1From the CORe (M.V., I.D., C.M., P.D.M.P., T.K.), Department of Medicine, University of Melbourne, Australia; Melbourne MS Centre (M.V.), Department of Neurology, Faculty of Medicine, P.J. Safarik University, Kosice, Slovakia; Melbourne MS Centre (P.D.M.P., T.K.), Department of Neurology, Royal Melbourne Hospital, Australia; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia; Multiple Sclerosis Center (F.P.), University of Catania, Italy; Dokuz Eylul University (S.O.), Konak/Izmir, Turkey; Hospital Universitario Virgen Macarena (G. Izquierdo, S.E.), Sevilla, Spain; Isfahan Neurosciences Research Center (INRC) (V.S.), Isfahan University of Medical Sciences (IUMS), Iran; Department of Neuroscience, Imaging, and Clinical Sciences (M.O.), University G. D'Annunzio, Chieti; IRCCS Istituto Delle Scienze Neurologiche di Bologna (A.L.); Dipartimento di Scienze Biomediche e Neuromotorie (A.L.), Universita di Bologna, Italy; Division of Neurology (R. Alroughani), Department of Medicine, Amiri Hospital, Sharq, Kuwait; CHUM MS Center and Universite de Montreal (A.P., C.L., M.G., P.D.), Quebec, Canada; Medical Faculty (M.T.), Ondokuz Mayis University, Samsun; KTU Medical Faculty Farabi Hospital (C. Boz), Trabzon, Turkey; Neuro Rive-Sud (F.G.), Longueuil, Quebec, Canada; Azienda Ospedaliera Universitaria di Modena (P.S.); Department of Biomedical (D.F.), Metabolic and Neurosciences, University of Modena and Reggio Emilia, Italy; CISSS Chaudière-Appalache (P.G.), Levis, Quebec, Canada; Central Clinical School (H.B.), Monash University; Department of Neurology (H.B., O.S.), The Alfred Hospital; Department of Neurology (K.B., O.S.), Box Hill Hospital, Eastern Health; Monash University (K.B., O.S.), Melbourne, Australia; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y.), American University of Beirut Medical Center, Lebanon; Hacettepe University (R.K.), Ankara, Turkey; Zuyderland Medical Centre (O. Gerlach), Department of Neurologie, Dr. H. van der Hoffplein 1, Sittard-Geleen, the Netherlands; School of Medicine and Public Health (J.L.-S.), University Newcastle; Department of Neurology (J.L.-S.), John Hunter Hospital, Hunter New England Health, Newcastle, Australia; MS Center (D.M.), Neurology Unit, Garibaldi Hospital, Catania; IRCCS Mondino Foundation (R.B.), Pavia, Italy; Cliniques Universitaires Saint-Luc (V.V.P.), Brussels; Université Catholique de Louvain (V.V.P.), Belgium; Ospedali Riuniti di Salerno (G. Iuliano); UOC Neurologia (E. Cartechini), Azienda Sanitaria Unica Regionale Marche-AV3, Macerata, Italy; Hospital de Sao Joao (M.J.S.), Universidade Fernando Pessoa, Porto, Portugal; Nemocnice Jihlava (R. Ampapa), Jihlava, Czech Republic; Brain and Mind Centre (M.B.), Sydney, Australia; Royal Victoria Hospital (S.E.H.), Belfast, UK; Hospital Germans Trias I Pujol (C.M.R.-T.), Badalona, Spain; Liverpool Hospital (S.H.), Sydney, Australia; Liverpool Hospital and Ingham Institute (S.H.), Australia; Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino (D.L.A.S.), Italy; Kommunehospitalet (T.P.), Aarhus, Denmark; Monash Medical Centre (E.G.B.), Melbourne; Flinders University (M.S.), Adelaide, Australia; University College Dublin and St. Vincent's University Hospital (C. McGuigan), Ireland; University of Queensland (P.A.M.); Royal Brisbane and Women's Hospital (P.A.M.), Australia; Department of Medicine and Surgery (F.G.), University of Parma; Department of Emergency and General Medicine (F.G.), Parma University Hospital, Italy; Hospital Italiano (E. Cristiano), Buenos Aires, Argentina; CSSS Saint-Jérôme (J.P.), Saint-Jerome, Quebec, Canada; Royal Hobart Hospital (B.V.T.), Australia; Hospital de Galdakao-Usansolo (J.L.S.Ã.-M.), Galdakao, Spain; Department of Neurology (G.L.), Ghent University Hospital, Corneel Heymanslaan 10; University Hospital Ghent (L.V.H.), Ghent, Belgium; Westmead Hospital (S.V.), Sydney; Austin Health (R.A.M.), Melbourne, Australia; South East Trust (O. Gray), Belfast, UK; Instituto de Investigación Sanitaria Biodonostia (J.O.), Hospital Universitario Donostia, San Sebastián, Spain; Hospital Fernandez (N.D.), Capital Federal, Argentina; Universidade Metropolitana de Santos (Y.D.F.), Santos, Brazil; and Geelong Hospital (C.S.), Geelong, Australia.
2From the CORe (M.V., I.D., C.M., P.D.M.P., T.K.), Department of Medicine, University of Melbourne, Australia; Melbourne MS Centre (M.V.), Department of Neurology, Faculty of Medicine, P.J. Safarik University, Kosice, Slovakia; Melbourne MS Centre (P.D.M.P., T.K.), Department of Neurology, Royal Melbourne Hospital, Australia; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia; Multiple Sclerosis Center (F.P.), University of Catania, Italy; Dokuz Eylul University (S.O.), Konak/Izmir, Turkey; Hospital Universitario Virgen Macarena (G. Izquierdo, S.E.), Sevilla, Spain; Isfahan Neurosciences Research Center (INRC) (V.S.), Isfahan University of Medical Sciences (IUMS), Iran; Department of Neuroscience, Imaging, and Clinical Sciences (M.O.), University G. D'Annunzio, Chieti; IRCCS Istituto Delle Scienze Neurologiche di Bologna (A.L.); Dipartimento di Scienze Biomediche e Neuromotorie (A.L.), Universita di Bologna, Italy; Division of Neurology (R. Alroughani), Department of Medicine, Amiri Hospital, Sharq, Kuwait; CHUM MS Center and Universite de Montreal (A.P., C.L., M.G., P.D.), Quebec, Canada; Medical Faculty (M.T.), Ondokuz Mayis University, Samsun; KTU Medical Faculty Farabi Hospital (C. Boz), Trabzon, Turkey; Neuro Rive-Sud (F.G.), Longueuil, Quebec, Canada; Azienda Ospedaliera Universitaria di Modena (P.S.); Department of Biomedical (D.F.), Metabolic and Neurosciences, University of Modena and Reggio Emilia, Italy; CISSS Chaudière-Appalache (P.G.), Levis, Quebec, Canada; Central Clinical School (H.B.), Monash University; Department of Neurology (H.B., O.S.), The Alfred Hospital; Department of Neurology (K.B., O.S.), Box Hill Hospital, Eastern Health; Monash University (K.B., O.S.), Melbourne, Australia; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y.), American University of Beirut Medical Center, Lebanon; Hacettepe University (R.K.), Ankara, Turkey; Zuyderland Medical Centre (O. Gerlach), Department of Neurologie, Dr. H. van der Hoffplein 1, Sittard-Geleen, the Netherlands; School of Medicine and Public Health (J.L.-S.), University Newcastle; Department of Neurology (J.L.-S.), John Hunter Hospital, Hunter New England Health, Newcastle, Australia; MS Center (D.M.), Neurology Unit, Garibaldi Hospital, Catania; IRCCS Mondino Foundation (R.B.), Pavia, Italy; Cliniques Universitaires Saint-Luc (V.V.P.), Brussels; Université Catholique de Louvain (V.V.P.), Belgium; Ospedali Riuniti di Salerno (G. Iuliano); UOC Neurologia (E. Cartechini), Azienda Sanitaria Unica Regionale Marche-AV3, Macerata, Italy; Hospital de Sao Joao (M.J.S.), Universidade Fernando Pessoa, Porto, Portugal; Nemocnice Jihlava (R. Ampapa), Jihlava, Czech Republic; Brain and Mind Centre (M.B.), Sydney, Australia; Royal Victoria Hospital (S.E.H.), Belfast, UK; Hospital Germans Trias I Pujol (C.M.R.-T.), Badalona, Spain; Liverpool Hospital (S.H.), Sydney, Australia; Liverpool Hospital and Ingham Institute (S.H.), Australia; Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino (D.L.A.S.), Italy; Kommunehospitalet (T.P.), Aarhus, Denmark; Monash Medical Centre (E.G.B.), Melbourne; Flinders University (M.S.), Adelaide, Australia; University College Dublin and St. Vincent's University Hospital (C. McGuigan), Ireland; University of Queensland (P.A.M.); Royal Brisbane and Women's Hospital (P.A.M.), Australia; Department of Medicine and Surgery (F.G.), University of Parma; Department of Emergency and General Medicine (F.G.), Parma University Hospital, Italy; Hospital Italiano (E. Cristiano), Buenos Aires, Argentina; CSSS Saint-Jérôme (J.P.), Saint-Jerome, Quebec, Canada; Royal Hobart Hospital (B.V.T.), Australia; Hospital de Galdakao-Usansolo (J.L.S.Ã.-M.), Galdakao, Spain; Department of Neurology (G.L.), Ghent University Hospital, Corneel Heymanslaan 10; University Hospital Ghent (L.V.H.), Ghent, Belgium; Westmead Hospital (S.V.), Sydney; Austin Health (R.A.M.), Melbourne, Australia; South East Trust (O. Gray), Belfast, UK; Instituto de Investigación Sanitaria Biodonostia (J.O.), Hospital Universitario Donostia, San Sebastián, Spain; Hospital Fernandez (N.D.), Capital Federal, Argentina; Universidade Metropolitana de Santos (Y.D.F.), Santos, Brazil; and Geelong Hospital (C.S.), Geelong, Australia. tomas.kalincik@unimelb.edu.au.
Background and objectives: The severity of multiple sclerosis (MS) varies widely among individuals. Understanding the determinants of this heterogeneity will help clinicians optimize the management of MS. The aim of this study was to investigate the association between latitude of residence, UV B radiation (UVB) exposure, and the severity of MS.
Methods: This observational study used the MSBase registry data. The included patients met the 2005 or 2010 McDonald diagnostic criteria for MS and had a minimum dataset recorded in the registry (date of birth, sex, clinic location, date of MS symptom onset, disease phenotype at baseline and censoring, and ≥1 Expanded Disability Status Scale score recorded). The latitude of each study center and cumulative annualized UVB dose at study center (calculated from National Aeronautics and Space Administration's Total Ozone Mapping Spectrometer) at ages 6 and 18 years and the year of disability assessment were calculated. Disease severity was quantified with Multiple Sclerosis Severity Score (MSSS). Quadratic regression was used to model the associations between latitude, UVB, and MSSS.
Results: The 46,128 patients who contributed 453,208 visits and a cumulative follow-up of 351,196 patient-years (70% women, mean age 39.2 ± 12 years, resident between latitudes 19°35' and 56°16') were included in this study. Latitude showed a nonlinear association with MS severity. In latitudes <40°, more severe disease was associated with higher latitudes (β = 0.08, 95% CI 0.04-0.12). For example, this translates into a mean difference of 1.3 points of MSSS between patients living in Madrid and Copenhagen. No such association was observed in latitudes <40° (β = -0.02, 95% CI -0.06 to 0.03). The overall disability accrual was faster in those with a lower level of estimated UVB exposure before the age of 6 years (β = - 0.5, 95% CI -0.6 to 0.4) and 18 years (β = - 0.6, 95% CI -0.7 to 0.4), as well as with lower lifetime UVB exposure at the time of disability assessment (β = -1.0, 95% CI -1.1 to 0.9).
Discussion: In temperate zones, MS severity is associated with latitude. This association is mainly, but not exclusively, driven by UVB exposure contributing to both MS susceptibility and severity.
Zhou Y, Claflin SB, Stankovich J, van der Mei I, Simpson S Jr, Roxburgh RH, Kalincik T, Blizzard L, Lugaresi A, Alroughani R, Sajedi SA, Butzkueven H, Pucci E, Spitaleri D, Granella F, Cristiano E, Yamout B, Hughes S, Gouider R, Sánchez Menoyo JL, Olascoaga J, McGuigan C, Shaw C, Kermode AG, Kasa K, Al-Harbi T, Altintas A, Laureys G, Fragoso Y, Hardy TA, Csepany T, Sirbu CA, Decoo D, Sas A, Alvarez-Cermeño JC, Kotkata K, Millán-Pascual J, Taylor BV.Mult Scler. 2020 Nov;26(13):1765-1774. doi: 10.1177/1352458519881994. Epub 2019 Oct 31.PMID: 31668127
