Do we need a new hypothesis to tackle progressive MS? #MSBlog #MSResearch
The asynchronous progressive MS hypothesis; what is it? #MSBlog #MSResearch
“The MRI study below demonstrates that lesions on MRI in MSers with relapse-onset or primary progressive MS are identical. They interpret that these clinical sub-types as being the same disease. This supports all the other evidence that there is are no biological differences between relapse-onset MS (RRMS & SPMS) and PPMS. The pathology and genetics of the two subtypes are the same. Similarly, when MS occurs in families and the first sibling develops RRMS the second and third siblings may develop either RRMS, or PPMS, in proportion to their incidence in the population. PPMSers are therefore unlucky in that they don’t present with a relapse that allows them to be diagnosed earlier when their chances of responding to a treatment and benefiting are greater. But I remain hopeful that DMTs will help PPMSers for two reasons; firstly, I think there is a therapeutic lag and we simply need to do longer PPMS trials (please see previous post on this topic) and secondly, I think PPMS affects different functional systems asynchronously; i.e. the asynchronous progressive MS hypothesis.”
“What is the asynchronous progressive hypothesis? I have made the argument in the past that the neurological systems to be affected first by progressive MS are those that have the most wiring and hence more likely to be hit by multiple lesions; this is why the motor system to the legs, bladder and the cerebellar or balance system are typically affected first when progressive disease starts. The other systems (vision, motor system to the upper arms, sensory system, cognition, etc.) tend to be affected later by ‘overt’ progressive disease. I say overt because there is MRI evidence that the progressive component of MS is present from the start of the disease. The only reason we don’t see it clinically is because the nervous system can compensate. However, once the compensatory systems fail progressive MS ensues. This does mean that we may have different windows of opportunity to impact on these different systems. In other words there are multiple windows of therapeutic opportunity to act and we should therefor shift our focus in PPMSers on trying to delay the onset of progression in systems that are still not clinically affected. To do this we need to shift our focus away from the EDSS and use multi-dimensional outcome measures that focus on the importance of the other functional systems. This is what is currently happening as part of the Progressive MS Alliance (PMSA).”
Epub: Kuchling et al. Identical lesion morphology in primary progressive and relapsing-remitting MS -an ultrahigh field MRI study. Mult Scler. 2014 Apr.
Background: Potential differences between primary progressive (PP) and relapsing-remitting (RR) multiple sclerosis (MS) have been controversially discussed.
Objectives and methods: In this study, we compared lesion morphology and distribution in MSers with PPMS and RRMS (nine in each group) using 7 T MRI.
Results: We found that gray and white matter lesions in PPMS and RRMS MSers did not differ in their respective morphological characteristics (e.g. perivascular p = 0.863, hypointense rim p = 0.796, cortical lesion count p = 0.436).
Conclusions: Although limited by a small sample size, our study results suggest that PPMS and RRMS, despite differences in disease course and clinical characteristics, exhibit identical lesion morphology under ultrahigh field MRI.