More than 7,000 investigators convened in Amsterdam on October 19-22, 2011 to present findings at a joint congress of ECTRIMS (European Committee for Treatment and Research in MS) and ACTRIMS (Americas Committee for Treatment and Research in MS). Over 1100 scientific presentations and display posters covered virtually every aspect of research to stop MS, restore function, and end MS forever. Among these were the latest results from pivotal clinical trials of emerging MS therapies, possible risk factors, underlying disease mechanisms, rehabilitation approaches, CCSVI, and much more. Read more here:

Nineteen platform or poster presentations related to Chronic Cerebrospinal Vascular Insufficiency and MS. Most reported on studies of the prevalence of CCSVI in people with MS compared to various types of controls, using different imaging technologies, with conflicting results. Some reported that venous abnormalities are common and equally prevalent in patients and controls (for example, Abstracts P1105 and P1108) and others found higher prevalence in people with MS compared to healthy controls (for example, Abstract P631 and P1106-pediatric MS). Presentations of note included:

• A platform presentation of preliminary results from an ongoing study of vein structure in autopsy specimens (by Claudiu Diaconu, Dr. Robert Fox and colleagues, Cleveland Clinic, Ohio) from seven people who had MS in their lifetimes, compared to six people who did not have MS. In this unblinded study, funded by the National MS Society, so far they have identified abnormalities inside the vein tubes (lumen) that drain the brain and found a variety of structural abnormalities and anatomic variations in both groups. However, they reported higher frequency of abnormalities in those who had MS (2 abnormalities in 2 out of 6 controls versus 9 abnormalities in 6 out of 7 MS patients). They noted that MR venography may be less effective than ultrasound for identifying these venous abnormalities, and that ultrasound that examines only vein wall circumference may miss some intraluminal abnormalities. (Abstract 134)
• A platform presentation by Dr. Florian Doepp (Charite University Medicine Berlin, Germany), describing the lack of a gold standard for evaluating cerebral venous flow and summarizing findings by his team, which includes vascular experts, that directly challenge and conflict with the original findings reported by Dr. Zamboni. (No abstract)
• A poster describing a controlled Italian multi-center study (CoSMo Study) currently in process that will ultimately evaluate venous abnormalities in 2,000 people. (Abstract P634)
• A poster by Drs. Kresimir Dolic, Robert Zivadinov and colleagues (University of Buffalo, NY) exploring results in 252 people who had undergone evaluation for CCSVI. They were evaluated for possible risk factors for being diagnosed with CCSVI. The risk factors were unrelated to whether they had MS, another neurological disease or condition, or were healthy controls. The investigators found that 27.8% of the pooled group met CCSVI criteria. In this group, factors in their medical history that were more frequent than in those who did not meet the CCSVI criteria included heart disease (especially murmurs), infectious mononucleosis, and irritable bowel syndrome. (Abstract P1128)

In April, 2011, more than 10,000 researchers and practicing neurologists from around the world gathered at the 63rd Annual Meeting of the American Academy of Neurology (AAN) in Honolulu. Over 500 presentations related to multiple sclerosis. National MS Society grantees/MS Society of Canada grantees were among those presenting novel findings on many different approaches to stopping MS, restoring function, and ending the disease forever. Here are some highlights. Get free access to the conference abstracts.

Five studies, including three posters and two platform presentations, related to studies of CCSVI (chronic cerebrospinal venous insufficiency) and MS.

Mei Lu, MD (Cleveland Clinic Cerebrovascular Center), a member of one of seven teams (http://www.nationalmssociety.org/news/news-detail/index.aspx?nid=3339) being supported to investigate CCSVI by the National MS Society (USA) and the MS Society of Canada, was lead author of a poster on factors, both physiological and technical, that can complicate screening for vein blockages using Doppler sonography (ultrasound) technology:

• They found that findings were often dependent on which operator conducted the ultrasound evaluation.
• The team reported that heartbeat irregularities, stages of breathing, head position and pressure applied by the operator could alter results.
• The team also reported that the state of hydration of the subject (whether they drank adequate amounts of fluids) could also impact results of several of the criteria used to determine CCSVI.
• They concluded that these complications may help explain the mixed results reported thus far related to CCSVI and MS, and that having consensus guidelines would help improve the standardization of ultrasound assessments related to CCSVI. (Abstract P01.263)

A platform presentation by the team of Florian Connolly, MD (Humboldt University, Berlin) described a study that measured venous blood flow and narrowing with Doppler sonography in 96 people with MS (75 relapsing-remitting, 21 secondary-progressive) and 20 healthy controls.

• As in a previous study published in 2010, in this larger sample of people they were unable to detect individuals who met more than one criterion for CCSVI.
• Except for one person with MS, blood flow direction was normal in internal jugular vein and vertebral veins.
• As in the previous study, the team found that blood volume flow tended to be higher in the upright position in people with MS compared to the healthy controls. (Abstract S01.001)

A poster from Yuval Karmon, MD, Robert Zivadinov, MD, and colleagues (University of Buffalo) focused on details from Phase I of what is planned as a controlled clinical trial of angioplasty to treat CCSVI (PREMiSe trial). This phase was an open-label evaluation comparing the use of three imaging methods (Doppler sonography, intravascular ultrasound, and catheter venography) to detect valve abnormalities of the internal jugular vein in 10 people with relapsing MS who fulfilled criteria for CCSVI.

• They found that Doppler sonography was a sensitive tool for detecting internal jugular valve abnormalities, and that its findings were comparable to invasive intravascular ultrasound.
• They found valve dysmobility frequently in this sample of patients diagnosed with CCSVI.
• According to the investigators, the next phase will include more people and will be a blinded and controlled study of angioplasty. Results of that trial will be released after they have completed the study. (Abstract P04.187)

A platform presentation from Katayoun Alikhanim MD (University of Calgary) and colleagues from across Canada focused on a study of the frequency of neck vein abnormalities in 67 people who visited an MS clinic (34 MS, 20 not MS, 7 possible MS, 6 CIS) using contrast-enhanced MR venography.

• The radiologist was blinded as to the condition of each patient.
• Abnormalities were found in 7 out of 34 with MS, 4 out of 20 not MS, 0 out of 7 possible MS and 1 out of 6 CIS.
• Those with MS with vein abnormalities were more likely to be older (average age about 52 years) and to have more disability (average EDSS 6.17) compared to those with normal veins (46 years, 3.57 EDSS). (Abstract S01.006)

A poster from Kresimir Dolic, MD, and colleagues (University of Buffalo) described a study to compare vein findings using Doppler sonography and MR venography and determine whether they were complementary. The study included 150 people with MS (104 relapsing-remitting, 38 secondary-progressive, 8 primary-progressive) and 63 healthy controls matched for age and sex.

• They found that Doppler sonography was more sensitive for detecting internal jugular vein flow abnormalities, while MR venography was more sensitive for detecting collateral veins.
• 98 (67.12%) of people with MS and 18 (28.57%) of healthy controls met criteria for CCSVI.
• People with MS had evidence of collateral veins more often than healthy controls. (Abstract P05.071)

Read more MS research from the AAN conference.

The International Society for Neurovascular Diseases (ISNVD) held its first annual conference in Bologna, Italy on March 14-15, 2011. Conference Chair was Dr. Paolo Zamboni of the University of Ferrara with workshop committee chairmen, Dr. Mark Haacke (USA) and Dr. Mark Godley (Canada). There were approximately 150 to 200 attendees.

The conference sessions included: CCSVI Imaging, Iron in Neurodegenerative Disorders, Update on Carotid Surgery and Stroke, Basic Sciences and Pathology of CCSVI and MS, Vascular Mechanisms in Neurological Disorders, Modeling CCSVI Hemodynamic andEndovascular Aspects and Treatment of CCSVI.

In addition, a workshop on Echo Colour Doppler (ECD )for the diagnosis of CCSVI was conducted as well as two sessions dedicated to scientific abstract presentations. The conference programme can be found on the International Society for Neurovascular Disease website.

Highlights of Sessions

CCSVI Imaging

From this session, it emerged that multiple-modality investigation, that is, investigation of CCSVI through the use of different kinds of imaging technologies (and combinations ) is extremely important in the future evaluation of CCSVI. In particular, the specific role, advantages and limitations of imaging technologies such as ultrasound, intravascular ultrasound (VUS), CT angiography, catheter venography as well as fusion imaging were reviewed.

There was significant discussion regarding the variable imaging findings of venous anatomy and some pitfalls of diagnosing CCSVI, specifically with regards to the challenges of imaging the azygous vein. Dr. Zivadinov from Buffalo reported on MRI findings of CCSVI and elaborated on differences in investigational findings between progressive and non-progressive forms of MS, as well as the concept of optimal technologies for distinct patient groups (e.g. those with early disease v/s late disease). Dr. Zivadinov emphasized the need to establish standardized guidelines for imaging CCSVI due to the imaging challenges presented by hemodynamics (the forces and mechanisms concerned with blood circulation).

Iron in Neurodegenerative Disorders

This session was dedicated to reviewing current understandings of the pathology (causes, processes, development and results) of neurodegenerative diseases such as Alzheimer's disease as well as MS.

Specific to MS, Dr. Zivadinov presented on the topic of whether iron deposition in MS is primary or secondary. That is, is iron accumulated early in the disease process or does it occur later on, as a result of, or following atrophy (a wasting away or decrease in size of a cell, tissue, or organ of the body because of disease or lack of use)? Many questions remain, including whether or not the measurement of iron should be a marker for MS. There was general agreement that environmental, genetic and biological factors play a significant role in the development of MS.

Abstracts Session

The Albany group, led by Dr. Mehta, presented results of their prospective analysis in treating 150 MS patients with presumed CCSVI. Treated individuals had to present with greater than 50% stenosis in either internal jugular veins or azygous veins as measured by catheter venography. 55% of treated individuals had relapsing remitting MS, 31% had secondary progressive MS and 11% had primary progressive MS. A total of 267 veins with greater than 50% stenosis were identified in 150 patients.

The Albany group concluded that there is an association between MS and CCSVI with associated clinical benefits of venous angioplasty and that their findings need to be confirmed through future blinded randomized clinical trials. Dr. Mehta reported improvements in 84 percent of patients who self-reported improvement in symptoms of balance, weakness, heat intolerance, memory loss and depression.

Criticisms from the audience included observations that standard outcome measures were not used, there was an absence of radiological measurements of brain lesions post treatment and there was concern with the techniques of stenosis measurement. Dr. Mehta stated that specific attention needs to be given to what role CCSVI plays in MS, which patients with MS may benefit from venous angioplasty and what are the most valid endpoints that should be measured.

Concurrent to the abstract section, a workshop was held on Echo Colour Doppler (ECD) for diagnosis of CCSVI. Sonographers currently leading imaging in Dr. Zamboni and Dr. Zivadinov's teams assessed current equipment and criteria for CCSVI. The sonographers also led a discussion on tips to best image for the CCSVI criteria and allowed for group discussion of best practices in ECD. The most highly debated topic during the discussion was on the 2^nd criteria of the CCSVI criteria, as many doctors and sonographers commented on the difficulty in examining and evaluating this criteria.

Basic Science and Pathology of CCSVI and MS

Within this session, Dr. Thanaporn from Stanford University presented results on a mouse model of CCSVI. The mices' veins were ligated (bound) in an attempt to block the veins and replicate CCSVI. The mice did not develop obvious neurological defects after this surgery, however, small functional differences between the mice that had their vein ligated versus those that were unligated were observed. Dr. Thanaporn noted that further work needs to be done in this area in order to determine whether CCSVI contributes to MS.

Endovascular Aspects and Treatment of CCSVI

Dr. Filippini reviewed the study design of the Italian multi-centered randomized control trial BRAVE DREAMS. 650 patients will be enrolled over a 12 month period. A variety of outcome measures will be studied. Concerns were expressed with regards to whether or not the outcome measures would meet standard clinical trial endpoints.

Dr. Siddiqui from Buffalo presented an update from the PREMISE trial. The study's primary outcome is to test for severe adverse events from venous angioplasty in MS patients with CCSVI. Other non-primary outcomes will be reported. Phase I (10 patients) was completed in the summer of 2010. Phase II will include an additional 20 patients. It should be noted that within these studies extensive blinding has been put in to place. In informal discussion, Dr. Siddiqui reported no complications thus far.

Dr. Zarebinski from Poland and his group reported on CCSVI-related procedures performed on 445 multiple sclerosis patients. These individuals underwent Doppler ECD and MRV prior to catheter venography. Outcome measures evaluated included the Expanded Disability Scale (EDSS), Fatigue Severity Scale (FSS), and the Multiple Sclerosis Impact Scale (MSIS-29). The procedures were performed by four interventional cardiologists. Stenosis based upon venography in either jugular or azygous vein was treated. The Polish group reported eight complications out of 445 patients treated including two vein thromboses and a total of six femoral vein access site complications of which three required open surgery (aneurysm, pseudo aneurysm, AV fistula). They also reported four procedures that were aborted prior to venoplasty due to technical failure in accessing the stenosis. The only statistically significant finding for neurological outcome reported was an improvement in the FFS. No statistically significant improvement was reported in either the EDSS or the MSIS-29.

Dr. Zamboni, as President of the ISNVD, answered questions during the press conference. He stated he was very pleased with the research presented at the meeting and felt that excellent progress was being made internationally in areas of imaging, development of animal models and treatments.