Venöse Multiple Sklerose | CCSVI

Ein offener Brief eines DMSG Mitgliedes an DMSG Schirmherrn Christian Wulff wurde zur Veröffentlichung zugesandt. 9. Juni 2010:

Sehr geehrter Herr Christian Wulff,

ich schreibe Ihnen als dem Schirmherrn der Deutschen Multiplen Sklerose Gesellschaft (DMSG) und bitte Sie, Ihren Einfluß in dieser Gesellschaft geltend zu machen, um sie zu einer aufgeschlossenen Haltung gegenüber einem therapeutischen und wissenschaftlichen Ansatz zu bewegen, den sie bislang – ihrem Ärztlichen Beirat folgend - ablehnt.

Durch die Arbeit des italienischen Gefäßchirurgen Prof. Paolo Zamboni ist vor wenigen Jahren ein Zusammenhang zwischen venösen Obstruktionen und dem Krankheitsbild der MS in das Blickfeld von Forschern und Betroffenen gerückt worden. Entsprechende Beobachtungen waren im Laufe der Medizingeschichte seit Charcot zwar immer wieder einmal gemacht worden, gerieten allerdings auch stets wieder in Vergessenheit – was zu einem Teil daran gelegen haben wird, daß heute angewandte, diagnostische Techniken – insbesondere nicht-invasive, bildgebende Verfahren wie MRT und Sonographie – in der Vergangenheit nicht zur Verfügung standen und eine therapeutische Konsequenz aus solchen Beobachtungen schwerlich hätte gezogen werden können.

1. PDFs are available for free of the Int Angiol. 2010 Apr;29(2) issue. Check out the previous article.

2. [doepp10a] Doepp F, Paul F, Valdueza JM, Schmierer K, Schreiber SJ: No cerebro-cervical venous congestion in patients with multiple sclerosis. Annals of Neurology. 2010. doi:10.1002/ana.22085. Article$
   Department of Neurology, University Hospital Charité, Humboldt University, Berlin, Germany; Barts and The London Queen Mary School of Medicine & Dentistry, London, UK

The MS societies of Canada and USA announced funding of seven CCSVI research projects!

Multiple Sclerosis Society of Canada, June 11, 2010
National Multiple Sclerosis Society, June 11, 2010

"Over $2.4 Million Committed to Support Seven Operating Grants to Explore the Relationship of CCSVI to Multiple Sclerosis."

FAQs about new CCSVI grants

New publications

• [ferlini10a] Ferlini A, Bovolenta M, Neri M, Gualandi F, Balboni A, Yuryev A, Salvi F, Gemmati D, Liboni A, and Zamboni P: Custom CGH array profiling of copy number variations (CNVs) on chromosome 6p21.32 (HLA locus) in patients with venous malformations associated with multiple sclerosis. BMC Med Genet. 2010 Apr;11(1):64. Epub 2010 Apr 28. PMID 20426824, doi:10.1186/1471-2350-11-64. Article, PDF.
  Abstract

  Background
  Multiple sclerosis (MS) is a complex disorder thought to result from an interaction between environmental and genetic predisposing factors which have not yet been characterised, although it is known to be associated with the HLA region on 6p21.32. Recently, a picture of chronic cerebrospinal venous insufficiency (CCSVI), consequent to stenosing venous malformation of the main extra-cranial outflow routes (VM), has been described in patients affected with MS, introducing an additional phenotype with possible pathogenic significance.
  Methods
  In order to explore the presence of copy number variations (CNVs) within the HLA locus, a custom CGH array was designed to cover 7 Mb of the HLA locus region (6,899,999bp; chr6:29,900,001-36,800,000). Genomic DNA of the 15 patients with CCSVI/VM and MS was hybridised in duplicate.
  Results
  In total, 322 CNVs, of which 225 were extragenic and 97 intragenic, were identified in 15 patients. 234 known polymorphic CNVs were detected, the majority of these being situated in non-coding or extragenic regions. The overall number of CNVs (both extra- and intragenic) showed a robust and significant correlation with the number of stenosing VMs (Spearman: r=0.6590, p=0.0104; linear regression analysis r=0.6577, p=0.0106). The region we analysed contains 211 known genes. By using pathway analysis focused on angiogenesis and venous development, MS, and immunity, we tentatively highlight several genes as possible susceptibility factor candidates involved in this peculiar phenotype.
  Conclusions
  The CNVs contained in the HLA locus region in patients with the novel phenotype of CCSVI/VM and MS were mapped in detail, demonstrating a significant correlation between the number of known CNVs found in the HLA region and the number of CCSVI-VMs identified in patients. Pathway analysis revealed common routes of interaction of several of the genes involved in angiogenesis and immunity contained within this region. Despite the small sample size in this pilot study, it does suggest that the number of multiple polymorphic CNVs in the HLA locus deserves further study, owing to their possible involvement in susceptibility to this novel MS/VM plus phenotype, and perhaps even other types of the disease.
• [qiu10a] Qiu J: Venous abnormalities and multiple sclerosis: another breakthrough claim? Lancet Neurol. 2010 May;9(5):464-5. PMID 20398855, doi:10.1016/S1474-4422(10)70098-3.
• [beal10a] Beal E: Vascular angioplasty for ms? Nat Rev Neurol. 2010 Apr;6(4):184. PMID 20383884. Article$.
• [rynor10a] Rynor B: Canadian trials to examine "liberation procedure" for multiple sclerosis. CMAJ. 2010 May:. PMID 20439450, doi:10.1503/cmaj.109-3251. PDF. See [trial_rodger10a] [trial_knox10a]

Announced studies

• [trial_zamboni10a] Zamboni P: Randomised controlled CCSVI treatment trial. Source (medpage interview at 2:15)
  Italy
  Abstract

  IRB: June 2010
  Start: Summer 2010
• [trial_dake10a] Dake M: CCSVI Study. Stanford University. Source (Video interview). Needs funding.
  Stanford University
  Abstract

  Start: 2010
• [trial_sinan10a] Sinan T, Al Khashan S, Safar H, Almuzaini AA, Bin naki AM, Al bader M, Bahzad M: CCSVI study Kuwait. ccsvikuwait.com. Study description, Introduction.
  Mubarak Hospital and other Hospitals of Kuwait
  Abstract

  AIM & OBJECTIVE:
  

  In Kuwait the MS patient is increasing and it is estimated about 2000-3000 patients. This program started in March. 2010, it is multidisciplinary approach, vascular diagnostic lab. doctor, vascular surgeon, and vascular intervention radiology, radiologist and neurologist.

  Our objective to diagnose MS patient with Chronic cerebrospinal venous insufficiency (CCSVI) and to evaluate them with Duplex scanning and magnetic resonance venography and to evaluate clinical and or radiological improvement of these cases after treating them with angioplasty with or without stent of the diseased affected part of the internal jugular vein.

  This method is a new application of a standard procedure that may be helpful in relieving some of the symptoms of MS patients with CCSVI and it was advocated in Italy, Poland and USA. In Kuwait we would like as usual to lead the way in the Gulf state and Arabian countries to study and assess the feasibility of such a new method of possible clinical improvement of some or all of the symptoms of MS patients which may help improve quality and functions of the patients and whether or not reach and meet our expectation, therefore we will do a pilot study of 100 patients and evaluate clinical improvement by a neurologist at 1, 3, 6, and 12 months. Colour Duplex scan at 1, 3, 6, 9, and 12 months intervals. MRV at 6 and 12 months intervals. MRI brain at 3, 6, and 12 months intervals. If the initial results of the study fulfilling our objectives then we will do more cases and continue the study for 1 year to include total 500 cases at least.

  SAMPLE SIZE:
  100 - 500 MS patients from all hospital.

• [trial_hubbard10a] Hubbard D: The fMRI BOLD Response in MS, Support for the CCSVI Hypothesis. Hubbard Foundation for fMRI Research. Grant Request (PDF)
  Hubbard Foundation for fMRI Research.
  Abstract

  Lay Summary
  The pathogenesis of MS remains unknown. The well-known inflammatory changes may not be causative and may not correlate with clinical symptoms or disability. A new theory of the cause of MS, known as CCSVI, has been proposed by Dr. Zamboni in Italy. According to this theory, inadequate drainage from neurons leads to leakage of iron-containing and immune cells across the blood-brain barrier, exposing neurons and myelin-producing cells to inflammation. In the past year, he found in MS patients narrowing of neck veins using ultrasound and reported clinical improvement by removing the obstructions in the internal jugular veins with percutaneous transluminal angioplasty. Dr. Haacke at Wayne State in Detroit and Dr. Zivadinov at the University of Buffalo have confirmed these findings using MRI venography. While promising, these methods do not address the drainage of blood from cerebral cortex directly. We present new data on a method to test cerebral cortex drainage, using functional MRI that measures cortex blood flow specifically. If our preliminary findings are confirmed, venous drainage from cortex is dramatically altered in MS patients, recognizable at the single subject level, further supporting the CCSVI hypothesis and promising a clinical test for this abnormality whether it is secondary to neck vein obstruction or delay in smaller veins in the brain.

  Scientific Abstract
  Chronic cerebrospinal venous insufficiency has been proposed by Zamboni and Haacke as the proximate cause of multiple sclerosis (MS). They have proposed using ultrasound and MRI venograms to study the large veins in the neck and head. We have shown in MS patients that functional MRI can demonstrate delayed venous recovery of the hemodynamic response to stimulation of frontal lobe function, providing direct evidence of venous insufficiency in the cerebral cortex and a potential index for evaluating potential treatments.

  Background and Significance
  Chronic cerebrospinal venous insufficiency (CCSVI) is the theory that the autoimmune neurodegeneration of MS may be triggered by narrowing of and restricted flow in the veins of the head and neck leading to venous hypertension and insufficiency. The theory has been recently reinvigorated by Zamboni who has conducted clinical studies showing cerebral and spinal outflow stenoses in a large group of MS patients. He proposes the resultant venous hypertension may damage the vessel wall further causing local proximal iron depositions as well as the long recognized inflammatory changes and demyelination. He has gone further proposing that interventional percutaneous transluminal angioplasty or stenting of the stenotic veins may be a treatment option for MS patients.

• [trial_tornatore10a] Tornatore C, Neville R: CCSVI treatment study. Georgetown University Hospital. Source
  Georgetown University Hospital, USA
  Abstract

  2 year study

Comparison by Charity Intelligence Canada of the Canadian studies [trial_rodger10a] and [trial_knox10a] which are seeking funding: PDF document.

Note: Kuwait offers angioplasty for CCSVI to all Kuwaitis affected by MS through the public health system. Source: CTV.

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