Effect of late-onset on multiple sclerosis phenotype and outcome: evidence from a multi-national registry

Amira Souissi; Francesco Patti; Tim Spelman; Clara Chisari; Amina Gargouri; Nevin John; Allan G. Kermode; Tomas Kalincik; Helmut Butzkueven; Seyed Aidin Sajedi; Jeannette Lechner-Scott; Izanne Roos; Guy Laureys; Bruce Taylor; Raed Alroughani; Samia J. Khoury; Richard Macdonell; Bianca Weinstock-Guttman; Eva Kubala Havrdova; Davide Maimone; Stephen Reddel; Marzena Fabis-Pedrini; Barbara Willekens; Abdorreza Naser Moghadasi; Patrice Lalive; Alessandra Lugaresi; Serkan Ozakbas; Claudio Solaro; Simón Cárdenas-Robledo; Vahid Shaygannejad; Masoud Etemadifar; Cavit Boz; Sara Eichau; Valentina Tomassini; Murat Terzi; Alexandre Prat; Mario Habek; Yolanda Blanco; Ayse Altintas; Oliver Gerlach; Recai Turkoglu; Katherine Buzzard; Olga Skibina; Aysun Soysal; Anneke van der Walt; Stella Hughes; Vincent van Pesch; Matteo Foschi; Andrea Surcinelli; Julie Prevost; Cristina Ramo-Tello; Chris McGuigan; Maria Jose Sa; Jens Kuhle; Daniele Spitaleri; Bhim Singhal; Radek Ampapa; Koen de Gans; Thor Petersen; Mihaela Simu; Emmanuelle Lapointe; Jose Luis Sanchez-Menoyo; Orla Gray; Justin Garber; Eduardo Aguera-Morales; Katrin Gross-Paju; Tamara Castillo-Triviño; Abdullah Al-Asmi; Nikolaos Grigoriadis; Jihad Inshasi; Talal Al-Harbi; Todd A. Hardy; Sudarshini Ramanathan; Melissa Cambron; Neil Shuey; Angel Perez sempere; Tunde Csepany; Irene Treviño-Frenk; Csilla Rozsa; Marija Cauchi; Rana Karabudak; Saloua Mrabet; Riadh Gouider

doi:10.1007/s00415-026-13632-4

Effect of late-onset on multiple sclerosis phenotype and outcome: evidence from a multi-national registry

Amira Souissi
, Francesco Patti
, Tim Spelman
, Clara Chisari
, Amina Gargouri
, Nevin John
, Allan G. Kermode
, Tomas Kalincik
, Helmut Butzkueven
, Seyed Aidin Sajedi
, Jeannette Lechner-Scott
, Izanne Roos
, Guy Laureys
, Bruce Taylor
, Raed Alroughani
, Samia J. Khoury
, Richard Macdonell
, Bianca Weinstock-Guttman
, Eva Kubala Havrdova
, Davide Maimone

Stephen Reddel, Marzena Fabis-Pedrini, Barbara Willekens, Abdorreza Naser Moghadasi, Patrice Lalive, Alessandra Lugaresi, Serkan Ozakbas, Claudio Solaro, Simón Cárdenas-Robledo, Vahid Shaygannejad, Masoud Etemadifar, Cavit Boz, Sara Eichau, Valentina Tomassini, Murat Terzi, Alexandre Prat, Mario Habek, Yolanda Blanco, Ayse Altintas, Oliver Gerlach, Recai Turkoglu, Katherine Buzzard, Olga Skibina, Aysun Soysal, Anneke van der Walt, Stella Hughes, Vincent van Pesch, Matteo Foschi, Andrea Surcinelli, Julie Prevost, Cristina Ramo-Tello, Chris McGuigan, Maria Jose Sa, Jens Kuhle, Daniele Spitaleri, Bhim Singhal, Radek Ampapa, Koen de Gans, Thor Petersen, Mihaela Simu, Emmanuelle Lapointe, Jose Luis Sanchez-Menoyo, Orla Gray, Justin Garber, Eduardo Aguera-Morales, Katrin Gross-Paju, Tamara Castillo-Triviño, Abdullah Al-Asmi, Nikolaos Grigoriadis, Jihad Inshasi, Talal Al-Harbi, Todd A. Hardy, Sudarshini Ramanathan, Melissa Cambron, Neil Shuey, Angel Perez sempere, Tunde Csepany, Irene Treviño-Frenk, Csilla Rozsa, Marija Cauchi, Rana Karabudak, Saloua Mrabet, Riadh Gouider

Razi University Hospital
Université de Tunis El Manar
University of Catania
Karolinska Institutet
MSBase Foundation
School of Clinical Sciences at Monash Health
University of Western Australia
Murdoch University
Royal Melbourne Hospital
Department of Medicine
Alfred Health
Monash University
Golestan University of Medical Sciences
University of Newcastle
Hunter New England Health
Ghent University
Royal Hobart Hospital
University of Tasmania
Department of Medicine—Amiri Hospital
American University of Beirut
University of Melbourne
Jacobs MS Center for Treatment and Research
Charles University
Centro Sclerosi Multipla
Concord Repatriation General Hospital
University of Antwerp
Tehran University of Medical Sciences
University of Geneva
University of Bologna
Izmir Ekonomi University
Ospedale Galliera
Universidad Nacional de Colombia
Isfahan University of Medical Sciences
Karadeniz Technical University
Hospital Universitario Virgen Macarena
Gabriele d'Annunzio University
Annunziata University Hospital
Ondokuz Mayis University
University of Montreal
University of Zagreb
Hospital Clínic of Barcelona
Koc University
Atrium Medical Center
Maastricht University
Ministry of Health, Turkey
Box Hill Hospital
Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases
Royal Victoria Hospital Belfast
Université catholique de Louvain
Ospedale S. Maria delle Croci
University of L'Aquila
CSSS Saint-Jérôme
Generalitat de Catalunya
University College Dublin
Centro Hospitalar Universitário de São João
University Fernando Pessoa
University of Basel
Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino
Bombay Hospital and Medical Research Centre
Nemocnice Jihlava
Groene Hart Ziekenhuis
Aarhus University
Victor Babes University of Medicine and Pharmacy
Université de Sherbrooke
Galdakao-Usansolo University Hospital
Biocruces Health Research Institute
South Eastern Health and Social Care Trust
Westmead Hospital
University of Córdoba
Florida International University
West Tallinn Central Hospital
Hospital Universitario Donostia
Sultan Qaboos University
Aristotle University of Thessaloniki
King Fahad Specialist Hospital, Dammam
University of Sydney
Az Sint-Jan Brugge,
Vincents Hospital
Hospital General Universitario de Alicante
Miguel Hernández University
University of Debrecen
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Jahn Ferenc Hospital
Mater Dei Hospital
Yeditepe University

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Multiple Sclerosis (MS) severity is influenced by several factors. Understanding the impact of age at disease onset may help to better characterize clinical and disease features across age groups. This study aimed to characterize the clinical features and disability outcomes of late-onset MS (LOMS) and very late-onset MS (vLOMS), compared to adult-onset MS (AOMS). Methods: We conducted an observational study using data from the MSBase registry and categorized patients based on age at MS onset: AOMS (18–39 years), transition onset (40–49 years), LOMS (50–59 years), and vLOMS (≥ 60 years). Disease progression was assessed using the 24 week confirmed disability progression, EDSS4 and 6 milestones, conversion to secondary progressive MS(SPMS), and the first progression independent of relapse activity (PIRA) event. Cox proportional hazard regression models were used to determine unadjusted hazard ratios(HR), and propensity score inverse probability of treatment weighting(PS-IPTW) balanced covariate distributions. Results: Among 81,236 patients, 5.2% had LOMS and 1% had vLOMS. Primary progressive MS was more frequent in LOMS and vLOMS (21.7 and 24%, respectively). Patients with LOMS and vLOMS had a significantly increased risk of 24 week confirmed disability progression (HR:LOMS = 1.39, vLOMS = 1.80), EDSS 4 (HR:LOMS = 2.14, vLOMS = 2.95), EDSS 6 (HR:LOMS = 2.33, vLOMS = 6.33), SPMS (HR:LOMS = 1.62, vLOMS = 2.38), and first PIRA event (HR:LOMS = 2.12, vLOMS = 2.93). Conclusion: LOMS and vLOMS exhibited a more progressive disease onset and higher disability milestones compared with AOMS.

Original language	English
Article number	114
Journal	Journal of Neurology
Volume	273
Issue number	2
DOIs	https://doi.org/10.1007/s00415-026-13632-4
State	Published - Feb 2026

Keywords

Aging
Immunosenescence
Multiple Sclerosis
Prognosis
Progression

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10.1007/s00415-026-13632-4

Cite this

Souissi, A., Patti, F., Spelman, T., Chisari, C., Gargouri, A., John, N., Kermode, A. G., Kalincik, T., Butzkueven, H., Sajedi, S. A., Lechner-Scott, J., Roos, I., Laureys, G., Taylor, B., Alroughani, R., Khoury, S. J., Macdonell, R., Weinstock-Guttman, B., Havrdova, E. K., ... Gouider, R. (2026). Effect of late-onset on multiple sclerosis phenotype and outcome: evidence from a multi-national registry. Journal of Neurology, 273(2), Article 114. https://doi.org/10.1007/s00415-026-13632-4

@article{30d1e6fbc48a45c8b45b524b62a982a2,

title = "Effect of late-onset on multiple sclerosis phenotype and outcome: evidence from a multi-national registry",

abstract = "Background: Multiple Sclerosis (MS) severity is influenced by several factors. Understanding the impact of age at disease onset may help to better characterize clinical and disease features across age groups. This study aimed to characterize the clinical features and disability outcomes of late-onset MS (LOMS) and very late-onset MS (vLOMS), compared to adult-onset MS (AOMS). Methods: We conducted an observational study using data from the MSBase registry and categorized patients based on age at MS onset: AOMS (18–39 years), transition onset (40–49 years), LOMS (50–59 years), and vLOMS (≥ 60 years). Disease progression was assessed using the 24 week confirmed disability progression, EDSS4 and 6 milestones, conversion to secondary progressive MS(SPMS), and the first progression independent of relapse activity (PIRA) event. Cox proportional hazard regression models were used to determine unadjusted hazard ratios(HR), and propensity score inverse probability of treatment weighting(PS-IPTW) balanced covariate distributions. Results: Among 81,236 patients, 5.2\% had LOMS and 1\% had vLOMS. Primary progressive MS was more frequent in LOMS and vLOMS (21.7 and 24\%, respectively). Patients with LOMS and vLOMS had a significantly increased risk of 24 week confirmed disability progression (HR:LOMS = 1.39, vLOMS = 1.80), EDSS 4 (HR:LOMS = 2.14, vLOMS = 2.95), EDSS 6 (HR:LOMS = 2.33, vLOMS = 6.33), SPMS (HR:LOMS = 1.62, vLOMS = 2.38), and first PIRA event (HR:LOMS = 2.12, vLOMS = 2.93). Conclusion: LOMS and vLOMS exhibited a more progressive disease onset and higher disability milestones compared with AOMS.",

keywords = "Aging, Immunosenescence, Multiple Sclerosis, Prognosis, Progression",

author = "Amira Souissi and Francesco Patti and Tim Spelman and Clara Chisari and Amina Gargouri and Nevin John and Kermode, \{Allan G.\} and Tomas Kalincik and Helmut Butzkueven and Sajedi, \{Seyed Aidin\} and Jeannette Lechner-Scott and Izanne Roos and Guy Laureys and Bruce Taylor and Raed Alroughani and Khoury, \{Samia J.\} and Richard Macdonell and Bianca Weinstock-Guttman and Havrdova, \{Eva Kubala\} and Davide Maimone and Stephen Reddel and Marzena Fabis-Pedrini and Barbara Willekens and Moghadasi, \{Abdorreza Naser\} and Patrice Lalive and Alessandra Lugaresi and Serkan Ozakbas and Claudio Solaro and Sim{\'o}n C{\'a}rdenas-Robledo and Vahid Shaygannejad and Masoud Etemadifar and Cavit Boz and Sara Eichau and Valentina Tomassini and Murat Terzi and Alexandre Prat and Mario Habek and Yolanda Blanco and Ayse Altintas and Oliver Gerlach and Recai Turkoglu and Katherine Buzzard and Olga Skibina and Aysun Soysal and \{van der Walt\}, Anneke and Stella Hughes and \{van Pesch\}, Vincent and Matteo Foschi and Andrea Surcinelli and Julie Prevost and Cristina Ramo-Tello and Chris McGuigan and Sa, \{Maria Jose\} and Jens Kuhle and Daniele Spitaleri and Bhim Singhal and Radek Ampapa and \{de Gans\}, Koen and Thor Petersen and Mihaela Simu and Emmanuelle Lapointe and Sanchez-Menoyo, \{Jose Luis\} and Orla Gray and Justin Garber and Eduardo Aguera-Morales and Katrin Gross-Paju and Tamara Castillo-Trivi{\~n}o and Abdullah Al-Asmi and Nikolaos Grigoriadis and Jihad Inshasi and Talal Al-Harbi and Hardy, \{Todd A.\} and Sudarshini Ramanathan and Melissa Cambron and Neil Shuey and sempere, \{Angel Perez\} and Tunde Csepany and Irene Trevi{\~n}o-Frenk and Csilla Rozsa and Marija Cauchi and Rana Karabudak and Saloua Mrabet and Riadh Gouider",

note = "Publisher Copyright: {\textcopyright} Springer-Verlag GmbH Germany, part of Springer Nature 2026.",

year = "2026",

month = feb,

doi = "10.1007/s00415-026-13632-4",

language = "English",

volume = "273",

journal = "Journal of Neurology",

issn = "0340-5354",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "2",

}

Souissi, A, Patti, F , Spelman, T, Chisari, C, Gargouri, A, John, N, Kermode, AG, Kalincik, T, Butzkueven, H, Sajedi, SA, Lechner-Scott, J, Roos, I, Laureys, G, Taylor, B, Alroughani, R, Khoury, SJ, Macdonell, R, Weinstock-Guttman, B , Havrdova, EK, Maimone, D, Reddel, S, Fabis-Pedrini, M, Willekens, B, Moghadasi, AN, Lalive, P, Lugaresi, A, Ozakbas, S, Solaro, C, Cárdenas-Robledo, S, Shaygannejad, V, Etemadifar, M, Boz, C , Eichau, S, Tomassini, V, Terzi, M, Prat, A, Habek, M, Blanco, Y, Altintas, A, Gerlach, O, Turkoglu, R, Buzzard, K, Skibina, O, Soysal, A, van der Walt, A, Hughes, S, van Pesch, V, Foschi, M, Surcinelli, A, Prevost, J, Ramo-Tello, C, McGuigan, C, Sa, MJ, Kuhle, J, Spitaleri, D, Singhal, B, Ampapa, R, de Gans, K, Petersen, T, Simu, M, Lapointe, E, Sanchez-Menoyo, JL, Gray, O, Garber, J, Aguera-Morales, E, Gross-Paju, K, Castillo-Triviño, T, Al-Asmi, A, Grigoriadis, N, Inshasi, J, Al-Harbi, T, Hardy, TA, Ramanathan, S, Cambron, M, Shuey, N, sempere, AP, Csepany, T, Treviño-Frenk, I, Rozsa, C, Cauchi, M, Karabudak, R , Mrabet, S & Gouider, R 2026, 'Effect of late-onset on multiple sclerosis phenotype and outcome: evidence from a multi-national registry', Journal of Neurology, vol. 273, no. 2, 114. https://doi.org/10.1007/s00415-026-13632-4

TY - JOUR

T1 - Effect of late-onset on multiple sclerosis phenotype and outcome

T2 - evidence from a multi-national registry

AU - Souissi, Amira

AU - Patti, Francesco

AU - Spelman, Tim

AU - Chisari, Clara

AU - Gargouri, Amina

AU - John, Nevin

AU - Kermode, Allan G.

AU - Kalincik, Tomas

AU - Butzkueven, Helmut

AU - Sajedi, Seyed Aidin

AU - Lechner-Scott, Jeannette

AU - Roos, Izanne

AU - Laureys, Guy

AU - Taylor, Bruce

AU - Alroughani, Raed

AU - Khoury, Samia J.

AU - Macdonell, Richard

AU - Weinstock-Guttman, Bianca

AU - Havrdova, Eva Kubala

AU - Maimone, Davide

AU - Reddel, Stephen

AU - Fabis-Pedrini, Marzena

AU - Willekens, Barbara

AU - Moghadasi, Abdorreza Naser

AU - Lalive, Patrice

AU - Lugaresi, Alessandra

AU - Ozakbas, Serkan

AU - Solaro, Claudio

AU - Cárdenas-Robledo, Simón

AU - Shaygannejad, Vahid

AU - Etemadifar, Masoud

AU - Boz, Cavit

AU - Eichau, Sara

AU - Tomassini, Valentina

AU - Terzi, Murat

AU - Prat, Alexandre

AU - Habek, Mario

AU - Blanco, Yolanda

AU - Altintas, Ayse

AU - Gerlach, Oliver

AU - Turkoglu, Recai

AU - Buzzard, Katherine

AU - Skibina, Olga

AU - Soysal, Aysun

AU - van der Walt, Anneke

AU - Hughes, Stella

AU - van Pesch, Vincent

AU - Foschi, Matteo

AU - Surcinelli, Andrea

AU - Prevost, Julie

AU - Ramo-Tello, Cristina

AU - McGuigan, Chris

AU - Sa, Maria Jose

AU - Kuhle, Jens

AU - Spitaleri, Daniele

AU - Singhal, Bhim

AU - Ampapa, Radek

AU - de Gans, Koen

AU - Petersen, Thor

AU - Simu, Mihaela

AU - Lapointe, Emmanuelle

AU - Sanchez-Menoyo, Jose Luis

AU - Gray, Orla

AU - Garber, Justin

AU - Aguera-Morales, Eduardo

AU - Gross-Paju, Katrin

AU - Castillo-Triviño, Tamara

AU - Al-Asmi, Abdullah

AU - Grigoriadis, Nikolaos

AU - Inshasi, Jihad

AU - Al-Harbi, Talal

AU - Hardy, Todd A.

AU - Ramanathan, Sudarshini

AU - Cambron, Melissa

AU - Shuey, Neil

AU - sempere, Angel Perez

AU - Csepany, Tunde

AU - Treviño-Frenk, Irene

AU - Rozsa, Csilla

AU - Cauchi, Marija

AU - Karabudak, Rana

AU - Mrabet, Saloua

AU - Gouider, Riadh

PY - 2026/2

Y1 - 2026/2

N2 - Background: Multiple Sclerosis (MS) severity is influenced by several factors. Understanding the impact of age at disease onset may help to better characterize clinical and disease features across age groups. This study aimed to characterize the clinical features and disability outcomes of late-onset MS (LOMS) and very late-onset MS (vLOMS), compared to adult-onset MS (AOMS). Methods: We conducted an observational study using data from the MSBase registry and categorized patients based on age at MS onset: AOMS (18–39 years), transition onset (40–49 years), LOMS (50–59 years), and vLOMS (≥ 60 years). Disease progression was assessed using the 24 week confirmed disability progression, EDSS4 and 6 milestones, conversion to secondary progressive MS(SPMS), and the first progression independent of relapse activity (PIRA) event. Cox proportional hazard regression models were used to determine unadjusted hazard ratios(HR), and propensity score inverse probability of treatment weighting(PS-IPTW) balanced covariate distributions. Results: Among 81,236 patients, 5.2% had LOMS and 1% had vLOMS. Primary progressive MS was more frequent in LOMS and vLOMS (21.7 and 24%, respectively). Patients with LOMS and vLOMS had a significantly increased risk of 24 week confirmed disability progression (HR:LOMS = 1.39, vLOMS = 1.80), EDSS 4 (HR:LOMS = 2.14, vLOMS = 2.95), EDSS 6 (HR:LOMS = 2.33, vLOMS = 6.33), SPMS (HR:LOMS = 1.62, vLOMS = 2.38), and first PIRA event (HR:LOMS = 2.12, vLOMS = 2.93). Conclusion: LOMS and vLOMS exhibited a more progressive disease onset and higher disability milestones compared with AOMS.

AB - Background: Multiple Sclerosis (MS) severity is influenced by several factors. Understanding the impact of age at disease onset may help to better characterize clinical and disease features across age groups. This study aimed to characterize the clinical features and disability outcomes of late-onset MS (LOMS) and very late-onset MS (vLOMS), compared to adult-onset MS (AOMS). Methods: We conducted an observational study using data from the MSBase registry and categorized patients based on age at MS onset: AOMS (18–39 years), transition onset (40–49 years), LOMS (50–59 years), and vLOMS (≥ 60 years). Disease progression was assessed using the 24 week confirmed disability progression, EDSS4 and 6 milestones, conversion to secondary progressive MS(SPMS), and the first progression independent of relapse activity (PIRA) event. Cox proportional hazard regression models were used to determine unadjusted hazard ratios(HR), and propensity score inverse probability of treatment weighting(PS-IPTW) balanced covariate distributions. Results: Among 81,236 patients, 5.2% had LOMS and 1% had vLOMS. Primary progressive MS was more frequent in LOMS and vLOMS (21.7 and 24%, respectively). Patients with LOMS and vLOMS had a significantly increased risk of 24 week confirmed disability progression (HR:LOMS = 1.39, vLOMS = 1.80), EDSS 4 (HR:LOMS = 2.14, vLOMS = 2.95), EDSS 6 (HR:LOMS = 2.33, vLOMS = 6.33), SPMS (HR:LOMS = 1.62, vLOMS = 2.38), and first PIRA event (HR:LOMS = 2.12, vLOMS = 2.93). Conclusion: LOMS and vLOMS exhibited a more progressive disease onset and higher disability milestones compared with AOMS.

KW - Aging

KW - Immunosenescence

KW - Multiple Sclerosis

KW - Prognosis

KW - Progression

UR - https://www.scopus.com/pages/publications/105029267510

U2 - 10.1007/s00415-026-13632-4

DO - 10.1007/s00415-026-13632-4

M3 - Article

C2 - 41634506

AN - SCOPUS:105029267510

SN - 0340-5354

VL - 273

JO - Journal of Neurology

JF - Journal of Neurology

IS - 2

M1 - 114

ER -

Effect of late-onset on multiple sclerosis phenotype and outcome: evidence from a multi-national registry

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