This Is MS Multiple Sclerosis Community: Knowledge & Support

Even progressive forms of MS show periods of "innate improvement" and/or stability naturally, without any treatment at all. Perhaps CCSVI treatment hasn't caused some reported improvements in those with RRMS or even progressive forms of MS, it could be a natural cycle of improvement or stabilization that has occurred. Even in those originally thought to not HAVE any improvements or stabilization due to the type of MS they had, a progressive form. This just emphasizes how critical blinded trials are to be able to distinguish if CCSVI treatment really does have any impact on MS beyond natural course of the disease and/or placebo effect.

http://www.ncbi.nlm.nih.gov/pubmed/22736751

Mult Scler. 2012 Jun 26. [Epub ahead of print]

Natural, innate improvements in multiple sclerosis disability.

Tremlett H, Zhu F, Petkau J, Oger J, Zhao Y; the BC MS Clinic Neurologists.

1Faculty of Medicine, Division of Neurology, University of British Columbia, Canada.

Abstract
Background:Improvements in multiple sclerosis (MS) disability have recently been reported in immunomodulatory drug (IMD) clinical trials and observational studies. However, improvements have rarely been examined in natural history or IMD naive patients. We investigated annual and biennial improvements in Expanded Disability Status Scale (EDSS) scores in British Columbia, Canada.

Methods:The British Columbian MS database was accessed for definite MS patients (1980-2009). Consecutive IMD-free EDSS scores one and two years apart (± 3 months) were examined; improvements (≥0.5,≥1,≥2 EDSS points) and sustained improvements (confirmed at one year) were described. The influence of patient characteristics on improvements was examined using logistic regression.

Results:From 16,132 EDSS scores, 7653 yearly and 5845 biennial EDSS intervals were available for 2961 and 2382 patients respectively. Of the yearly intervals, 14.9% showed an improvement (≥0.5 points), 8.3% ≥1 point and 2.2% ≥2 point improvement, with nearly half being sustained. Corresponding worsenings were observed in 32.9%, 20.5% and 7.9% respectively, with stability in just over half (53%). Biennial findings were similar. Characteristics generally associated with improvements included: female sex, younger age, shorter disease duration, relapsing-onset and presence of moderate disability (compared with mild or advanced) and a previous episode of worsening (disassociated from a relapse). However, improvements were also observed after periods of stability and in primary-progressive MS.

Conclusion:Improvements in MS disability over one or two years are not unusual. We suggest the term 'innate improvements'. Our findings have implication for the design of clinical trials and observational studies in MS targeting improvements on the EDSS.

PMID: 22736751 [PubMed - as supplied by publisher]

Not possible. I had symptom improvement the next day. I was able to walk with my feet next to each other. I walked with my feet 1 1/2 feet apart for over two years prior to the surgery. The babinski sign disappeared, I could stay awake longer and had cut back my provigl dosage. Migraines ceased. Nerve pain in my arm gone. No more tramadol, gabapentin, and Valium. Many other symptoms disappeared or lessened. It was not placebo for me.

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Welcome the brand new day

Also not possible; after 4 years of declining several improvements after treatment that hold until now (2 years after treatment)

I have had 3 CCSVI treatments. No measurable improvement. I understand I am only a single case amongst millions of people with MS, and therefore I cannot say with any certainty (especially with the improvement reports on this site, such as yours) that MS & CCSVI are unrelated, far from it.

Thanks Eric for posting it.

This paper shows that very few MS trials are satisically valid unless they are very large. Blinding an invasive procedure (CCSVI) to an awake patient is not feasible, so why demand it? Having de-stenosis is a personal choice of treating CCSVI syndrome or not. After 2 years I think it was a rational choice but there is no 'proof'.
MarkW

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Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 10 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html

So, if EDSS is not an accurate measure of MS progression, white matter lesions are not good measures, nor is symptom relief---what can be used to chart progression in MS---for all clinical trials, be they interventional venoplasty, nutritional/lifestyle studies or drugs--?

Gray matter atrophy. It's the only parameter tied directly to debilitation and progression. It appears before white matter lesions, and continues after the white matter inflammation of MS is gone.


http://www.biomedcentral.com/1471-2377/12/9

This is what is being followed in my husband. His gray matter now looks normal, three years after venoplasty, atrophy is reversed. Yes, he's had symptom relief, improvement in EDSS...but this measurable parameter has changed, and will be monitored for the rest of his life. I suggest other pwMS ask to have their gray matter assessed. This is an accurate measure of neurodegeneration. (BTW, why wasn't this posted on the Tysabri or stem cell forums, only here??)
cheer

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Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
dual stents placed 5/09
CCSVI in MS

I would say that the call for action needs to be for randomized controlled trials on CCSVI treatment on the symptoms and the disease course of the syndrome known as CCSVI. This means separating it out from MS. It means looking at symptoms that have been considered MS symptoms but may instead be CCSVI symptoms.

Whether or not MS as measured by EDSS spontaneously improves in 15% of patients would not have an impact on a trial specific to CCSVI and CCSVI symptomatology.

Research to see if CCSVI treatment impacts the disease course of MS is a further step down the line. It's like looking at diabetes treatment to see if it impacts heart disease. If there is an association between the two illnesses, diabetes treatment might positively impact heart disease. But there are no calls to avoid treating diabetes if it does not impact heart disease, because diabetes is an established disease of its own. We would benefit from research that establishes CCSVI as a disease or syndrome with its own symptom complex.

But to discuss the research in the first post specifically, does anyone have research stating how reliable the EDSS measurement is? Inter-rater reliability and intra-rater reliability? My understanding has been that EDSS scores poorly on reliability because it relies on the interpretation of the neurologist. The improvement in 15% of MS patients could be due to the poor reliability of the test.


http://tinyurl.com/6nc8og5

I don't think EDSS is the right measurement tool for CCSVI trials.

http://www.neurology.org/content/40/6/971.short


the point value of EDSS change was included in the research eric posted, let's see

If we discount any data that shows less than a 1 point change, we are looking at improvement in 8% of MS patients and worsening in 20%. Since this data includes people with relapsing-remitting MS, there is nothing particularly novel here.

Cece, I think I really agree with you regarding the measures of MS. But, on a side note, its my disability (ie EDSS) that I personally am really the most interested in right now. Show me a trial that shows reducing EDSS, and I will jump on it

I do however think we need to clarify MS's relationship with CCSVI, and why there appears to be such a cross over with CCSVI, and why those that have CCSVI & MS, do not respond to treatment as others (ie ME!) we have come so far with people like Dr S, but we have so much further to go, so I think breaking CCSVI a little away from MS may help clear the muddy waters, and also stop the neuro's messing where they are not wanted.

I dug up some more on the research that UBC compiled on those with natural MS progression and found a presentation by Professor Tremlett---it appears that what we thought we knew about MS progression is not really true---

(oh, and BTW, eric....please note that the UBC researchers address clinical trials for DMTs.
So, this post should have been placed in general, or in any of the drug forums. But since it's here---let's discuss what it really means.)



http://www.mstrust.org.uk/professionals ... 012_06.jsp

Men and women take about the same time to get to a 6 on EDSS, when measured over a lifetime. The older at dx, the better. MS relapses naturally decrease over time, and the drugs don't benefit older pwMS. That's some pretty important info, I'd say.

Again...if relapses do not affect progression....than what does? Some of the CCSVI researchers will be following gray matter atrophy pre and post venoplasty. That's a good thing.
cheer

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Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
dual stents placed 5/09
CCSVI in MS

I have for years been concerned that the efficacy of "MS" treatments is measured against placebo, rather than a statistically valid expectation of the progress of disease over a long (5 years or more) period of time. Drug trials being as expensive as they are, and successfully tested drugs for "MS" being as expensive as they are, nobody but the prospective vendor wins, when "placebo", AKA sugar pills, is used for a scientific measurement.

This disease is highly variable. It killed a man knew, when I was 18, and he was 30. It was not pretty. He had kids. He had no relapse-free period. As far as I knew anyway, SPMS and PPMS were supposed to be relapse-free.

Yet I had a neurologist who refused me any treatment whatsoever, and said "maybe it'll just burn itself out."

I have been tested and measured almost to death. But what do we really know about expected events over, say, a 10-20 year span? If all we know is that "everyone is different", I suggest we know nothing at all. Is it that unpredictable, or are we just barking up all the wrong trees?

If we know the late stage outcome, but we have no idea what causes it or how the treatments work, how can anyone say they will not work after some fixed time, or some fixed level of disability? Maybe if we had continued to test past that point, things would have changed dramatically, or death rates would have even got lower. If the drug has not been around for that long, how can we say we know enough about it to deny treatment to anyone? Yet I have heard that same argument for all "DMDs, and even Ampyra.

I think it's amazing how powerful our prognostic abilities are. It seems a 2-year trial is enough time to establish that it just won't ever do anything for people with SPMS or PPMS. (We all know what it really means: it won't get them back to work, and that's all insurance companies care about.)

I have read from several sources, early death doesn't happen in "MS". I know some people who would disagree.

To get back to the forum topic, I don't believe we know more about "MS" than we thought. About CCSVI, maybe. The most telling phrase I read in your quote was: Something congenital there, ya think? Or maybe it's an STD...

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"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'_MS' is over - if you want it
Patients sans/without patience

I think the birth date vs. dx date was simply a measuring tool, one eye...to see how long it took pwMS to get to a 6 on the EDSS-- this is because men usually progress faster, but women are dx younger. Although I agree with your congenital comment, I don't think the UBC neurologist do
But I was interested to see that an older male dx isn't terrible (as Jeff's neuro keeps saying), and DMTs may not benefit older folks, anyway. Since Jeff was dx at age 43 and is now 49 and progression/relapse free, that was comforting news. And yes, everyone is sure different!
cheer

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Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
dual stents placed 5/09
CCSVI in MS

The fact that time since birth is more significant than time since dx in predicting length of time to "other outcomes" surely means: time since dx does not predict those outcomes as well. You could argue it does not have very much meaning at all, since the length of time it take to get to a diagnosis varies, by sex, by the invention of MRI, by many arbitrary and random things. But if age since birth does have significance in spite of all that, I would argue something that happened or had already happened at day 0 affects all the outcomes you are talking about. Maybe the patient was born stupid, I don't know what perinatal event it was, but until somebody says they have a better way of predicting the future, I say you're on to something.

I think all these discoveries in this study are very consistent with the congenital nature of the condition. BTW statistics don't help with individual cases, unless the odds are very close to 100%. I know as many men Jeff's age as your example (of Jeff) for whom an older male dx was terrible. Regardless of what your neuro might say. In fact I know more than one, and they have very different levels of terrible.

I still respond to those who say DMDs may not benefit a person, by saying, they also may benefit them. I have 2-year studies on pwMS. What's your evidence? I say the burden of proof is on the person saying no. That's because yes is a more difficult thing to say. JMHO.

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"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'_MS' is over - if you want it
Patients sans/without patience

'Since birth' is of greater importance in a disease when chronic longterm neurodegeneration is the key process. 'Since diagnosis' or since relapses and/or progression began would be of greater importance if the relapses themselves cause the neurodegeneration.

Exactly, Cece. Dr. Tremlett even stated that relapses were not connected to long term disability in the study. Dr. Tremlett stressed the need to really look at the results of this study, because soon we will no longer have a large group of treatment naive patients--and the natural history of MS disease progression will be lost.
cheer

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Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
dual stents placed 5/09
CCSVI in MS