There was a new post from the Bard
Zamboni P et al. Assessment of cerebral venous return by a novel plethysmography method. Journal of Vascular Surgery [Epub ahead of print]
resonance imaging and echo color Doppler (ECD) scan techniques do not
accurately assess the cerebral venous return. This generated
considerable scientific controversy linked with the diagnosis of a
vascular syndrome known as chronic cerebrospinal venous insufficiency
(CCSVI) characterized by restricted venous outflow from the brain. The
purpose of this study was to assess the cerebral venous return in
relation to the change in position by means of a novel cervical plethysmography method.
Methods: This was a single-center,
cross-sectional, blinded case-control study conducted at the Vascular
Diseases Center, University of Ferrara, Italy. The study involved 40
healthy controls (HCs; 18 women and 22 men) with a mean age of 41.5 ±
14.4 years, and 44 patients with multiple sclerosis (MS; 25 women and 19
men) with a mean age of 41.0 ± 12.1 years. All participants were
previously scanned using ECD sonography, and further subset in HC (CCSVI
negative at ECD) and CCSVI groups. Subjects blindly underwent cervical
plethysmography, tipping them from the upright (90°) to supine position
(0°) in a chair. Once the blood volume stabilized, they were returned to
the upright position, allowing blood to drain from the neck. We
measured venous volume (VV), filling time (FT), filling gradient (FG)
required to achieve 90% of VV, residual volume (RV), emptying time (ET),
emptying gradient (EG) required to achieve 90% of emptying volume (EV)
where EV = VV-RV, also analyzing the considered parameters by receiver
operating characteristic (ROC) curves and principal component
Results: The rate at which venous
blood discharged in the vertical position (EG) was significantly faster
in the controls (2.73 mL/second ± 1.63) compared with the patients with
CCSVI (1.73 mL/second ± 0.94; P = .001). In addition,
respectively, in controls and in patients with CCSVI, the following
parameters were highly significantly different: FT 5.81 ± 1.99 seconds
vs 4.45 ± 2.16 seconds (P = .003); FG 0.92 ± 0.45 mL/second vs 1.50 ± 0.85 mL/second (P < .001); RV 0.54 ± 1.31 mL vs 1.37 ± 1.34 mL (P = .005); ET 1.84 ± 0.54 seconds vs 2.66 ± 0.95 seconds (P
< .001). Mathematical analysis demonstrated a higher variability of
the dynamic process of cerebral venous return in CCSVI.
venous return characteristics of the patients with CCSVI were markedly
different from those of the controls. In addition, our results suggest
that cervical plethysmography has great potential as an inexpensive
screening device and as a post-operative monitoring tool.
Once validated by others, tools to screen and monitor efficacy (if present) duration will be very useful.
Simka M et al. Diagnostic accuracy of current sonographic criteria for the detection of outflow abnormalities in the internal jugular veins.Phlebology. 2012 Apr 23. [Epub ahead of print]
OBJECTIVES: This study was aimed at evaluation of the diagnostic value of Doppler sonography for the assessment of abnormalities in the internal jugular veins (IJVs).
You can read the the conclusion and maybe you will argue that it depends on protocol.
[P05.125] A Pathologic Evaluation of Chronic Cerebrospinal Venous Insufficiency (CCSVI) Claudiu I. Diaconu, Susan Staugaitis, Jennifer McBride, Cynthia Schwanger, Alexander Rae-Grant, Robert Fox
OBJECTIVE: To assess for venous abnormalities possibly related to CCSVI in MS and control cadavers.
Chronic cerebrospinal venous insufficiency is a new theory of MS
pathogenesis involving alterations in cerebral venous outflow. There has
been little pathologic study of venous structures related to CCSVI.
We harvested bilateral internal jugular (IJV), subclavian,
brachiocephalic, and azygos (AZY) veins from 7 deceased MS patients and 6
non-MS controls. Veins were flushed, injected with silicone, dissected
en bloc, and fixed. All valves and structural abnormalities were
characterized and photographed using a stereomicroscope.
Valvular and other intraluminal abnormalities with potential
hemodynamic consequences were identified in 5 of 7 MS patients (7
abnormalities) and in 1 of 6 controls (1 abnormality). These
abnormalities included circumferential membranous structures (1 MS; 1
control), longitudinally-oriented membranous structures (3 MS), single
valve flap replacing IJV valve (2 MS), and enlarged and malpositioned
valve leaflets (1 MS). Significant stenosis was seen in 2 MS and 1
control. Additionally, several minor anatomic variations without
expected hemodynamic consequences were observed similarly in both MS and
controls. These included valves with 3 leaflets, the presence of AZY
valves, additional (duplicate) normal-appearing IJV valves, and small
accessory valve leaflets. Histologic evaluation is underway and will be
reported along with additional cases. CONCLUSIONS: Post mortem
examination of the IJV and AZY veins in MS and non-MS controls
demonstrated a variety of structural abnormalities as well as anatomic
variations. Vein wall stenosis occurred at similar frequency in both
groups. However, the frequency of intraluminal abnormalities with
possible hemodynamic consequences appeared higher in MS patients
compared to healthy controls, although the current sample size is
limited. These results suggest that MRV studies evaluating vein wall
stenoses may be less effective than ultrasound in identifying venous
abnormalities in CCSVI. In addition, CCSVI ultrasound studies should
include focused evaluation of intraluminal abnormalities
You can read the conclusions, but surely it is important to have performed the ultrasound to check that the criteria of CCSVI was fullfilled before assessing histologically. Without this knowledge there are clear problems, but if there was 100% specificity for MS as originally claimed then that would not be an issue. However I think most other studies are not showing a 100% and so this is important in the validity of the study.
systematic review was undertaken to examine the evidence of an
association between chronic cerebrospinal venous insufficiency (CCSVI)
and multiple sclerosis (MS) using rigorous methodological analyses.
It has been proposed that MS is caused by ultrasound detectable
abnormalities in the anatomy and flow of intra and extra-cerebral veins,
a condition termed CCSVI.
DESIGN/METHODS: A literature search of
Ovid MEDLINE, the Cochrane Central Register of Controlled Trials and
EMBASE was conducted. Eligible studies used ultrasound to diagnose CCSVI
and compared MS patients with either healthy controls (HC) and/or
patients with other neurological diseases (OND). A random effects model
was used and odds ratios (OR) and I2 values were generated.
Eight studies compared the frequency of CCSVI in MS patients vs. HC; 4
studies compared MS vs. OND. CCSVI diagnosis was more common in MS vs.
HC (OR 13.5, p=0.002), but there was marked heterogeneity in both the
frequency and magnitude of this association. A statistically significant
but reduced association remained using the most conservative analysis
(OR 3.4, p=0.02), which involved removing Zamboni’s initial study and
adding a negative CCSVI study. The studies comparing MS and OND also
found CCSVI more commonly in MS, but this was not statistically
significant (OR 32.5, p=0.09). The OR dropped to 3.4 (p=0.11) with
removal of Zamboni’s study. No study reported tests of blinding of
technicians or radiologists.
CONCLUSIONS: This systematic review
did find a statistically significant greater odds of CCSVI in MS
patients vs. HC, but not in MS vs. OND. Limitations including
uncertainty regarding blinding and marked heterogeneity of the results,
and do not allow for definitive conclusions. These early results raise
the possibility that CCSVI may not be MS-specific, and it may follow,
not precede onset of disease. Further high quality controlled studies
are needed to definitively determine if CCSVI is truly associated with
Dolic et al.
To investigate the association between presence of a newly proposed
vascular condition called chronic cerebrospinal venous insufficiency
(CCSVI) and environmental factors in a large volunteer control group
without a known central nervous system pathology.
role of intra- and extra-cranial venous system impairment in the
pathogenesis of various vascular, inflammatory and neurodegenerative
neurological disorders, as well as in aging, has not been studied in
DESIGN/METHODS: The data were collected in a prospective
study from 252 subjects who were screened for medical history as part of
the entry criteria and participated in the case-control study of CCSVI
prevalence in multiple sclerosis (MS) patients and were analyzed post
hoc. All participants underwent physical and Doppler sonography
examinations, and were assessed with a structured environmental
questionnaire. Fullfilment of ≥ 2 positive venous hemodynamic (VH)
criteria on Doppler sonography was considered indicative of CCSVI
diagnosis. Risk and protective factors associated with CCSVI were
analyzed using logistic regression analysis.
(27.8%) subjects presented with CCSVI diagnosis and 153 (60.7%)
presented with one or more VH criteria. The presence of heart disease
(p=.001), especially heart murmurs (p=.007), a history of infectious
mononucleosis (p=.002), and irritable bowel syndrome (p=.005) were
associated with more frequent CCSVI diagnosis. Current or previous
smoking (p=.029) showed a trend for association with more frequent CCSVI
diagnosis, while use of dietary supplements (p=.018) showed a trend for
association with less frequent CCSVI diagnosis.
Risk factors for CCSVI differ from established risk factors for
peripheral venous diseases. Vascular, infectious and inflammatory
factors were associated with higher CCSVI frequency.
Conclusions say it all, but as these people also had MS where history of mononucleosis and smoking are risk factors for MS, it would not be surprising if there was some concordance.
[S10.005] A Study of CCSVI with Imaging-Blinded Assessment: Neurosonography Update
Barreto, Staley Brod, Thanh-Tung Bui, James Jamelka, Larry Kramer,
Kelly Ton, Alan Cohen, John Lindsey, Flavia Nelson, Ponnada Narayana,
chronic cerebrospinal venous insufficiency (CCSVI) exist, is it
associated with multiple sclerosis (MS), and what tools might establish
its presence? We sought to determine if neurosonography (NS) provides
reliable information on cerebral venous outflow patterns, if NS findings
are supported by 3T magnetic resonance venography (MRV), and if NS
and/or MRV reflect transluminal venography findings. We detail NS
findings on the first 193 participants. BACKGROUND: CCSVI is postulated to have a role in MS pathogenesis. DESIGN/METHODS:
TB, blind to the subject’s diagnosis, used high resolution B-mode
imaging with color and spectral flow Doppler to investigate extracranial
and intracranial venous drainage. Results were evaluated by ADB with
neither subject contact nor patient information; only KT and JSW could
access the complete database. RESULTS: 10 healthy controls, 18
cerebrovascular diseases, 27 other neurological diseases, 138 MS (7
clinically isolated syndrome, 80 relapsing remitting, 35 secondary
progressive, 15 primary progressive, 1 progressive relapsing) were
studied. MS patients were older than non-MS subjects (48.4±9.8 v
44.3±11.4 years), durations from first symptoms and diagnosis of
13.7±9.4 and 10.3±8.0 years, and EDSS 2.9±2.0. 47 subjects fulfilled one
of five criteria for CCSVI proposed by Zamboni; 8 fulfilled two
criteria and none fulfilled >2 criteria. The distribution of subjects
with 0, 1 or 2 criteria did not differ significantly across all
diagnostic groupings, between MS and non-MS subjects, or within the MS
subgroups. No significant differences emerged between MS and non-MS
subjects for measures of cross-sectional areas of the internal jugular
veins at fixed anatomic sites or for extracranial or intracranial venous
flow rates. CONCLUSIONS: NS findings described as CCSVI are much
less prevalent than previously reported and do not distinguish MS from
other subjects. Data will be updated prior to the meeting. Correlations
of NS and MRV for 37 MS subjects are reported separately.
This is a pretty damming report against the CCSVI concept being real…. but the protocol was not the Prof Z way I hear you say.
[S10.006] Prospective, Case-Control Study of CCSVI with
Imaging-Blinded Assessment: Progress Report Correlating Magnetic
Resonance Venography with Neurosonography. Larry
Kramer, Houston, TX, Andrew Barreto, Sugar Land, TX, Thanh-Tung Bui,
Staley Brod, James Jemelka, Kelly Ton, Alan Cohen, John Lindsey, Flavia
Nelson, Ponnada Narayana, Jerry Wolinsky, Houston, TX
Does chronic cerebrospinal venous insufficiency (CCSVI) exist, is it
associated with MS, and what tools might establish its presence? Steps
included: determine if neurosonography (NS) provides information on
cerebral venous outflow patterns suitable as a first screen, learn if NS
findings are supported by 3T magnetic resonance venography (MRV) of the
head, neck, chest, abdomen and pelvis, and evaluate if NS and/or MRV
reflect ‘true’ venous anatomy seen by transluminal venography (TV). This
report details the correlation of MRV and NS findings on the first 37
MS participants to undergo both procedures. BACKGROUND: CCSVI has a postulated role in multiple sclerosis (MS). DESIGN/METHODS:
Participants provided informed consent. Extracranial and intracranial
venous drainage was investigated with high resolution B-mode imaging
with color and spectral flow Doppler, performed and recorded by TB,
blind to the subject’s diagnosis. MRV utilized AblavarTM to improve
vascular visualization. NS results were evaluated by ADB, MRV images by
LAK; neither had access to subject information or the other’s data. Only
KT and JSW had complete database access. RESULTS: MS clinical
phenotypes included 1 clinically isolated syndrome, 24 relapsing
remitting, 6 secondary progressive, 5 primary progressive and 1
progressive relapsing. Delay from NS to MRV was 160±77 days. NS
identified 14/37 subjects fulfilling 1 of 5 Zamboni criteria for
anomalous venous outflow; only 1/37 fulfilled 2 criteria required for
CCSVI. MRV identified 5/37 subjects with venous stenosis; 1 Type A and 4
Type C patterns. A Zamboni score <2 by NS was concordant with a
normal venous vascular patterns on MRV for 31/36 subjects, but
discordant for the subject with Zamboni score on NS of 2. CONCLUSIONS:
There was reasonable correlation of between independent assessments of
Zamboni scores on NS and patterns on MRV. These studies suggest that
findings described as CCSVI are not common.
Therefore one must ask why treat a condition that evidence is suggesting does not really exist. Anyway lets wait for the trials and see if the treatment is beneficial
There have been other meeting abstracts
OBJECTIVES: Recently an association has been made
between Multiple Sclerosis (MS) and Chronic Cerebrospinal Venous
Insufficiency (CCSVI) characterized by stenosis and reflux of the
principal extracranial venous drainage including the Internal Jugular
veins (IJV) and the Azygous veins (AZV). This is the first angiographic
study to quantitatively analyze the impact of percutaneous balloon
angioplasty (PTA) on flow dynamics across these lesions.
METHODS: 50 IJV from MS patients with CCSVI and 12
IJV from healthy volunteers underwent detailed angiographic evaluation.
Technical components of all venograms were standardized. Quantitative
analysis included the contrast time of flight (TOF) from the mid IJV to
the superior vena cava, and the primary venous emptying time (PVET),
quantified as >50% of venous emptying, from the IJV. The TOF and PVET
were recorded in patients with CCSVI prior and subsequent to balloon
angioplasty, as well in normal healthy subjects. All data was
prospectively collected, and statistical analysis was performed using
two-tailed Student’s test.
RESULTS: Of the 50 CCSVI-MS patients with IJV
stenosis >70% and reflux underwent balloon angioplasty, technical
success defined as <20% residual IJV stenosis was achieved in 78%
(44/50). Table describes the pre- and post-angioplasty TOF and PVET in
patients with CCSVI, as well as in healthy non-MS patients without any
treatment. CCSVI patients were noted to have a significant improvement
in both the TOF and PVET following balloon angioplasty that paralleled
healthy non-MS subjects.
CONCLUSIONS: Results of this prospective pilot study
suggest an association between MS and CCSVI, which results in
abnormally elevated TOF and PEVT through the IJV. Furthermore, balloon
angioplasty these lesions improves the hemodynamic parameters that are
comparable to healthy non-MS patients.
MS patients with CCSVI
Mean Time (sec.)
There is still no clarity and some reports may have been missed (based on pubmed) or were too uninteresting/irrelevant to comment on but some interesting publications have been published this month, there may be a weight of evidence building towards the negative side. We must remember that meeting abstracts have not been properly peer-reviewed and we will need to wait until they are published. I think I will concentrate on published obersvations in future also as the subjects in meetings abstracts will occur elsewhere and this gives bias and the information keeps appearing, unless we hear of the results of the blinded trials.
Why do we not take comments on these posts?
Experience-We learn from the past. I know that this would be managable whilst comments are being read first, but it also saves us being accused of selecting what goes public.
We are sure many of you would like to make sensible comments that are valid to the debate, but due to probably a minority who spoil it for the majority, we have no desire to recieve and are saddened by the personal abuse that we sometimes, have to endure, such as the beginning of this month and a few days ago and yesterday and the day before that and that etc. We hope you understand.
We are essentially giving you the information and you can make you own mind up! Should we stop posting on this subject, well no because it is topical and you can see the weight of evidence accumulate, but is is only a very small part of MS research..
More Next Month, No Doubt