Do patients’ and referral centers’ characteristics influence multiple sclerosis phenotypes? Results from the Italian multiple sclerosis and related disorders register
Authors: Bergamaschi Roberto , Beghi Ettore , Bosetti Cristina , Ponzio Michela , Santucci Claudia , Lepore Vito , Mosconi Paola ,   on behalf of the Italian Multiple Sclerosis and Related Disorders Register Centers Group and the Scientific Committee of Italian SM and Related Disorders Register, Aguglia U. , Amato M. P. , Ancona A. L. , Ardito B. , Avolio C. , Balgera R. , Banfi P. , Barcella V. , Barone P. , Bellantonio P. , Berardinelli A. , Bergamaschi R. , Bertora P. , Bianchi M. , Bramanti P. , Morra V. Brescia , Brichetto G. , Brioschi A. M. , Buccafusca M. , Bucello S. , Busillo V. , Calchetti B. , Cantello R. , Capobianco M. , Capone F. , Capone L. , Cargnelutti D. , Carrozzi M. , Cartechini E. , Cavaletti G. , Cavalla P. , Celani M. G. , Clerici R. , Clerico M. , Cocco E. , Confalonieri P. , Coniglio M. G. , Conte A. , Corea F. , Cottone S. , Crociani P. , D’Andrea F. , Danni M. C. , De Luca G. , de Pascalis D. , De Riz M. , De Robertis F. , De Rosa G. , De Stefano N. , Corte M. Della , Di Sapio A. , Docimo R. , Falcini M. , Falcone N. , Fermi S. , Ferraro E. , Ferrò M. T. , Fortunato M. , Foschi M. , Gajofatto A. , Gallo A. , Gallo P. , Gatto M. , Gazzola P. , Giordano A. , Granella F. , Grasso M. F. , Grasso M. G. , Grimaldi L. M. E. , Iaffaldano P. , Imperiale D. , Inglese M. , Iodice R. , Leva S. , Luezzi V. , Lugaresi A. , Lus G. , Maimone D. , Mancinelli L. , Maniscalco G. T. , Marfia G. A. , Marini B. , Marson A. , Mascoli N. , Massacesi L. , Melani F. , Merello M. , Meucci G. , Mirabella M. , Montepietra S. , Nasuelli D. , Nicolao P. , Passantino F. , Patti F. , Peresson M. , Pesci I. , Piantadosi C. , Piras M. L. , Pizzorno M. , Plewnia K. , Pozzilli C. , Protti A. , Quatrale R. , Realmuto S. , Ribizzi G. , Rinalduzzi S. , Rini A. , Romano S. , Romeo M. , Ronzoni M. , Rossi P. , Rovaris M. , Salemi G. , Santangelo G. , Santangelo M. , Santuccio G. , Sarchielli P. , Sinisi L. , Sola P. , Solaro C. , Spitaleri D. , Strumia S. , Tassinari T. , Tonietti S. , Tortorella C. , Totaro R. , Tozzo A. , Trivelli G. , Ulivelli M. , Valentino P. , Venturi S. , Vianello M. , Zaffaroni M. , Zarbo R. , Trojano Maria , Battaglia Mario Alberto , Capobianco Marco , Pugliatti Maura , Ulivelli Monica , Mosconi Paola , Gasperini Claudio , Patti Francesco , Amato Maria Pia , Bergamaschi Roberto , Comi Giancarlo 
Published: June 2022

Abstract

Background

Multiple sclerosis (MS) is characterized by phenotypical heterogeneity, partly resulting from demographic and environmental risk factors. Socio-economic factors and the characteristics of local MS facilities might also play a part.

Methods
This study included patients with a confirmed MS diagnosis enrolled in the Italian MS and Related Disorders Register in 2000–2021. Patients at first visit were classified as having a clinically isolated syndrome (CIS), relapsing–remitting (RR), primary progressive (PP), progressive-relapsing (PR), or secondary progressive MS (SP). Demographic and clinical characteristics were analyzed, with centers’ characteristics, geographic macro-areas, and Deprivation Index. We computed the odds ratios (OR) for CIS, PP/PR, and SP phenotypes, compared to the RR, using multivariate, multinomial, mixed effects logistic regression models.

Results
In all 35,243 patients from 106 centers were included. The OR of presenting more advanced MS phenotypes than the RR phenotype at first visit significantly diminished in relation to calendar period. Females were at a significantly lower risk of a PP/PR or SP phenotype. Older age was associated with CIS, PP/PR, and SP. The risk of a longer interval between disease onset and first visit was lower for the CIS phenotype, but higher for PP/PR and SP. The probability of SP at first visit was greater in the South of Italy.

Discussion
Differences in the phenotype of MS patients first seen in Italian centers can be only partly explained by differences in the centers’ characteristics. The demographic and socio-economic characteristics of MS patients seem to be the main determinants of the phenotypes at first referral.