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.

Al Zahra Hospital Isfahan University of Medical Sciences Isfahan Iran

Amiri Hospital Kuwait City Kuwait

AORN San Giuseppe Moscati Avellino Avellino Italy

Bombay Hospital Institute of Medical Sciences Mumbai India

Brain and Mind Research Institute Sydney New South Wales Australia

C Mondino National Neurological Institute Pavia Italy

CHUM Hôpital Notre Dame Montreal Canada

CISSS Chaudiere Appalaches Levis Quebec Canada

Cliniques Universitaires Saint Luc Brussels Belgium

Department of Basic Medical Sciences Neuroscience and Sense Organs University of Bari Bari Italy

Department of Biomedical and NeuroMotor Sciences Alma Mater Studiorum Università di Bologna Bologna Italy

Department of Medicine Royal Melbourne Hospital University of Melbourne Melbourne Victoria Australia

Department of Neurofarba Section of Neurosciences University of Florence Florence Italy

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University Prague General University Hospital Prague Czech Republic

Department of Neurology Eastern Health Monash University Box Hill Victoria Australia

Department of Neurology Faculty of Medicine Center of Clinical Neuroscience 1st General University Hospital and Charles University Prague Prague Czech Republic

Department of Neurology Golestan University of Medical Sciences Gorgan Iran

Department of Neurology Mayis University Samsun Turkey

Department of Neuroscience Universitu of Modena e Reggio Emilia Nuovo Ospedale Civile S Agostino Estense Modena Italy

Department of Neuroscience University of Parma Parma Italy

FLENI Buenos Aries Argentina

Flinders University and Medical Centre Adelaide South Australia Australia

Geelong Hospital Geelong Victoria Australia

Groene Hart Ziekenhuis Gouda The Netherlands

Hospital de Galdakao Usansolo Galdakao Spain

Hospital Ecoville Curitiba Brazil

Hospital Fernandez Capital Federal Argentina

Hospital Germans Trias 1 Pujol Badalona Spain

Hospital Italiano Buenos Aries Argentina

Hospital Universitario Virgen de Valme Sevilla Spain

Hospital Universitario Virgen Macarena Sevilla Spain

INEBA Buenos Aries Argentina

IRCCS Istituto delle Scienze Neurologiche UOSI Riabilitazione Sclerosi Multipla Bologna Italy

John Hunter Hospital University of Newcastle Hunter Medical Research Institute Newcastle New South Wales Australia

Liverpool Hospital Liverpool New South Wales Australia

Menzies Institute for Medical Research University of Tasmania Hobart Tasmania Australia

Neuro Rive Sud Hôpital Charles LeMoyne Quebec Quebec Canada

Neurology Unit ASUR Marche AV 3 Macerata Italy

Ospedali Riuniti di Salerno Salerno Italy

St Andrew's Place Brisbane Australia

St Vincent's Hospital Melbourne Victoria Australia

Ulster Hospital Dundonald UK

University Hospital San Carlos IdISSC Madrid Spain

Westmead Hospital Sydney New South Wales Australia

Nat Rev Neurol. 2017 Jan;13(1):3. doi: 10.1038/nrneurol.2016.181. PubMed

References provided by Crossref.org

Examining the environmental risk factors of progressive-onset and relapsing-onset multiple sclerosis: recruitment challenges, potential bias, and statistical strategies

Management of multiple sclerosis patients in central European countries: current needs and potential solutions