Rewriting the prognosis of multiple sclerosis in Brazil: a 25-year perspective on evolving diagnostic criteria

• References

In this issue of Arquivos de Neuropsiquiatria, Menezes et al.[1] investigate whether the progressive adoption of more sensitive diagnostic criteria – from Poser through successive McDonald revisions – may be associated with less disability accumulation in patients with relapsing-remitting multiple sclerosis. To investigate this, the authors conducted a 25-year retrospective cohort study of 491 patients diagnosed between 1994 and 2019 in Sao Paulo, Brazil. This question is important because multiple sclerosis is the most common relapsing demyelinating disease of the central nervous system,[2] and its prognosis may have changed over the past 25 years.

A key finding of Menezes et al. was that patients diagnosed in Epoch 3 (2011–2019) - McDonald 2010 and 2017's criteria - had a 63% lower risk of reaching EDSS 6.0 than those in Epoch 1 (1994–2001) - Posner's criteria. One explanation is that the newer diagnostic criteria reduced the median time to first disease-modifying therapy from three to two years and dramatically increased the proportion of patients treated before their second relapse (from 2.7% to 24.4%). By enabling diagnosis at the very first demyelinating event – such as optic neuritis, for which multiple sclerosis is a leading cause[3]–these more sensitive criteria ensure patients start treatment sooner, further minimizing early disability accrual.

A second contributing factor may be the introduction of high-efficacy therapies. A meta-analysis of 3,467 participants showed that early use of high-efficacy agents was associated with a 30% reduction in the risk of EDSS worsening at five years compared with escalating strategy.[4] [5] Likewise, the Brazilian MS Cohort (BRANDO) found that regions with higher average EDSS scores had lower rates of high-efficacy prescriptions – such as natalizumab – underscoring the impact of access to high-efficacy treatments.[6] While more sensitive diagnostic criteria can raise concerns about misdiagnosis and overtreatment, real-world data from MS referral centers show that misdiagnosis with the 2017 McDonald criteria remains low.[7] Furthermore, these centers follow standardized care protocols – endorsed by the Brazilian Academy of Neurology and the Brazilian Committee for Treatment and Research in Multiple Sclerosis (BCTRIMS) – to proactively monitor and minimize treatment-related adverse events.[8] [9]

Another notable finding of Menezes et al.'s study was a 53% lower hazard of conversion to SPMS in the most recent epoch compared to the Poser era. This is especially significant given the limited efficacy of both on-label and off-label disease-modifying therapies in preventing disability accrual in progressive MS.[10]

Ultimately, the dramatic decline in disability progression and SPMS conversion over time likely reflects three game-changing advances in Brazil: the adoption of more sensitive diagnostic criteria enabling earlier recognition, the slashing of delays to treatment initiation, and the vastly expanded access to high-efficacy therapies. Together, these shifts have fundamentally reshaped the MS prognosis – demonstrating that when diagnosis is early and potent DMTs are within reach, the trajectory of this disease can indeed be rewritten.

Conflict of Interest

Guilherme Diogo Silva participated on scientific advisory board for AMGEN, and received speaking fees from Novartins, and travel grants from Biogen, EMS, and Roche. Dagoberto Callegaro has no conflict of interest to declare.

Authors' Contributions

Conceptualization: GDS, DC; project administration: DC; supervision: DC; writing - original draft: GDS; writing - review & editing: DC.

Data Availability Statement

No new data were generated or analyzed in this study.

• References

• 1 Menezes FTL, Alencar JMD, Lopes AB. et al. The impact of changing diagnostic criteria on disability in a Brazilian multiple sclerosis cohort. Arq. Neuro-Psiquiatr 2025; 83 (06) s00451809662
  Thieme ConnectPubMedSearch in Google Scholar
• 2 Silva GD, Apóstolos-Pereira SL, Callegaro D. Estimated prevalence of AQP4 positive neuromyelitis optica spectrum disorder and MOG antibody associated disease in São Paulo, Brazil. Mult Scler Relat Disord 2023; 70: 104488
  CrossrefPubMedSearch in Google Scholar
• 3 Terrim S, Silva GD, de Sá E Benevides Falcao FC. et al. Real-world application of the 2022 diagnostic criteria for first-ever episode of optic neuritis. J Neuroimmunol 2023; 381: 578140
  CrossrefPubMedSearch in Google Scholar
• 4 Pipek LZ, Mahler JV, Nascimento RFV. et al; BCTRIMS (Comitê Brasileiro de Pesquisa e Tratamento em Esclerose Múltipla). The myths that drive therapeutic inertia in multiple sclerosis: a cost-effectiveness analysis of high-efficacy drugs in Brazil. Arq. Neuro-Psiquiatr 2024; 82 (01) 1-2
  Thieme ConnectPubMedSearch in Google Scholar
• 5 Pipek LZ, Mahler JV, Nascimento RFV, Apóstolos-Pereira SL, Silva GD, Callegaro D. Cost, efficacy, and safety comparison between early intensive and escalating strategies for multiple sclerosis: A systematic review and meta-analysis. Mult Scler Relat Disord 2023; 71: 104581 https://www-sciencedirect-com.accesdistant.sorbonne-universite.fr/science/article/pii/S2211034823000858
  CrossrefPubMedSearch in Google Scholar
• 6 Damasceno A, Tauil CB, Sato HK. et al. Epidemiological study on multiple sclerosis in Brazil: demographic and clinical characteristics according to geographic distribution – a BRANDO study. Arquivos de Neuro-Psiquiatria 2024;
  Thieme ConnectSearch in Google Scholar
• 7 Tieppo EMS, Silva GD, Silva TFFD. et al. Misdiagnosis in multiple sclerosis in a Brazilian reference center: Clinical, radiological, laboratory profile and failures in the diagnostic process-Cohort study. Mult Scler 2023; 29 (14) 1755-1764
  CrossrefPubMedSearch in Google Scholar
• 8 Gomes ABAGR, Feo LB, Silva GD. et al. Reducing infection risk in multiple sclerosis and neuromyelitis optica spectrum disorders: a Brazilian reference center's approach. Arq. Neuro-Psiquiatr 2022; 80 (10) 1057-1066
  Thieme ConnectPubMedSearch in Google Scholar
• 9 Becker J, Ferreira LC, Damasceno A. et al. Recommendations by the Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and the Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) on vaccination in general and specifically against SARS-CoV-2 for patients with demyelinating diseases of the central nervous system. Arq. Neuro-Psiquiatr 2021; 79 (11) 1049-1061
  Thieme ConnectPubMedSearch in Google Scholar
• 10 Silva GD, Castrillo BB, Apóstolos-Pereira SL, Callegaro D. Is there a role for off-label high-efficacy disease-modifying drugs in progressive multiple sclerosis? A network meta-analysis. Acta Neurol Scand 2022; 146 (05) 403-409
  CrossrefPubMedSearch in Google Scholar

Address for correspondence

Publication History

Received: 02 June 2025

Accepted: 10 June 2025

Article published online:
02 July 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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• References

• 1 Menezes FTL, Alencar JMD, Lopes AB. et al. The impact of changing diagnostic criteria on disability in a Brazilian multiple sclerosis cohort. Arq. Neuro-Psiquiatr 2025; 83 (06) s00451809662
  Thieme ConnectPubMedSearch in Google Scholar
• 2 Silva GD, Apóstolos-Pereira SL, Callegaro D. Estimated prevalence of AQP4 positive neuromyelitis optica spectrum disorder and MOG antibody associated disease in São Paulo, Brazil. Mult Scler Relat Disord 2023; 70: 104488
  CrossrefPubMedSearch in Google Scholar
• 3 Terrim S, Silva GD, de Sá E Benevides Falcao FC. et al. Real-world application of the 2022 diagnostic criteria for first-ever episode of optic neuritis. J Neuroimmunol 2023; 381: 578140
  CrossrefPubMedSearch in Google Scholar
• 4 Pipek LZ, Mahler JV, Nascimento RFV. et al; BCTRIMS (Comitê Brasileiro de Pesquisa e Tratamento em Esclerose Múltipla). The myths that drive therapeutic inertia in multiple sclerosis: a cost-effectiveness analysis of high-efficacy drugs in Brazil. Arq. Neuro-Psiquiatr 2024; 82 (01) 1-2
  Thieme ConnectPubMedSearch in Google Scholar
• 5 Pipek LZ, Mahler JV, Nascimento RFV, Apóstolos-Pereira SL, Silva GD, Callegaro D. Cost, efficacy, and safety comparison between early intensive and escalating strategies for multiple sclerosis: A systematic review and meta-analysis. Mult Scler Relat Disord 2023; 71: 104581 https://www-sciencedirect-com.accesdistant.sorbonne-universite.fr/science/article/pii/S2211034823000858
  CrossrefPubMedSearch in Google Scholar
• 6 Damasceno A, Tauil CB, Sato HK. et al. Epidemiological study on multiple sclerosis in Brazil: demographic and clinical characteristics according to geographic distribution – a BRANDO study. Arquivos de Neuro-Psiquiatria 2024;
  Thieme ConnectSearch in Google Scholar
• 7 Tieppo EMS, Silva GD, Silva TFFD. et al. Misdiagnosis in multiple sclerosis in a Brazilian reference center: Clinical, radiological, laboratory profile and failures in the diagnostic process-Cohort study. Mult Scler 2023; 29 (14) 1755-1764
  CrossrefPubMedSearch in Google Scholar
• 8 Gomes ABAGR, Feo LB, Silva GD. et al. Reducing infection risk in multiple sclerosis and neuromyelitis optica spectrum disorders: a Brazilian reference center's approach. Arq. Neuro-Psiquiatr 2022; 80 (10) 1057-1066
  Thieme ConnectPubMedSearch in Google Scholar
• 9 Becker J, Ferreira LC, Damasceno A. et al. Recommendations by the Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and the Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) on vaccination in general and specifically against SARS-CoV-2 for patients with demyelinating diseases of the central nervous system. Arq. Neuro-Psiquiatr 2021; 79 (11) 1049-1061
  Thieme ConnectPubMedSearch in Google Scholar
• 10 Silva GD, Castrillo BB, Apóstolos-Pereira SL, Callegaro D. Is there a role for off-label high-efficacy disease-modifying drugs in progressive multiple sclerosis? A network meta-analysis. Acta Neurol Scand 2022; 146 (05) 403-409
  CrossrefPubMedSearch in Google Scholar