This Is MS Multiple Sclerosis Community: Knowledge & Support

Dr. Adrian Siddiqui presenting "IVUS consensus" No studies comparing IVUS with standard venography

Dr. Siddiqui: great resolution with IVUS to find stenosis. Less operator dependent. Only way to image azygos vein

Dr. Siddiqui just showed film of IVUS in healthy and diseased azygos veins while patient was breathing. Wow!

Dr. Siddiqui: IVUS showed more abnormalities in azygos veins than IJVs. Good for balloon sizing.

Dr. Siddiqui: sad fact: 30,000 treated, but data only collected on ~300. Treatment w/out data collection unacceptable

Dr. Siddiqui: difficult to correlate asymmetry because of lesion location. However Zamboni's original data attempted this

Intravascular Ultrasound for detection of Azygous and Internal Jugular vein (IJV) abnormalities as part of the
PREMiSe (Prospective Randomized Endovascular therapy in Multiple Sclerosis) study

Y Karmon1,2, R Zivadinov3, B Weinstock-Guttman2, C Kennedy3, K Dolic3, K Marr3, V Valnarov3, A Siddiqui1

1Department of Neurosurgery, 2The Jacobs Neurological Institute, and the 3Buffalo Neuroimaging Analysis Center, State
University of New York, Buffalo, NY

BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI) is a condition recently reported in patients with multiple
sclerosis (MS) [1]. A set of 5 extra- and trans-cranial venous Doppler Sonography (DS) criteria was proposed [1, 2] and reported
to be in accordance with catheter venography (CV) for the depiction of both Azygous and IJV stenosis [1, 3]. Despite being
the “gold standard” for assessing vascular problems, angiography only provides a luminography with little data on the vessel's
wall, or intraluminal structures. Our aim was to investigate for presence and type of mechanical impediments to the cranial/
spinal cord venous drainage and suspected deranged flow using CV based intravascular ultrasound (IVUS).

METHODS: PREMiSe is an endovascular angioplasty study enrolling patients with relapsing MS according to the revised
McDonald criteria[4,5], and who had Expanded Disability Status Scale [6] between 0-5.5 and fulfilled ≥2 CCSVI Doppler
sonography criteria at screening. The study was planned in two phases. The first phase was an open label and included 10
patients, whereas the second phase is placebo-controlled, blinded and randomized and will include total of 20 patients. The
current study is based on 10 patients participating in phase I and 16 in phase II. CV comprised visualization of AZY vein, right
IJV (RIJV) and left IJV (LIJV) in that order [3]. IVUS was performed using IVUS Eagle Eye Gold catheter (Volcano, CA), across
suspected stenotic segments (≥50% restriction) of the IJV's and azygous vein (AZY), in the phase I, and in all vessels in the phase
II. Abnormal predefined IVUS parameters included the presence of stenosis, presence or absence of respiratory pulsatility
and the presence of various intraluminal defects (septa, multiple channeled vein, intraluminal hyperechoic filling defect,
double/parallel lumen), and abnormally thickened wall.

RESULTS: The study included twenty six patients (mean age 45.7, SD=9.7; male=9, females=17; average disease duration
10.1 years) with clinical and MRI proven MS (20 Relapsing remitting MS, 6 secondary progressive MS) that have fulfilled ≥2
CCSVI Doppler sonography criteria at screening. Out of 18 Azygous veins that were investigated with IVUS, 16 (88%) demonstrated
various intraluminal defects. Pulsatility was reduced in 7 (38.8%), and stenosis was demonstrated in 10 (55.5%). IVUS
of LIJV detected intraluminal defects in 7 out of 22 patients, reduced pulsatility in 14, and stenosis in 8. All patients who had
a stenosis by IVUS also demonstrated intraluminal defects. IVUS of the RIJV showed intraluminal anomalies in 4 patients
(20%), reduced pulsatility in 10 (50%), and stenosis in 5 (25%) patients out of 20 patients investigated.

CONCLUSIONS: Detailed IVUS imaging demonstrated a very high rate of intraluminal anomalies in the azygous vein during
the PREMiSe study. Similar anomalies were also found in the LIJV and RIJV in lower rates respectively. Stenosis demonstrated
by IVUS was demonstrated in a decreasing order in the azygous vein, left IJV and RIJV as well. IVUS provides
diagnostic advantages over "gold standard" CV in detecting intraluminal extra-cranial venous abnormalities indicative of
CCSVI.

Yuval Karmon..given by Dr Siddiqui
Intravascular ultrasound for detection of azgos and IJV abnormalities and part of the PREMISE study
Angiography only provides a luminography with little data on the vessel wall
Angioplasty study double blind. 19 pt enrolled in the study
Catheter and IVUS performed
Looked at azygos was the lead in intravascular abnormalities 88%
LIJV the second most commonly affected vein
All with stenosis had intraluminal problems
Rijv only 20% intraluminal and stenosis
Ivus imaging demonstrated a very high rate of intraluminal anomalies in the azygous veing
Similar anomalies on the LIJV but less than the azygos
IVUS provides diagnostic advantages

Dr Siddiqui
Premise study
Randomized placebo control
Multidisciplinary approach( several disciplines)
Ms is a chronic progressive disease
Dr Siddiqui discussed all the difficulties in designing the PREMISE study
Safety and effects of venoplasty
IRB approved with the entire team
How was it funded…you cannot get funded for sham procedures
Expensive study to conduct.
$25000 per pt no reimbursement for docs or patients…only for equipment.
They partnered with the hospital, and device companies Phase 1
10 rrms with ccsvi
Phase 11 1 pt away from completing study

from page 68 of ISNVD 2012 abstracts http://www.isnvd.org/files/ISNVD%20Abstract%20Book.pdf

How does reduced pulsatility factor into CCSVI? It is unusual to have 16 out of 18 azygouses be abnormal, but this is looking at more than just stenosis and intraluminal abnormalities, and also including reduced pulsatility.

The conclusion is a familiar one: IVUS provides diagnostic advantages over catheter venography alone, because the intraluminal abnormalities of CCSVI can best be seen on IVUS.

pulmonary arterial pulsatility (the relative increase in vessel area during the cardiac cycle)