CCSVI Syndrome by Team ZAMBONI - Key Papers

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

Re: CRUCIAL PAPERS - CCSVI Syndrome by Team ZAMBONI

Postby 1eye » Sat Dec 01, 2012 4:39 pm

A guitar oriented person's $0.02: an annulus is a ring. Your third finger is your ring finger, so it's called annular.
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Re: CRUCIAL PAPERS - CCSVI Syndrome by Team ZAMBONI

Postby NHE » Sat Dec 01, 2012 11:17 pm

MarkW wrote:It is 2 months since I bumped Prof Zamboni's work. The most recent paper from Team Zamboni..........
"CCSVI can be inserted in the list of multiple factors involved in MS pathogenesis."
Here are three crucial papers which must be read for an overview of CCSVI syndrome:
First - http://phleb.rsmjournals.com/cgi/reprint/25/6/269
Then - http://www.functionalneurology.it/common/php/p ... 1ead753ee5
Next - http://www.ingentaconnect.com/content/m ... 8/art00006
-----------------------


Hi Mark,
Here's a post in the Forums FAQ that describes why the two URLs in your post don't work.

site-support-f2/topic5284-15.html#p197371

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Re: CRUCIAL PAPERS - CCSVI Syndrome by Team ZAMBONI

Postby MarkW » Tue Dec 11, 2012 10:20 am

Bumped for Anonymoose:
Zamboni writes that MS is multi-factorial:
http://www.ingentaconnect.com/content/m ... 8/art00006
MarkW

PS Thanks for the tip NHE.
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 10 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Re: CRUCIAL PAPERS - CCSVI Syndrome by Team ZAMBONI

Postby MarkW » Fri Jan 11, 2013 10:04 am

This is the first time in 2013 that I have bumped Prof Zamboni's
words saying that MS is multi-factorial and how CCSVI could fit
into MS.
MarkW
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 10 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Re: CRUCIAL PAPERS - CCSVI Syndrome by Team ZAMBONI

Postby MarkW » Sat Feb 02, 2013 5:12 am

Hello Everyone,
My 1000th post on TiMS is to highlight Prof Zamboni's papers. If you are new to TiMS these are crucial to your understanding of CCSVI. If you have been posting on the CCSVI forum for some time and have not read these papers in in last 12 months, please refresh your memory.
Kind regards,
Mark
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 10 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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CCSVI Syndrome by Team ZAMBONI

Postby MarkW » Thu May 23, 2013 1:53 pm

Thanks Cece for posting this. I added it to the Zamboni papers. MarkW
http://koti.mbnet.fi/hiihoo/ccsvi/The%2 ... %20the.pdf

Cece wrote:http://koti.mbnet.fi/hiihoo/ccsvi/The%20omohyoid%20muscle%20entrapment%20of%20the.pdf
The omohyoid muscle entrapment of the internal jugular vein. A still unclear pathogenetic mechanism

Sergio Gianesini1, Erica Menegatti1, Francesco Mascoli2,
Fabrizio Salvi3, Stefano Bastianello4 and Paolo Zamboni1

Abstract
Objectives: To evaluate the role of the omohyoid muscle anatomic variants as a possible reversible cause of internal
jugular vein extrinsic compression.

Method: We describe a chronic cerebro-spinal venous insufficiency patient, who presented a omohyoid muscle entrapment
of the internal jugular vein, confirmed by both magnetic resonance venography and ultrasound investigation.
A omohyoid muscle surgical transection together with a patch angioplasty was performed.

Results: The surgical procedure led to both IJV flow restoration and neurological improvement.

Conclusions: The omohyoid muscle compression on the internal jugular vein seems to be a possible cause of venous
obstruction, but several anatomical and patho-physiological aspects need further investigations. Such picture might cause
balloon venous angioplasty inefficacy and needs to be preoperatively considered.

Two things were treated: a muscle was snipped that was compressing the jugular, and the jugular itself underwent a patch angioplasty, which is when the jugular is cut lengthwise and a patch of additional vein is sewn in to make the jugular bigger.

Since both a patch angioplasty and a muscle transection occurred, then we don't know which of the two procedures gets the credit for the neurological and blood flow improvements, but there were improvements!
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 10 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Case Report: CCSVI Syndrome by ZAMBONI

Postby MarkW » Sun Jun 09, 2013 7:01 am

Case report from Prof Zamboni. Use weblink to see photos, words below....................MarkW
http://www.angiologist.com/uniquely-vas ... fficiency/

Chronic cerebrospinal venous insufficiency (CCSVI) is a newly described vascular entity. It is characterized by restricted venous outflow from the brain and spinal cord through the internal jugular (IJV) and/or azygos (AZ) veins (Figure 1), or sometimes, through the external vertebral plexuses. (1-5)

Left) Catheter venography of the internal jugular vein in healthy control; Right) Stenosis (arrows) and collateral circles activated in a CCSVI case, both studied by the means of catheter venography.

Clinical Vignette: CCSVI in multiple sclerosis patients

A 41 year old woman, diagnosed with relapsing-remitting multiple sclerosis, came to our office with the following history. She underwent color Doppler and phlebographic evaluation 3 years ago in an interventional center. The pre-assessment disability score (EDSS), (normal range0 to 10), was 3. The investigation revealed a CCSVI related left IJV stenosis, associated with a color Doppler detectable blocked outflow and linked to an M-mode evident fixed valve apparatus. (14) A PTA was performed leading to an effective IJV widening at 6 month follow up. At the same time the EDSS decreased to 2 and the patient described a clinical improvement of the pre-assessment reported paresthesia and fatigue.

At 1 year follow up the EDSS was 3 again and the patient reported recurrent fatigue that she had been experiencing for several months. Further investigation revealed a CCSVI related left IJV tandem obstruction. At mid cervical level B-mode color Doppler demonstrated an IJV obstruction mirrored by an MRV imaging. In both cases a pencil tip pencil sign was demonstrated (Figure 2). The color Doppler assessment highlighted a left IJV dynamic flow obstacle caused by an extrinsic compression (Figure 2), that could be relieved by yawning.

Top: the arrow in the MRV indicates an obstruction of the left IJV due to external compression. Bottom: left, particular of the tip pencil sign mirrored on the right by the correspondent high-resolution B-mode imaging of the left IJV.

At the caudal level a color Doppler detectable blocked outflow was demonstrated. The flow abnormality was linked to a M-mode evident fixed valve leaflet.

Considering a further PTA pointless, an open surgical access was placed. The macroscopic evidence of the extrinsic stricture, caused by a fibrotic and short OM intermediate tendon on the IJV, lead to the surgical transection of the two muscular bellies. In addition, endophlebectomy of the terminal IJV permitted the removal of a fibrotic septum. The procedure was completed by patch angioplasty by using an autologous great saphenous vein. The patient tolerated the procedure well and neither major nor minor complications were reported.

At 2 years follow up after the surgical operation, the color Doppler assessment detected a persistent and monodirectional physiologic IJV flow, which improved considerably from being absent pre-operatively to the post-procedural 300 ml/min. The a EDSS value remained 1 and the patient did not report any other multiple sclerosis like relapses.

Pathophysiology and diagnosis of CCSVI

Occlusion of the extracranial venous pathways can take various forms, including the presence of intraluminal septa, membranes, and immobile valves, as well as segmentary hypoplasia of the veins. (1-5) Similar intraluminal obstructions and hypoplasia\agenesis have been documented for other malformations of the venous tree. These have been documented with a combination of techniques (intra and extravascular ultrasounds, catheter and MR venography). (6-7)

It is difficult to accurately non-invasively screen for CCSVI, due to the high operator-dependency of echo color Doppler (ECD) sonography techniques. For this reason the reported prevalence of CCSVI measured by the means of ECD is highly heterogeneous in the literature. However this diagnosis may be important to make. Specifically, CCSVI may be associated with neurodegenerative disorders such as multiple sclerosis (MS) – something that has generated considerable scientific controversy, (8-12) A meta-analyses revealed that CCSVI was found mainly in multiple sclerosis (MS) patients (OR 4, 95% CI 1-11), but was also possibly associated to other neurodegenerative diseases. Complicating matter further, it has also been found in healthy controls. (13)

CCSVI and brain pathophysiology

CCSVI appears to strongly influence two pivotal aspects of brain pathophysiology: parenchymal perfusion and cerebrospinal fluid (CSF) flow. CCSVI affects the venous return and MRI studies have shown that it is strongly associated with hypoperfusion of brain parenchyma, (Figure 3). Interestingly, this has consistently been described in multiple sclerosis patients yet the autoimmune theory of the disease cannot explain it. (15-16)

A: MRI perfusion study of the brain in a 33 yo, relapsing remitting, CCSVI-MS patient with score 5 at ECD venous haemodynamics severity score(16-17).B: MRI perfusion study of thebrain in a 38 yo, relapsing remitting, CCSVI-MS patient with score 12 at ECD venous haemodynamics severity score.The dark areas indicate lower perfusion in the patient B with higher restriction of venous outflow.

Furthermore, CCSVI is linked to altered CSF dynamics (17-18), suggesting that intracranial hydrodynamic regulatory mechanism may be impaired in individuals who exhibit CCSVI. CSF is filtered at the capillary level and flows in a closed circuit. The end terminal is represented by the cerebral venous system, which in CCSVI exhibits a hampered outflow. Interestingly, PTA of the jugular and azygous veins improves both CSF flow and velocity as blindly assessed in the brain by the means of 3TMR. (19) Such an effect on CSF dynamics seems particularly relevant because in neurodegenerative disorders CSF reduced flow is inversely related to accumulation of T2 lesions at MRI. (20)

CCSVI and Interventional procedures

PTA of the jugulars and azygous system is considered a safe procedures, whereas the risk is increased if a stent is used.(21-23) Clinical and QoL improvements have been reported in a number of prospective and case control studies following interventional procedures, (24-30) and a double blinded randomized trial is currently enrolling. (31) Read more about venoplasty for multiple sclerosis.

References for CCSVI

1. Zamboni P, Galeotti R, Menegatti E, et al. Chronic cerebrospinal venous insufficiency in patients with
multiple sclerosis. J Neurol Neurosurg Psychiatry 2009, 80(4):392-399.
2. Zivadinov R, Ramanathan M, Dolic K, Marr K, Karmon Y,Siddiqui AH, Benedict RH, WeinstockGuttman B Chronic cerebrospinal venous insufficiency in multiple sclerosis: diagnostic, pathogenetic,
clinical and treatment perspectives. Expert Rev Neurother. 2011 Sep;11(9):1277-94.
3. Dolic K, Marr K, Valnarov V, Dwyer MG, Carl E, Karmon Y, Kennedy C, Brooks C, Kilanowski C,
Hunt K, Siddiqui AH, Hojnacki D, Weinstock-Guttman B, Zivadinov R. Intra-and extraluminal
structural and functional venous anomalies in multiple sclerosis, as evidenced by 2 noninvasive imaging
techniques. AJNR Am J Neuroradiol. 2012 Jan;33(1):16-23..
4. Zivadinov R, Marr K, Cutter G, et al Prevalence, sensitivity, and specificity of chronic cerebrospinal
venous insufficiency in MS. Neurology 2011;77(2):138-144.
5. Bastianello S, Bergamaschi F, Viselner G, et al. An international multicenter observatory on prevalence
of CCSVI in MS. BMC Neurology, 2011 11:132.
6. Lee BB, Bergan J, Gloviczki P, Laredo J, Loose DA, Mattassi R, Parsi K,Villavicencio JL, Zamboni P;
International Union of Phlebology (IUP). Diagnosis and treatment of venous malformations. Consensus
document of the International Union of Phlebology (IUP)-2009. Int Angiol. 2009 Dec;28(6):434-51
7. Lee BB, Laredo J, Neville R: Embryological background of truncular venous malformation in the
extracranial venous pathways as the cause of chronic cerebrospinal venous insufficiency. International
Angiology 2010 April;29(2):95-108
8. Doepp F, Paul F, Valdueza JM, Schmierer K, Schreiber SJ. No cerebrocervical venous congestion in
patients with multiple sclerosis. Ann Neurol. 2010; 68:173-83.
9. Mayer CA, Waltraud P, Matthias WL, Nedelmann M, Bechmann I, Steinmetz, Ziemann. The perfect
crime? CCSVI not leaving a trace in MS. J Neurol Neurosurg Psychiatry. 2011;82:436-440.
10. Baracchini C, Perini P, Calabrese M, Causin F, Rinaldi F, Gallo P. No evidence of chronic cerebrospinal
venous insufficiency at multiple sclerosis onset. Ann Neurol. 2011;69:90-9.
11. Wattjes MP, van Oosten BW, de Graaf WL, Seewann A, Bot JC, van den Berg R, Uitdehaag BM,
Polman CH, Barkhof F.J No association of abnormal cranial venous drainage with multiple sclerosis: a
magnetic resonance venography and flow-quantification study.Neurol Neurosurg Psychiatry.
2011:82(4):429-35.
12. Centonze D, Floris R, Stefanini M, Rossi S, Fabiano S, Castelli M, Marziali S, Spinelli A, Motta C,
Garaci FG, Bernardi G, Simonetti G. Proposed chronic cerebrospinal venous insufficiency criteria do not
predict multiple sclerosis risk or severity. Ann Neurol. 2011;70:52-9.
13. Laupacis A, Lillie E, Dueck A, Straus S, Perrier L, Burton JM, Aviv R, Thorpe
K, Feasby T, Spears J. Association between chronic cerebrospinal venous
insufficiency and multiple sclerosis: a meta-analysis. CMAJ. 2011;183(16):E1203-112
14. Zamboni P, Morovic S, Menegatti E, Viselner G, Nicolaides AN. Screening for
chronic cerebrospinal venous insufficiency (CCSVI) using
ultrasound–recommendations for a protocol. Int Angiol. 2011 Dec;30(6):571-97.
15. D’haeseleer M, Cambron M, Vanopdenbosch L, De Keyser J. Vascular aspects of multiple sclerosis.
Lancet Neurol. 2011;10(7):657-66.23.
16. Zamboni P, Menegatti E, Weinstock-Guttman B, et al. Hypoperfusion of brain parenchyma is associated
with the severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a
cross-sectional preliminary report. BMC Med 2011; 9:22.
17. Zamboni P, Menegatti E, Weinstock-Guttman B, et al. The severity of chronic cerebrospinal venous
insufficiency in patients with multiple sclerosis is related to altered cerebrospinal fluid dynamics. Funct
Neurol 2009, 24(3):133-138.
18. Zamboni P, Menegatti E, Weinstock-Guttman B, et al. CSF dynamics and brain volume in multiple
sclerosis are associated with extracranial venous flow anomalies: a pilot study. Int Angiol 2010;
29(2):140-148.
19. Zivadinov R, Magnano C, Galeotti R, Schirda C, Menegatti E, Weinstock-Guttman B, Marr K,
Bartolomei I, Hagemeier J, Maria Malagoni A, Hojnacki D, Kennedy C, Carl E, Beggs C, Salvi F,
Zamboni P. Changes of Cine Cerebrospinal Fluid Dynamics in Patients with Multiple Sclerosis Treated
with Percutaneous Transluminal Angioplasty: A Case-control Study. J Vasc Interv Radiol. 2013
Jun;24(6):829-38.
20. Magnano C, Schirda C, Weinstock-Guttman B, Wack DS, Lindzen E, Hojnacki D, Bergsland N,
Kennedy C, Belov P,Dwyer MG, Poloni GU, Beggs CB, Zivadinov R. Cine cerebrospinal fluid imaging
in multiple sclerosis. J Magn Reson Imaging. 2012 Oct;36(4):825-34.
21. Ludyga T, Kazibudzki M, Simka M, Hartel M, Swierad M, Piegza J, Latacz P, Sedlak L, Tochowicz M.
Endovascular treatment for chronic cerebrospinal venous insufficiency: is the procedure safe?
Phlebology. 2010 Dec;25(6):286-95.
22. Petrov I, Grozdinski L, Kaninski G, Iliev N, Iloska M, Radev A. Safety profile of endovascular treatment
for chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Endovasc Ther. 2011
Jun;18(3):314-23.
23. Mandato KD, Hegener PF, Siskin GP, Haskal ZJ, Englander MJ, Garla S, Mitchell N, Reutzel L, Doti C.
Safety of endovascular treatment of chronic cerebrospinal venous insufficiency: a report of 240 patients
with multiple sclerosis. J Vasc Interv Radiol. 2012 Jan;23(1):55-9.
24. Zamboni P, Galeotti R, Menegatti E, Malagoni AM, Gianesini S, Bartolomei I, Mascoli F, Salvi F. A
prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J
Vasc Surg. 2009 Dec;50(6):1348-58.
25. Hubbard D, Ponec D, Gooding J, Saxon R, Sauder H, Haacke M. Clinical improvement after
extracranial venoplasty in multiple sclerosis. J Vasc Interv Radiol. 2012 Oct;23(10):1302-8.
26. Zamboni P, Galeotti R, Weinstock-Guttman B, Kennedy C, Salvi F, Zivadinov R. Venous angioplasty in
patients with multiple sclerosis: results of a pilot study. Eur J Vasc Endovasc Surg. 2012 Jan;43(1):116-22.
27. Salvi F, Bartolomei I, Buccellato E, Galeotti R, Zamboni P. Venous angioplasty in multiple sclerosis:
neurological outcome at two years in a cohort of relapsing-remitting patients. Funct Neurol. 2012 JanMar;27(1):55-9.
28. Beelen R, Maene L, Castenmiller P, Decoene V, Degrieck I. Evolution in quality of life and
epidemiological impact after endovascular treatment of chronic cerebro-spinal venous insufficiency in
patients with multiple sclerosis. Phlebology. 2012 Mar;27 Suppl 1:187-9.
29. Denislic M, Milosevic Z, Zorc M, Ravnik IZ, Mendiz O. Disability caused by multiple sclerosis is
associated with the number of extra cranial venous stenoses: possible improvement by venous
angioplasty. Results of a prospective study. Phlebology. 2012 Nov 30. [Epub ahead of print]
30. Radak D, Kolar J, Sagic D, Ilijevski N, Tanaskovic S, Aleksic N, Marinkovic J, Mitrasinovic A, Radak
S, Babic S, Matic P, Vlajinac H. Percutaneous angioplasty of internal jugular and azygous veins in
patients with chronic cerebrospinal venous insufficiency and multiple sclerosis: early and mid-term
results. Phlebology. 2013 Apr 5. [Epub ahead of print]
31. Zamboni P, Bertolotto A, Boldrini P, Cenni P, D’Alessandro R, D’Amico R, Del Sette M, Galeotti R,
Galimberti S, Liberati A, Massacesi L, Papini D, Salvi F, Simi S, Stella A, Tesio L, Valsecchi MG,
Filippini G; Chair of the Steering Committee. Efficacy and safety of venous angioplasty of the
extracranial veins for multiple sclerosis. Brave dreams study (brain venous drainage exploited against
multiple sclerosis): study protocol for a randomized controlled trial. Trials. 2012 Oct 3;13:183.
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 10 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Re: CCSVI Syndrome by Team ZAMBONI - Key Papers

Postby 1eye » Mon Jun 10, 2013 8:49 am

Thanks for this. It is nice to know that, when some physicians are willing to allow their contemporaries to treat, PTA may be followed by other successes.

Too bad that in all the hullabaloo over who has the biggest dick, something that was tried with some success in Canada, as an alternative to fetal cells, is now co-opted by the FDA and will be considered a drug, to prop up a bloated industry.

As usual, human life is secondary to money. Well, I guess any professional killer could have told me that.
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'MS' is over - if you want it
Patients sans/without patience
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