Table 1: Clinical markers of MS disability progression reported in longitudinal natural history studies.


Male genderShorter time to walking assistance need (i.e., EDSS score 6) and/or transition to the SP phase[2429]
Older ageOlder age at onset associated with shorter time to EDSS 6 and/or to SP phase [2428, 30, 31]
Progressive coursePP MS patients reach relevant disability milestones in a significantly shorter time compared to RR MS cases[2427, 30]
Multifocal presentationSymptoms/signs of multiple CNS sites involvement at onset are associated with shorter time to EDSS 6 and/or SP phase compared to monofocal presentation[27, 30]
Motor symptomsMS patients with pyramidal and/or cerebellar involvement at onset reach EDSS 6 more rapidly compared to patients with optic nerve or sensory symptoms (no influence on time to SP MS) [24, 25]
Incomplete recoveryShorter time to EDSS 6 and/or transition to the SP phase[25, 27, 30]
Relapse rateShorter time to second attack and higher relapse number in first 2–5 years after onset are associated with more rapid progression to EDSS 6 and transition to the SP phase[24, 25, 27, 29, 32]

EDSS: expanded disability status scale; PP: primary progressive; RR: relapsing remitting; SP: secondary progressive.