Dr. Sandy MacDonald's paper on doppler ultrasound techniques

[Cece]

https://docs.google.com/file/d/0B0L9MiV ... edit?pli=1

The Use of Doppler Ultrasound in the Diagnosis
of Chronic Cerebrospinal Venous Insufficiency

Sandy McDonald, RVT, RPVI, MD, FRCS(C), FACS, and J. Blake Iceton, RVT, BSE

Chronic cerebrospinal venous insufficiency (CCSVI) may be associated with multiple
sclerosis, and its treatment has been shown to potentially benefit patients with this
condition. Color-assisted duplex imaging is used to assess the anatomical and physiolog-
ical parameters of cerebrospinal venous function and to diagnose CCSVI. Standardized
examination protocols as well as the diagnostic criteria used are important elements in
ensuring reproducibility of results between centers. The objective of this article is to
describe the technique our laboratory has used to assess patients for the presence of
CCSVI using Doppler ultrasound.

Recently published in Techniques in Vascular and Interventional Radiology by our favorite Canadian IR, Dr. Sandy MacDonald, these are the full Zamboni protocols for the diagnosis of CCSVI.

According to Joan over at the facebook page CCSVI in MS, none of the NMSS funded doppler studies have utilized the full protocol, which is dismaying.

[MarkW]

I realise that research is published many months after the work is performed but CCSVI advocates need to say that external doppler ultrasound is a guide to CCSVI syndrome if used by skilled, trained people. Could someone update Dr MacDonald that invasive catheter venograms and intravascular ultrasound is the gold standard for CCSVI diagnosis?
MarkW

[Cece]

The diagnosis of CCSVI can be difficult. Although the contemporary description of CCSVI began largely with abnormalities found on a Doppler ultrasound examination of the internal jugular veins (IJVs), some have advocated for magnetic resonance venography as a noninvasive modality to diagnose CCSVI, whereas others believe that catheter venography with or without the use of intravascular ultrasound may represent the gold standard for diagnosis. A noninvasive test that can be used to reliably diagnose CCSVI and identify patients who should undergo a more invasive catheter-based venogram is clearly desirable. Doppler ultrasound using the technique described by Zamboni et al3 is presently being used by many for that purpose. This article will describe the ultrasound technique used to diagnose CCSVI and will also review the data that has been reported in terms of ultrasound’s ability to make this diagnosis.

It's in his second paragraph. I agree with Dr. MacDonald that a noninvasive test is desirable, especially for people who lack a clear diagnosis of MS. But I do not think any person with MS should stop short of the venogram with ivus. There is an abstract from Dr. Siskin that concluded, "Findings on a Zamboni-protocol US are not associated with findings on contrast venography in light of the high false negative rate; 99% of the patients with a negative US had a significant stenosis and/or flow abnormality treated with angioplasty. A prospective study is needed to define the role of US and other modalities in the non-invasive diagnosis of CCSVI."
http://www.sirmeeting.org/index.cfm?do= ... s&abs=2088

[MarkW]

Thanks for the detail Cece. I am at my in-laws so don't have access to a library to review the paper. I hoped that screening using the Neck Collar would be commonplace by now, so that we could say that doppler US was last decade's method. Must spend more time on the SIR meeting notes.
MarkW

[1eye]

Correct me if I'm wrong but I think Dr. MacDonald was trained in Ferrara and since he does the angioplasty as well, is well qualified to judge whether a person has CCSVI. I think (again, might be wrong) that he was not finding CCSVI until he had received training in Italy, and has sent people from his lab to get trained there.

Some rumours from neurologists were saying that testing in Barrie always resulted in a positive result, but I know better, as the first time I went there it was negative, the second time positive (after the procedure with Dr. Siskin, and nine months later).

I think it is not a good idea to disparage any doctor or facility that does not meet one's personal criteria for the procedure, especially if not even an M.D. One may have had input to NICE, without being an IR. He is one.

I would hope that those performing the procedure would set the standards, and that Dr. MacDonald is one in Canada who does. People in this forum are just that: mostly at least semi-anonymous "bloggers". Nobody who is not an MD should be giving medical advice if they want to avoid liability for it.

We are all in the same boat as regards the science and medicine. There is no national or international consensus, and even if NICE sets some kind of standards in the UK, many of the people here are not from there, and their local doctors are being jerked around by the FDA or other government committees, or medical governing bodies. I think one of our problems might be that many people have opinions and power, but are not qualified as IRs, or vascular experts of the caliber of Dr. MacDonald or Dr. Mehta. Many seem to be experts on the drug remedies, and some even work for drug companies, but do not necessarily do the procedure.

[MarkW]

Correct me if I'm wrong but I think Dr. MacDonald was trained in Ferrara and since he does the angioplasty as well, is well qualified to judge whether a person has CCSVI. I think (again, might be wrong) that he was not finding CCSVI until he had received training in Italy, and has sent people from his lab to get trained there.
Some rumours from neurologists were saying that testing in Barrie always resulted in a positive result, but I know better, as the first time I went there it was negative, the second time positive (after the procedure with Dr. Siskin, and nine months later).
I think it is not a good idea to disparage any doctor or facility that does not meet one's personal criteria for the procedure, especially if not even an M.D. One may have had input to NICE, without being an IR. He is one.
I would hope that those performing the procedure would set the standards, and that Dr. MacDonald is one in Canada who does. People in this forum are just that: mostly at least semi-anonymous "bloggers". Nobody who is not an MD should be giving medical advice if they want to avoid liability for it.
We are all in the same boat as regards the science and medicine. There is no national or international consensus, and even if NICE sets some kind of standards in the UK, many of the people here are not from there, and their local doctors are being jerked around by the FDA or other government committees, or medical governing bodies. I think one of our problems might be that many people have opinions and power, but are not qualified as IRs, or vascular experts of the caliber of Dr. MacDonald or Dr. Mehta. Many seem to be experts on the drug remedies, and some even work for drug companies, but do not necessarily do the procedure.

The person who wrote "MS-experts-in-Britain-have-to-open-their-minds" (article http://www.telegraph.co.uk/health/83598 ... minds.html) disagrees with you 1eye. The qualification of MD does not mean that the MD's view is always correct. You could view my challenges to Dr Arata on the use of IVUS. I challenged Prof Sclafani on the design of his proposed $5M trial but I trusted him to perform my second venoplasty. Dr MacDonald does not use venograms and IVUS on pwMS, so like me he is reviewing the work of others. My challenge to Dr MacDonald is that he wrote "some have advocated for magnetic resonance venography as a noninvasive modality to diagnose CCSVI, whereas others believe that catheter venography with or without the use of intravascular ultrasound may represent the gold standard for diagnosis" rather than saying invasive catheter venography with intravascular ultrasound is the gold standard for diagnosis of CCSVI syndrome in Spring 2012. The current literature and leading practice says that venograms and IVUS must be used in combination by a skilled practitioner to detect instances of CCSVI syndrome. NICE did not get this fact correct and very few clinics in the globe are using both tools. I will continue to challenge researches or reviewers (MDs or otherwise) so that pwMS have reliable information on CCSVI syndrome.
Kind regards,
MarkW

[Cece]

I challenged Prof Sclafani on the design of his proposed $5M trial but I trusted him to perform my second venoplasty.

Gotta challenge you on this statement, dear Mark: you thought you were challenging him on the trial design of his proposed trial, but he had actually been answering a what-if question that had nothing to do with his own proposed trial. Dr. Sclafani has not released any plans or design for his actual trial.

I trusted Dr. Sclafani as well for both my procedures. No challenge there.

I also have a great deal of respect for Dr. MacDonald. There are small abstracts supporting the use of IVUS in CCSVI, but not yet a critical mass of such studies that we can say with scientific certainty that venogram plus ivus is the gold standard, although I too believe that it is.

Doppler ultrasound was critical to Dr. Zamboni's process of investigating CCSVI, back in the early 2000s when he had not yet taken it further to the point of actual endovascular treatment. We are seeing studies recreate some of the steps he took back then. He looked at autopsied jugular veins back in the early 2000s; the Cleveland Clinic looked at them in 2011. There are many studies that have attempted to recreate his doppler ultrasound findings, since those were what justified taking the exploration further into actual catheter venograms and treatment, so it is good to have a paper dealing with the protocols and techniques of the ultrasound methods. It will also be good when the plethysmography neck collars are further researched in CCSVI. I only know of a study by Dr. Simka that is underway, as well as one completed by Dr. Zamboni, when it comes to plethysmography, which I too see as a potentially more reliable and reproducible method. But that needs proving as well.

[MarkW]

Hello Cece,
I am a pendant being less than precise, totally unforgivable. I should have said I challenged DrS's answer to the question:
"What formal steps should be made in order for the scientific community to acknowledge beyond doubt that CCSVI is real and has non-trivial consequences?"
I post the whole of my comment below for clarity.
A trial to prove to Neurologists that CCSVI is a symptom of MS, which should be treated, must include over 1000 subjects, otherwise the statistics are invalid. Neurologists are demanding 'double blind placebo controlled trials' which are just not feasible. IRs are trying to design and perform such studies and in my rarely humble opinion are falling into the trap set by the Neuros. CCSVI UK and I convinced NICE that sham trials were impossible, against the wishes of the neuros, a small win.
The more I study about MS the more I think that it is a multifactorial disease and the human race does not understand the etiology of MS. Let's simply treat symptoms of MS, including CCSVI and an over active immune system.
Best wishes,
MarkW

What formal steps should be made in order for the scientific community to acknowledge beyond doubt that CCSVI is real and has non-trivial consequences?
A - Take 1-2 hundred patients, half with MS and half healthy controls with no symptoms and compare their venography and IVUS blindly. if there is a difference we establish by gold standards once and for all that patients with MS have abnormal venous drainage. If there is no difference, then we go home.
B - Take 1-2 hundred patients with MS, catalog all signs and symptoms, divide them into two groups: one group receives venoplasty, or valvuloplasty using venography and IVUS to confirm successful treatment, the other group receives a sham operation. Both groups blinded to whether they have had treatment or sham. Compare improvements in symptoms for a year.Determine whether there is a benefit in the treated patients. DO NOT focus on whether there MS improves or not. That is a study for later.
That is my opinion.

I am going to try to acheive the impossible and question your trial design Dr S and stay on polite terms with TiMS posters. I hope you will take my comments as thoughts from a critical friend.
I see a flaw in the first trial (my label A) as it assumes that CCSVI is unique to MS. If CCSVI occurs in other early stage (pre-diagnosis) neurovascular diseases then you could find stenoses in healthy controls. Also as MS is a multi-factorial disease there are likely to be pwMS who do not have stenoses. If either or both of these senarios occur then the main discussion (introduced by Neuros) will be that CCSVI is not the cause of MS.
Your second trial (my label B) is too small in size to be conclusive. The MS group has too many sub-groups in it to allow statistically valid data to be generated. New MS drug trials are very large in size in order to acheive statistical significance and many barely acheive this despite their large size. In the UK, the use of complete sedation to conduct Sham Trials would probably not gain ethical approval (NICE has not demanded sham trials in IPG420).
I am tending towards a '500 controlled case study' (then group findings) as the trial method most likely to succeed for CCSVI in pwMS. I see the main problem for IRs in such a study being that the same diagnosis and treatment regime must be used (no improvements during the trial) for all 500 case studies. That is not the way IRs work in my limited knowldge, IRs tweak the method as you use it.
So my question on your trial design is 'are you sure?'
Kind regards,
MarkW

[masci]

Hello, Mark. I completely agree with you that the fake interventions are a trap set by the neuro. Unfortunately, even the prof. Zamboni had to submit to this imposition, to be able to see accepted his Brave Dreams. I am Italian, and Brave Dreams' start is shifted from month to month, because additional checks are required every day.

[Neigh]

My challenge to Dr MacDonald is that he wrote "some have advocated for magnetic resonance venography as a noninvasive modality to diagnose CCSVI, whereas others believe that catheter venography with or without the use of intravascular ultrasound may represent the gold standard for diagnosis" rather than saying invasive catheter venography with intravascular ultrasound is the gold standard for diagnosis of CCSVI syndrome in Spring 2012.

A challenge to you, MarkW, is to stop being, as you yourself called it, pedantic, about MRI, Doppler, and wordings like 'with or without', 'may represent' or 'is'. You might discourage acceptance of some of the science. At its worst, advice by the unqualified about surgical procedures can result in destabilization or worse. I think IRs would agree with neurologists on that.

I am wary also about 'expert patients', or patients who believe having a disease gives them not only an interest, but a degree or specialization. There again, I would rather believe the initials, but track records give a doctor's degrees much more weight. They are my "Gold Standard". BTW, is gold a standard in the UK? The US was taken off it in the nineteen thirties, I think.

In engineering, bug-hunting after the problem is fixed is discouraged. So is fixing what isn't broken. I imagine there are cut-and-dried cases where IVUS, or some other tool, is not required. I will leave it to experts like Dr. MacDonald to write the papers, and to decide on tools and standards.

This in no way implies I have any illusions that a degree confers infallibility to doctors, who are as human as I am. I would be one of the last to believe that about an MD. Some specialists, surgeons, and even GPs I have met and read about, were actually dangerous. I have to admit, before I came to this site I had never heard of an IR, but the wrong person could get those initials, too.

Here, the doctors who usually decide what specialist to first send us to, when we require one, are GPs. That's why they are being targeted in magazines they usually have in their waiting rooms. BTW my new GP uses a computer for a lot of things, and doesn't have paper for sick people to share, in his waiting room. I think virulent diseases are also often spread by stethoscopes. Slowly, the guard is changing.

[1eye]

sorry, klutzy fingers used another alias.

[Cece]

I imagine there are cut-and-dried cases where IVUS, or some other tool, is not required.

I have to disagree. If you accept the idea that precise sizing is crucial in the treatment of CCSVI, because of the risk of undertreatment due to undersizing or vein injury due to oversizing, and you accept that IVUS is the only tool by which a doctor can be precise in his measurements because it gives you exact CSA of the vein, as opposed to the diameter of the vein as seen on venogram that would only be precise if the vein were a true circle and not an oval, then the conclusion is that IVUS is required in all cases, because IVUS is the only tool that can provide the precise sizing.

But it is not universally accepted that precise sizing is necessary.

[MarkW]

My challenge to Dr MacDonald is that he wrote "some have advocated for magnetic resonance venography as a noninvasive modality to diagnose CCSVI, whereas others believe that catheter venography with or without the use of intravascular ultrasound may represent the gold standard for diagnosis" rather than saying invasive catheter venography with intravascular ultrasound is the gold standard for diagnosis of CCSVI syndrome in Spring 2012.

A challenge to you, MarkW, is to stop being, as you yourself called it, pedantic, about MRI, Doppler, and wordings like 'with or without', 'may represent' or 'is'. You might discourage acceptance of some of the science. At its worst, advice by the unqualified about surgical procedures can result in destabilization or worse. I think IRs would agree with neurologists on that.

My short answer Neigh/1eye is no.
I restate:
-MRV does not detect all instances of stenoses. It helps an IR see the venous anatomy to plan his/her investigation.
-Doppler ultrasound gives varying results with different operators and only detects stenoses not hidden by bones.
-MRI does not detect all instances of stenoses.
-Catheter venograms and intravascular ultrasound of a vein are required to detect stenoses in that vein. Fact.
These are facts reported by researchers or practitioners not my opinions. I simply analyse reasearch of leading practitioners and report them for pwMS to use or ignore as they see fit. I do not see many other undertaking this analysis. My aim is to assist pwMS to choose the best way of spending their money if they are considering a procedure for CCSVI syndrome.
Not sure what your aims are Neigh/1eye.
MarkW

[MarkW]

Hello, Mark. I completely agree with you that the fake interventions are a trap set by the neuro. Unfortunately, even the prof. Zamboni had to submit to this imposition, to be able to see accepted his Brave Dreams. I am Italian, and Brave Dreams' start is shifted from month to month, because additional checks are required every day.

Thanks for your comment Masci. Many of us in the UK informed NICE that a sham trial is impossible. I credit CCSVI UK with getting so many submissions to NICE, it was around 400 in total. I repeat my words on sham research to NICE below in case they help anyone preparing a dossier for their regulatory body.
Hope your wait in Italy is not too long, Masci.
Kind regards,
MarkW

 Trials comparing venoplasty against sham is a research dream. (Page 5).
NICE DRAFT:
1.2 NICE encourages further research on venoplasty for CCSVI in MS. Clinical trials should be controlled, ideally comparing venoplasty against sham. Technical success should be clearly defined and should include measurement of pressure gradients across treated vein segments before and after venoplasty. Outcomes should include clinical and quality of life measures.
MAW Comment;
(i) Trials comparing venoplasty against sham is a research dream. Real life patient experiences, including my own, report that balloon venoplasty (inflation of the balloon) is felt during treatment. In some cases pain is reported and local pain killers (eg Fentanyl via catheter) are used. Heavy sedation of patients in order to facilitate a sham trial would place trial subjects under increased risk, due to the sedative drug. I doubt that heavy sedation of patients would be accepted by any UK ethics committee and it is certainly not in the best interests of the trial subjects (people with Multiple Sclerosis).
(ii) Technical success for the treatment of CCSVI syndrome should be restricted to clearly defined observations of CCSVI syndrome, as described by Prof. Zamboni (ref 1). Observations and recording of the vein valves treated using Intravascular Ultrasound (IVUS) should be the initial success criteria of treating CCSVI syndrome. Ultrasound records before and after venoplasty must be the primary measure of success for treating CCSVI syndrome. Recently reported methodology (ref 3) measuring flow differences may be used in further research. However such studies are likely to be small-scale ones due to funding issues, as noted in NICE’s documentation.
(iii) Outcomes measuring clinical and quality of life measures are unusual for initial trials for the treatment of a syndrome. Such studies will be required once a generally agreed treatment procedure for CCSVI syndrome is in place. This is yet to happen, and could take several years.
==================================================================================================
NICE FINAL (IPG420):
1.2 NICE encourages further research on percutaneous venoplasty for CCSVI for MS, in the form of robust controlled clinical trials. Studies should clearly define selection criteria and patient characteristics. They should also clearly define technical success which may include measurement of pressure gradients across treated vein segments before and after venoplasty. Outcomes should include clinical and quality of life measures.
==================================================================================================

[MarkW]

I imagine there are cut-and-dried cases where IVUS, or some other tool, is not required.

I have to disagree. If you accept the idea that precise sizing is crucial in the treatment of CCSVI, because of the risk of undertreatment due to undersizing or vein injury due to oversizing, and you accept that IVUS is the only tool by which a doctor can be precise in his measurements because it gives you exact CSA of the vein, as opposed to the diameter of the vein as seen on venogram that would only be precise if the vein were a true circle and not an oval, then the conclusion is that IVUS is required in all cases, because IVUS is the only tool that can provide the precise sizing.
But it is not universally accepted that precise sizing is necessary.

I agree with you Cece on IVUS for sizing. You also posted an Italian study which showed that stenoses (eg webs and spectums) are missed if IVUS is not used. So IVUS is also essential for complete diagnosis of that vein. I simply advise pwMS that catheter venography and intravascular should be on their 'essential tools check list" when selecting a clinic/doctor. Also an expert who investigates many veins is also essential before pwMS spend their own money.
Will we get the message across to pwMS eventually???
Best wishes,
MarkW