Extracranial venous stenosis is an unlikely cause of MS

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

Postby jimmylegs » Tue Nov 09, 2010 5:42 pm

thumbs up all :) THIS is ThisIsMS :)
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Postby Cece » Tue Nov 09, 2010 5:48 pm

CCSVIhusband wrote:EDIT:
Also a great point Cece ... I remembered that point from Dr. Sclafani (and also my wife's doctor said the same thing) ... but I'm not a wizard at this site (linking, etc) and can't find his stuff like you can.

I remember a phrase (ok, in this case it was "Beirut study") and go to google and search site:thisisms.com beirut study drsclafani

No wizardry involved.... :)
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Postby dreddk » Tue Nov 09, 2010 6:01 pm

Methodology

"The venographies were performed and reported by a
vascular radiologist with 25 years experience in vascular
and interventional radiology, who was blinded to
the patient’s clinical data. The procedure was performed
in a specialized angiography suite (Philips,
Eindhoven, Netherland). Under sterile conditions and
local anesthesia, the right femoral vein was catheterized.
A 5F vertebral curve catheter (Boston Scientific,
USA) and 0.035-inch curved Terumo wire (Terumo,
Japan) were used to selectively catheterize the IJVs.
Views of the IJVs were then obtained in held inspiration;
anteroposterior (AP), 30 right anterior oblique
(RAO) and 30 left anterior oblique (LAO) projections
were obtained. The AV was then selected and catheter
advanced to the level of the lower thoracic segment at
around the D8 vertebra. AP and 60 LAO views were
obtained. Magnified views of the proximal AV were
added when necessary.

The presence of a stenosis of the IJV was reported
when the three following criteria were fulfilled: 50% or
more narrowing of the lumen, delayed clearance of the
contrast column across the lesion and absence of valve
leaflets. The last two criteria were used to avoid misdiagnosis
secondary to prominent IJV valves or extrinsic
impression on the veins from nearby structures such
as sternocleidomastoid muscle, esophagus or others.
Filling of so-called collateral veins was difficult to
assess because of variable connections between the
internal and external jugular venous systems. The
degree of stenosis was considered as the narrowest
lumen of all the views relative to the caliber of the
IJV on that particular view. Abnormalities of the AV
lumen were reported as observed.

MRI data

Patients with documented EVS had all available brain
and spine MRIs since disease onset reviewed. Only
MRIs with intravenous contrast enhancement were
considered. The MRI scans were reported by a trained
neuroradiologist who was not aware of the clinical presentation
or venography data. The topographic distribution
of all Gadolinium-enhanced (Gdþ) lesions was
determined based on four anatomic regions: left hemisphere,
right hemisphere, posterior fossa and spinal
cord. The hemisphere anatomic region included the
ipsilateral optic nerve. MRIs done within 30 days of a
previous MRI were not considered for review."
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Postby dreddk » Tue Nov 09, 2010 6:04 pm

92% of Late MS (MS) subjects had Vein Stenosis versus 24% of Early MS and 9% of CIS.


LMS.

In the LMS group were patients with RRMS as
per the revised McDonald’s criteria with disease
duration of more than 10 years.

– Expanded Disability Status Scale (EDSS) of 0–6.5
– Signing an informed consent for the procedure
– Normal renal function
Exclusion criteria were:

– Primary or secondary progressive MS
– Other autoimmune or neurological diseases
– Systemic vascular disease
– Cerebral vascular malformations.

EMS comprised two groups:

1. Patients with clinically isolated syndrome (CIS)
defined as a single first clinical event suggestive of
MS of less than 1 year duration, lasting for more
than 24 h, excluding paresthesia or cerebral dysfunction,
and a brain MRI showing at least 2 clinically
silent T2 lesions with a size of at least 3 mm, at least
one of which being ovoid, periventricular or
infratentorial.

2. Patients with relapsing remitting MS (RRMS) as per
the revised McDonald’s criteria with disease duration
of less than 5 years.8
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Postby dreddk » Tue Nov 09, 2010 6:07 pm

Conclusion

"In conclusion, we think that EVS is a late manifestation
in MS, and is unlikely to induce a state of CCSVI
since only a minority of patients has a single venous
stenosis early in the disease. It is more likely to be a
secondary phenomenon, possibly present in other neurological
diseases, reflecting chronic brain disease and
atrophy. The exact mechanism of such process is
unclear, since the extracranial venous system, especially
in the spinal cord, has never been adequately investigated
in chronic neurological diseases. We hypothesize
that chronic degenerative brain diseases resulting in significant
brain atrophy and tissue loss might lead to a
decrease in the volume of venous drainage, resulting
ultimately in venous stenosis. In MS specifically,
chronic perivenous inflammation might hypothetically
lead to release of certain inflammatory mediators that
might alter the venous endothelium or lead to venous
valvulitis resulting in venous stenosis."
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Postby scorpion » Tue Nov 09, 2010 7:01 pm

For layman like me: These are the basics,right?

Venography WAS performed.

It was very rare to find stenosis in early MS.

However it was fairly common in late stage MS.
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Postby dreddk » Tue Nov 09, 2010 7:08 pm

Yep, correct. Just posted the different sections to save debate over how the study might have been done
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Postby Cece » Tue Nov 09, 2010 7:08 pm

dreddk wrote:The presence of a stenosis of the IJV was reported
when the three following criteria were fulfilled: 50% or
more narrowing of the lumen, delayed clearance of the
contrast column across the lesion and absence of valve
leaflets. The last two criteria were used to avoid misdiagnosis
secondary to prominent IJV valves or extrinsic
impression on the veins from nearby structures such
as sternocleidomastoid muscle, esophagus or others.
Filling of so-called collateral veins was difficult to
assess because of variable connections between the
internal and external jugular venous systems. The
degree of stenosis was considered as the narrowest
lumen of all the views relative to the caliber of the
IJV on that particular view. Abnormalities of the AV
lumen were reported as observed.

It's interesting that with all that excluded, they still found stenosis in 12 out of 13 of people with RR MS of over 10 years.

It's insane that they considered the presence of valve leaflets as a disqualification when that's what CCSVI is: outflow obstructions, as drsclafani recently put it, either from stenosis or very frequently from malformed valves. I have malformed valves on both sides, yet would not be counted as CCSVI in this study.

50% is also too high, in a low flow situation such as veins. But that's a minor point, excluding valves from counting as CCSVI is the major point.
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Postby Lyon » Tue Nov 09, 2010 7:09 pm

.
Last edited by Lyon on Sun Nov 20, 2011 5:24 pm, edited 1 time in total.
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Postby scorpion » Tue Nov 09, 2010 7:31 pm

I think the Buffalo study found 22% of people without MS had what they defined as stenosis. This matches closely with the amount of people with MS who had stenosis(24%) in this study who were early in the disease process. It looks like, just based on these results, stenosis in people with MS correlates with the length of time time they have had MS. It would seem to follow that the liberation procedure should than be more effective for people who have had MS for a number of years since that is when stenosis is the greatest yet it is claimed the liberation procedure is more effective for people with early MS. :?
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Postby dreddk » Tue Nov 09, 2010 7:35 pm

Cece wrote:
It's insane that they considered the presence of valve leaflets as a disqualification when that's what CCSVI is: outflow obstructions, as drsclafani recently put it, either from stenosis or very frequently from malformed valves. I have malformed valves on both sides, yet would not be counted as CCSVI in this study.
.


From the paper I believe presence of leaflets was excluded so as not to have false positives caused by prominent IJV valves which may be unrelated to MS.

"In comparison, Zamboni et al.’s series
included 35 RRMS patients with mean disease duration
of 4 years, all of whom had evidence of EVS.

The difference between our results and those of Zamboni
and colleagues can be due to many factors.
Extracranial SV is not routinely used in neurological
practice and therefore lacks standards for ‘normals’,
which is reflected by the paucity of series in the literature
addressing the subject. The caliber of the IJV is
dependent on many factors including patient’s position,
breathing (inspiration vs. expiration), compression by
nearby structures (such as sternocleidomastoid muscle
or carotid artery for IJV and esophagus in the case of
AV), and prominent IJV valves, all of which can give a
picture of pseudostenosis (Figure 3). Furthermore, congenital
variations in the size of the IJVs are common,
particularly on the left which is commonly smaller than
the right (see Figure 2). One of our patients had an
absent IJV on the left side, with drainage occurring
through the external jugular network. We rigorously
excluded all those confounding factors in our SV studies,
and performed all contrast injections during held
inspiration to avoid misdiagnosis. Moreover, a diagnosis
of EVS was contingent on the presence of delay in
contrast clearance across the lesion which reflects a
functional consequence of the venous stenosis."
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Postby Cece » Tue Nov 09, 2010 7:44 pm

scorpion, this Beirut study is essentially invalid. They looked for stenosis only and invalidated if a patient had a valve problem. But CCSVI is valve problems.

dreddk, yes, that was their reasoning, but their reasoning was wrong. I am upset at this, I want research that we can believe in, even if it came out with results in oppposition to my belief that CCSVI is causal to MS then those would be the results. Instead they are wasting their time and ours on studies that look for stenosis only and exclude valves.

Also when they exclude impressions, that is wrong too. An impression can be a result of excessively low flow in the vein, caused not by the impression (such as the carotid impression) but by those aforementioned incompetent valves lower down. When the valves are treated, the vein fills and the impression goes away, the docs have watched this in the operating room. This is also CCSVI.
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Postby Cece » Tue Nov 09, 2010 7:48 pm

dreddk wrote:One of our patients had an
absent IJV on the left side, with drainage occurring
through the external jugular network. We rigorously
excluded all those confounding factors in our SV studies,
and performed all contrast injections during held
inspiration to avoid misdiagnosis."

Oh, yes, exclude that guy for sure. 8O

A missing jugular is CCSVI.

I won't even address the held inspiration. Which sounds like valsalva. Which hides rather than finds CCSVI.
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Postby dreddk » Tue Nov 09, 2010 7:52 pm

Cece

I think the issue you raise is relative. If you broaden the definition of CCSVI then you will pick up more genuine cases, but you will also collect false positives and the relative difference will remain between CIS and LMS.

The authors also looked at it from another angle which is quite interesting and again indicates CCSVI may not cause MS:

"Could CCSVI be a contributing factor in a subcategory
of MS patients causing a more severe or accelerated
disease?

To test this hypothesis we looked at our
EMS group. Patients with and without stenosis had
comparable EDSS (1.433 vs. 0.86, p¼0.85) with similar
disease duration (2.1 vs. 2.4 years, p¼0.52), and for the
subgroup with RRMS the annualized relapse rate since
disease onset was similar (1.411.02 vs. 1.561.02,
p¼0.78 ). Finally, if CCSVI is a causative factor in
MS, a certain topographic correlation should be present
between site of EVS and anatomic localization of
the clinical relapses or Gdþ lesions on MRI. We retrospectively
reviewed all Gd-enhanced brain and spine
MRIs performed on the 19 patients with EVS since
disease onset and could not find such a correlation
(Table 4). The presence of EVS did not correlate with
increased Gdþ lesions on MRI. We also did not find
any evidence of a correlation between site of EVS and
anatomic localization in all 14 relapses suffered since
disease onset by EMS patients, 10 of which were
assessed prospectively at our center (Table 3)."
Last edited by dreddk on Tue Nov 09, 2010 7:56 pm, edited 3 times in total.
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Postby ikulo » Tue Nov 09, 2010 7:52 pm

scorpion wrote:I think the Buffalo study found 22% of people without MS had what they defined as stenosis. This matches closely with the amount of people with MS who had stenosis(24%) in this study who were early in the disease process. It looks like, just based on these results, stenosis in people with MS correlates with the length of time time they have had MS. It would seem to follow that the liberation procedure should than be more effective for people who have had MS for a number of years since that is when stenosis is the greatest yet it is claimed the liberation procedure is more effective for people with early MS. :?


This study didn't address the question of treatment, so one should not attempt to draw any conclusions about the efficacy of angioplasty to treat any type of MS based solely on this study.
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