Chunrong Tao1, Steve Simpson1, Ingrid van der Mei1, Leigh Blizzard1, Eva Havrdova2, Dana Horakova3, Vahid Shaygannejad4, Alessandra Lugaresi5,6, Guillermo Izquierdo7, Maria Trojano8, Pierre Duquette9, Marc Girard9, Franois Grand'Maison10, Pierre Grammond11, Raed Alroughani12, Murat Terzi13, Celia Oreja-Guevara14, Seyed Aidin Sajedi15, Gerardo Iuliano16, Patrizia Sola17, Jeannette Lechner-Scott18, Vincent Van Pesch19, Eugenio Pucci20, Roberto Bergamaschi21, Michael Barnett22, Cristina Ramo23, Bhim Singhal24, Daniele LA Spitaleri25, Mark Slee26, Freek Verheul27, Ricardo Fernández Bolaños28, Maria Pia Amato29, Edgardo Cristiano30, Franco Granella31, Suzanne Hodgkinson32, Marcela Fiol33, Orla Gray34, Pamela McCombe35, Maria Laura Saladino36, José Luis Sánchez Menoyo37, Neil Shuey38, Steve Vucic39, Cameron Shaw40, Norma Deri41, Walter Oleschko Arruda42, Helmut Butzkueven43,44, Tim Spelman43, Bruce V Taylor1. 1. Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia. 2. Department of Neurology, Faculty of Medicine, Center of Clinical Neuroscience, 1st General University Hospital and Charles University in Prague, Prague, Czech Republic. 3. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague, General University Hospital, Prague, Czech Republic. 4. Al-Zahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran. 5. Department of Biomedical and NeuroMotor Sciences (DIBINEM), Alma Mater Studiorum-Università di Bologna, Bologna, Italy. 6. IRCCS Istituto delle Scienze Neurologiche-"UOSI Riabilitazione Sclerosi Multipla", Bologna, Italy. 7. Hospital Universitario Virgen Macarena, Sevilla, Spain. 8. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy. 9. CHUM-Hôpital Notre Dame, Montreal, Canada. 10. Neuro Rive-Sud, Hôpital Charles LeMoyne, Quebec, Quebec, Canada. 11. CISSS Chaudiere-Appalaches, Levis, Quebec, Canada. 12. Amiri Hospital, Kuwait City, Kuwait. 13. Department of Neurology, Mayis University, Samsun, Turkey. 14. University Hospital San Carlos, IdISSC, Madrid, Spain. 15. Department of Neurology, Golestan University of Medical Sciences, Gorgan, Iran. 16. Ospedali Riuniti di Salerno, Salerno, Italy. 17. Department of Neuroscience, Universitu of Modena e Reggio Emilia, Nuovo Ospedale Civile S. Agostino/Estense, Modena, Italy. 18. John Hunter Hospital, University of Newcastle, Hunter Medical Research Institute, Newcastle, New South Wales, Australia. 19. Cliniques Universitaires Saint-Luc, Brussels, Belgium. 20. Neurology Unit, ASUR Marche-AV 3, Macerata, Italy. 21. C. Mondino National Neurological Institute, Pavia, Italy. 22. Brain and Mind Research Institute, Sydney, New South Wales, Australia. 23. Hospital Germans Trias I Pujol, Badalona, Spain. 24. Bombay Hospital Institute of Medical Sciences, Mumbai, India. 25. AORN San Giuseppe Moscati Avellino, Avellino, Italy. 26. Flinders University and Medical Centre, Adelaide, South Australia, Australia. 27. Groene Hart Ziekenhuis, Gouda, The Netherlands. 28. Hospital Universitario Virgen de Valme, Sevilla, Spain. 29. Department of Neurofarba, Section of Neurosciences, University of Florence, Florence, Italy. 30. Hospital Italiano, Buenos Aries, Argentina. 31. Department of Neuroscience, University of Parma, Parma, Italy. 32. Liverpool Hospital, Liverpool, New South Wales, Australia. 33. FLENI, Buenos Aries, Argentina. 34. Ulster Hospital, Dundonald, UK. 35. St Andrew's Place, Brisbane, Australia. 36. INEBA, Buenos Aries, Argentina. 37. Hospital de Galdakao-Usansolo, Galdakao, Spain. 38. St Vincent's Hospital, Melbourne, Victoria, Australia. 39. Westmead Hospital, Sydney, New South Wales, Australia. 40. Geelong Hospital, Geelong, Victoria, Australia. 41. Hospital Fernandez, Capital Federal, Argentina. 42. Hospital Ecoville, Curitiba, Brazil. 43. Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia. 44. Department of Neurology, Eastern Health, Monash University, Box Hill, Victoria, Australia.
Abstract
BACKGROUND: Age at onset (AAO) in multiple sclerosis (MS) is an important marker of disease severity and may have prognostic significance. Understanding what factors can influence AAO may shed light on the aetiology of this complex disease, and have applications in the diagnostic process. METHODS: The study cohort of 22 162 eligible patients from 21 countries was extracted from the MSBase registry. Only patients with MS aged ≥16 years were included. To reduce heterogeneity, only centres of largely European descent were included for analysis. AAO was defined as the year of the first symptom suggestive of inflammatory central nervous system demyelination. Predictors of AAO were evaluated by linear regression. RESULTS: Compared with those living in lower latitudes (19.0-39.9°), onset of symptoms was 1.9 years earlier for those at higher latitudes (50.0-56.0°) (p=3.83×10-23). A reciprocal relationship was seen for ambient ultraviolet radiation (UVR), with a significantly increasing AAO for patients with MS per each quartile increment of ambient UVR (p=1.56×10-17). We found that the AAO of female patients was ∼5 months earlier than male patients (p=0.002). AAO of progressive-onset patients with MS were ∼9 years later than relapsing-onset patients (p=1.40×10-265). CONCLUSIONS: An earlier AAO in higher latitude regions was found in this worldwide European-descent cohort and correlated inversely with variation in latitudinal UVR. These results suggest that environmental factors which act at the population level may significantly influence disease severity characteristics in genetically susceptible populations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
BACKGROUND: Age at onset (AAO) in multiple sclerosis (MS) is an important marker of disease severity and may have prognostic significance. Understanding what factors can influence AAO may shed light on the aetiology of this complex disease, and have applications in the diagnostic process. METHODS: The study cohort of 22 162 eligible patients from 21 countries was extracted from the MSBase registry. Only patients with MS aged ≥16 years were included. To reduce heterogeneity, only centres of largely European descent were included for analysis. AAO was defined as the year of the first symptom suggestive of inflammatory central nervous system demyelination. Predictors of AAO were evaluated by linear regression. RESULTS: Compared with those living in lower latitudes (19.0-39.9°), onset of symptoms was 1.9 years earlier for those at higher latitudes (50.0-56.0°) (p=3.83×10-23). A reciprocal relationship was seen for ambient ultraviolet radiation (UVR), with a significantly increasing AAO for patients with MS per each quartile increment of ambient UVR (p=1.56×10-17). We found that the AAO of female patients was ∼5 months earlier than male patients (p=0.002). AAO of progressive-onset patients with MS were ∼9 years later than relapsing-onset patients (p=1.40×10-265). CONCLUSIONS: An earlier AAO in higher latitude regions was found in this worldwide European-descent cohort and correlated inversely with variation in latitudinal UVR. These results suggest that environmental factors which act at the population level may significantly influence disease severity characteristics in genetically susceptible populations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Authors: Michael T Shaw; Natalie O Pawlak; Ariana Frontario; Kathleen Sherman; Lauren B Krupp; Leigh E Charvet Journal: Front Neurol Date: 2017-06-02 Impact factor: 4.003
Authors: Grace D Reilly; Awng Shar Mahkawnghta; Pia L Jelinek; Alysha M De Livera; Tracey J Weiland; Chelsea R Brown; Keryn L Taylor; Sandra L Neate; George A Jelinek; Claudia H Marck Journal: Front Neurol Date: 2017-05-31 Impact factor: 4.003
Authors: Chunrong Tao; Steve Simpson; Bruce V Taylor; Leigh Blizzard; Robyn M Lucas; Anne-Louise Ponsonby; Simon Broadley; Ingrid van der Mei Journal: Front Neurol Date: 2018-06-08 Impact factor: 4.003