It is looking more and more like the wheels of the CCSVI theory are comming off the wagon. Unfortunately, I think no matter how much evidence is provided that refutes CCSVI, some people are not going to give up on this thoery.
But I found an interesting article regarding the different types of MS (RRMS and PPMS) and the reduction in thymic output and also a mention of immune system rebooting:
Direct analysis of thymic export suggests that thymic alterations occur early in life in RRMS and PPMS, either at the time of MS onset or before and that the thymic ‘defect’ persists throughout life, as indicated by low but constant levels of thymic export with increasing age. In other words, our findings suggest an early-onset of thymic involution in MS.
One study of immunoablation/autologous stem cell transplantation as a treatment of MS showed that the posttransplant MS patients ‘rebooted’ their immune system such that the thymus produced new Tcells having a diverse TCR repertoire . This finding is not inconsistent with our results: RRMS over age 40 continue to generates recent thymic emigrants, which contain the majority of naïve T cell TCR diversity , although this generation is at significantly lower levels than age matched
I think there may be an age component between RRMS and PPMS such that the thymus may be more deficient in creating healthy T-cells as one ages (or progresses in disease). It seems analogous to people that are struck with rheumatoid arthritis as they age.
This makes me think that maybe this has an influence of the effectiveness of HCST on PPMS patients.
I have to completely agree that perhaps its human nature that some would hold onto a sinking ship (CCSVI), even as it slowly goes down. In the end I think Douglas MacAurther's paraphrased-quote will be proven correct; "Old [unproven MS cures] never die, they just fade away." I suspect that the last person to hold onto a thoroughly non-existent or disproven therapy will eventually give up decades from now, if ever.
I'm sincerely sorry. . . . this posting is not, and should not be about that subject. . . . .
I sincerely appreciate you're sharing of the paper about the age-relation of the MS disease morphology (relapsing vs. progressive). This is quite interesting as I had not read this before, especially the section on "Increased naive T-cell proliferation and TCR signalling in MS." I agree with you in that the overall subject has some strong pursuation to make me think that there 'must' be some association of age with disease onset & evolution type.
Not to be argumentative but just to throw this out (because the whole area in general is so poorly understood). . . . as most people know, the first sigma of MS patient population age at time of onset & diagnosis is in the general age range of 20 years to 40 years of age. But for some strange (and unknown) reason there is a greater incidence of progressive patients initially diagnosed in the second sigma stratification of newly-diagnosed MS patients that are PPMS, which includes the people under 20 years of age. I really wonder (because I have no idea or speculative concept) as to why such a relatively disproportionate number of young people would have an onset of PPMS as compared to the overall population of all MS patients. (Its sad to see anyone getting such an unfortunately & insideously poorly-treatable case of MS).
BTW. . . . your thinking in the direction of why HSCT may be statistically less efficacious on progressive cases sounds very plausible to me.
Well, the march of research continues and hopefully more answers will be revealed someday. In the meantime, please keep the research papers you uncover coming. I enjoy learning from them. Thank you!