Dr. Sclafani at ISNVD

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Dr. Sclafani at ISNVD

Postby Cece » Mon Feb 20, 2012 10:28 am

Dr. Sclafani: IVUS needed to detect each valve. Dr. Arslan: Right equipment makes the difference; IVUS not needed
Dr. Sclafani on recurrence of symptoms: angioplasty may have benefits not related to MS symptoms ovr 20 yrs b/c of better flow
Dr. Sclafani: "Blinding patients is not possible."
Dr. Sclafani: no consensus on degree of stenosis in imaging, but consensus reached on how to measure stenosis
Dr. Sclafani: 3 months is too long to wait for follow up ultrasound to save the vein if a thrombus is present
Dr. Sclafani to Angela: cross sectional measurement with U/S w/b more useful to IRs than diameter to choose balloon size

I was telling my husband last night about ISNVD, and he may have been humoring me by listening, because it would seem the depth of my interest in all things CCSVI is greater than the depth of his. But he pointed out that Dr. Sclafani and I were at one point in disagreement about the length of time to wait after ballooning to get a routine follow-up exam. When I was treated a year ago, Dr. Sclafani suggested three months for follow-up, and when my left vein kept hurting after the procedure, I was able to get in locally with Dr. Cumming for a one-month doppler check for thrombosis. It was good for peace of mind and because when it comes to clots, time is vein. Now with Dr. Sclafani saying that three months is too long for follow-up if thrombosis is present, we are in agreement. And ... let's see ... I side with Dr. Sclafani over Dr. Arslan about the necessity of IVUS for detecting each valve. I would be interested in what Dr. Arslan means about the right equipment being needed: are there IRs with better or worse angiography suites? Should that factor into our decision of where to go?

Is it impossible to blind patients? It's not technically impossible, with the use of anesthesia, and there are a few IRBs in place with blinding. It is ethically concerning. It is likely that any patient in such a trial would try to guess what group they're in. 'Wow' results would be unlikely to come from the sham group, unless there is some 'wow' placebo going on, which I suppose is the concern. Nonresults could come from the sham group or from nonresponders in the treatment group. There's expectations too. I've heard people say the treatment did not work, because they got cogfog and fatigue improvements but no mobility improvements. I prefer Dr. Dake's plan of 3 month sham trial vs Dr. Siskin's 2 year sham, but Dr. Siskin's is underway and Dr. Dake's is not, and I am very glad that there is a blinded trial underway. I would have to say that perfectly blinding patients is not possible, but good enough blinding is possible, because there is room to wonder which group you're actually in, and some of the benefit to the sham group is in the doctor's care outside of the procedure itself. So see? That almost sounds like I disagree with Dr. Sclafani.
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Re: Dr. Sclafani at ISNVD

Postby Cece » Mon Feb 20, 2012 3:34 pm

Dr. Sclafani: changing criteria for U/S by deleting criteria #2 eliminates eligibility for some patients for venography
Dr. Sclafani: don't exclude symptomatic patients from having venography based on screening test
Dr. Sclafani: at least half a million people need to be screened (US data)
500,000 people with MS in the US. And if doppler ultrasound is accurate about 80% of the time, then 100,000 will get an inaccurate diagnosis?

Reducing the number of criteria but still requiring two criteria to be met, out of four instead of out of five, would eliminate some patients' eligibility. And doppler ultrasound is not accurate enough to rely on if it means missing the chance to have the procedure. Especially in syptomatic patients! And if chronic fatigue is a symptom of CCSVI, very few among us are not symptomatic.
Anne Kingston@anne_kingston

Dr. Sal Sclafani: What's slowing CCSVI research "more than anything is lack of neurological collaboration." Zivadinov agrees
Sclafani says, "We are looking at a downstream cause for an upstream problem."
https://twitter.com/#!/thinkccsvi
Last edited by Cece on Tue Feb 21, 2012 7:15 am, edited 2 times in total.
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Re: Dr. Sclafani at ISNVD

Postby marcstck » Mon Feb 20, 2012 5:16 pm

Cece wrote:
Is it impossible to blind patients? It's not technically impossible, with the use of anesthesia, and there are a few IRBs in place with blinding. It is ethically concerning. It is likely that any patient in such a trial would try to guess what group they're in. 'Wow' results would be unlikely to come from the sham group, unless there is some 'wow' placebo going on, which I suppose is the concern. Nonresults could come from the sham group or from nonresponders in the treatment group. There's expectations too. I've heard people say the treatment did not work, because they got cogfog and fatigue improvements but no mobility improvements. I prefer Dr. Dake's plan of 3 month sham trial vs Dr. Siskin's 2 year sham, but Dr. Siskin's is underway and Dr. Dake's is not, and I am very glad that there is a blinded trial underway. I would have to say that perfectly blinding patients is not possible, but good enough blinding is possible, because there is room to wonder which group you're actually in, and some of the benefit to the sham group is in the doctor's care outside of the procedure itself. So see? That almost sounds like I disagree with Dr. Sclafani.


Hey, Cece, thanks for providing these links and info. Your dedication is commendable.

Regarding blinded trials and the possibility of getting "wow" effects from a sham group, you most certainly could expect to get some "wow" results from patients receiving a sham procedure. One famous example of this was a trial done on Parkinson's patients, which involves opening the skull to gain access to the brain in order to inject a medication deep into the organ. Half of the patients who were in the trial had actual brain surgery (in other words, their skulls were cut open) but no medication injected. Many of those in the sham group reported dramatic improvements in their Parkinson's symptoms (severe tremors, etc.), some lasting for as long as a year. Similar results were seen in a trial involving knee surgeries in which some patients received sham procedures…

The placebo effect is very real, and can be very powerful. It should not be mistaken for someone "imagining" their improvements, or making shit up. It's been found that the more dramatic the procedure being trialed, the more dramatic the placebo effect can be. Actual physiological changes happen as a result of the patient believing they have been treated. The mind/body connection cannot be overstated. The placebo effect is a very complex issue, and patients with high degrees of expectation who go to great lengths to get treated (like MS patients seeking CCSVI venoplasty) have the highest likelihood of experiencing the placebo effect.

This is not to say that the results people are seeing post CCSVI venoplasty are all placebo effect, I'm sure most are not. But I'm equally sure that some are, as it's a given that a subset of patients will experience the placebo effect as a result of undergoing a treatment protocol. This neither disparages the patient nor the technique involved, and is one of the most important reasons blinded trials are necessary. Many a treatment has found success within a trial patient population, but no more than the same success seen in the placebo group, and thus the treatment is ultimately deemed a failure.

Thanks again, keep up the good work…
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Re: Dr. Sclafani at ISNVD

Postby Cece » Mon Feb 20, 2012 7:28 pm

I will be looking forward to a blog post from you, Marc, summarizing all of this! There is so much to dig through.

Yes, I remember that Parkinson's research. Surprising results.

For what it's worth, there has also been recent research showing little difference between placebo and untreated groups:
http://www.nejm.org/doi/full/10.1056/NE ... 5243442106
http://onlinelibrary.wiley.com/doi/10.1 ... E01.d02t04
I am not sure what to think. And a sham group comes at the cost to the patient, of not being treated, potentially for up to two years, and of undergoing the risks of angiography without the benefits.
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Blinding patients is not possible - Dr Sclafani

Postby MarkW » Tue Feb 21, 2012 4:21 am

Cece wrote:
Dr. Sclafani: "Blinding patients is not possible."


Hello Cece,
Thanks for postings from Orlando, very helpful.
The TiMS forum drew the same conclusions last year as Dr S is saying at ISNVD 2012. I am disappointed that some ISNVD leaders are still calling for double blind trials. I expected Dr Hubbard to appreciate why patients can feel balloons being inflated (sometimes it hurts). Please convey patient experience to the meeting - what do we know we are only patients !!!
IRs could become like neuros (who know best for pwMS) if the are not careful.

Hello Marc,
The difference from your examples and for those undergoing de-stenosis is that we were awake. Using anethestic for no medical purpose is considered unethical in trials. Placebo is a well documented effect from drugs but a sham surgical procedure (which causes discomfort) on an awake patient is virtually impossible.

Kind regards,
MarkW
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 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
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Re: Dr. Sclafani at ISNVD

Postby Cece » Tue Feb 21, 2012 2:14 pm

The CCSVI leaders calling for double-blinded trials were Dr. Zivadinov and Dr. Hubbard, weren't they? I could double-check. Both Dr. H and Dr. Z are neurologists, which might mean they are more accustomed to the certainty that comes with double-blinding and less accustomed to the technical challenges and ethics of double-blinding trials of a surgical procedure.

I have to agree about the questionability of using anesthesia for no medical reason, in order to blind the trial. Anesthesia has risks. http://www.mayoclinic.com/health/anesth ... TION=risks
But we have been at this for years now. A properly conducted blinded trial would give more conclusive results and might establish CCSVI as standard care. Insurance companies and Medicare are looking for evidence, which a blinded trial would more conclusively provide.

I've loved the tweets from Orlando, especially since I am not there myself. I'm on overload just from the tweets and abstracts!

Here's an abstract from Dr. Sclafani:
page 48 of 2012 isnvd abstracts http://www.isnvd.org/files/ISNVD%20Abstract%20Book.pdf
Consequences of venous obstruction involving other vascular beds (Salvatore Sclafani, USA)


This presentation will focus upon venous obstructions caused by compressive forces outside the cerebrospinal venous circuit that may result in OUTFLOW obstruction or increased INFLOW into the cerebrospinal venous circuit. Venous thoracic outlet syndrome relates to obstruction of the axillary or subclavian vein as it exits the chest over the first rib. Also known as Paget Schroetter disease, it is a thrombosis caused by subclavian stenosis, often after vigour exercise. Patients present with a painful swollen and cyanotic upper extremity with weakness and paresthesia. Collateral veins are visible in the chest and shoulder. On occasion, it may cause OUTFLOW obstruction of the valvular area of the inferior jugular vein and may increase INFLOW into the cerebrospinal circuit by collaterals extending into the neck from the upper extremity. Renal vein stenosis caused by compression, most commonly by the aorta and superior mesenteric artery, is referred to as the Nutcracker phenomenon when asymptomatic and the Nutcracker syndrome when symptoms are present. Symptoms and signs include proteinuria, hypertension, unilateral hematuria, chronic back or pelvic pain, varicoeles and pelvic congestion syndrome, and, interestingly, chronic fatigue. MRI, CT and ultrasound are noninvasive screening tests; venography with hemodynamic measurements and intravascular ultrasound are confirmatory. In renal vein obstruction, hemiazygous and ascending lumbar collaterals may become cerebrospinal INFLOW veins of significance because renal venous blood flow is so great (500 ml/min). Endovascular stenting and reimplantation or transposition procedures are the treatment of choice. May- Thurner syndrome describes a clinical scenario associated with compression of the left iliac vein between the right common iliac vein and the lower lumbar spine. Originally thought to occur in young overweight teenaged and young adult women, it is found in about 37% of patients with history of DVT or reflux. Symptoms include progressive leg edema with no history of thrombotic problems, venous claudication, and mild complaints consistent with chronic venous insufficiency. Physical examination can demonstrate mild to severe edema, chronic leg skin changes, development of varicosities, significant venous collateral vessels, and ulceration. CT and MR may show compression, but venography with hemodynamic measurements and intravascular ultrasound are definitive. Venous collateral vessels include cross pelvic venous drainage and the left ascending lumbar vein that can act as a cerebrospinal INFLOW vein. Failure to treat the stenosis after iliac DVT is associated with persistent occlusive disease. Treatments include thrombectomy or thrombolysis and stenting.
You can see the emphasis on outflow vs inflow, since that was previously misunderstood by other IRs. The consensus document stated that there was not yet enough evidence to recommend looking at or treating the renal and iliac veins, but that is only the 2012 consensus. I expect the 2013 or 2014 or 2015 consensus to state otherwise. Dr. Sclafani has a tendency to be right.
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Re: Dr. Sclafani at ISNVD

Postby marcstck » Tue Feb 21, 2012 2:57 pm

Cece wrote:I will be looking forward to a blog post from you, Marc, summarizing all of this! There is so much to dig through.

Yes, I remember that Parkinson's research. Surprising results.

For what it's worth, there has also been recent research showing little difference between placebo and untreated groups:
http://www.nejm.org/doi/full/10.1056/NE ... 5243442106
http://onlinelibrary.wiley.com/doi/10.1 ... E01.d02t04
I am not sure what to think. And a sham group comes at the cost to the patient, of not being treated, potentially for up to two years, and of undergoing the risks of angiography without the benefits.


In all honesty, I'm not sure how to present the presentations given at ISNVD. Most of them seem to be recapping older research, I don't see much new here that jumps off the screen. Perhaps some of the outcome studies, but the findings seem quite disparate, therefore hard to draw any conclusions from them. We seem to be stuck in a lull as far as insights into CCSVI goes. Patients haven't been tracked, so we have little new info on mid to long-term outcomes. We still have the same old problem with high rates of restenosis. Both MRV and sonography seem riddled with room for inaccurate readings. IVUS seems to be a clear step forward, but has met with resistance from IRs. We have the valve only vs. whole vein argument, which seems far from resolution. We not only have disagreement between the different disciplines, but also within the IR community itself.

It's all really quite frustrating. Despite the problems with blinded studies, in this case some of way to do them really must be found. We're not just talking about trialing a new surgical procedure, but trying to ascertain whether or not CCSVI is a standalone syndrome, connected to MS, connected to a variety of neurologic diseases, or simply a natural variance that just hasn't been looked at previously. We've seen lots of studies on patients with MS, with results scattered all across the spectrum. What we really need are studies of healthy controls, to ascertain the prevalence of CCSVI in the general population, and to try to get a handle on the variables that come together to make CCSVI a part of the MS puzzle. I think the postmortem studies hold the most promise in this regard (ascertaining the rates of CCSVI in healthy subjects), and I hope that Dr. Fox is building a more robust database over time.

I think I'm going to do a "State of the Union" type post about CCSVI, simply summarizing where we are right now in regards to research, treatment effectiveness and availability, and emerging themes.

We should get some decent data from the seven ongoing MS Society funded trials, which are due to report their two-year results in June or July. Based on their 18 month results, though, most of the studies won't be finished at 24 months. Still, they should have some hard data to report. Of course, since they were funded by the MS societies, if their results are anything but a validation of CCSVI, there will be suspicions of conspiracy.

Unfortunately, rather than increased clarity, in some ways the picture seems to only be getting more muddled. For whatever reason, I get significantly more e-mail from blog readers that have been disappointed with their treatment outcomes than those who are satisfied. Some even blame me for "pushing CCSVI treatment", something I have really tried to avoid doing. I guess some people read what they want to read…
Last edited by marcstck on Tue Feb 21, 2012 4:15 pm, edited 2 times in total.
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Re: Dr. Sclafani at ISNVD

Postby Lyon » Tue Feb 21, 2012 3:50 pm

Pretty level headed, thanks Mark.
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Re: Dr. Sclafani at ISNVD

Postby David1949 » Tue Feb 21, 2012 6:29 pm

Where can I buy some of that placebo effect? :-)

But seriously if the effect is that great isn't there some way we can harness it to our advantage? Hypnosis maybe?
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Re: Dr. Sclafani at ISNVD

Postby Cece » Wed Feb 22, 2012 9:53 am

Some more tweets from Danielle Rheume, about Dr. Sclafani's presentation on other veins:
Sclafani: Focus on issues with iliac & renal veins. Too bad there isn't more understanding of their importance in CCSVI.
Sclafani on Paget Schroetter Disease possibly impacting cervical collaterals
Sclafani giving important iliac and renal examples. Jugulars and azygous are just tip of CCSVI iceberg.
Yes! Sclafani "Treatment of the internal jugular and azygous veins may not be sufficient for flushing out all of the contributors to CCSVI."
Discussion of the effect of renal vein stenosis on CCSVI is new this year, isn't it? It may be a small subset of CCSVI patients who have renal stenosis involvement, but if you're in that subset, treatment of this may make a difference in outcome.

Also new is the discussion of pharmaceutical treatments for CCSVI. The keynote speaker, Dr. Chopp, challenged the current focus on lesions and disease activity in MS, suggesting that instead the focus should be on the healthy tissue that remains. He suggested niacin and something else (Viagra?) as possible pharmaceutical treatment, such as is done in strokes. Dr. Driscoll suggested Diamox, which increases cerebral perfusion. I think this is an exciting new avenue, because not everyone will have 100% resolution of CCSVI through venoplasty alone.

All the outcome studies suggest low complications and varying degrees of improvement.

I would say on average I get more messages from people who have had successful treatments than those who have not, but clearly there is a variety of outcomes happening. I think your presentation of CCSVI has been balanced, Marc.

David, I suppose go into CCSVI treatment expecting the absolute best and most wonderful outcome. Not just expecting it, but knowing that it will happen. This is bad advice, because of the importance of having reasonable expectations. But to maximize placebo effect, then you'd want to maximize belief that on the other side of an outpatient procedure lies everything you want back that MS has taken away.
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Re: Dr. Sclafani at ISNVD

Postby drsclafani » Fri Feb 24, 2012 10:52 pm

What I meant was that many patients who have angioplasty have soreness in the chest and the neck after angioplasty. You can blind someone during the rpcoedure, but i find it difficult to imagine that someone with soreness in the chest or neck a few days later would not figure that out
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Patient contact: ccsviliberation@gmail.com
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Re: Dr. Sclafani at ISNVD

Postby marcstck » Fri Feb 24, 2012 11:02 pm

drsclafani wrote:What I meant was that many patients who have angioplasty have soreness in the chest and the neck after angioplasty. You can blind someone during the rpcoedure, but i find it difficult to imagine that someone with soreness in the chest or neck a few days later would not figure that out


I had a real procedure (at least I think I did) and I didn't have soreness in my chest and neck afterwards. Did you pull a fast one on me, Dr. Sclafani?
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Re: Dr. Sclafani at ISNVD

Postby Cece » Fri Feb 24, 2012 11:05 pm

My right side of my neck was sore for a week, and the left side was sore for over a month. It's a good point.
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Re: Blinding patients is not possible - Dr Sclafani

Postby drsclafani » Fri Feb 24, 2012 11:42 pm

MarkW wrote:
Cece wrote:
Dr. Sclafani: "Blinding patients is not possible."


Hello Cece,
Thanks for postings from Orlando, very helpful.
The TiMS forum drew the same conclusions last year as Dr S is saying at ISNVD 2012. I am disappointed that some ISNVD leaders are still calling for double blind trials. I expected Dr Hubbard to appreciate why patients can feel balloons being inflated (sometimes it hurts). Please convey patient experience to the meeting - what do we know we are only patients !!!
IRs could become like neuros (who know best for pwMS) if the are not careful.

Hello Marc,
The difference from your examples and for those undergoing de-stenosis is that we were awake. Using anethestic for no medical purpose is considered unethical in trials. Placebo is a well documented effect from drugs but a sham surgical procedure (which causes discomfort) on an awake patient is virtually impossible.

Kind regards,
MarkW


The IRs were not in a majority during this meeting. I think there were more people with background in MRI. The IRs remain clinically focused but the meeting spent about one of five days on IR,
Salvatore JA Sclafani MD
Patient contact: ccsviliberation@gmail.com
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