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Updated: Jun 10, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
The natural history of secondary progressive multiple sclerosis
Marcus Koch1, Elaine Kingwell, Peter Rieckmann
1Department of Neurology, University Medical Centre Groningen, GZ Groningen, The Netherlands. m.w.koch@neuro.umcg.nl
Background:
The onset of secondary progression is a pivotal event in the course of relapsing-remitting (RR) multiple sclerosis (MS). Patients with secondary progressive MS (SPMS) experience continuous worsening of symptoms independent of the occurrence of relapses. Possible risk factors associated with the onset of SPMS remain under investigated in natural history studies of MS disease course.
Methods:
We used Kaplan-Meier survival analyses and Cox regression models to investigate the influence of gender, onset age and onset symptoms on time to and age at SPMS in British Columbia (BC) MS patients with a RR disease onset who were not exposed to immunomodulatory drugs.
Results:
Of 5778 patients in the BCMS database with definite MS, 5207 (90%) had an RR onset. Median time to SPMS was 21.4 years (95% CI 20.6 to 22.2), reached at a median age of 53.7 years (95% CI 53.1 to 54.3). Male gender and motor onset symptoms were associated with a shorter time to and a younger age at SPMS. A younger age at disease onset was associated with a longer time to SPMS but also with a younger age at secondary progression. Other onset symptoms were not associated with time to, or age at, SPMS.
Conclusions:
We identified three factors influencing the onset of SPMS in untreated patients with RRMS: motor onset symptoms and male gender were associated with both a shorter time to and a younger age at SPMS. A younger age at disease onset should not be viewed as indicating a better prognosis.
Insights
Male gender and motor symptoms shorten the time to secondary progressive multiple sclerosis (SPMS). Younger age at disease onset leads to earlier SPMS, indicating a poorer prognosis for relapsing-remitting multiple sclerosis (RRMS) patients.
Area of Science:
- Neurology
- Clinical Research
- Epidemiology
Background:
- Secondary progressive multiple sclerosis (SPMS) is a critical stage in the relapsing-remitting multiple sclerosis (RRMS) disease course.
- Patients with SPMS experience continuous symptom worsening, irrespective of relapses.
- Risk factors for SPMS onset require further investigation in natural history studies.
Purpose of the Study:
- To investigate factors influencing the time to and age at SPMS onset.
- To analyze the impact of gender, age at onset, and initial symptoms on SPMS development.
- To examine these factors in a cohort of untreated RRMS patients.
Main Methods:
- Kaplan-Meier survival analyses were employed.
- Cox regression models were utilized.
- Data from the British Columbia (BC) MS database of untreated RRMS patients were analyzed.
Main Results:
- Median time to SPMS was 21.4 years, occurring at a median age of 53.7 years.
- Male gender and motor onset symptoms were linked to a shorter time to and younger age at SPMS.
- Younger age at disease onset correlated with a longer time to SPMS but an earlier age at secondary progression.
Conclusions:
- Motor onset symptoms and male gender accelerate the time to and reduce the age of SPMS onset.
- A younger age at disease onset does not signify a better prognosis in MS.
- These findings identify key predictors for SPMS development in untreated RRMS patients.
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