Next week Prof G is at ECTRIMS and the news starts here
Multiple stenosis or multiple sclerosis?
G. Panczel, C. Rozsa, K. Kovacs, I. Szikora, Z. Berentei, I. Gubucz, M. Marosfoi, A. Rozsa (Budapest, HU)
Introduction.
An alternative etiology of MS named chronic cerebrospinal venous
insufficiency (CCSVI) has recently been proposed by Zamboni et al. By
venous ultrasound (US) and venography they found venous stenosis present
in all MS patients and none of control subjects, most of these stenoses
were multiple, affecting mainly the internal jugular veins both sides
but also the azygos and vertebral veins. The aim of our study was to
determine if cerebral venous outflow –evaluated by Doppler US and venous
DSA- differs significantly in MS patients and controls.
Patients and methods. We enrolled 20 patients (47,1 ± 10,8 y, 6
males, 14 females) who were scheduled for a control angiography after
interventional therapy of intracerebral aneurysm and had no venous
pathology or MS. 14 MS patients were also enrolled who underwent a
CCSVI interventional work-up abroad (45,4 ± 12,8 y; 5 males, 9
females). Stenosis of proximal IJV was measured by DSA, flow volume (FV)
was measured by duplex US and IJV patency was evaluated by power-US
method.
Results. DSA examination: 80% of controls had >50% stenosis in
the right and 94.7% on the left side; mean degree of stenosis was 69
±17% and 73 ± 13% (right and left IJV). All MS patients also had IJV
stenosis, mean value of stenosis was 62 ±14% and 66 ± 13% (right and
left IJV). There was no significant difference in the degree of stenosis
between groups.
US measurements: FV of IJV was normal in both groups, both sides
(controls: right: 692 ± 430 ml/min; left: 502 ± 303 ml/min; MS patients:
right: 603 ± 469 ml/min; left: 584 ± 319 ml/min;). None of the patients
and controls had IJV stenosis on power duplex US.
Discussion. Normal FV and power duplex US findings proved that the
IJV stenosis shown by DSA was not real. The virtual stenosis is
explained by the fact that the contrast agent descending the IJV is
diluted at the venous confluence by the non-contrast blood stream of
subclavian vein raising a false impression of a local high-grade
stenosis. We concluded that haemodynamically significant venous stenosis
–a key feature of CCSVI, cannot be found in MS patients.
Fact or artifact this study argues for the latter
Endovascular treatment of CCSVI in patients with multiple sclerosis: clinical outcome of an Italian cohort of 462 cases
A.
Ghezzi, P.O. Annovazzi, M.P. Amato, R. Balgera, P. Banfi, M. L.
Bartolozzi, R. Bergamaschi, A. Bertolotto, A. Bianchi, A Bosco, E.
Capello, M. Capobianco, R. Capra, P. Cavalla, R. Clerici, G. Coarelli,
E. Cocco, N. De Rossi, C. Di Tillio, M.T. Ferrò, A. Gallo, P. Gallo, L.
Lamantia, A. Lugaresi, G. Lus, S. Malucchi, L. Moiola, L. Provinciali,
F. Patti, P. Perini, P. Perrone, A. Protti, M.E. Rodegher, P. Rossi, M.
Rottoli, M. Rovaris, G. Salemi, M. Salvetti, I. Simone, M.R. Tola, M.
Trojano, F. Vitetta, M.G. Marrosu, G. Comi and MS Study Group, Italian
Society of Neurology
Backgound and objectives Although the
relationship between MS and CCSVI is not defined and there is no proven
demonstration that endovascular treatment of CCSVI is effective to
improve MS evolution, many patients decide to undergo such a treatment.
The Italian Multiple Sclerosis Study Group-Italian Society of Neurology
has promoted a multicentric study to collect clinical information on MS
subjects who have spontaneously decided to be submitted to endovascular
treatment.
Results. 31 Italian MS centres have participated to this study. A
form has been standardized to collect complete demographic, clinical,
MRI and safety data. All consecutive MS patients who have declared
(spontaneously or asked by physicians) to have been submitted to
endovascular treatment of CCSVI have been included in the database.
Complete data are available of 462 patients (279 females) (mean age
44+/-10 y), 45% with RR-MS , 55% with SP/PP-SM. The mean EDSS score
before the intervention was 5.0+/-2.0. After a mean follow up of
30.7+/-36.1 weeks, the mean EDSS was 5.1+/-2.0 and 98 patients developed
one or more relapses (tot. 144). MRI data of 171 patients were
available, after a follow up of 28 weeks, showing the appearance of new
T2 or gadolinium enhancing lesions in 61 patients. A subjective clinical
improvement was reported by 53% of patients; clinical status was
unchanged in 33% and worsened by 15% of cases. In subjectively improved
patients the mean pre-intervention EDSS was 4.9+/-2.0; it was 5.0+/-2.1
after the surgical procedure. Serious adverse events have been observed
in 15 cases: jugular venous thrombosis in 7, inguinal haematoma in 3,
ischaemic stroke in 2, post-ischemic encephalopathy in 1, hydrocephalus
in 1; one subject died because of myocardial infarction 3 months after
the intervention.
Conclusions. The results of our study, with the limitations due to
the observational design, do not show any clear beneficial effect of
endovascular treatment for CCSVI in MS. The subjective positive effects
reported by about 50% of patients can be largely due to the high
expectation of patients for an intervention called “liberation”. The
intervention is not totally free from serious adverse events, which
occurred in 15/462 cases.
So about 50% of Msers felt better but on at least disability scales there was no improvement, so not quite as impressive as many of the Youtube videos. The group appear to suggest that this is due to a placebo effect. There were some (about 3-4%) serious side-effects from having the treatment
A prospective follow-up of the venous haemodynamics in patients with MS: the fluctuating natural course of CCSVI
L.H. Visser, L. van den Berg, A. van der Zande, G. van den Berg, B. Westerhuis (Tilburg, Maassluis, NL)
Introduction:
A new treatable venous disorder, chronic cerebrospinal venous
insufficiency (CCSVI), has been proposed in patients with multiple
sclerosis (MS). The natural course of CCSVI has not been examined yet.
Moreover, its relation with iron metabolism is suggested but has not
been examined prospectively.
Methods: We performed extra- and transcranial echo colour Doppler
(ECD) in 90 MS patients and 41 healthy controls (HC), applying the same
methods used by Zamboni et al. To document the natural course of venous
haemodynamics a random subgroup of 52 patients and 28 HC were
re-examined by ECD. Indices of iron metabolism and presence of
peripheral signs of impaired venous flow were also examined.
Results: First ECD showed CCSVI in 8 (8.9%) of the 90 MS patients
and 0 HC (p=0.11). The 8 CCSVI-positive MS patients were older (P=0.02),
had less often RR-MS (P=0.02) and had more neurological disability
(P=0.001) and longer duration of disease (P=0.02) in comparison to the
82 CCSVI-negative MS patients. Multivariate analysis revealed that EDSS
remained an independent factor associated with CCSVI (Odds ratio 1.89
(95 %CI 1.17-3.05, p-value 0.009). CCSVI-positive patients had more
often bilateral telangiectasia at the legs (P=0.008), reticular veins
(P=0.006) and venous stasis dermatitis (P=0.004). The diagnosis CCSVI
could not be reconfirmed in 3 out of 5 patients at follow-up, while 2
new CCSVI-MS patients were detected. No relation was found between CCVSI
and impaired iron metabolism in MS patients.
Conclusions: CCSVI is uncommon and is a secondary epiphenomenon in
MS and is related with more neurological disability and presence of
varicose veins at the legs. Determining CCSVI by ECD is unreliable
because of the fluctuating natural course of the extracranial venous
haemodynamics.
A systematic review of the association between chronic cerebrospinal venous insufficiency and multiple sclerosis
J.M. Burton on behalf of the Canadian CCSVI Systematic Review Group
Background:
It has been proposed that multiple sclerosis (MS) is caused by
ultrasound detectable abnormalities in the anatomy and flow of intra and
extra-cerebral veins, a condition termed chronic cerebrospinal venous
insufficiency (CCSVI).
Objectives: This updated systematic review, supported by the
Canadian Institutes of Health Research, was undertaken to examine the
evidence of an association between CCSVI and MS using rigorous methods.
Methods: Literature searches of the electronic databases Ovid
MEDLINE (2005-March 2012), the Cochrane Central Register of Controlled
Trials (2005-March 2012) and EMBASE (2005-March 2012) were undertaken.
Studies had to report original data in a peer-reviewed publication, use
either Doppler ultrasonography or magnetic resonance venography (MRV),
and assess MS patients vs healthy controls (HC) and/or those with other
neurological disorders (OND). Cochrane Review manager was used to
generate odds ratios and plots.
Results: There are now 14 studies in this review comparing the
frequency of CCSVI by ultrasonography in MS patients, 11 of which
compared MS vs HC, and 5 of which compared MS vs OND. CCSVI was
diagnosed more frequently in MS patients vs HC (OR 8.11, 95% CI 2.85,
23.09), but with extremely high heterogeneity of frequency and magnitude
of association (I2=84%). Sensitivity analysis on this data awaits the
addition of more studies. Five studies comparing MS to OND found a
higher frequency of CCSVI in MS, but heterogeneity was considerable and
results not statistically significant. Three small studies of MRV in MS
vs HC found no significant differences between groups. MS clinical
outcomes could not be interpreted as trials were neither randomized nor
properly controlled. Most trials did not follow patients beyond the
peri-procedure period but reported a small number of early complications
including arrhythmias, hemorrhage and vein wall dissection/ rupture.
Case reports of post-procedure complications have documented stent and
cerebral vein thrombosis, PE, accessory nerve injury, hemorrhage and
death.
Conclusion: This systematic review found a statistically
significant association between CCSVI and MS vs HC, but not clearly
between MS and OND. However, heterogeneity and methodological
limitations pertaining to randomization methods, control groups and
failure to blind prevent a definitive conclusion. At present, results
demonstrate only an association between CCSVI and MS, not a causal
relationship
Chronic cerebrospinal venous insufficiency in MS/CIS is not consistently observed with a blinded ultrasound protocol
K. Knox, J. Gitlin, S. Harvey, C. Hayward, S. Wiebe, C. Voll, P. Szkup, R. Otani (Saskatoon, CA)
Criteria
proposed by Zamboni et al. for Chronic Cerebrospinal Venous
Insufficiency (CCSVI) were initially reported to be 100% associated with
Multiple Sclerosis and never seen in controls. Subsequent research has
not replicated these findings. Multiple factors are suggested to have a
role in the reproducibility of findings, including duration of disease
and blinding of the ultrasonographer.
Objective: To evaluate the prevalence of CCSVI in MS, clinically
isolated syndrome (CIS), and age-matched healthy controls using a
blinded approach.
Methods: Five subjects with MS, ten with CIS, and fifteen healthy
controls were recruited to participate. Two experienced
ultrasonographers were trained in the Zamboni protocol for the
assessment of CCSVI criteria: 1) Reflux in internal jugular veins (IJV)
and/or vertebral veins (VV) >0.88 seconds; 2) Reflux in deep cerebral
veins >0.5 seconds; 3) Cross sectional IJV area <= 0.3cm2; 4) No
Doppler-detectable flow in the IJVs or VVs; and 5) Reverted postural
flow of the main cerebral venous outflow pathways. Subjects were scanned
on either a Philips or ESAOTE device. Nine subjects (1 MS, 1 CIS, 7
controls) were assessed for the five proposed CCSVI criteria. In 21
subjects, the 2nd CCSVI criterion was not assessed due to technicalities
and delays in obtaining Health Canada approval for use of the ESAOTE.
In order to maintain blinding, a research assistant positioned and
covered the subjects, exposing the neck prior to the arrival of the
ultrasonographer. Subjects were instructed not to speak during the
procedure and to facilitate this, background music was played. A
research assistant remained in the room during all procedures.
Assessment of blinding through an exit survey was completed by the
ultrasonographer.
Results: Median ages were 47.00 (MS), 44.14 (CIS), and 44.61 years
(controls). Median duration of disease since symptom onset were 27.67
(MS) and 2.86 years (CIS). Four of five subjects with longstanding MS,
0/10 subjects with CIS and 2/15 control subjects fulfilled >=2
criteria for CCSVI. Blinding of the ultrasonographer was maintained for
29/30 subjects.
Conclusion: This pilot study could not confirm that CCSVI is present
only in disease (MS or CIS) and never in controls when evaluated by
blinded ultrasonographers trained in the Zamboni CCSVI protocol. We
provide a detailed description of blinding methods not routinely
reported previously and this may be important in the interpretation of
the CCSVI literature.
So this study did not confirm the original incidence of CCSVI with MS and health controls, but this study did report that more MSers had CCSVI criteria than controls in a blinded study.
However you can have the alternative Take from the Hubbard Foundation...no CoI there then click Here
Dr Hubbard Foundation reported "Thirteen of the 21 abstracts were ultrasound studies and predictably were negative, inconclusive, and/or repetitive. I think we have all learned that ultrasound is not able to provide diagnostic criteria for the hypothesis of chronic cerebro-spinal venous insufficiency, and internal jugular ultrasound will not help us understand what is happening in the small veins of the CNS white matter where MS lesions occur.
Labels: CCSVI