SPMS definition and pathophysiology.

SPMS is defined as the progressive accumulation of disability after an initial relapsing course, with or without occasional relapses and minor remissions1

Active disease may be defined clinically or on imaging1:

  • Clinical: relapses, acute or subacute episodes of new or increasing neurologic dysfunction followed by full or partial recovery, in the absence of fever or infection.
  • Imaging (MRI): occurrence of contrast-enhancing T1 hyperintense or new or unequivocally enlarging T2 hyperintense lesions.


SPMS may be a result of inflammation that accumulates from the start2–5

 Icon for peripherally-driven inflammation

Peripherally driven inflammation2

  • Occurs when circulating immune cells temporarily damage the brain2
  • Leads to relapses2
Icon for central inflammation and neurodegeneration

Central inflammation and neurodegeneration2,3

  • The activation of CNS-resident immune cells is independent of peripheral inflammation and can worsen when immune cells become trapped after crossing the blood-brain barrier2,3
  • May lead to neurodegeneration, irreversibly damaging white and grey matter2

Chart showing how inflammatory activity changes during the progression of MS from relapsing-remitting MS to secondary progressive MS with active disease and to secondary progressive MS.

*SPMS with active disease is defined as the presence of relapses and/or the occurrence of T1 or new or enlarging T2 lesions.1

CNS, central nervous system; MS, multiple sclerosis; RRMS, relapsing-remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis.


In most clinical contexts, signs of transition are often unclear and SPMS is diagnosed retrospectively6,7

When transitioning to SPMS, patients may notice a range of changes in disability.

Patients with lower relapse frequency but increasing disability could be transitioning to SPMS.

Icons showing some common signs that may indicate progession to secondary-progressive MS. Cognitive changes include impaired concentration, trouble forming words, and slower information processing. Physical changes include increasing fatigue, accumulating bowel and bladder dysfunction, and difficulty walking or balancing.

SPMS, secondary progressive multiple sclerosis.

Many patients will progress along the MS spectrum to SPMS10

Infographic showing the proportion of relapsing-remiting MS patients who progress to secondary-progressive MS. About 1 in 4 progress within 10 years, 1 in 2 progress within 20 years, and over 3 in 4 progress within 20 years.

From an analysis of 14,211 patients with MS. Amongst the 3169 patients who had at least 10 years of observation, 723 reached SPMS.11

DMTs, disease-modifying therapies; RRMS, relapsing-remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis.


CNS, central nervous system; MRI, magnetic resonance imaging; MS, multiple sclerosis; RRMS, relapsing-remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis.


  1. Lublin FD et al. Neurology. 2014;83:278–286.
  2. Dendrou CA et al. Nat Rev Immunol. 2015;15:545–558.
  3. Kutzelnigg A et al. Brain. 2005;128(Pt 11):2705–2712.
  4. Ziemssen T et al. J Neurol. 2016;263:1053–1065.
  5. Lassman H et al. Nat Rev Neurol. 2012;8(11):647–656.
  6. Sumowski JF et al. Neurology. 2018;90:278–288.
  7. Amato MP et al. J Neurol. 2013;260:1452–1468.
  8. Gross HJ, Watson C. Neuropsychiatr Dis Treat. 2017;13:1349–1357.
  9. Achiron A et al. J Neurol Neurosurg Psychiatry. 2005;76:744–749.
  10. Larochelle C et al. Trends Neurosci. 2016;39(5):325–339.
  11. Khurana V, Medin J. Poster presented at: the 7th Joint ECTRIM-ACTRIMS Meeting, 25–28 October 2017, Paris, France.
  12. Bergamaschi R et al. Eur J Neurol. 2015. 22(6):981–989.
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