Classification of progressive MS


Typically the onset of disease progression in MS is ‘silent’ and differs from person to person. Not surprisingly, attempts at defining at least clinically has not been an exact science.

In a letter to Annals of Neurology Gil-Perotin et al. (Valencia) ask an important question, whether progression during the relapsing phase of MS is the same as in secondary progression (refer to MS-EPIC Team Silent Progression in Disease Activity-Free Relapsing Multiple Sclerosis. Ann Neurol. 2019; 00:1-14), or is there what is called bout onset progressive MS (BOPMS, includes single attack progressive MS and progressive MS after RRMS onset) where pre- and post-progression relapses accelerate time to progressive disease (refer to Mateo Paz Soldan Relapses and disability accumulation in progressive multiple sclerosis. Neurology 2015; 84(1): 81–88).

In biological terms the first is the pure progressive model defined by brain volume loss, whilst the latter is the focal inflammatory model (defined by T1/T2 lesion volumes). If you focus on this, by definition there is neuro-axonal loss (defined by neurofilament release) during both processes; so the two are not disparate in occurrence i.e. at least superficially; progressive MS pathophysiologically (disordered physiological processes associated with disease or injury) is the one and same disease process. However, the temporal process of neuro-axonal loss may differ, owing to differences in the underlying pathobiology (mechanisms of disease), and this is what we don’t know. Is the focal inflammatory model therefore, purely synaptic damage, whilst brain volume loss is the loss of large myelinated axons? And, where and how does regeneration and neuroplasticity fit into all of this?

If we re-think progressive MS along these lines, we will have a better understanding of the changes occurring at a clinical level.

If you disagree, then I’d like to hear your view point.

About the author

Neuro Doc Gnanapavan


  • It has been demonstrated that patients with RRMS and SPMS have
    antibodies directed towards oligodendrocyte precursor cell lines, but only the
    SPMS patients had antibodies directed towards a neuronal cell line.49 This
    supports the idea that the concept of epitope spreading is important in MS.

    What is secondary progressive disease?
    From a clinical point of view SPMS is a loss of function that occurs slowly
    and gradually over years or even decades. Relapses tend to be absent or
    mild. SPMS cannot be treated successfully,25 and therapy can at best achieve
    slowing of deterioration.26 From an imaging standpoint, SPMS is
    characterized by axonal damage and increasing atrophy of the brain and
    spinal cord.27 This axonal damage can be measured in the CSF of MS
    patients as increased levels of neurofilament.

    Joachim Burman

    uppsala universitet

    Ps:This “colective cyborg” is saying (once again ) that relapse are independen of long term disability
    Whats your take on that?


  • This has been answered before…DMT control focal inflammation but do little for the long term smoldering inflammation that leads to diffuse brain atrophy and progressive disease. Reason newly diagnosed forego DMT for hsct.

    Long‐term worsening is common in relapsing MS patients, is largely independent of relapse activity, and is associated with accelerated brain atrophy. We propose the term silent progression to describe the insidious disability that accrues in many patients who satisfy traditional criteria for relapsing–remitting MS.

    .The appearance of silent progression during the RRMS phase and its association with brain atrophy suggest that the same process that underlies SPMS likely begins far earlier than is generally recognized and support a unitary view of MS biology, with both focal and diffuse tissue destructive components, and with inflammation and neurodegeneration occurring throughout the disease spectrum.

    Moreover, as relapses and focal white matter lesions are brought under excellent control by disease‐modifying therapies for RRMS, the effectiveness of these agents against silent progression is likely to represent a key determinant of their relative value.



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