ISNVD Feb 8, 2014
Session I. A multi-Modality Approach to Extra Cranial Venous Disease
Dr Zivadinov session chairperson
1. The Current Status of Ultra sound Imaging for the Screening of CCSVI...Dr Marcello Mancini...Univ. Naples
ccsvi can be non invasively diagnosed by combined transcranial and extracranial echo doppler
CCSVI more frequent in MS than in normal controls
Italian study 1800 subjects
the assessment of CCSVI was highly operator dependent... the echo color doppler is an ideal tool for assessing cerebral venous return
What is the Normal Jugular Vein Valve Function?....Dr Erica Menegatti
using echo doppler they were able to see the motility of the IJV valve leaflets in healthy volunteers
findings 50% showed absent valve on 1 side
in healthy subjects in IJV leaflets are always mobile and open in up right position
62% of HC with valve absence at least of one side suggests a progressive loss of motility.
Prevalence of Extracranial Venous Narrowing on Catheter Venography in pwMS
CCSVI more prevalent in pwMS?
BC Saskatchewan study...published in Lancet
evaluate the frequency of venous stenosis in pwMS vs controls, and siblings of MS patients.
ultrasound trained in Ferrara and used the Zamboni criteria
the subjects were blinded
the venography protocol was developed with Gary Siskin, MD and an SIR discussion group
standardized upright and supine venography measures
no significant differences in each group but MS patients felt moderately better.
Dr Zamboni challenged this study!!!!
Identifying CCSVI with Cervical Plethysmography
measured in normal controls
hydrostatic gradient in cerebral venous outflow
upright there is negative hydrostatic pressure
zero hydrostatic pressure in supine
posture shows restricted venous outflow in ccsvi vs normal when the system is stressed through change in position
the system fills up quicker because the outlet pathways are restricted in CCSVI
Diagnostic Contributions of Catheter Venography for Screening of CCSVI
Dr Hector Ferral
limitations of catheter venography is radiation exposure contrast media and may miss subtle issues.
review the Venographic protocols of CCSVI
reviewed 8 papers.
R femoral vein is the easiest access
power injection most popular
Delayed emptying is an important criteria...greater than 6 sec is severe
patients with severe stenosis had emptying between 6 and 27 sec
r femoral vein( Dr Zamboni said in PPMS the L entrance is better)
catheter straight multi-perforated
contrast depends on IVUS availability
position of pt is supine
multimodal approach is important
What Additional information Can Intravascular ultrasound Provide?
looked at azygos and IJV
IVUS is the best evaluation tool and was compared to catheter venography
Molecular Markers of Abnormal CNS Hemodynamics
Dr. Steven Alexander PhD
endothelial cells are important they create the bBB
abnormal pressure patterns.. links to neurodegenerative disease.Vascular stress is related to neurodegenerative disease. intra abdominal hypertension disturbs BBB
endothelial cells under shear or stress release micro-particles can affect distant gene expression
APP is associated with neurovascular disease and is a precursor to amyloid
oscillating shear causes increased APP which is released into the brain.
altered pressure can rapidly and reversibly modulate BBB
Different shear patterns alter brain endothelial transcription factors
Some transcription factors and microRNA's between cells as a novel form of distant site epigenetic modification
APP is released by brain endothelial cells and is packaged into micro-particles
Differential transfer of APP laden micro-particles may contribute to several forms of neurovascular degeneration
State of the Art1: Why we need a multi-modality diagnostic approach for CCSVI
MR, catheter venography, ultra sound, and IVUS all have positive aspects.
PREMISE study used a multi-modality approach
ISNVD has a position statement for the screening for diagnosis of CCSVI
Two abstracts were presented:
Abstract 1: Extracranial brain draining veins in a mouse: Assessment by high resolution ultrasound and MR angiography of the neck
Brain drains from the external jugular in the mouse and in humans it is IJV's
Abstract 2: Inverse relationship between IJV narrowing and increased brain volumes in healthy individuals
IJV narrowing has been implicated in CNS pathologies
Similarly brain volume reduction...atrophy...has also been linked to CNS pathologies
However, IJV narrowing and atrophy have never previously been linked
Assessment of the relationship between IJV CSA and atrophy in healthy individuals
the hypothesis is increased narrowing...stenosis...would correlate with increased atrophy...reduced brain volume
Secondary outcome is assessment of age effects and cervical location on these potential associations
IJV narrowing was not associated with brain atrophy...mechanism unknown
Dr Ziv Haskal Moderator
Designing an endovascular trial...What elements are essential and why CCSVI trials might differ from Disease Modifying trials
Dr Kottil W. Rammohan...Neurologist Univ. Miami(director of MS center)
what is the short term effect of the procedure
Long term benefits....as a stand alone or adjunct to a disease modifying treatment (DMT)
any trial has to be blinded
no trials have been done that meets the test of Cochran Review .
Essential elements of all clinical trials.
evidence, population, intervention. comparison, outcome , time (EPICOT)
Defining CCSVI is the biggest problem
Should use ambulation as an evaluation tool
"having an open label trial is unconscionable"
State of the Art :Current results of safety and efficacy of CCSVI therapy in MS patients
Gary Siskin (Dr Dake presented)
studies have demonstrated very low adverse events with venoplasty. It is a very safe procedure
improvement in a majority of patients but not all. Patients with severe delayed flow did not do as well as those with moderately delayed flow
EDSS at one month and one year significantly improved
cutting balloons are safe for those patients who had failed venoplasties.
Procedural Endpoints. How to Best measure Meaningful Flow Impairment, Inter and Post Procedural Therapy
IVUS Driven Intervention..provides accurate information of vascular pathology shows, webs, valves, dissection, intramural problems.
Optimizing Pure Venographic Therapy : there is no validated approach
Intervention Studies in 2014
The Time is Ripe for Primary and Replicative Therapy Trials in MS
science is not linear, often not in types of therapeutics
what happened in MS and CCSVI?
the venoplasty is less dangerous than present treatment (DND's)
it's time for more research
Therapy Trials Need to Wait. The Landscape has changes
Dr Kottil W. Rammohan
Are we ready to do a randomized controlled trial? Dr Zamboni's trial was replicated by Dr Troulbasse and could not reproduce the same results in Vancouver.
Dr Hubbard and challenges Dr Rammohan and says MS has not been proven to be immune modulated.
Abstract 3...A report of 4 cases of anterior cranial fossa dural arteriovenous fistula: surgical consideration and technique using intraoperative indocyamine green angiography.
Abstract 4...Classification of venous outflow in the extracranial vessels in a large cohort of MS patients.
Sean Sethi...with Dr Haacke's research group
4th study showing abnormal flow in the IJV
used MRi and assessed the the IJV
MS subjects wer classified as stenotic or non stenotic
did flow quantification at c2/c3 and c5/6
61% of the MS were stenotic
CCSVI and Parkinson's
In MS patients, iron deposition occurs in both the basal ganglia and midbrain similar to what is seen in idiopathic Parkinson's Disease.
23 PD patients and 23 Normal Controls
there are abnormal structural and flow findings in PD patients.
Etiologies of jugular venous abnormalities in transient monocular blindness
Dr Chun-Yu Cheng
sudden painless transient visual loss
there is venous outflow resistance in the IJV
IJV stenosis is found in in transient monocular blindness
Age Related White Matter Changes, Alzheimer's Disease and Jugular Venous Reflux
Dr Clive Beggs
Pilot study and IJV reflux.
JVR is associated with age related white matter changes, particularly in posterior brain regions.
12 pts with AD 17 healthy controls 24 mild cognitive impairment
dirty appearing white matter is a region of intermediate signal intensity between that of T2 lesions which may develop into lesions later on.
AD patients had significantly reduction of dirty white matter, and increased lesion formation
JVR and brain atrophy
increased brain volume in grey and white matter...
venous blood pooling is a possiblity
Cerebral venous drainage impairment in idiopathic intracranial hypertension
Dr Noam Alperin
venous drainage in supine and upright postures
in the upright posture, venous drainage shifts from the jugular to secondary veins and is significantly less pulsatile
Headache and venous abnormalities
Dr Wei-Ta Chen
vein related cerebrovascular disorders with headache
cerebral venoos thrombosis
dural arteriovenous fistula
carotid cavernous fistula
Headache disorders with venous abnormalities
idiopathic intracranial hypertension
spontaneous intracranial hypotension
IIH is not benign...they may lose vision
endovascular stenting is one tx option
spontaneous intracranial hypotension=
orthostatic headache, neck tightness, subjective hearing symptoms
evidence of CSF leakage on imaging
TX of SIH:
bed rest, hydration, epidural blood patch
unilateral, throbbing,associated symptoms are nausea, photophobia and phonophobia, duration 4-72 hrs
aura...visual, sensory, aphasia,motor
if you compress bilat IJV it can make migraine worse.
IJV volume increases during attack
decreased in IJV compliance in migraine
venous hypertension occurs during a migraine
venous abnormalities involve in high altitude associated neurological disorders
Dr Mark Wilson
what happens when you are gradually exposed to increased altitude?
can get a headache, mountain sickness or
high altitude cerebral edema
those with HA's had large venous sinuses
being in space is not good for your eyes due to venous hypertension
Cerebral venous drainage impairment and cerebral small vessel disorders
Dr Han-Hwa Hu
CVDI linked to small artery disease
association with impaired cerebral auto-regulation
association with lacuna stroke
association with white matter diseases
There were a couple of presentations that followed but because of my "brain overload" I decided to take a break.
Will post again tomorrow!