My CtrlAltDel - Status

[CVfactor]

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:

<shortened url>

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 [36]. 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 [37], although this generation is at significantly lower levels than age matched
controls [23].

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.

[georgegoss]

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:

<shortened url>

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 [36]. 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 [37], although this generation is at significantly lower levels than age matched
controls [23].

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!

[czapski]

This the first time I see information about early onset of PPMS - most data show that average age of first symptoms is 10 years above that in RRMS.

[shucks]

So what do you guys think of hsct for those NEWLY diagnosed with ppms? I would think that at least in the initial onset, a treatment like this still is much more effective than any other treatment, even if it only helps half of the folks who get it.

[HUD45]

I am not sure of exactly what you mean newly diagnosed Shucks but I was diagnosed withPPMS in 2007 and I am currently seeking HSTC treatment in Israel. I have met with Dr. Slavin and he recommends the HSTC. I am all in here and due to start treatment later this week.

The data is less clear than RRMS cases I admit but like almost all other ms research there is far less of it to study. I think the chances of successull outcome are greater the earlier treated but we already know that.

The data I have seen shows in ambulatory cases of PPMS treated with HSTC, treatment is effective in 60-75% of cases. More of a gamble on effectivness but I am gonna go for it.

[georgegoss]

HUD. . . Kudos to you for your great resolve in getting HSCT in Israel. Although not a gauranteed outcome, clearly the odds are very much in your favor. Even advanced non-ambulatory PPMS patients have a 66% chance of stopping the disease. So your ambulatory status should indicate an even better probability and bolsters the odds for possible symptomatic improvement. And since you're in the holy land, if prayer will improve the odds or make it better there are people here that will be doing so for you, including me. I'm looking forward to know the result months down the road following your treatment. If I were a betting man in Vegas, I'd be putting my chips on the likelyhood your underlying MS disease activity will be completely stopped. Sincerest best wishes.

This the first time I see information about early onset of PPMS - most data show that average age of first symptoms is 10 years above that in RRMS.

Czapski, you are completely correct that the "average" age of PPMS onset is nearly ten years following the average for RRMS cases. But you know the old saying popularized by Mark Twain. . . "Lies, damn lies and statistics." The mean or median average does not explain the bimodal distribution of the onset curve in the second sigma stratum, skewing the average age up. So although it is far more common for older people to get PPMS, it also occurs in a younger population as well. I think this graph is a good example to show this relative age-related phenomenon (which sort of indicates that if one were to be afflicted with MS, the odds of a benign course are better if the age of onset is in the first sigma range as compared to first developing MS when older or younger which does not bode as well for a mild course of the disease). . .

http://1.bp.blogspot.com/-wctt9TyWZw4/T ... %2Bage.jpg

And just for interest I also found a 2006 paper that describes some of the overall morphological evololution of MS subtypes including a lot of data on progressive. . .

The natural history of multiple sclerosis: a geographically based study 9: Observations on the progressive phase of the disease

http://brain.oxfordjournals.org/content/129/3/584.long

[HUD45]

Statistics indeed..... In my opinion, one of the simplest and most important reasons that PPMS is not "oficially diagnosed" until a later age is the gradual onset initially of symptoms of disease and likleyhood that MRI lesions are very difficult to see if not present at all. When gathering such data for studies the diagnosis must be confirmed by these findings, therfore delaying the diagnosis for potentially many years.

Consequently, when seeking HSCT treatment these lack of so called concrete diagnosis criteria can be a detriment. Hopefully in the future better diagnostic tools will be available and also more access to the various HSCT treatments as well.

[georgegoss]

Statistics indeed..... In my opinion, one of the simplest and most important reasons that PPMS is not "oficially diagnosed" until a later age is the gradual onset initially of symptoms of disease and likleyhood that MRI lesions are very difficult to see if not present at all. When gathering such data for studies the diagnosis must be confirmed by these findings, therfore delaying the diagnosis for potentially many years.

Consequently, when seeking HSCT treatment these lack of so called concrete diagnosis criteria can be a detriment. Hopefully in the future better diagnostic tools will be available and also more access to the various HSCT treatments as well.

Makes complete plausible sense to me, Hud. Especially considering that there are some MSers that take years to be conclusively diagnosed. No question that because PPMS cases lack specifically-identifiable episodes, tracking of EDSS deterioration is the only (medically) practical way to eventually arrive at a diagnosis.

If HSCT were to be considered as a viable treatment for PPMS cases (it is!) such as yourself, it would be nice to evolve the diagnostic criteria to open up the option of HSCT for progressive cases earlier where the treatment is better-likely to have a more favorable outcome. In the words of Dr. Mark Freedman (Ottowa General Hospital) doing HSCT for MS, "time is brain," meaning that the longer you wait, the more you lose. I'm very happy to know that you don't have to wait any longer.

[Daisy3]

It's a shame the treatment is not available in the UK. They won't even take people on for stem cell trials if their ppms. Last I heard, going private somewhere else in the world cost you the earth and there are no guarantees.

[georgegoss]

It's a shame the treatment is not available in the UK. They won't even take people on for stem cell trials if their ppms. Last I heard, going private somewhere else in the world cost you the earth and there are no guarantees.

Just like everything in nature, there are no certainties. Just probabilities, Something outside the pervue of the doctors.

However Daisy, don't feel too badly about HSCT not being available to progessive patients in the UK. As of today the same applies here in the US (for both primary AND secondary) where such patients are completely unable to receive the treatment here. Such patients would need to seek HSCT treatment overseas. A list of 'legitimate' treatment locations I have been compiling:

http://themscure.blogspot.com/2011/06/g ... -have.html

You're correct about the high cost. (Generally the biggest hurdle to getting the treatment.) However, within a few weeks I'll be able to add to the list another facility that is just now treating a PPMS patient for a relatively low cost (perhaps in the $30-$40K range) in India. I hope to have that info up in another three weeks, or so.

[Daisy3]

If you do George, that would be very welcome.

It can't hurt to check out all options. I don't want us to spend so much money and then be disappointed but life can be like that sometimes..

[bspotts1]

HUD,
i'm very excited about you going to israel for HSCT....my wife was dx ppms in 2009 and we are contemplating the same...reading everything we can from george and others. couple of quick questions:
if i could ask your age...my wife is 62 and was of course excluded from the MIST and the HALT-MS trial but george thinks she would be accepted at heidelberg. also, what will be your chemo protocol with slavin (if any)? i wasn't aware he included chemo in his treatments. in fact, i wasn't aware he did hemotopoietic stem cell transplants, i thought he just did mesenchymal stem cell infusions. also, will the entire procedure be completed in israel? i thought i read that he harvested the stem cells in israel but had to do the infusion somewhere else...maybe that was early-on and he has changed that necessity.

thanks for your information and GOOD LUCK to you!!!

brad in sarasota

[georgegoss]

HUD,
i'm very excited about you going to israel for HSCT....my wife was dx ppms in 2009 and we are contemplating the same...reading everything we can from george and others. couple of quick questions:
if i could ask your age...my wife is 62 and was of course excluded from the MIST and the HALT-MS trial but george thinks she would be accepted at heidelberg. also, what will be your chemo protocol with slavin (if any)? i wasn't aware he included chemo in his treatments. in fact, i wasn't aware he did hemotopoietic stem cell transplants, i thought he just did mesenchymal stem cell infusions. also, will the entire procedure be completed in israel? i thought i read that he harvested the stem cells in israel but had to do the infusion somewhere else...maybe that was early-on and he has changed that necessity.

thanks for your information and GOOD LUCK to you!!!

brad in sarasota

Hi Brad,

I don't want to answer for Hud, I'm sure he can add his own relevant feedback. I just wanted to add a few comments in addition to what Hud is likely to answer. . .

Slavin does do mesenchymal (MSC) infusion therapy (that includes the infusion arm of treatment in Switzerland so it will be required to travel to both Israel and Switzerland over a period of three months). For me I personally would not do the MSC protocol as "first-attempt" treatment because it is very unlikely to stop the underlying progression of MS disease activity. (Although, I might be serious to try it following HSCT since it might have a positive effect to repair already-existing nerve damage following stopping of the disease with HSCT.) The HSCT protocol that includes chemotherapy does have the ability to stop the underlying disease, and Slavin offers such treatment and will do so for patients of any age. Age is not a restriction for his acceptance.

Be sure to read the section on the following page that summarizes Slavin's various CTCI facility protocols in TelAviv where Hud is right now, which may answer some of your questions:

http://themscure.blogspot.com/2011/06/g ... -have.html

I'm sure Hud will have some valuable info of his own to share.

This is definitely an available option for progressive patients that I would consider for myself if in the same situation.

- George

[Asher]

Day +65 post transplantation

HSCT is a hefty and pricy procedure and the urge to justify such a choice is therefore almost inevitable. This is the breeding ground for Placebo. Being aware of this, I try hard to remain as objective and realistic as possible.

In the past 2 weeks I started feeling lousy. Like the MS symptomes are creeping back. I went back to George's blog in which he describes the post transplantation recovery journey in great detail: http://themscure.blogspot.com/2010_02_01_archive.html

Here is a quote from George's blog:

Temporary worsening of existing (RRMS) symptoms - The clinical trials have shown a high incidence of transitory worsining of some existing symtoms in MS treated patients directly following the transplantation procedure (likely due to the chemo stress on the body). However, this effect seemed to resolve in a matter of a few months (at most) with no permanently added disability. As for me, for several months following the treatment (starting at about the end of my hospital stay) I had some leg spasticity. Spasticity is common in many people that have MS, but I previously never had a problem with spasticity. My neurologist prescribed some Baclofen for me (of which I'm not completely sure if it helped, or not). But anyway, the spasticity has resoved about four months following hospital discharge. Clearly a temporary condition. I stopped taking the Baclofen upon symptomatic resolution. I'm sure this effect of type and duration will differ for different people.

This is (and the rest of the stuff George describes too) an exact description of what I am experiencing now. To me this indicates that the recovery process, and the symptoms and side effects that go with it, follow a pretty predictable course. No need to worry thus, just a call for patients.

Besides this temporary worsening of excising symptoms (mainly leg spasticity and fatigue), I am gradually recovering lost muscle mass and my hair showing first signs of recovery, reminding me of the guy I once was I am still very optimistic about the future and am looking foreword to the months ahead.

[CVfactor]

Hi Asher,

I believe you are well on your way to stopping the progression of MS and I think both you and George have a lot of courage in undertaking this procedure.

But I was wondering why other people who have had HSCT do not post here on this website? It seems there should have been many patients with MS who underwent this during the many trials.

It would be good to here their experiences also. It may be that they were turned off because of the many fanatics who are on here, but I think this part of the forum is a safe haven for people who actually believe in truth.