DrSclafani answers some questions

[DrDiana]

Hi EJC,
I'm not sure what you mean by eye "syndromes", but I know that many people have brighter, clearer vision even on the table when they have their CCSVI procedure. I *think* it is from two mechanisms:
1) The same hypoxia that affects the brain also affects the eyes. We can see that when we look into the eyes. The arteries are too small, and the veins are too big. I had conjectured that endothelin 1 may be the cause of the arteriole constriction, but I'm considering other things, too. If venous blood is not flowing out (and often times CSF is not flowing out), something's gotta give, right? The skull is fixed. So either the brain gets squished (and sometimes a Chiari begins), or easier, the arterial blood has a harder time getting IN. So the vision dims. If angioplasty allows more venous flow OUT (or you do something to allow more CSF out), more oxygenated blood can go IN, brightening the vision immediately.
2) Blood thinners: this is one reason I ask the question. Most patients with EDS end up on blood thinners, and we get strokes easier (ditto M.S. patients). If we have narrowing, partial blockages, etc of venous blood outflow, do the blood thinners allow more blood to exit easier? I didn't get any effects from angioplasty beyond feeling clearer headed for a few days. My son received no improvements. BUT we weren't given blood thinners post-procedure. We are on them now and doing well.

I DO see a fair amount of adult onset strabismus (an eye turns, usually inward). Is that the syndrome you are talking about? High intracranial pressure can cause a palsy of the lateral rectus. Because EDS patients are loosey-goosey, we often wear soft cervical collars at night to allow for continued CSF drainage. Many of us use Diamox (it lowers the amount of CSF produced) to correct the symptoms of hydrocephalus -- including eye turns.

Hope that helps.
;)

[dlynn]

Dr. Sclafani,
Is body weight a factor in determining the possibility of clotting in a stent?
If collagen does change in the blood (Dr. Dianas' question), does the change affect the endothelium?
Does PCS affect fertility and the ability to carry full term?
Does NCS always cause other venous issues?
Do you know of anyone whose double vision has been alleviated by PTA?
Is the use of stents becoming more acceptable to IRs'?
Is a CCSVI diagnosis required before you would consider a patient?
Thank you!

[EJC]

Hi EJC,
I'm not sure what you mean by eye "syndromes", but I know that many people have brighter, clearer vision even on the table when they have their CCSVI procedure. I *think* it is from two mechanisms:
1) The same hypoxia that affects the brain also affects the eyes. We can see that when we look into the eyes. The arteries are too small, and the veins are too big. I had conjectured that endothelin 1 may be the cause of the arteriole constriction, but I'm considering other things, too. If venous blood is not flowing out (and often times CSF is not flowing out), something's gotta give, right? The skull is fixed. So either the brain gets squished (and sometimes a Chiari begins), or easier, the arterial blood has a harder time getting IN. So the vision dims. If angioplasty allows more venous flow OUT (or you do something to allow more CSF out), more oxygenated blood can go IN, brightening the vision immediately.
2) Blood thinners: this is one reason I ask the question. Most patients with EDS end up on blood thinners, and we get strokes easier (ditto M.S. patients). If we have narrowing, partial blockages, etc of venous blood outflow, do the blood thinners allow more blood to exit easier? I didn't get any effects from angioplasty beyond feeling clearer headed for a few days. My son received no improvements. BUT we weren't given blood thinners post-procedure. We are on them now and doing well.

I DO see a fair amount of adult onset strabismus (an eye turns, usually inward). Is that the syndrome you are talking about? High intracranial pressure can cause a palsy of the lateral rectus. Because EDS patients are loosey-goosey, we often wear soft cervical collars at night to allow for continued CSF drainage. Many of us use Diamox (it lowers the amount of CSF produced) to correct the symptoms of hydrocephalus -- including eye turns.

Hope that helps.
;)

It is a tremendous help thanks.

The syndromes I was referring to specifically are :-

Internuclear opthalmoplegia
One and half syndrome

I don't want to take Dr S thread off at too much of a tangent (despite this all being connected) so please feel free to reply to me ont his thread so we don't cause clutter.

http://www.thisisms.com/forum/chronic-c ... 22238.html

[Robnl]

Hi Doc,

Today the upright mri was done, i sent you an email with attachment wiith images, 6MB total. Hopefully it's not too large...

Regards,

Robert

[CureOrBust]

Dr S, I would be interested in your view on what if any extra info you can gleam from an upright MRI?

[Cece]

Happy 4th of July!

[Vladimir]

I live in Russia. Sorry for my English.
Dear Dr. Sclafani.
I already four times done balloon angioplasty. Every time after that there were obvious improve my health.
But every time this improvement was short-lived. About three-four days.
The most important is the improvement of sleep and the fog in my head also disappeared diplopia.
I was doing a balloon angioplasty at short intervals (06.12.12 + 21.03.13 + 24.04.13).
I am now convinced that the balloon therapy does not bring to me, stable and long-term effect.
The last time (05.06.13) I definitely wanted to put stents.
Prof. Dr. med. Horst Sievert told me after venogram, that in my case it is ready to put a stent only blocking the subclavian vein.
I refused such a proposal because "jails" for the side branch is a bad option therapy.
I asked the doctor why I cant get a standard stent installation option as other patients with CCSVI.
He answered that with my anatomy jugular vein, if you place a stent with the edge of the Bifurcation it may shift to the top like a cork.
Dear Dr. Sclafani, look at the shape of my internal that of jugular veins and tell me if she really is unsuitable for stenting procedures?

06.12.2012 in Bulgaria Prof. Dr. Grozdinski and Dr. Ivo Petrov.
LEFT IJV (first venogram) up to angioplasty


05.06.2013 "CardioVasculäres Centrum Frankfurt" Prof. Dr. med. Horst Sievert
LEFT IJV (Now after all angioplasties)
The left IJV twice did angioplasty balloon 16 mm. and twice with two parallel balloon.
The maximum diameter of 25.28 mm.




06.12.2012 in Bulgaria Prof. Dr. Grozdinski and Dr. Ivo Petrov.
RIGHT IJV (first venogram) up to angioplasty
Also, MRI scans showed "hypoplasia of the right transverse sinus".
https://dl.dropboxusercontent.com/u/776 ... plasty.png

05.06.2013 "CardioVasculäres Centrum Frankfurt" Prof. Dr. med. Horst Sievert
But during the last angiography "right internal jugular vein" Prof. Dr. Sievert said that the diameter of the right internal jugular vein about 15 mm. all the way to the brain.
So I've been having doubts about the correctness of the finding of hypoplasia of the sinus.
RIGHT IJV (before the last angioplasty)
https://dl.dropboxusercontent.com/u/776 ... lasty).png

RIGHT IJV (Now after all angioplasties)
This time the balloon with diameter 16 mm was applied. But he was not fully inflated, the waist was visible.
https://dl.dropboxusercontent.com/u/776 ... sties).png


I recently read about this method of stenting.
The “Y” Stent: A Technique Using Nitinol Stents to Treat Bifurcations.
doi: http://dx.doi.org/10.1583/1545-1550(200 ... U>2.0.CO;2

This publication is an example of installation “Y” stent at the junction of the right jugular and subclavian vein.
(Creation of a bifurcated stent in the central venous system (Fig. 3)
A similar configuration was also used to treat lesions affecting the confluence of jugular and subclavian veins.)
Dr. Sclafani, somebody now practicing this method stenting?
Maybe you know any other way to solve my problem?
На всякий случай я высылаю вам
Just in case I also wrote you a message with links for downloading files (.zip) with images of catheter angiography in DICOM format.

Thanks in advance.

[drsclafani]

I live in Russia. Sorry for my English.
Dear Dr. Sclafani.
I already four times done balloon angioplasty. Every time after that there were obvious improve my health.
But every time this improvement was short-lived. About three-four days.
The most important is the improvement of sleep and the fog in my head also disappeared diplopia.
I was doing a balloon angioplasty at short intervals (06.12.12 + 21.03.13 + 24.04.13).
I am now convinced that the balloon therapy does not bring to me, stable and long-term effect.
The last time (05.06.13) I definitely wanted to put stents.
Prof. Dr. med. Horst Sievert told me after venogram, that in my case it is ready to put a stent only blocking the subclavian vein.
I refused such a proposal because "jails" for the side branch is a bad option therapy.
I asked the doctor why I cant get a standard stent installation option as other patients with CCSVI.
He answered that with my anatomy jugular vein, if you place a stent with the edge of the Bifurcation it may shift to the top like a cork.
Dear Dr. Sclafani, look at the shape of my internal that of jugular veins and tell me if she really is unsuitable for stenting procedures?

06.12.2012 in Bulgaria Prof. Dr. Grozdinski and Dr. Ivo Petrov.
LEFT IJV (first venogram) up to angioplasty


05.06.2013 "CardioVasculäres Centrum Frankfurt" Prof. Dr. med. Horst Sievert
LEFT IJV (Now after all angioplasties)
The left IJV twice did angioplasty balloon 16 mm. and twice with two parallel balloon.
The maximum diameter of 25.28 mm.




06.12.2012 in Bulgaria Prof. Dr. Grozdinski and Dr. Ivo Petrov.
RIGHT IJV (first venogram) up to angioplasty
Also, MRI scans showed "hypoplasia of the right transverse sinus".
https://dl.dropboxusercontent.com/u/776 ... plasty.png

05.06.2013 "CardioVasculäres Centrum Frankfurt" Prof. Dr. med. Horst Sievert
But during the last angiography "right internal jugular vein" Prof. Dr. Sievert said that the diameter of the right internal jugular vein about 15 mm. all the way to the brain.
So I've been having doubts about the correctness of the finding of hypoplasia of the sinus.
RIGHT IJV (before the last angioplasty)
https://dl.dropboxusercontent.com/u/776 ... lasty).png

RIGHT IJV (Now after all angioplasties)
This time the balloon with diameter 16 mm was applied. But he was not fully inflated, the waist was visible.
https://dl.dropboxusercontent.com/u/776 ... sties).png


I recently read about this method of stenting.
The “Y” Stent: A Technique Using Nitinol Stents to Treat Bifurcations.
doi: http://dx.doi.org/10.1583/1545-1550(200 ... U>2.0.CO;2

This publication is an example of installation “Y” stent at the junction of the right jugular and subclavian vein.
(Creation of a bifurcated stent in the central venous system (Fig. 3)
A similar configuration was also used to treat lesions affecting the confluence of jugular and subclavian veins.)
Dr. Sclafani, somebody now practicing this method stenting?
Maybe you know any other way to solve my problem?
На всякий случай я высылаю вам
Just in case I also wrote you a message with links for downloading files (.zip) with images of catheter angiography in DICOM format.

Thanks in advance.

Dear Vladimir
i received your private message upon returning from holidays.

As I said, I am pleased to try to help you but it must be through my personal patient email. You can understand that it is impossible to keep records of all my patients through TIMS and far more practical in a private manner.

Looking at the images, i think that you have always been underdilated. I would think that a much large balloon would be necessary in your case, but i must review your records and then discuss this with you through
ccsviliberation@gmail.com, where I keep my personal patient correspondence.

Talk to you soon.

DrSclafani

[drsclafani]

Hi Dr. Sal, Can I trouble you with two quick questions? I'd be so grateful for your input.
1) Did anyone ever determine why the collagen in the veins seemed to turn from collagen 1 to collagen 3? Do you know if there is a similar change in something like pelvic congestion syndrome?

2) Has anyone ever compared the CCSVI study results, separating them for the patients who received blood thinners post-op and those who did not? (Upon casual observation, it seems that the 'received blood thinners group' tended to do better, but I could be wrong.)

Thank you so, so much for your continued dedication!
;) Diana

Hi Diana
sorry for the delays in responding.

Zamboni believes that The collage problem is genetic and present in utero. I recall a paper that showed that the gene for this problem resides on same chromosome as some of the MS markers.

But i am no geneticist, that is for sure. THey barely had genetics when I went to medical school.

There is pitiful data on PCS, pelvic congestion syndrome. But my anecdotal experience is that a lot of those patients that I see have minor expressions of some symptoms and signs of EDS, POTS, etc.

My experience is much better since I routinely gave anticoagulation, especially after i started using pradaxa. the use of antiplatelet therapy alone, such as aspirin and or plavix, is insufficient in my experience.

I am obsessed with avoiding thrombosis and detected it as early as possible. I ask all my patients to get an ultrasound to look for clots within a week of stopping anticoagulation. And i continue aspirin therapy for at least six months for its antiinflammatory properties. But the evidence is again anecdotal and not part of a trial.

A hematology colleague in Montreal likes to keep my patients on anticoagulation much longer but i havent any evidence that it makes a difference.

But for sure, anticoagulation is essential in reducing thrombosis.

[drsclafani]

Dr. Sclafani,
Is body weight a factor in determining the possibility of clotting in a stent?
If collagen does change in the blood (Dr. Dianas' question), does the change affect the endothelium?
Does PCS affect fertility and the ability to carry full term?
Does NCS always cause other venous issues?
Do you know of anyone whose double vision has been alleviated by PTA?
Is the use of stents becoming more acceptable to IRs'?
Is a CCSVI diagnosis required before you would consider a patient?
Thank you!

weight and diet may have some consequences, but those risks are much clearer in lower extremity clots. Stents clot when blood flow is insufficient, in thrombogenic patients, such as those with hyper coagulability, such as Protein C and S deficiencies, etc; those who smoke tobacco, those with upstream obstructions, those who do not get adequate anticoagulation to name a fewer of the more common reasons.

I do not think that collagen in the blood is an issue

PCS seems to develop after pregnancies with higher frequency but i havent read anything that says that pcs prevents or causes difficulty (other than pain to the mother)..

NCS is very often asymptomatic, called the nutcracker phenomenon. It seems to be more prevalent and more stenotic in patients with MS

i have had patients whose double vision improved or reverted to normal vision after treatment of ccsvi.

I think that stents have always been a part of IRs armentarium. It is just limited in its use by many of us. I think that most patients (>95%) do not need stents, certainly stents should rarely be placed during the first treatment.

Sorry Dlynn. what would i be considering patients for ?

[drsclafani]

Dr S, I would be interested in your view on what if any extra info you can gleam from an upright MRI?

CSF fluid dynamics, instabilities of the spine

I do not do it very often, cureorbust

DrS

[dlynn]

Dr. Sclafani,
Is a CCSVI (or restenosis) diagnosis required before you would consider a patient for PTA?
For a 5th procedure, would you consider stents?

[DrDiana]

Thank you so much, Dr. S!
If you ever come across that genetics article, comparing the genes for collagen and MS, I'd LOVE to see it! (Unfortunately - ha), I'm being forced to delve into genetics, SNP's, etc. Ugh.

As you know, I'm trying to figure out MS by going through the 'back door' -- studying collagen disorders (we tend to develop MS, and we get CCSVI and congestive pelvic syndrome, etc). Once demyelination occurs, the symptoms/signs of interstitial cystitis, gastroparesis/constipation and even brain fog and ocular fundus changes can be difficult to figure out (is it due to demyelination or another cause?). People with collagen disorders and CCSVI without MS perhaps can give us some answers.

I'll just mention to you that most Ehlers-Danlos patients (collagen disorders) are being put on some sort of blood thinners -- too many of us develop strokes, DVT's, etc, even without genetic thrombotic disorders. I just wonder if the folks who had angioplasty (especially the ones with EDS), but didn't get good results (like my son and I), could have gotten a better result with blood thinners. I'd love to see the current results of CCSVI studies evaluated based on who received blood thinners! I'm even curious if some of those "stenosed" transverse sinuses may have been thromboses...

BTW, do you treat congestive pelvic syndrome? How about testing "kinked" carotid arteries? My hubby has one of those, and he is losing short-term memory. It may be unrelated, but seeing that kink sure bothers me!

Thanks so much, Dr. Sal!

[cheerleader]

Dear Dr. Diana and Dr. Sclafani--

Here's the most recent publication on altered collagen expression--a shift to type III-- in the jugular veins of people with MS.
http://www.ncbi.nlm.nih.gov/pubmed/22770861

Here are my notes from the first CCSVI conference in 2009, where Dr. Guilio Gabbiani first presented his research on the changes in collagen in jugular veins of those with MS.

Dr. Guilio Gabbiani from the Centre Medical Universitaire in Geneve, Switzerland
speaking on jugular wall changes in MS. His laboratory was interested in the fibrotic changes. He was interested in learning the importance of venous morphology, and is surprised so little is known.
Comparing arteries to veins:
Arteries are thicker and there is more resistance.
Veins contain smooth muscle cells, and arteries never contain smooth muscle cells.

Dr. Gabbiani took 5 specimens from IJV tissue removed by Dr. Zamboni from some of the patients he treated endovascularly. The tissue was from the area NOT damaged by angioplasty.
He compared it to healthy tissue from autopsy controls.
He looked at eosin, hematoxylin, Miller’s elastic stain and masons truchrome.
He found smooth muscle cells were numerous and increased in MS compared to controls. He then used isoelectric focusing to measure contractions in the smooth muscle cells via actin heterogeneity to ID the smooth muscle cells in the veins.
There is an increased expression of smooth muscle actin in MS, much more than controls.

By red staining for collagen and using unpolarized and polarized light, he saw that there is less collagen 1 type fibers in the MS jugular vein tissue, and more collagen III fibers in MS. This was the exact opposite of the controls.

Connective tissue in MS switches from collagen I to collagen III and this takes place in the IJVs. This switch also happens in fibromatosis, colloids and hypertrophied scars, and this remodeling may play a role in CCSVI disturbances.

Dr. Lee makes a comment...
This collagen conversion from I to III happens in the arteries had no idea it could happen in the veins as well!

answer: Collagen III is stiffer, and fibrosis takes place for some reason. There was no inflammation on the tissue samples, but inflammation might have occurred before the the intervention and the fibrotic changes happened. All is still speculation, we do not know.

Dr. Zivadinov asks, so the testing was in the normal, non-stenosed part of the IJV?

Answer: Yes, we are trying to examine the normal part of the vein not affected by stenosis.

https://www.facebook.com/note.php?note_id=131482162210

As far as genetic links--Dr. Ferlini has been investigating the shared CNVs of venous disease and MS--

The CNVs contained in the HLA locus region in patients with the novel phenotype of CCSVI/VM and MS were mapped in detail, demonstrating a significant correlation between the number of known CNVs found in the HLA region and the number of CCSVI-VMs identified in patients. Pathway analysis revealed common routes of interaction of several of the genes involved in angiogenesis and immunity contained within this region. Despite the small sample size in this pilot study, it does suggest that the number of multiple polymorphic CNVs in the HLA locus deserves further study, owing to their possible involvement in susceptibility to this novel MS/VM plus phenotype, and perhaps even other types of the disease.

http://www.ncbi.nlm.nih.gov/pubmed/20426824
cheer

[Cece]

Also there's the ccsvi/ms 2010 genetic research from Zamboni but no mention of collagen in it. I couldn't find anything in googlescholar comparing genes for collagen and for MS. I'm stumped!

http://www.biomedcentral.com/1471-2350/11/64
Custom CGH array profiling of copy number variations (CNVs) on chromosome 6p21.32 (HLA locus) in patients with venous malformations associated with multiple sclerosis