Victoria, Australia. 32. Department of Medicine at Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia. 33. Department of NEUROFARBA, University of Florence, Florence, Italy. 34. Department of Neurology, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy.
Abstract
OBJECTIVE: To assess prognostic factors for a second clinical attack and a first disability-worsening event in pediatric clinically isolated syndrome (pCIS) suggestive of multiple sclerosis (MS) patients. METHODS: A cohort of 770 pCIS patients was followed up for at least 10 years. Cox proportional hazard models and Recursive Partitioning and Amalgamation (RECPAM) tree-regression were used to analyze data. RESULTS: In pCIS, female sex and a multifocal onset were risk factors for a second clinical attack (hazard ratio [HR], 95% confidence interval [CI] = 1.28, 1.06-1.55; 1.42, 1.10-1.84, respectively), whereas disease-modifying drug (DMD) exposure reduced this risk (HR, 95% CI = 0.75, 0.60-0.95). After pediatric onset MS (POMS) diagnosis, age at onset younger than 15 years and DMD exposure decreased the risk of a first Expanded Disability Status Scale (EDSS)-worsening event (HR, 95% CI = 0.59, 0.42-0.83; 0.75, 0.71-0.80, respectively), whereas the occurrence of relapse increased this risk (HR, 95% CI = 5.08, 3.46-7.46). An exploratory RECPAM analysis highlighted a significantly higher incidence of a first EDSS-worsening event in patients with multifocal or isolated spinal cord or optic neuritis involvement at onset in comparison to those with an isolated supratentorial or brainstem syndrome. A Cox regression model including RECPAM classes confirmed DMD exposure as the most protective factor against EDSS-worsening events and relapses as the most important risk factor for attaining EDSS worsening. INTERPRETATION: This work represents a step forward in identifying predictors of unfavorable course in pCIS and POMS and supports a protective effect of early DMD treatment in preventing MS development and disability accumulation in this population. Ann Neurol 2017;81:729-739.
OBJECTIVE: To assess prognostic factors for a second clinical attack and a first disability-worsening event in pediatric clinically isolated syndrome (pCIS) suggestive of multiple sclerosis (MS) patients. METHODS: A cohort of 770 pCIS patients was followed up for at least 10 years. Cox proportional hazard models and Recursive Partitioning and Amalgamation (RECPAM) tree-regression were used to analyze data. RESULTS: In pCIS, female sex and a multifocal onset were risk factors for a second clinical attack (hazard ratio [HR], 95% confidence interval [CI] = 1.28, 1.06-1.55; 1.42, 1.10-1.84, respectively), whereas disease-modifying drug (DMD) exposure reduced this risk (HR, 95% CI = 0.75, 0.60-0.95). After pediatric onset MS (POMS) diagnosis, age at onset younger than 15 years and DMD exposure decreased the risk of a first Expanded Disability Status Scale (EDSS)-worsening event (HR, 95% CI = 0.59, 0.42-0.83; 0.75, 0.71-0.80, respectively), whereas the occurrence of relapse increased this risk (HR, 95% CI = 5.08, 3.46-7.46). An exploratory RECPAM analysis highlighted a significantly higher incidence of a first EDSS-worsening event in patients with multifocal or isolated spinal cord or optic neuritis involvement at onset in comparison to those with an isolated supratentorial or brainstem syndrome. A Cox regression model including RECPAM classes confirmed DMD exposure as the most protective factor against EDSS-worsening events and relapses as the most important risk factor for attaining EDSS worsening. INTERPRETATION: This work represents a step forward in identifying predictors of unfavorable course in pCIS and POMS and supports a protective effect of early DMD treatment in preventing MS development and disability accumulation in this population. Ann Neurol 2017;81:729-739.
Authors: Antonio Giorgio; Jian Zhang; Maria Laura Stromillo; Francesca Rossi; Marco Battaglini; Lucia Nichelli; Marzia Mortilla; Emilio Portaccio; Bahia Hakiki; Maria Pia Amato; Nicola De Stefano Journal: Front Neurol Date: 2017-11-14 Impact factor: 4.003
Authors: Jonathan D Santoro; Michael Waltz; Greg Aaen; Anita Belman; Leslie Benson; Mark Gorman; Manu S Goyal; Jennifer S Graves; Yolanda Harris; Lauren Krupp; Timothy Lotze; Soe Mar; Manikum Moodley; Jayne Ness; Mary Rensel; Moses Rodriguez; Teri Schreiner; Jan-Mendelt Tillema; Emmanuelle Waubant; Bianca Weinstock-Guttman; Brigitte F Hurtubise; Shelly Roalstad; John Rose; T Charles Casper; Tanuja Chitnis Journal: Neurology Date: 2020-07-20 Impact factor: 9.910