Revesz et al. A comparison of the pathology of primary and secondary progressive multiple sclerosis. Brain. 1994 Aug;117 ( Pt 4):759-65.
The course and disease pattern of PPMS differ from those of the more common SPMS form.
The observation by MRI that the frequency of enhancement with gadolinium (intravenous contrast material), a marker for blood-brain barrier leakage, is significantly less in the PPMS form, has led to the hypothesis that inflammation is less intense in this group.
To test this, the investigators studied postmortem material from 9 cases judged from a retrospective analysis of case notes to show clear clinical evidence of either PPMS or SPMS disease. 578 lesions were analysed. There was significantly more inflammation in SPMS (as judged by the frequency of perivascular (around blood vessels) cuffing and cellularity (number of cells) in the brain tissue) than in PPMS disease. These observations have implications for therapeutic strategies in progressive MS.
“I am aware that this is an old study. However, it demonstrates that there may be a quantitative difference in the amount of inflammation between PPMS and SPMS, but not a qualitative difference. This means that under the microscope both types are similar. In addition, to this there is a large amount of other data suggesting that PPMS is not different to SPMS.”
“Did you know that it not uncommon in siblings pairs with MS for one to have relapse-onset disease and the other to have PPMS? The figure from the UK sibling study is in fact 23% (please see article and table below). This indicates to me that relapse onset and PPMS are likely to be the same disease.”
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| (33.7+27) / (84+68.3+33.7+39.3+27+9.7) x 100 = 23% |
You posted this at 5:20am! What gives?Interesting post, though. You have always argued that PPMS and PPMS are, in your opinion, the same disease.PPMS seems more severe to me. You can't control PPMS with the current crop of drugs. It is beyond treatment and causes more disability than other forms of MS. It's a hardcore form of MS.I'd opt for any other form of MS than PPMS. It's the worst kind of MS.
I agree. PPMS is the worst kind of MS, not to mention the most hopeless. The neurologist basically tells you his/ her team don't know what exactly is happening to you but his/ her team will monitor the situation. That's not good enough.Shame on any neurologist who claims that they feel they're doing enough to serve the needs of PPMS'ers. If PPMS'ers felt valued by their neurological team then there wouldn't be such a recognised acknowledgement that PPMS'ers feel undervalued compared to those with RRMS.In truth, pretty much everyone with MS becomes progressive. It's a fact, and until scientists actually stop focussing on the ostensible ease of treating RRMS over PPMS, there will be no real progress in the field of effectively treating multiple sclerosis.
Re: "PPMS seems more severe to me."There is good data that once MS'ers enter the SPMS stage of the disease they progress at the same rate as MS'ers with PPMS. The difference is that PPMS starts 10 years later than relapse-onset disease, i.e. 40yrs vs. 30yrs. The way I interpret this is that PPMS is the same as relapse-onset disease the only difference is that the relapsing phase of the disease is not seen. Please see my previous post on this topic: http://multiple-sclerosis-research.blogspot.com/2011/08/disease-course-of-ppms.html
Re: "In truth, pretty much everyone with MS becomes progressive. It's a fact, and until scientists actually stop focussing on the ostensible ease of treating RRMS over PPMS, there will be no real progress in the field of effectively treating multiple sclerosis."No not everyone develops progressive MS, but the majority do. You have to remember that this data was collected in the pre-DMT era and we remain hopeful that early treatment, in particular early aggressive therapy, will change this. Unfortunately, we don't have long enough follow-up to be confident about this at this point in time.
Re: "If PPMS'ers felt valued by their neurological team …"We try; it is not that we undervalue PPMS'ers it is the stark reality that we don't have any therapies that work. This may change; as you are aware there are two clinical trials running at present in PPMS, with more to follow. I remain hopeful that one of these trials, or possibly all of them, will turn out to be positive. What we can't do, however, is offer you DMTs that don't work, or have not been shown to work.
Don' you think that people with PPMS simply aren't aware of having had relapses in the past, or can't remember them? There may be many peopl who've had a bit of numbness or pins and needles and it has gone after a few weeks – easily forgotten inthe scheme of things. I grant you that a more serious relapse is not something you'd forget in a hurry.
Re: "Don' you think that people with PPMS simply aren't aware of having had relapses in the past, or can't remember them?"Yes, this does happen. However, in some cases you push and ask for a history of previous events and you can't find them. You must forget that somewhere between 5 and 20% of PPMS'ers go into have relapses and they get classified as having progressive-relapsing MS. So the clinical course can change.
Prof G,Thanks for sharing your thoughts on different issues relating to this disease. Your comments have really made me wonder what is known about MS:- it was considered auto-immune, now possibly not;- it was considered to be primarily inflammatory, now possibly primarily neuro-degenerative;- evidence indicated EBV was involved, now possibly EBV + another virus;- RRMS and PPMS were considered separate disease, now probably the same disease.Given the uncertainty set out above, are we looking at another 20 years to come up with some actual answers? As someone with MS, amsd I right to feel a bit down? I was dx 8 years ago and, apart from Tysabri, new treatments have been thin on the ground. I really was hoping that within a decade of being dx there would be a sniff of a treatment to encourage repair (doh!).Will ectrims/actrims next week offer me any hope?
Re: "… it was considered auto-immune, now possibly not"Similar to the Bradford-Hill Criteria for causation there are a set of criteria that you need to fulfil to make MS an autoimmune disease. Unfortunately, MS does not tick enough of the boxes to convince me. The problem is that most of the experimental support for MS being an autoimmune disease comes from EAE. Unfortunately, EAE is not MS. This is why I am have an open mind to what is causing MS and I have a strong suspicion that it may be due to a virus (EBV) or several viruses (dual viral hypothesis); more on this later.
Re: "… it was considered to be primarily inflammatory, now possibly primarily neuro-degenerative."This has been discussed in detail on this blog and hopefully this argument will be settled in the next few years with the open-label observation of the cohorts of MS'ers treated with aggressive therapies early on in the disease course. Watch this space!
Re: "RRMS and PPMS were considered separate disease, now probably the same disease."At a personal level, I have never considered them different diseases. I reviewed the field in the mid 90's and was convinced then; nothing has subsequently been published to change my mind. I will blog on this later to explain my thinking in more detail.
Prof G,I have read all the posts on the different issues. The point I was making was that we are still very much in no-mans land. You've posted articles on 19th century MS researchers and I'm wondering what they would think of where we are now.If the target isn't myelin, this is not good news for all the myelin repair projects underway e.g. Anti-lingo anti-body.If I was a betting man, I'd put my money on the worse case scenario – MS is primarily a neuro-degenerative disease. I'd focus all my efforts on neuro-protective strategies + strategies to rid the body of EBV. Once this is achieved I'd focus on strategies to promote axonal / neuronal repair. I suspect that a poll of patients would support this focus.