SPMS may be defined as the progressive accumulation of disability after an initial relapsing course, with or without occasional relapses and minor remissions1
Many patients will progress along the spectrum to SPMS2
Diagnosis
*From an analysis of 14,211 patients with MS. Amongst the 3169 patients who had at least 10 years of observation, 723 reached SPMS.3
- There are no consistently accepted diagnostic definitions for SPMS1
- It is usually diagnosed retrospectively in the clinic by a history of gradual worsening after an initial course of RRMS1
- No clinical imaging, immunological or pathological criteria can determine the transition point between RRMS and SPMS1
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.4
Some common signs may indicate progression to SPMS:
Classification
- The Lublin criteria classifies SPMS into active and non-active disease, which reflects whether inflammation and new lesion formation is ongoing1,8
- 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.
Understanding progression
SPMS may be a result of inflammation that accumulates from the start9–12
Peripherally driven inflammation9
- Occurs when circulating immune cells temporarily damage the brain
- Leads to relapses
Central inflammation and neurodegeneration
- 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 barrier9,10
- May lead to neurodegeneration, irreversibly damaging white and grey matter9
†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; DMT, disease-modifying therapy; MRI, magnetic resonance imaging; MS, multiple sclerosis; RRMS, relapsing-remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis.
References
- Lublin FD, Reingold SC, Cohen JA, et al. Neurology. 2014;83(3):278–286;
- Larochelle C et al. Trends Neurosci. 2016;39(5):325–339.
- Khurana V, Medin J; Poster presented at: the 7th Joint ECTRIM-ACTRIMS Meeting, 25–28 October 2017, Paris, France;
- Lorscheider J, Buzzard K, Jokubaitis V, et al. Brain. 2016;139:2395-2405;
- Amato MP et al. J Neurol. 2013;260:1452–1468;
- Gross HJ, Watson C. Neuropsychiatr Dis Treat. 2017;13:1349–1357;
- Achiron A et al. J Neurol Neurosurg Psychiatry. 2005;76:744–749;
- Baecher-Allan C, Kaskow BJ, Weiner HL. Neuron. 2018;97(4):742–768;
- Dendrou CA et al. Nat Rev Immunol. 2015;15:545–558;
- Kutzelnigg A et al. Brain. 2005;128(Pt 11):2705–2712;
- Ziemssen T et al. J Neurol. 2016;263:1053–1065;
- Lassman H et al. Nat Rev Neurol. 2012;8(11):647–656.
