International Society for Neurovascular Disease (March 2011)

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

Postby Cece » Tue Mar 15, 2011 8:22 am

Deadly CSF oscillations? 8O

Gait disturbances within six weeks of blocking the jugulars!! And this is in mice, who do not have the postural differences with the jugulars the way it would if it were in chimps, who would make a better animal model and yet are expensive and more ethically concerning.

Do you think immune modulators would have a difference on these mice? This would help separate out if the immune effects are directly from the vascular blockages or if the immune effects are from a secondary condition of hyperactive or autoimmune-prone immune system reacting to the primary condition of the blockages. (The mice do not have that secondary condition, so if the immune modulators have an effect, then that is good news and the blockages are more likely to be the primary direct cause of the immune response.)

I think EAE can be discarded, it does not need to be incorporated into the CCSVI model, that is like saddling a new car with an old tire!

Will look forward to hearing more from Dr. Beggs. I don't understand how CSF is affected by all of this, but there is a Zamboni paper on CSF, isn't there? I could reread and see if I glean more now, I have a more oxygenated brain these days. And I want a CCSVI hydraulic mechanical model toy too!

Sou, would you say that the conference did a good job of bringing together the vascular and the neurological side or is it still mostly weighted to the vascular guys? Dr. Hubbard and Dr. Zlokovic and Dr. Salvi would be prominent neurologists in attendance, are they fairly alone in that regard?
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Postby zinamaria » Tue Mar 15, 2011 8:34 am

Great reporting Sou! Thanks so much for the update. This is very exciting!
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Postby cheerleader » Tue Mar 15, 2011 8:40 am

Thanks, Sou--
have reposted your report on FB. keep it coming!
Would love to see professor Clive Beggs hydraulic mechanical model of CCSVI. He sounds like quite the scientist...can't imagine him wasting his time on CCSVI models if he didn't believe there was something worth investigating. Especially since he is also a microbiologist.


Prof. Beggs is an experienced research manager who has attracted research funding in the region £1,300,000. As such he has been Principle Investigator on various projects investigating, UV air disinfection, negative air ionisation, the ventilation of hospital buildings, the airborne dissemination of Clostridium difficile, and the influence of humidity on the spread Gram-negative bacterial infection. In the course of these investigations he has developed considerable expertise in the epidemiology of hospital acquired infection, aerobiology and biophysics. As a biologist, he has experience experimenting with microorganisms and modelling their behaviour; as an engineer, he has a good understanding of the clinical environment, and considerable experience in the design and analysis of engineering systems. By combining these two areas of expertise, he has been able to pioneer the innovative application of engineering principles/technology to the control of infection in hospitals – a field hitherto the domain of clinicians and microbiologists. In doing so, he has been able to open up an important and much neglected field, and has been able to make significant original contributions to the knowledge base. He has authored over 70 peer reviewed publications and is frequently invited to speak at scientific meetings.

http://www.eng.brad.ac.uk/?p=staf_prof&usercode=cbbeggs

cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby fogdweller » Tue Mar 15, 2011 8:47 am

sou wrote:Dr Thanaporn's mouse model is still under development. The mice developed gait disturbances after 6 weeks of blocking their jugular veins, however the severity was significant but not disabling. The next step is trying to compare it or incorporate it to EAE. The funny part will be the testing of immune modulators on this new model to see what (or what doesn't) happens!

...


I have felt for some time that the AEA model is not much use. I do not believe anymore that MS is an autoimmune disease. The immune response is "clean-up" activity of the C cells that generally follows inflammatory damage. They shouldn't be in the CNF, and that is innapropriate, but they are not themselves causing the damage and all to time trying to figure out why they are attacking the mylen has been wasted, since they are not themselves attacking the mylen. The failure of adequate cirrculation and drainage of the blood has caused the damage...inadequate oxygen supply and waste product build-up.

The AEA model was developed by creating an autoimmune mouse with MS-like symptoms, and then used to show that MS involved autoimmunity. Rather circular.

Very exciting reporting Sou !! Thanks from all the TIMS members who couldn't be there!!
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Postby Cece » Tue Mar 15, 2011 9:02 am

DrCumming and drsclafani, I hope we hear from you too when you are back or when you are able!!
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Postby prairiegirl » Tue Mar 15, 2011 9:23 am

sou wrote:Given Dr Zlokovic's discoveries proving that neurodegeneration can't but follow vascular abnormalitites and Dr Begg's model explaining how venous obstructions far away on the venous side can cause a deadly CSF oscilation throughout the CNS, along with hypoperfusion/oligaemia, I wonder who can still insist that normal people have occuded cerebral veins. Even if somebody have, they are not normal. The time bomb is there.

It is so interesting to read your reports from the conference! Thanks, Sou; look forward to your next missive.
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Postby MarkW » Tue Mar 15, 2011 9:52 am

Sou reported:
I am in the conference room. I am finding some time to write to the board because stroke related presentations are taking place. What I have felt so far is that the whole CCSVI theory is really in its infancy, but there is a widepread conviction that vascular issues preceed CNS damage.

Sou, I am also envious of you being in Bologna. I hope many on TiMS appreciate that CCSVI is in its infancy, not a finalsed disease. A syndrome at this time not yet (if ever) a disease.

I would expect a group of vascular specialists to conclude that vascular issues precede CNS (myelin or axon ?) damage. In the next few years someone will discover if astrocyte death comes before or after CCSVI and BBB changes. Then the order of the genetic transcription could be determined and the environmental factors which facilitate transcription may be determined. Probably more than a decade away and most probably multifactorial.

In the meantime, I hope the best methods of diagnosis and treatment of vein stenosis and valve issues are documented.

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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Postby sou » Tue Mar 15, 2011 10:56 am

Hi.

There was a simply fantastic idea, again from Dr Zamboni:

Plethysmography!!!

The patient wears a collar, which measures the volume of the fluids in the neck. At first, he is upright, sitting in a chair. When the volume stabilizes, the chair is aggressively tilted, bringing the patient in supine position. The volumes keep getting continuously measured and this postural change increases the volume in the neck. Again, the patient is aggresively tilted to the sitting upright position and what a miracle! MS patient's volume take a looooooong time to decrease again! Normal subject's fluid volume dereases almost instantly...

This completely eliminates the operator's special training dependency! Just press a button and you have answered whether CCSVI is present or not. Then use the doppler to see what is going on. Brilliant????
Shortest joke: "We may not be able to cure MS but we can manage its symptoms."
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Postby Motiak » Tue Mar 15, 2011 11:05 am

Are the Plethysmography observations something they've seen or just what they expect to see?
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Postby sou » Tue Mar 15, 2011 11:12 am

They have presented the results of a study with 50 MS/50 healthy participants. Unfortunately my old netbook does not have a CD-ROM drive, so I can't see whether the presentations are contained so as to post the graphs.
Shortest joke: "We may not be able to cure MS but we can manage its symptoms."
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Postby 1eye » Tue Mar 15, 2011 11:13 am

I wonder who can still insist that normal people have occuded cerebral veins. Even if somebody have, they are not normal. The time bomb is there.


My mother died of a heart condition. But she also died because she voluntarily discontinued her dialysis. She had an autoimmune/vascular disease which destroyed her kidneys - vasculitis. She never had any MS-like symptoms, but a primary vascular morbidity. How much of that was congenital, I wonder? She only got sick very late in life.
"Try - Just A Little Bit Harder" - Janis Joplin
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'MS' is over - if you want it
Patients sans/without patience
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Postby Motiak » Tue Mar 15, 2011 11:15 am

I know it's not the exact same thing but it reminds of how if I lean my head back and then bring my head back to looking straight I get vertigo and feel sick for ~30 second.
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Postby Cece » Tue Mar 15, 2011 11:32 am

sou, you are wonderful! I've been trying to get a grasp on plethysmography since it appeared on the ISNVD poster a few months ago!

So when the patient is supine, both the healthy and the MS patient experience increases in volume in the neck? Then when they sit up, the healthy patient's neck volume instantly decreases, but the MS patient's does not, because of congestion because of blockages.

Yes, it is brilliant. :)

No special training. Fantastic.

And what about other neurological conditions? How do ALS patients or Parkinson's patients or migraine patients respond to plethysmography? (I know, no answers yet.)
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Postby sou » Tue Mar 15, 2011 11:47 am

Cece wrote:Deadly CSF oscillations?


The inadequate blood outflow raises the pressure, until it reaches to the point that it is enough to move the blocked blood through the "Starling resistor" and the blockage. This pressure is passed to the CSF, which presses the CNS and, all of a sudden, the pressure is decreased. And this is going on FOR LIFE!


Sou, would you say that the conference did a good job of bringing together the vascular and the neurological side or is it still mostly weighted to the vascular guys? Dr. Hubbard and Dr. Zlokovic and Dr. Salvi would be prominent neurologists in attendance, are they fairly alone in that regard?


It was quite biased towards vascular specialists. However, the feeling I got was that we are about to live a unification of CNS pathologies to a, let's say, Chronic Neuromicrovascular Insufficiency.
Shortest joke: "We may not be able to cure MS but we can manage its symptoms."
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Postby Cece » Tue Mar 15, 2011 12:02 pm

Press release - posted by Cheer on Facebook

Press Release of March 15, 2011

ISNVD Annual Meeting

ISNVD is the International Society for Neurovascular Disease,

at present highly committed to the study of CCSVI


Bologna, March 14 and 15, 2011


Many of the issues which are still open on the relationship between CCSVI and MS found an answer at the ISNVD (International Society for Neurovascular Disease) Annual Meeting. The Society, chaired by Prof. Paolo Zamboni, held its meeting in Bologna (Italy) on March 14-15, 2011 under the High Patronage of the President of the Italian Republic.

The Meeting – attended by registered physicians, researchers and accredited journalists – was preceded by a preliminary meeting of the International Scientific Committee on Sunday March 13. It was organized in the form of a Consensus Conference with the purpose of defining minimum starting points in the approach to the investigated diseases.

There was a great deal of interest in the research of CCSVI, the vascular condition discovered by Prof. Paolo Zamboni from the University of Ferrara, which seems to interfere with progression of Multiple Sclerosis.

The history of CCSVI recognition has indeed gone through a tortuous pathway, more so in Italy than in foreign countries. However, last Spring the Italian Higher Health Council assessed the “18-months’ results of a preliminary experience of correcting the stenosing lesions” as promising and regarded Prof. Zamboni’s observations as “being of undoubted interest and worth being further investigated with all the tools currently available to medical research”.

Highly distinguished world experts attended the Meeting in Italy, not only to confront themselves with the new scenarios opened up by this discovery, but also to discuss the independent studies successfully carried out by the most famous Universities in the world during the past two years.

The Meeting will be a milestone for CCSVI research: among the most significant presentations were those documenting the on-going experiences at the University of Stanford and UCSD, to mention just a few.

In particular, data were presented to show whether CCSVI is associated with MS (recent studies by several independent groups) and how CCSVI treatment with angioplasty may change and/or improve the MS symptoms as pointed out by recent studies performed with this type of treatment with the approval of the Ethics Committees of several Universities of the world.


The following were among of the main topics of discussion:


EPIDEMIOLOGY OF CCSVI IN MS

Many different groups from all over the world clearly showed by the means of gold standard catheter venography that the prevalence of CCSVI in MS is more than 90% of the cases (USA, Greece, Poland, Jordan, ….).

To the contrary the prevalence of CCSVI in healthy people has been calculated in a study by using CT angiography in less than 8% of cases (Wayne state University, Michigan).

Prof. Bastianello present the data of an international epidemiology observatory that collected more than 700 cases with ECD carried out by trained staff. It is the first large multicenter study on CCSVI while those conducted so far were simply single-center studies.

The result of this non invasive study clearly confirm the data above because the percentage of MS patients with ccsvi is 86%.


ROLE OF OXYGENATION AND TISSUE DRAINAGE

Among the questions that were answered at the Meeting was also a fundamental one which relates to the observation made by Bruce Trapp from Cleveland (one of the most eminent MS researchers) according to whom nerve cell damage and death are due to an axonal asphyxial phenomenon which has not been yet completely clarified.


Data from a joint study conducted with perfusional MRI by the University of Buffalo, Prof. Zamboni and Dr Salvi (see relevant press release) - soon to be published in the BMC Medicine journal - were presented in Bologna by Prof. Robert Zivadinov, showing that this asphyxial cell phenomenon could be related to severe obstruction of the extracranial veins, thus providing a first substantial answer to asphyxial hypothesis in MS.

ROLE OF IRON

Major contributions were presented on the role of iron, with particular reference to its build-up around the veins, which is one of the key points of the CCSVI theory.

One of the pivotal observations is that iron builds up around the cerebral veins, even in the white matter. This is what mostly differentiates MS from many other inflammatory and neurodegenerative diseases.

The role of iron in nervous system degeneration was the subject of a dedicated session with a presentation by Prof. Iadecola from NY, one of the greatest experts in Alzheimer’s disease.


ADVANCED DIAGNOSTIC IMAGING


Over and above the well-established gold standard of catheter phlebography which was presented by Dr Roberto Galeotti, one of the pioneers in the use of this technique, all the new diagnostic tools developed for CCSVI during the past two years were reviewed during the opening session of the Meeting chaired by Profs. Haacke and Salvatore on Monday morning. The groups of Wayne State University, Detroit, and of the Buffalo Neuroimaging Analysis Center of the University of Buffalo presented a large amount of emerging data on advanced diagnostic techniques.

Concerning the screening methods – in which patients are mostly interested - new achievements have been proposed. From the diagnostic standpoint, one of the main objections is that diagnosis of CCSVI is being too dependent of Eco-Colour-Doppler and on the reading skills of the physician, therefore not always reproducible.


To avoid this, Prof. Zamboni and his team at the Center for Vascular Diseases of the Ferrara Hospital have developed a new diagnostic technique, i.e. cervical plethysmography. Data were presented how this non-invasive tool will allow for preliminary screening and diagnosis with high diagnostic reliability without being operator-dependent
.

Cervical plethysmography is currently a prototype which is not yet commercially available but has some advantages: the test lasts only 5 minutes and makes it possible to obtain a final answer in 85% of cases.

However, this test does not rule out the need for ECD which must be performed if a subsequent patency procedure is to be carried out. Therefore, this new diagnostic method may become a fast and cheap screening procedure.

TREATMENTS

Concerning endovascular treatment, one can state that the highest level of scientific evidence is generated by double-blind randomized trials which require a long time for completion.

In science it is well-known, however, that scientific evidence can also come from several observational studies which independently and scientifically measure the effects of a certain treatment in a very high number of patients.

Additional evidence was provided by the results of two American studies which were among the first to be carried out in this field. They are observational studies which measure the effects of angioplasty on a very large number of patients. They can be regarded as a corollary and driving element for other studies such as those which are about to be carried out in Italy.

The outcome of over 1,000 cases treated in different studies all over the world were presented. The most fascinating piece of research is the one of Dr D. Hubbard from the University of California San Diego.

Functional MRI is a real-time technique which makes it possible to identify the plastic changes that the brain undergoes during functional brain activities.

The cognitive skills of a group of 20 subjects with MS were measured by having them perform a series of memory and operational drills under functional MRI control.

After the necessary examinations, the San Diego team performed angioplasty on all 20 subjects with MS. When re-checked using functional MRI, they showed significant improvement in their cognitive skills which no longer differed from those of the healthy controls used for comparison.


A second treatment study was presented by Dr M. Mehta from Albany Medical Center, NY, who studied 150 consecutive MS patients where he identified almost 300 jugular and azygos veins with significant stenosis and performed angioplasty.

In the post-operative phase, he monitored important aspects such as chronic fatigue which is one of the most disabling symptoms of MS and one with no therapeutic response.

Chronic fatigue improved significantly in all surgical patients. This was further confirmed by more than 25% increase in the quality of life scores as measured by physiatrists who were unaware of the surgical procedure one year after angioplasty.


Data are also available from the Polish Center of Katowice which alone operated on more than 1,000 patients, while Dr M. Zarebinski presented the data of 420 patients who underwent venoplasty in Warsaw.

This study confirmed the safety of the treatment, since in this and all other studies no complications or deaths were recorded. The study also confirmed significant improvement in chronic fatigue and quality of life.

Finally, Dr A. N. Siddiqui from Buffalo showed some preliminary data on a randomized trial which is currently being carried out on 30 patients at the Departments of Neurosurgery and Neurology of the University of Buffalo.


ANIMAL MODELS

As requested by many Scientific Committees throughout the world to legitimate research, the results of the development of animal models of CCSVI were presented by Stanford University, showing a correlation between reduced venous function and impaired motor ability.


OTHER VASCULAR DISEASES THAT WERE DISCUSSED:

The Meeting was not limited to CCSVI but also covered important associations with other vascular diseases; for example, Costantino Iadecola spoke about Alzheimer’s disease and vascular dementia; many national and international experts talked about carotid artery treatment for stroke prevention; finally, Dr Fabrizio Salvi spoke about the unusual symptoms observed in his clinical practice in conjunction with cerebral venous diseases.

The vascular mechanisms involved in neurodegeneration were outlined in the keynote lecture of the Meeting which was delivered by a well-known neuroscientist, Prof. Berislav Zlokovic from Rochester NY.



Under the High Patronage of the President of the Italian Republic


Under the Patronage of:

Senate of the Italian Republic; Emilia Romagna Region; Province of Ferrara; City of Bologna; City of Ferrara; Alma Mater Studiorum - University of Bologna; University of Ferrara; Ordine Provinciale dei Medici Chirurghi e degli Odontoiatri di Bologna (Medical Association of the Province of Bologna); Ordine dei Medici Chirurghi e degli Odontoiatri della Provincia di Ferrara (Medical Association of the Province of Ferrara); SICVE Italian Society of Vascular and Endovascular Surgery.


Sponsorship

The Organizing Committee of the ISNVD Annual Meeting wishes to thank the following foundations, banks and companies for supporting the event: Fondazione Cassa di Risparmio in Bologna;

Platinum sponsor: ESAOTE;

Gold sponsor: Boston Scientific. Delivering what next and CARIFE, Gruppo Bancario Cassa di Risparmio di Ferrara;

Silver Sponsor: Flebysan and Volcano.

Special acknowledgement: Ducati


All the material disclosed at the Meeting is available on line on the following Website:

www.isnvdannualmeeting.org
Last edited by Cece on Tue Mar 15, 2011 12:08 pm, edited 1 time in total.
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