MS Network of Care Multiple Sclerosis Network of Care Australia

A Voice for People Affected by MS


 
  Historical Background

'MS is not primarily an autoimmune disease'

A B C D E F G H I J K L M N O P Q R S T U V W X-Y Z
 
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Demographics
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Genetic Factors
 
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Pain Management
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Respite
Road Map
 
Satisfaction Levels
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Sleep Importance
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Temperature Intolerance
Testimonials
Transport
Trials - clinical
 
Vascular Issues
Vitamin D
 
 
ABOUT THE NETWORK
 
Our Vision
Becoming Involved
Donations
A to Z Master Index
Advanced Research 
About HorizonsSCAN
 
POPULAR BOOKMARKS
 
About MS
About CCSVI
Advocacy
 
Benchmarking 
Blood Brain Barrier
Blood Flow Issues
Bookmarks - all
Brain Plasticity
Brain's Vasculature
 
Carers
Cardiovascular Issues
Change Management
Chronic Infections
Clinical Trials
Cognitive Issues
 
Demographics
Diet
 
Endothelial Issues
Evaluation 
Exercise   
 
Fatigue
Financial Planning 
Future Directions
 
Genetic Factors
 
Healthy Eating 
Homecare
Hope
 
Inflammation
Innovation   
 
Leadership 
Lifestyle Issues
Lympathetic System
 
Medications
Misdiagnosis
Misinformation
 
NDIS 
Nutrition  
Needs and Issues
Neuronal Death
Neurovascular Issues
News Headlines
 
Pain Management
Parliament's Role
Patient-Centred Care
 
Quality  of Life
 
Rehabilitation
Respite
Road Map
 
Satisfaction Levels
Shortfalls in Support
Sleep Importance
Social Media Impact
Stem Cells
Support Networks
 
Temperature Intolerance
Testimonials
Transport
Trials - clinical
 
Vascular Issues
Vitamin D
 
 
 
 
ABOUT THE NETWORK
 
Our Vision
Becoming Involved
Donations
A to Z Master Index
Advanced Research 
About HorizonsSCAN
 
POPULAR BOOKMARKS
 
About MS
About CCSVI
Advocacy
 
Benchmarking 
Blood Brain Barrier
Blood Flow Issues
Bookmarks - all
Brain Plasticity
Brain's Vasculature
 
Carers
Cardiovascular Issues
Change Management
Chronic Infections
Clinical Trials
Cognitive Issues
 
Demographics
Diet
 
Endothelial Issues
Evaluation 
Exercise   
 
Fatigue
Financial Planning 
Future Directions
 
Genetic Factors
 
Healthy Eating 
Homecare
Hope
 
Inflammation
Innovation   
 
Leadership 
Lifestyle Issues
Lympathetic System
 
Medications
Misdiagnosis
Misinformation
 
NDIS 
Nutrition  
Needs and Issues
Neuronal Death
Neurovascular Issues
News Headlines
 
Pain Management
Parliament's Role
Patient-Centred Care
 
Quality  of Life
 
Rehabilitation
Respite
Road Map
 
Satisfaction Levels
Shortfalls in Support
Sleep Importance
Social Media Impact
Stem Cells
Support Networks
 
Temperature Intolerance
Testimonials
Transport
Trials - clinical
 
Vascular Issues
Vitamin D
 
 
ABOUT THE NETWORK
 
Our Vision
Becoming Involved
Donations
A to Z Master Index
Advanced Research 
About HorizonsSCAN
 
POPULAR BOOKMARKS
 
About MS
About CCSVI
Advocacy
 
Benchmarking 
Blood Brain Barrier
Blood Flow Issues
Bookmarks - all
Brain Plasticity
Brain's Vasculature
 
Carers
Cardiovascular Issues
Change Management
Chronic Infections
Clinical Trials
Cognitive Issues
 
Demographics
Diet
 
Endothelial Issues
Evaluation 
Exercise   
 
Fatigue
Financial Planning 
Future Directions
 
Genetic Factors
 
Healthy Eating 
Homecare
Hope
 
Inflammation
Innovation   
 
Leadership 
Lifestyle Issues
Lympathetic System
 
Medications
Misdiagnosis
Misinformation
 
NDIS 
Nutrition  
Needs and Issues
Neuronal Death
Neurovascular Issues
News Headlines
 
Pain Management
Parliament's Role
Patient-Centred Care
 
Quality  of Life
 
Rehabilitation
Respite
Road Map
 
Satisfaction Levels
Shortfalls in Support
Sleep Importance
Social Media Impact
Stem Cells
Support Networks
 
Temperature Intolerance
Testimonials
Transport
Trials - clinical
 
Vascular Issues
Vitamin D
 
 
 
 

 
This area of the Road Map provides snapshots of many of the key research outcomes that collectively underpin emerging understandings about multiple sclerosis progression.
Highlights Include:
  1.  Fibrinogen - impedes neural impulses that control movement    9.  Pregnancy, Blood flow and MS - the Vascular Connection
  2.  A Patients Perspective - Text Books are being rewritten 10.  Common Questions and  Answers
  3.  Looking Backwards Towards the Future - Swank was right 11.   In the Beginning - Relief from many underlying MS disabilities
4.  An Avalanche of ''Game Changing'' Neurovascular Research 12.  Talking Points, Prevalence, Safety, Benefits, Screening and Mem-net
  5. Disability Progression associated with Vascular irregularities 13.  Benchmarks for investigating CCSVI Irregularities       
  6. Nitric Oxide, Endothelial Health Lymphatic/Glymphatic Systems 14.  Broader Issues including, CPN, Lyme other Neurological & Autonomic disorders.
7.  Sunshine, Vitamin D, Iron Imbalances  & Realistic Expectations  15.  Key Turning Points  and Understanding Divergent Outcomes   
  8.  What else is Being Learnt?  Some Neurovascular Snapshots 16.  Early Days -  A Startling Find - Confirmation by Peers
Display all CCSVI Research Abstracts
Text Books are being Rewritten
The Oxford Textbook series is the foremost international textbook of medicine. Unrivalled in its coverage of the scientific aspects and clinical practice of medicine and its subspecialties, it is a diagnostic fixture in the offices and wards of physicians around the world. The 2016 edition of the Oxford Textbook of Vascular Surgery features a full chapter (chapter 10.8) on Chronic Cerebrospinal Venous Insufficiency (CCSVI) that puts to rest early scepticism and misinformation in relation to CCSVI  - hear more from Joan Beal.
Given that the respected Oxford Textbook editors identify this research as both expert and important it is difficult to comprehend why there is not far greater emphasis on the the translation of what has been learnt into patient benefits and reduced government outlays. It is well argued that the better detection and treatment of CCSVI conditions across MS populations warrants a very high place on the list of global MS rehabilitation imperatives. In this context the advanced imaging capability enabled by 7 Tesla MRI is proving to be a highly significant diagnostic and research tool.
An Abundance of Evidence
On 22 December 2015, the Journal of Neurology and Neuroscience published commentary by Emeritus Professor Bernhard HJ Juurlink, College of Medicine, University of Saskatchewan, Canada, titled ''Time to Revisit Non-Pharmacological Research Approaches to Ameliorate Multiple Sclerosis Symptoms'' which he introduced as follows
   ''There is an abundance of evidence that MS is not primarily an autoimmune disease but is a disease where there is first damage to the blood-brain barrier as well as the oligodendrocyte-myelin unit; this damage then elicits an immune response in a subset of people that have an immune system predisposed to attacking myelin-associated antigens''  
He went on to provide a brief overview of the evidence for arterial compliance problems, intracranial compliance problems, venous return problems and hypoperfusion problems in MS. Professor Juurlink's summations need to be read in parallel with the outcomes of Dr Bavera's long term follow up of multiple sclerosis patients treated with PTA for diagnosed CCSVI conditions. Following are details of many of the historical backgrounds also associated with Professor Juurlink's summations.
What is CCSVI? 
Blood flow takes twice as long (when compared with the normal) in many people diagnosed with Multiple Sclerosis (MS). Known as Chronic  Cerebro Spinal Vascular Insufficiency (CCSVI this condition is present in more than 80% of those with MS and is independent of disease duration or disability level. Evidence is evolving that this hypoperfusion condition is associated with a range of chronic conditions including hypoxia, focal lesion formation, diffuse axonal degeneration, cognitive dysfunction, and fatigue.
Relief It is also being demonstrated that treatment for this condition can provide significant, and at times immediate, relief from many of the most common chronic disabilities associated with MS.  These developments, pioneered by Professor Zamboni and colleagues, have resulted in the treatment of tens of thousands of pwMS across the globe.  See also the much earlier, but insightful, comments by Professor Roy Swank regarding vascular associations with MS.
 
Relief from many Underlying MS Chronic Disabilities

It is being consistently shown that the proper treatment of this vascular condition, by long standing, safe and minimally invasive medical interventions, can result in dramatic (and at times immediate) improvements in many of the most common symptoms of multiple sclerosis. What is being learnt is not advanced as a "cure" but is strengthening knowledge about underlying issues whereby vascular irregularities can underpin MS progression.. In the words of one of the Australian early adopters:

 
"Time flies when you've got your health back. Has it really been 5 years since people with MS started having angioplasty to clear their blocked jugular veins? I personally went from being unable to work for 12 months (and rapidly declining) to having the majority of my symptoms recede. I've been able to go back to full time employment, and enjoy my free time pain free, for all these years...Helen
 
Of Equal Importance  - An Avalanche of New Knowledge
Insights Of equal importance, is the avalanche of ongoing research much of which is independent of, but complementary to, the real world knowledge being gained by vascular specialists when treating people with MS for this condition. The 'game changing'' significance of this new research is reflected in comments by many well regarded medical researchers - some examples follow: The list is indicative and by no means exhaustive
  * There is unequivocal evidence that fibrinogen is extensively deposited in the motor cortex of those with progressive MS. This impedes the generation of neural impulses that control the execution of movement.  - July 2017
  * Low dose iron supplements induce a DNA damage response in human endothelial cells within minutes - February 2016.
  * Researchers confirmed significant associations between VEGF and the severity of Multiple Sclerosis -  June 2016

  * ''Vitamin D promotes vascular regeneration by acting directly on endothelial cells to prevent vascular leak'' - October 2015
   
  * A study from the Gladstone Institutes shows that ''a single drop of blood in the brain is sufficient to activate an autoimmune response akin to multiple sclerosis (MS)''..These findings offer a completely new way of thinking about how the immune system attacks the brain—it puts the blood in the driver’s seat of the onset and progression of disease - October 2015
   
  * ''Ongoing longitudinal studies highlight many benefits in restoring vascular blood flow via angioplasty'' - October 2015
   
  * A stunning discovery about the existence of the brains dedicated lymphatic draining system ''raises a tremendous number of questions that now need answers, both about the workings of the brain and the diseases that plague it''. There’s an enormous array of other neurological diseases, from autism to multiple sclerosis, that must be reconsidered in light of the presence of something science insisted did not exist - June 2015
   
  * Evidence is evolving that cerebral hypoperfusion in MS is associated with chronic hypoxia, focal lesion formation, diffuse axonal degeneration, cognitive dysfunction, and fatigue. ''Restoring CBF may therefore emerge as a new therapeutic target in MS'' - June 2015
   
  * The International Society for Neurovascular Disease describes multiple sclerosis research being undertaken at the Alfred Hospital Melbourne Australia as: ''one of  the worlds most sophisticated research projects into palliating, treating and curing neurovascular diseases, such as multiple sclerosis'' - March 2015
   
  * 'Multiple sclerosis endothelial (blood flow) malfunctions can be traced to a single set of genes'' - March 2015.
   
  * ''In people with MS blood flow takes twice as long when compared with the normal''. This slowdown is independent of MS duration or disability level - Feb 2015.
   
  * ''Increasingly large population studies consistently identify more than 80% of the MS population as having CCSVI related vascular irregularities'' - December 2014.
   
  * ''Inadequate blood flow to neurons may indeed be the cause of neurodegeneration in MS, AND that this was a vascular problem, NOT a problem initiated by white matter lesions'' - August 2014.
   
  * 'MEM-net acts as a blind control for the Echo-Color-Doppler ultrasound (CCSVI) report eliminating another source of possible human error and subjective interpretation of the examination.'  We hope that in the future, everyone will use this data collection tool for all scientific work on this topic'' - July 2014.
   
  * ''This discovery helps explain the molecular underpinnings of diseases like MS and ... has the potential to be a game-changer in terms of how we treat neurological conditions'' - June 2014.
   
* ''Our latest finding gives us a new way of thinking about brain disease ... that some conditions assumed to be caused by faulty neurons could actually be problems with faulty blood vessels''- June 2014.
   
  * ''Once we realized the importance of endothelial signalling in the regulation of blood flow in the brain, we wondered whether overlooking the vascular endothelium might have led researchers to misinterpret their results'' - June 2014.
   
  * ''The lack of endothelial cells in the internal jugular vein intraluminal obstacles is a (further) abnormality found in course of chronic cerebrospinal venous insufficiency''. June 2014
   
  * ''Adverse levels of ‘bad’ fats in the blood are closely linked to the level of disability in people with MS and the rate of disability progression'' - June 2014.
   
  * ''These findings are paradigm-shifting by redefining inflammatory disease from one of microbial activation of inflammatory mechanisms leading to ..... disease, to one of microbial disruption of homeostatic mechanisms that control inflammatory processes'' - June 2014.
   
  * ''Further larger investigations on iron genes should become mandatory in MS''. Understanding the exact mechanism by which iron acts in the brain causing MS and how the brain would be impacted by iron chelation/supplementation could potentially furnish precious prognostic information and novel insights for alternative personalized treatments - August 2012.  



Stunning Discoveries - The Brains Lymphatic and Glymphatic Draining Systems
Discoveries .The lymphatic system provides a slow flow of fluid from our organs and tissues into the bloodstream. It returns fluid and proteins that leak from blood vessels, provides passage for immune and inflammatory cells from the tissues to the blood, and hosts key niches for immune cells. How this system develops has not previously been well understood,
   
Physical Forces Dictate Lymphatic Development
In July 2015 it was established that the early flow of lymph fluid is a critical factor in the development of mature lymphatic vessels. Once the primary lymph vessels are in place, an enormous amount of maturation has to happen, and what we’ve found is that the maturation process is triggered by physical forces from the earliest flow of lymph fluid in a developing embryo, Researchers explored the consequences of interrupting that flow as regards long-term adverse effects on those vessels and valves..The findings represent a big step forward in the basic scientific understanding of lymphatic system development.
Overturning Decades of Textbook Teaching
June 2015 highlighted the stunning discovery by researchers at University of Virginia School of Medicine that overturns decades of textbook teaching, It is now known that the brain is directly connected to the immune system by vessels previously thought not to exist. Described as ''very well hidden” they follow a major blood vessel down into the sinuses, an area difficult to image
Researchers said“It’s so close to the blood vessel, if you don’t know what you’re after, you just miss it -.that such vessels could have escaped detection when the lymphatic system has been so thoroughly mapped throughout the body is surprising on its own, but the true significance of the discovery lies in the effects it could have on the study and treatment of  diseases like multiple sclerosis
Discovered were functional lymphatic vessels, (watch short videos here or here or here, lining the dural sinuses that expressed all of the molecular hallmarks of lymphatic endothelial cells able to carry both fluid and immune cells from the cerebrospinal fluid connected to the deep cervical lymph nodes. The discovery may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.. It changes entirely the way we perceive the neuro-immune interaction.
Something Science Insisted did not Exist
The unexpected presence of the lymphatic vessels raises a tremendous number of questions that now need answers, both about the workings of the brain and the diseases that plague it. For example, take Alzheimer’s disease. Researchers said “In Alzheimer’s, there are accumulations of big protein chunks in the brain. We think they may be accumulating in the brain because they’re not being efficiently removed by these vessels. The vessels look different with age, so the role they play in aging is another avenue to explore. And there’s an enormous array of other neurological diseases, from autism to multiple sclerosis, that must be reconsidered in light of the presence of something science insisted did not exist'' - find out more.
An MS Perspective

When commenting on these developments MS advocate Joan Beal said ''Lymphatic ducts drain lymph into veins in the neck (the right and left subclavian veins at their junctures with the internal jugular veins). Valves in the lymphatic ducts at their junctures with the veins prevent the entrance of blood into the lymphatic vessels. The implication of these discoveries is monumental. If lymphatic vessels do not have adequate drainage, due to a stenotic dural sinus, mechanical impingement or venous problems, the brain's immune system and cleansing system will not function properly'' -  read more of Joan's comments.

.

Importance of  Sleep..

 

In some respects the foregoing developments build upon research in 2013 (relating to the glymphatic system) that highlighted the importance of deep sleep in enabling the brain to clear toxins and to also facilitate myelin repair -.a topic that many MS organisations have since incorporated into education and awareness programs.

 

Synergy with CCSVI understandings

 

The new knowledge about the processes whereby the brain cleans toxins from its environment fits well with what is being learnt regarding CCSVI.- further emphasising the importance of the clinical trial being conducted at the Alfred Hospital Melbourne Australia

Click here to access a wealth of information about new lymphatic understandings.

Enhancing The Clinical Knowledge Base
By addressing the issue of vascular associations with multiple multiple from entirely new and rapidly evolving clinical perspectives this new research appears to go a significant way in validating the first hand experiences of the tens of thousands treated for CCSVI conditions across the globe, as well as providing an enhanced clinical foundation to build upon. The associations between this new knowledge and the treatment of MS related fatigue is one example - click here for details.
Key Messages and Expectations
Messages A large proportion of the MS population is being shown to have CCSVI related vascular abnormalities. A clinical trial being conducted at the Alfred Hospital, Melbourne Australia, puts this figure at 80% (preliminary figure)  - which is broadly equivalent to expectations. It is being shown that treatment for this condition can provide relief from many of the most common symptoms experienced by many of those with multiple sclerosis.
While minimally invasive angioplasty is a frequent starting point to rectify this condition it isn't necessarily a universal solution. Angioplasty is not suitable for every problematic vein, and vein specialists need to assess individual veins to determine the appropriate course of action (if any). For example, some vascular specialists may identify vascular by-passes as a possible option. Click here to watch a short video that illustrates the diversity of ways in which CCSVI conditions may present differently from one individual to the next. These variations can also make it difficult to reliably compare the outcomes of some clinical trials.

A key message is that the condition of CCSVI needs to be separated from the procedure/s appropriate to its best treatment. More about protocols developed by the International Society for Neurovascular Disease
Given that vascular imbalances, including an inability to properly deal with inflammation, can contribute to disease progression, it makes good sense to also adopt lifestyle choices that enhance vascular health - rather than place additional pressure on what, for many, may already be a compromised vascular system. Proper nutrition, appropriate exercise and effective sleep readily spring to mind. 
In some situations it may also be necessary to address underlying chronic inflammatory issues. For example there is evidence for the respiratory pathogen Chlamydophila (Chlamydia) pneumoniae (cpn) being a causal factor in some variants of multiple sclerosis.
Running in parallel with this new knowledge are strengthened concerns about the extent to which other chronic conditions are mistaken for, or associated with, MS. A misdiagnosis or incomplete diagnosis can not only cause patients potential harm but also cost health care systems untold millions of dollars a year. Misdiagnoses not only means patients are getting expensive and potentially harmful treatments they don't need, but they are also not getting the appropriate treatment for the diseases they may have. This issue has been addressed in the draft Australian CCSVI Implementation Strategy in the following terms:
 
"Screening for possible vascular irregularities be undertaken during the diagnostic stages of MS as a prerequisite to qualifying for immunotherapy subsidies". The newly developed MEM-net process appears well suited to underpin a national program of this nature.
 
More About Australian  Experience
Awareness In May 2011, as an adjunct to World MS Day, the Australian MP Janelle Saffin, raised the issue of vascular associations with Multiple Sclerosis in the Australian Parliament. Subsequently all 225 parliamentary representatives were lobbied on this matter.  The issue achieved further momentum through ongoing media coverage and Parliamentary presentations.
These processes proved valuable in not only creating awareness of this important issue but also in developing a draft national Action Strategy built around areas of difference and common ground. The commencement of a CCSVI clinical trial at the Alfred Hospital in Melbourne and the establishment of CCSVI Australia as an incorporated body were the highlights of extraordinarily efforts by the Australian MS community. MS Australia described the Alfred trial as vital and encouraged funding support.
On the downside is the (so far) failure of the incoming Liberal/National coalition government to follow through on a September 2012 commitment to the previous government whereby MS Australia agreed to "actively work with the Alfred Hospital to engage funds to complete this vital research" and also asked for "parliamentary support in advocating for funding support of the trial to the National Health and Medical Research Council and the Minister for Health to ensure the future of this vital research". Equally disappointing is a lack of response to requests to put in place a national process to monitor those being treated outside of clinical trials to capture relevant information.
Beyond Uncertainty
For some time an undercurrent of misinformation created uncertainty/disbelief/hostility (with some) that vascular irregularities could possibility contribute to MS progression. This undercurrent was  underpinned by a (sometimes) disturbing apprent lack of expertise in screening for potential CCSV conditions, including the proper interpretation of examinations. Of significance, the potential for greater consistency in the use of Echo-Color-Doppler ultrasound (ECD) to detect CCSVI conditions became available via a web accessible computer based program called MEM-net.
The MEM-net algorithm acts as a blind control for the ECD report eliminating another source of possible human error and subjective interpretation of the examination.  The developers said "We hope that in the future, everyone will use this data collection tool for all scientific work on this topic" - read more about this potentially game changing resource.
More expansive (and at times very recent) research further diminishes the relevance of this early bias against the possibility of vascular associations with MS symptoms. It also highlights an urgent need for far greater emphasise and priority to be placed on both neurovascular research and the mechanisms by which people diagnosed with MS are screened in relation vascular irregularities. The draft Action Strategy, developed in 2012 by the Australian CCSVI Reference Group, details what is needed and identifies the starting point as "fully funding of the already commenced trial at the Alfred Hospital in Melbourne"
How We All can Help           
The total cost of this ongoing trial is $450,000 of which nearly $330,000 has already been achieved primarily as a result of purpose specific donations by the MS community and Service Organisations (example. While it seems entirely appropriate that this significant "community commitmentbe matched by Australian Governments and MS Australia - all of whom have acknowledged the trial as vital - this is yet to happen. Individual or Organisational donations can be made through CCSVI  Australia
Multiple Sclerosis as a Neurovascular Disorder - What Else is Being Learnt?
Snapshots The following "research snapshots" viewed collectively, provide insight about why inter-related vascular system irregularities are being shown to underpin the development of neurovascular diseases, including, but not limited to, multiple sclerosis.
 
 
  Blood Clotting Protein (Fibrinogen) Triggers Immune attack on the Brain
 
An October 2015 study from the Gladstone Institutes shows that a single drop of blood in the brain is sufficient to activate an autoimmune response akin to multiple sclerosis (MS).
   This is the first demonstration that introduction of blood in the healthy brain is sufficient to cause peripheral immune cells to enter the brain, which then go on to cause brain damage. They discovered that injecting just one drop of blood into the brain set off the brain’s immune response, kick-starting a chain reaction that resulted in inflammation and myelin damage.
  What’s more, scientists were able to pinpoint a specific protein in the blood, the blood-clotting factor fibrinogen, as the trigger for the disease-causing process.  These findings question a long-held paradigm that myelin-specific T cells initiate inflammation in the brain through activation of microglia and brain macrophages. 
Scott Zamvil, MD, PhD, a professor of neurology at the University of California, San Francisco and co-author on the paper said “This study demonstrates that the original paradigm may also occur in reverse. Namely, initial activation of microglia and brain macrophages may activate T cells..These findings offer a completely new way of thinking about how the immune system attacks the brain—it puts the blood in the driver’s seat of the onset and progression of disease - find out more.
  Related Findings
 

In July 2017 Oxford University researchers provided unequivocal evidence that, in the case of those with progressive M.S, fibrin(ogen) is extensively deposited in their motor cortex, where regulation of fibrinolysis appears perturbed. This severe fibrin(ogen) deposition is accompanied by significantly reduced neuronal density. The role of the primary motor cortex is to generate neural impulses that control the execution of movement. Future studies are needed to clarify the source and acknowledged neurotoxicity of fibrin(ogen), and its potential impact on clinical disability.

 

In November 2017, Akassoglou and her team from the Gladstone Institute uncovered another, yet unexpected effect of blood leaking into the brain.“We found that fibrinogen stops adult stem cells from transforming into the mature cells that produce myelin. This blockade could be harmful for regeneration in the brain” The regeneration of myelin in the brain is critical for diseases like MS, stroke, neonatal brain injury, and Alzheimer’s disease. Now, the scientific community might get closer to making that happen.

  Repairing myelin by eliminating the toxic effects of vascular damage in the brain is a new frontier in disease therapeutics,” said Lennart Mucke, MD, director of the Gladstone Institute of Neurological Disease and professor of neurology at UCSF. “This could change the way we think about how to repair the brain.” Researchers can now look for new ways to target fibrinogen as a way to restore regenerative functions in the central nervous system. This could lead to novel therapies to help patients with MS and many other diseases associated with myelin.
  Role of Regulatory T Cells
  Research published by Queen's University, Belfast in March 2017 reports that while regulatory T cells (Treg) promote oligodendrocyte differentiation and (re)myelination Treg-deficient mice exhibited substantially impaired remyelination and oligodendrocyte differentiation, which was rescued by adoptive transfer of Treg in brain slice cultures. Treg accelerated developmental myelination and remyelination,  directly promoted oligodendrocyte progenitor cell differentiation and myelination in vitro. Researchers identified CCN3 as a Treg-derived mediator of oligodendrocyte differentiation and myelination in vitro. These findings reveal a new regenerative function of Treg in the CNS, distinct from immunomodulation. Although the cells were originally named 'Treg' to reflect immunoregulatory roles, this also captures an emerging, regenerative Treg functions.
  More about Fibrinogen

 
What is the impact of Vascular Problems on MS Progression?
  In February 2015 PLOS ONE reported on the outcomes of a significant study that found in people with MS it takes double the transit time for blood to flow in and out of the head, when compared with normal people. This blood flow slowdown is independent of MS duration or disability level. They also observed ''the strong Cerebral Circulation Time difference between control group and MS patients explains hypoperfusion, which pre-empts myelin breakdown and MRI detectable white matter lesions''
These issues were discussed in the July 2011 edition of the Lancet - Neurology. Researchers said, inter alia, "the pathology of MS might be the consequence of a chronic state of impaired venous drainage from the CNS, for which the term chronic cerebrospinal venous insufficiency (CCSVI) has been coined. .... some elements of CCSVI might be explained by slower cerebrospinal venous blood flow secondary to the reduced cerebrospinal perfusion in patients with MS compared with healthy individuals" - read more
  Vascular Irregularities - A Substantial increased MS Risk
  The January 2010 edition of the most highly read peer reviewed neurology journal, Neurology, reported on a Canadian study on 8,983 pwMS, that concluded that vascular  comorbidity, whether present at MS symptom onset, diagnosis, or later in the disease course, is associated with a substantially increased risk of disability progression in MS and that the impact of treating vascular comorbidities on disease progression deserves investigation. The study demonstrated that the median time between diagnosis and a need for ambulatory assistance was 18.8 years in patients without vascular problems and 12.8 years in patients with vascular comorbidities - In other words, pwMS, who also have a vascular problem, experience a progression in MS issues at a significantly greater rate than those without known vascular issues. The researchers also observed that "treatment of vascular comorbidities may represent an avenue for treating MS" - read more

In December 2015 the journal The Neurologist cautioned Neurologists to be aware of the clinical presentation and pathophysiology of cardiovascular dysfunction in MS so as to ameliorate cardiovascular symptoms, prevent cardiovascular complications, and choose therapeutic agents that do not worsen underlying cardiovascular disease. The clinical presentation and pathophysiology of cardiovascular dysfunction in MS are reviewed, as are the cardiovascular toxicities of MS therapies, fingolimod and mitoxantrone.  Similar guidance,  some 15 years earlier (February 2000), is referenced by Pubmed.
  Vascular issues and MS were the subject of research (June 2009), by Professor Zamboni, whereby vein abnormalities were shown to inhibit the flow of deoxygenated blood back to the heart - a condition referred to in the literature as chronic cerebrospinal venous insufficiency (CCSVI).  In many cases it has been possible to correct this condition, using an established day surgery vascular procedure known as balloon angioplasty, resulting in significant improvements in many of the most common symptoms of MS
  More about Endothelial Defects in Multiple Sclerosis  Populations
 
Consistent with the findings of Swank, Schelling and Charcot, in April 2006, researchers at the Departments of Neurology and Molecular and Cellular Physiology, Louisiana State University and the Division of Haematology/Oncology, University of Miami School of Medicine, led by Dr. J. Stephen Alexander, published a manuscript titled "Multiple sclerosis as a vascular disease". In doing so they said "Here we focus on MS as a vascular disease".
  "The reason for such an explicit manuscript is to clearly show the role of cerebral endothelial cells (CECs) as the doorway for trafficking inflammatory cells to provoke the flood of cytokine and chemokine within the Central Nervous System". Dr. Alexander said "The concept of endothelial dysfunction in MS is not new but is certainly under-investigated. We hope to share our inclination that endothelial cells are key elements in MS pathogenesis and consequently to promote vascular targeting as the next frontier for the treatment of this incurable condition"
  On 30 January 2017 In an paper titled "Endothelial Wnt/β-catenin signaling reduces immune cell infiltration in multiple sclerosis''  MS neurologist Lawrence Steinman (Stanford University) said "endothelial cells form a unique blood–brain barrier that is broken down in multiple sclerosis. Disruption of the blood–brain barrier is a defining and early feature of multiple sclerosis that directly damages the central nervous system , promotes immune cell infiltration, and influences clinical outcomes. There is an urgent need for new therapies to protect and restore BBB function, either by strengthening endothelial tight junctions or suppressing endothelial vesicular transcytosis".
  In March 2017, in a publication titled "Emerging Roles of Endothelial Cells in Multiple Sclerosis Pathophysiology and Therapy", Dr Alexander summed up subsequent research in the following terms "the complex pathogenesis of MS can only be appreciated when and if vascular contributions are recognized as a significant part of MS etiology. Indeed, many novel therapies for MS target the mechanistically relevant vascular inflammatory features of these conditions and implicate cerebrovascular endothelial cells (CECs) as the “failing gatekeeper” of the blood-brain barrier (BBB)

He went to say "CEC and their metabolically and biochemically coupled cells (astrocytes, glia and neurons) establish and regulate several types of intercellular junctions which isolate the circulation from the brain as the functional neuro- and gliovascular units of the BBB. In health, the BBB generally isolates the brain parenchyma from immune cells and blood-borne neurotransmitters (glutamate, norepinephrine, serotonin) controlling solute exchange into and out of the CNS by a system of pumps, channels, and pores, requiring a continuous and significant energy expenditure".
  Population Studies Reinforce Vascular Connection
  Also in March 2017 the Multiple Sclerosis Network of Care Australia provided details of comparisons between large population studies by Multiple Sclerosis Research Australia (MSRA) in 2012, the (then) Multiple Society of NSW in 2001 and the Multiple Sclerosis International Federation (MSIF) in 2012, and published research relating to the long term outcomes (2011 to 2015) of successfully treating CCSVI conditions with Angioplasty/Venoplasty. As foreshadowed by Dr Alexander this comparison showed that the symptoms relieved through the successful PTA treatment of CCSVI irregularities (across all MS sub types) corresponded significantly with the top 20 symptoms identified by these highly regarded population studies

Further Afield

  Joan Beale, a globally acknowledged advocate for those living with MS, reports that in 2007 she raised the question of associations between vascular irregularities and  MS with a premiere endothelial cell scientist at Stanford University only to be advised ''that not many neurologists were interested in looking at the disease from the vascular angle, as they were already convinced MS was a purely autoimmune disease''.
  Genetic Associations
* Almost a decade later, on March 30, 2015, the Federation of American Societies for Experimental Biology (FASEB) reported on research whereby while stroke, epilepsy, multiple sclerosis, amyotrophic lateral sclerosis (ALS) and traumatic brain injury each affect the central nervous system differently, they share common defects in the blood-brain barrier that can be traced to a single set of genes. To protect the brain from harm, endothelial cells lining the blood vessels around the brain form a barrier that lets only very specific molecules move from the blood to the brain. In people with certain diseases or brain injuries, the barrier doesn't work properly and can allow dangerous molecules or pathogens into the brain.

Researchers said ''For these diseases, the blood-brain barrier dysfunction is a significant contributor to symptoms and disease progression, so if we can stop the endothelial cells from going down this path, we could possibly limit the progression and the severity of these diseases. Our goal is to identify the mechanisms that lead to this disruption of the blood-brain barrier in these diseases" - more on this topic


MS  Populations have Significant Endothelial Impairments

On February 19, 2015 PubMED referenced research that assessed endothelial function in patients with MS and in healthy controls. It found a significant impairment of endothelial function in MS populations compared to age matched controls with low burden of vascular risk factors. Enrolled were 46 patients with a diagnosis of relapsing-remitting MS and age-matched population of 31 healthy subjects. Endothelial function was assessed using peripheral arterial tonometry and expressed as reperfusion hyperemia index (RHI).

On 27 June 2014 a study was published (Zamboni et al) about endothelium defects found in the internal jugular vein of patients with CCSVI conditions. Seven patients were studied using a scanning electron microscope - specifically the ultrastructure of intraluminal defects in the internal jugular veins . Intraluminal septa and/or defective valves blocking the flow in the distal internal jugular vein were studied together with the adjacent wall and compared with control specimen. It was found that the internal jugular veins’ wall showed a significant derangement of the endothelial layer as compared to controls

Surprisingly, no endothelial cells were found in the defective cusps, and the surface of the structure is covered by a fibro-reticular lamina. Researchers concluded "Although the lack of endothelial cells in the internal jugular vein intraluminal obstacles is a further abnormality found in course of chronic cerebrospinal venous insufficiency, our investigation cannot clarify whether this finding is primary or caused by progressive loss of endothelium in relation to altered haemodynamic forces and/or to a past post-thrombotic/inflammatory remodelling. Click here to access the full text of this very significant finding.
  Click here to display all abstracts relating to endothelial defects in people with MS
  Hypoperfusion as a Cause of Hypoxia, Lesion Formation, Cognitive Problems and Fatigue
* On 24 June 2015 the Journal of Cerebral Bloodflow and Metabolism reported perfusion-weighted imaging studies that demonstrated  a widespread cerebral hypoperfusion in patients with MS, which is present from the early beginning to more advanced disease stages. This reduced cerebral blood flow (CBF) appears to be mediated by elevated levels of the potent vasospastic peptide endothelin-1 in the cerebral circulation. Evidence is evolving that cerebral hypoperfusion in MS is associated with chronic hypoxia, focal lesion formation, diffuse axonal degeneration, cognitive dysfunction, and fatigue. Restoring CBF may therefore emerge as a new therapeutic target in MS. See also the much earlier, but insightful, comments by Professor Roy Swank on this topic.
  Find out more about the impact of perfusion/hypoperfusion on MS progression
* Plaque Development

In 23 April 2015
PubMED reported on the results of a three year longitudinal study illustrating that people with MS experience increased venous diameters or increased oxygen consumption in early MS plaques - underpinning a relationship between veins and plaque development. MS plaques, which were newly detected during the study period, showed significantly higher venous volumes compared to the pre-plaque area 1 year before plaque detection and the corresponding normal-appearing white matter (NAWM) regions. Venous volumes in established MS plaques, which were present in the first scans, were significantly higher compared to the NAWM and controls.
For a more expansive discussion regarding relationships between vascular irregularities and the formation of MS plaques check out the research by Franz Schelling and a summary by Joan Beal

 
Impact on supply of Oxygen and Nutrients to the Brain
 
A related study published on 18 August 2014 in the JAMA Neurology journal examined how the brain reacts or responds with blood flow when there is vasodilation (a process known as , cerebrovascular reactivity, or CVR). This function is extremely important, as neurons need adequate blood flow to provide glucose and oxygenation.  A healthy endothelium (lining of the blood vessels) would normally respond to circumstances of inadequate blood flow by widening vessels and allowing for more blood to flow (CBF) to the brain. Without this response  the brain will not function properly, and neurons can potentially die.

Patients with MS had a significant decrease of cerebrovascular reactivity compared with controls. This decrease in CVR correlated to gray matter atrophy, but did not correlate with white matter lesions. Their conclusion was that inadequate blood flow to neurons may indeed be the cause of neurodegeneration in MS And that this was a vascular problem, NOT a problem initiated by white matter lesions.
..
  Critical Role of Endothelial Cells in Controlling Vascular Inflammation - A Paradigm Shift in Thinking
 
The glycoprotein Del-1 is produced in blood vessel endothelium. In November 2008 Pubmed reported on research that concluded  'Del-1 is an endogenous inhibitor of inflammatory cell recruitment and could provide a basis for targeting leukocyte-endothelial interactions in disease'" - find out more
  Patients with MS had a significant decrease of cerebrovascular reactivity compared with controls. This decrease in CVR correlated to gray matter atrophy, but did not correlate with white matter lesions. Their conclusion was that inadequate blood flow to neurons may indeed be the cause of neurodegeneration in MS And that this was a vascular problem, NOT a problem initiated by white matter lesions. .
  Studies found that Del-1 acts as a gatekeeper that thwarts the movement and accumulation of immune cells like neutrophils, reducing inflammation. While neutrophils are needed to effectively respond to infection or injury, when too many of them accumulate in a tissue, the resulting inflammation can itself be damaging.

In November 2014 Researchers from the University of Pennsylvania" identified the molecule Del-1 a key protein that is able to reduce the severity of a disease equivalent to MS in mice. While researching Del-1 in other tissues, such as gums and lungs, it was found that Del-1 is also highly expressed in the brain. In addition, genome-wide screens indicate that the Del-1 gene may contribute to multiple sclerosis risk. Researchers said "Because Del-1 has been found to be associated with susceptibility to not only multiple sclerosis, but also Alzheimer’s, it’s possible that a properly functioning version of this protein might help guard against that disease’s effects as well" - more about this research.

In September 2012 the National Institute of Dental and Craniofacial Research when commenting on the inflammation inhibiting role of Del-1 said "These research findings are paradigm-shifting by redefining inflammatory disease from one of microbial activation of inflammatory mechanisms leading to periodontal disease to one of microbial disruption of homeostatic mechanisms that control inflammatory processes".

The notion of ''rebalancing'' homeostatic mechanisms seems consistent with what is being learnt in treating venous abnormalities associated with Chronic Cerebro Spinal Vascular Insufficiency(CCSVI) and also with the emerging outcomes of some stem cell therapies. On 18 July 2013 researchers identified the vascular endothelium, as playing a critical role in inflammation control. Endothelial responses are carefully orchestrated to neutralize the source of injury. However, if the injury persists, these sustained responses may result in endothelial dysfunction, which plays a critical role in the pathophysiology of vascular disease.

Researchers go on to say ''the role of the bioactive sphingolipid S1P and its receptor S1PR2 in the regulation of endothelial responses to injury is just beginning to be understood. In this article, we have described the critical role of S1PR2 in endothelial inflammation both in vivo and in vitro''

See also March 2015 developments relating to defects in the blood-brain barrier of people with MS that can be traced to a single set of genes.
Click here to display all abstracts relating to endothelial defects in people with MS
 
* Connection between the Nervous System and Vascular  System

On 8 June 2011 ScienceDaily reported on research that shows that a key molecule of the vascular system directs axons during the formation of neural circuits. This connection between the nervous system and the vascular system could be a good starting point for the development of therapies for neurodegenerative diseases. Researchers said "One of the key molecules of the vascular system is the vascular endothelia growth factor, better known as VEGF. We discovered that VEGF is able to attract nervous system axons. More specifically, we identified Flk-1 as the receptor responsible for this effect, making it a prime target for the development of therapies to re-grow axons after lesions of the central nervous system or neurodegenerative diseases." find out more about this breakthrough research.
In June 2016 researchers confirmed significant associations between VEGF and the severity of Multiple Sclerosis. In a study titled ''The Association between Vascular Endothelial Growth Factor-related Factors and Severity of Multiple Sclerosis'' researchers said '''previous studies have demonstrated that vascular endothelial growth factor (VEGF) can trigger angiogenesis as well as inflammation through binding to its membranous receptor-1 on endothelial and inflammatory cells.

We found an increase in circulatory level of VEGFR1 expressing cells and the serum level of VEGF as well as sVEGFR1 in MS patients compared to healthy controls (p<0.001). The greater severity of MS, the higher VEGFR1 expressing cells (ρ=0.47; p<0.001), serum level of VEGF (ρ=0.44; p<0.001), and sVEGFR1 (ρ=0.76; p<0.001).  we found a significant association between the EDSS score and sVEGFR1 (β=0.007; p<0.001).  Our findings revealed that circulatory membranous as well as soluble expression of VEGFR1 increases during angiogenic and inflammatory phenomena of MS. Such increase may exacerbate the symptoms and cause more disability''. In short -  more VEGF in Multiple Sclerosis = more collateral circles = more severe CCSVI = more disability.
  Observations by Joan Beal
  What's MOST IMPORTANT to understand in all of this is that VEGF shows up when the body is deprived of OXYGEN due to slowed blood flow. This study doesn't mention that the body tries to create new blood vessels (called angiogenesis) with VEGF--in order to restore oxygenation. So, a brain that is hypoperfused due to CCSVI will show higher levels of VEGF in the blood. The heart and brain are connected. It's not some crazed autoimmune system causing this---it's simply less oxygen being delivered through a compromised vasculature. That's all you need to account for higher serum levels of VEGF in people with MS - more from Joan on this topic.
  More about VEGF associations
 
  Increasing Blood Flow
*
In February 2011 researchers at the University of North Carolina at Chapel Hill reported discovering that a molecule -- called Wnt1 -- can improve the function of endothelial progenitor cells, increasing the blood flow to organs that previously had been cut off from the circulation. The finding could enhance clinical trials already testing these powerful cells in patients hospitalised with cardiac arrest

The study, published in the FASEB (Federation of American Societies for Experimental Biology) Journal, is the first to show that the Wnt1 protein, one of a family of 19 such molecules, can stimulate blood vessel formation. - read more.

 
* Multiple Sclerosis Game Changer  - Finally Understanding a Leaky Blood-Brain Barrier

In June 2014 researchers from the Federation of American Societies for Experimental Biology solved the mystery of exactly how vascular inflammation is responsible for creating gaps between endothelial cells allowing toxins and other molecules access to the brain. This discovery helps explain the molecular underpinnings of diseases like MS. Researchers said “this study has the potential to be a game-changer in terms of how we treat neurological conditions”.

Researchers found that a molecule, called 'microRNA-155,' is responsible for creating gaps through the complex structures that form the tight connections between endothelial cells whereby inflammation weakens the blood-brain barrier, allowing toxins and other molecules access to the brain.

Not only does this discovery help explain the molecular underpinnings of diseases like MS, but also opens an entirely new avenue for developing therapies that can help penetrate the Blood-Brain Barrier to deliver lifesaving drugs. According to Ignacio A, Romero, Ph.D., "We are beginning to understand the mechanisms by which the barrier between the blood and the brain becomes leaky in inflammatory conditions" more about this development. 

 
* Further Insight into how the Brain Regulates its Blood  Flow

Also in June 2014, in a study titled "A Critical Role for the Vascular Endothelium in Functional Neurovascular Coupling in the Brain" published (12 June 2014) in the Journal of the American Heart Association, researchers at Columbia Engineering report that they have identified a new component of the biological mechanism that controls blood flow in the brain. Led by Elizabeth M. C. Hillman, associate professor of biomedical engineering, the team demonstrated, for the first time, that the vascular endothelium plays a critical role in the regulation of blood flow in response to stimulation in the living brain. “We think we’ve found a missing link in our understanding of how the brain dynamically tunes its blood flow to stay in sync with the activity of neurons,” says Hillman,


Earlier studies identified small pieces of the puzzle, but we didn’t believe they formed a cohesive ‘big picture’ that unified everybody’s observations. Our new finding seems to really connect the dots.”  Hillman found that the vascular endothelium, the inner layer of blood vessels, plays a critical role in propagating and shaping the blood flow response to local neuronal activity. “Once we realized the importance of endothelial signalling in the regulation of blood flow in the brain, we wondered whether overlooking the vascular endothelium might have led researchers to misinterpret their results.”

“Our latest finding gives us a new way of thinking about brain disease—that some conditions assumed to be caused by faulty neurons could actually be problems with faulty blood vessels, This gives us a new target to focus on to explore treatments for a wide range of disorders that have, until now, been thought of as impossible to treat. The brain’s vasculature is a critical partner in normal brain function. We hope that we are slowly getting closer to untangling some of the mysteries of the human brain.”

  The Sunshine Factor and MS Progression - What is it All About?
 
A major clue about sunshine's benefits has emerged from a 20 year study of nearly 30,000 Swedish women.. In March 2016 investigators, from the world-renowned Karolinska Institute in Stockholm, concluded that avoiding the sun is actually as bad for you as smoking
  The Nitric Oxide Connection - Impact on Blood Flow
Their research indicates that sunlight may protect against a wide range conditions, including multiple sclerosis. This benefit has nothing to do with vitamin D. Instead, it is due to the fact that when our skin is exposed to the sun a compound - called nitric oxide - is released in our blood vessels which in turn lowers blood pressure by causing blood vessels to widen, This discovery further emphasises the role of cardiovascular disorders, including CCSVI conditions in MS progressions. It may also lead to better understandings about the higher  prevalence of MS in colder climates - more about nitric oxide.
  Impact of Latitude
 

In November 2016 the Journal of Neurology Neurosurgery & Psychiatry reported on an analysis of 22,000 MS patients across 21 countries that further illustrates the importance sunlight in the development of MS. It found that those further from the equator develop symptoms of MS earlier, They found that for every 10 degree increase in latitude the onset of the symptoms began almost 10 months earlier. They also  found that patients in countries with the lowest UVB levels developed symptoms almost two years earlier than those in countries with highest levels. Average winter UVB levels varied greatly between countries, with Mexico’s nearly 18 times higher than Denmark’s. 

Dr Sorrel Bickley, head of biomedical research at the UK MS Society said “We’ve known for many years that people living in less sunny climates are more likely to develop MS, and this study indicates that a lack of sunlight could also contribute to when the first symptoms of MS appear".

 

  Nitric Oxide - A Common Denominator
While researchers also supposed an association with levels of vitamin D, they made  no reference to the even larger body of research (March 2016) that identifies the critical role of sunshine in maintaining vascular health. A common denominator relating to multiple sclerosis, vascular health and colder climates is the role of sunshine generated nitric oxide in maintaining endothelial health. Given that it is now known that many with MS have impaired vascular drainage (either congenital and/or acquired) an ongoing  reduced supply of nitric oxide can seriously degrade an already compromised vascular system potentially leading to CCSVI conditions - more about nitric oxide. 
  In this regard in July 2017 Oxford University researchers provided unequivocal evidence (see earlier) that the blood clotting protein Fibrinogen triggers an immune attack on the Brain whereby severe Fibrinogen deposits in the motor cortex are accompanied by significantly reduced neuronal density. The role of the primary motor cortex is to generate neural impulses that control the execution of movement. .
Role of Nitric Oxide regarding MS remissions during Pregnancy
 

There is significant evidence that pregnancy is associated with a reduced relapse rate, particularly during the last trimester. The Pregnancy and Multiple Sclerosis (PRIMS) trial, which looked at 269 pregnancies, found that pregnancy resulted in a 70% reduction in relapse rate in the third trimester with a corresponding increase in the relapse rate in the three months after childbirth. Despite the increase in the period after childbirth, 72% of women experienced no relapses during this period.

 While the reasons for these "pregnancy related" fluctuations are yet to be properly understood there are striking similarities between what is being learnt regarding the ovarian peptide hormone Relaxin (especially as it relates to the function of nitric oxide) in regulating blood flow dynamics during pregnancy and the irregular bloodflows experienced by the majority of those with MS. More about pregnancy and MS.

  The Ultra Violet Connection - Regulatory B Cells
  There is also growing evidence (9 June 2016) that sunlight has a protective ultra violet effect against MS, whereby UV light can affect cells in the body which control the immune system, protecting against autoimmune disease. Associate Professor Byrne said that ''all this evidence points to sunlight activating a unique subset of B cells in lymph nodes, and this is an important event in UV-mediated protection from autoimmune demyelination''. Whether UV-protection from autoimmunity is mediated by the activation of regulatory B cells has never been considered before - more about B cells
  The Vascular Connection - Vitamin D  Promotes Endothelial Repair
*  
In July 2014 in a paper published by the American Heart Association titled "Vitamin D Promotes Vascular Regeneration" researchers reported that Vitamin D supplementation in healthy volunteers increased the number of circulating CD45-CD117+Sca1+Flk1+ angiogenic myeloid cells which are thought to promote regeneration after vascular injury. Similarly, in mice, Vitamin D supplementation promoted re-endothelialization in the carotid artery injury model.

Researchers commented "the dramatic effects observed in the present study indicate the high efficiency of the treatment - thus, studies on the effect of vitamin D supplementation for vascular repair in humans, for example after balloon angioplasty, are warranted"  - read the full text of this research. While broad associations between Vitamin D and MS progression have long been referenced in the literature this study provides important clinical evidence of specific circumstances whereby this can happen.

Subsequent research. published on 15 October 2015, affirms the significance of vitamin D as follows ''our data suggests the presence of an alternative signaling modality by which D acts directly on endothelial cells to prevent vascular leak. The finding that D and its metabolites modulate endothelial stability may help explain the clinical correlations between low serum vitamin D levels and the many human diseases with well-described vascular dysfunction phenotypes''.

A Closer Look at Vitamin D

For many years, vitamin D supplements have been recommended in high quantities for patients with a range of problems. However, most recent high-quality studies on vitamin D supplementation no longer support such claims. Nevertheless, many patients who take vitamin D supplements still report feeling better. This begs the question: Why!? 

 

  It is important to take a closer look at “vitamin” D. The various forms of vitamin D are not actually vitamins in the traditional sense but share a close structural and functional resemblance to steroids and, when taken as a supplement, act in a manner similar to that of other steroid-based medications. These medications, such as prednisone, work by slowing the activity of the immune system.
  Vitamin D Supplements
On 16 June 2016 concerns regarding vitamin D supplements were reinforced when the University of Alberta Faculty of Medicine & Dentistry published research that examined the evidence for 10 common beliefs about vitamin D. The beliefs range from the ability of vitamin D to reduce falls and fractures, improve depression and mental well-being, prevent rheumatoid arthritis, treat Multiple Sclerosis, and lessen incidences of cancer and mortality. The review found little evidence that supplementation with this vitamin has much of an effect at all - More about concerns of this nature
 
  More about the Sunshine Factor and MS progression.
 
* Promoting Myelin Repair

In February 2014 Vittorio Gallo, PhD, Director of the Center for Neuroscience Research at Children's National Health System, George Washington University School of Medicine and Health Sciences (SMHS) reported that the molecule, Endothelin-1 (ET-1), is shown to inhibit repair of myelin. Myelin damage is a hallmark characteristic of MS. The study demonstrates that blocking ET-1 pharmacologically or using a genetic approach could promote myelin repair. .
  More about Myelin Repair
 
* Importance of Deep Sleep in the Production of Myelin

Recent research also suggests that failing to clear away some toxic proteins may play a role in brain disorders. It demonstrated that brain cells shrink during sleep to open up the gaps between neurons and allow fluid to wash the brain clean. Scientists at the University of Wisconsin, Madison discovered that sleep allows the body to reinforce the production of myelin, which provides insulation for the brain’s neuronal wiring.

 Researchers said these findings could lead to new insights into brain repair and multiple sclerosis.
   
   
 

Looking Backwards Towards the Future  -  Swank was Right
Reflections Decades earlier, the late Professor Swank a pioneer in MS research, said in relation to venous abnormalities "the frequent location of the pathological lesions (plaques, or areas of demyelination) in the brain and spinal cord surrounding small venous channels, suggest that the small blood vessels (microcirculation), which includes the arterioles, capillaries and venules, play a role in the genesis of multiple sclerosis  - watch an interview with Professor Swank. .
This contention is supported by his observations that small arterioles and venules of the brain and spinal cord are thickened, often tortuous, nodular, and alternately constricted and dilated". He went on to say "..recent study of the cerebral blood flow (CBF)......revealed significant reduction of the flow in patients with MS ... there was a progressive, generalized decrease in CBF....The rates of decrease were significantly greater than in normals, and they correlated directly with the speed of progress of the disease." About current understanding regarding cerebral blood flow
   
In July 2017 Oxford University researchers added weight to Professor Swanks vascular associations with MS progression by providing unequivocal evidence that, in the case of those with progressive MS, the blood clotting protein fibrinogen is extensively deposited in their motor cortex.  This severe fibrinogen deposition is accompanied by significantly reduced neuronal density. The role of the primary motor cortex is to generate neural impulses that control the execution of movement. Future studies are needed to clarify the source and acknowledged neurotoxicity of fibrin(ogen), and its potential impact on clinical disability.
 
* Slowing  Down of Cerebral Blood Flow

In postulating a cause for these small blood vessel obstructions and decrease in blood flow: he said: "A search for a mechanism that could cause both an interference with, and slowing down of, the cerebral... blood flow, and breakdown of the blood-brain barrier in the central nervous system, leads to a consideration of the circulatory changes observed  in a number of species, including man, following large saturated fat meals." He followed this up with an intervention trial, where he gave people with MS a low saturated fat diet, with startling results. More about later understandings regarding the role of blood flow perfusion/hypoperfusion on MS progression.

Professor Jelinek (Australia) when highlighting the aforementioned work of Professor Swank said (2010) "It is extraordinary that we in the medical profession have ignored Swank's work for so long. In hindsight, not only did he develop his theories from basic observational epidemiological studies, as we do today, but he did laboratory work to confirm the likely causes of circulatory problems in MS are characterised by narrowing of vessels and reduced blood flow. He then showed that changing the diet from saturated to unsaturated fats stopped disease progression".  More about nutrition issues and MS.




Decades later (June 2014) researchers led by Dr Ingrid van der Mei at the Menzies Research Institute Tasmania, showed that adverse levels of ‘bad’ fats in the blood are closely linked to the level of disability in people with MS and the rate of disability progression. This important finding suggests that simple lifestyle modifications, such as diet and exercise, may slow the rate of disability progression in MS because these changes will help to reduce the levels of ‘bad’ fats that are circulating in the body.



Associated research (May 2014) from the Oregon Health & Science University showed that people with multiple sclerosis who for one year followed a plant-based diet very low in saturated fat had much less MS-related fatigue at the end of that year — and significantly less fatigue than a control group of people with MS who didn't follow the diet. While the number of trial participants was relatively small, study leaders believe the significantly improved fatigue symptoms merited further and larger studies.



In February 2015 PLOS ONE reported on the outcomes of a significant study, using Digital Subtracted Angiography, that evaluated aspects of both arterial and venous cerebral vascular blood flow in eighty MS patients and a control group, Researchers found that in people with MS it takes double the time (transit time) for blood to flow in and out of the head, when compared with normal people. This blood flow slowdown is independent of MS duration or disability level. They illustrated that this slowed blood flow is NOT due to MS progression and also observed ''the strong Cerebral Circulation Time (CCT) value difference between control group and MS patients explains hypoperfusion, which pre-empts myelin breakdown and MRI detectable white matter lesions''.

Researchers concluded 'that the high intravascular resistance is a constant finding in MS patients, possibly taking place at an early stage of the disease. Therefore cerebrovascular changes are not solely the result of a late chronic inflammatory process. Indeed, if the microvascular dysfunction was a consequence of lesion load or brain atrophy, high CCT values would be expected to increase with EDSS and disease duration. The absence of a correlation between lesion volume and CCT confirms that hemodynamic alteration is not related to parenchymal lesion and other MS-linked clinical features, but rather, is a pathognomonic feature of disease.

For further (early days) information about irregular blood flow and multiple sclerosis click here.

   
 
  Getting it right

Professor Jelinek went on to say "Zamboni's contribution has been to focus us again on this mechanism. His work suggests that once the damage is done, opening up the narrowed vessels surgically provides relief; but Swank's lifelong research makes us realise that, in all probability, if we wish to make a real difference long term, dramatic dietary changes are necessary".

Dr Paul Thibault (Australia) builds upon this foundation by associating bacterial infections with the inflammation that we now know underpins the
breakdown of the blood brain barrier. He advocates for an appropriate antibiotic protocol as part of an overall remedial process. Only time will tell about the extent to which bacterial infections influence this process.
More than MS is involved.
   
 
 
Analysing Blood Flow in People with Multiple Sclerosis
In a relatively short 3 part video presentation (July 2011) titled 'From Stenoses to Fatigue and Scleroses' Dr Trevor Tucker PhD draws on the Physics of Fluid Dynamics to provide an enhanced perspective on what is being learnt from examining people with Multiple Sclerosis who also have a CCSVI condition. In doing this he observes that the "the analysis of blood flow in multiple sclerosis, based on Fluid Dynamics, has never been carried out". His presentation illustrates how the flow and pressure characteristics predicted by Fluid Dynamics match characteristics seen in multiple sclerosis.
He illustrates the formation of areas of localised high pressure, discusses blood flow through the brains capillary bed, and demonstrates how localised high pressure areas can reduce the supply of oxygen, glucose and blood flow through the brain. He also examines the impact of high pressure areas (localised hypertension) on the blood brain barrier and its potential relationship to MS. He hypothesises that such local hypertension can result in damage to myelin with consequential outcomes - watch this highly informative presentation.
More about the impact of pulse wave irregularities
An Insightful Overview
On 27 August 2011 Dr. David Jernigan provided an insightful overview of many of these developments
David Jennigan He said "a new treatment process, often perceived to be radical by uninformed medical professionals, is breathing new life, hope, and often, unforeseen improvements into neuromuscular and neurodegenerative diseases of virtually every type. The new treatment process provides intervention for a condition that has been called Chronic Cerebro Spinal Vascular Insufficiency (CCSVI)"
   
He went on to say "however, research and clinical doctors are now considering a more accurate name, Chronic Cerebro Spinal Vascular Hypertension (CCSVH), since the latest realizations are that there is increased intracranial blood pressure occurring within one or more of the major veins in the head and neck.

"A poignant reality is there is enough direct and clear evidence of significant patient improvements that it should be deemed “doctor irresponsibly” not to order vascular diagnostic MRI/MRA image screening for patients with any suspect neurodegenerative or neuromuscular diagnosis". - read more about Dr Jernigan's overview

*  Blood Glucose Deficiencies are a Predictor of MS Progression

In February 2013 the journal Neurology reported on a study that observed "Vascular comorbidities are associated with disability in MS but whether serum glucose levels are a significant predictor of disability has not been studied". Researchers concluded "Glucose levels are a strong predictor of disability progression as measured by EDSS and timed walk. Further studies examining this association longitudinally are necessary to prove a causal relation between glucose levels and disability progression. This can open the way for testing some of the multiple interventions used in diabetes as potential MS disease modifying agents". This issue was also touched on by Dr Arata in 2011 when he discussed blood flow through the brains capillary bed, and demonstrated how localised high pressure areas can reduce the supply of oxygen, glucose and blood flow through the brain. More about glucose and MS.
 
Impact of Iron Imbalances
In November 2006 Professor Paolo Zamboni, from the University of Ferrara, first identified the similarities between an impaired venous drainage of the lower limbs and multiple sclerosis in his publication "The Big Idea." Chronic venous insufficiency can cause a breakdown of red blood cells, resulting in an increase of free hemoglobin levels. Zamboni said ''findings support the hypothesis above described, which proposes local iron overload as the initial signal of the inflammatory chain in MS''.

A decade later (16 November 2016) this is exactly what a team of London researchers also reported. They concluded ''An underlying low-grade chronic intravascular haemolysis is a potential source of the iron whose deposition along blood vessels in multiple sclerosis plaques contributes to the neurodegeneration and consequent brain atrophy seen in progressive disease. Chelators of free serum iron will be ineffective in preventing this neurodegeneration, because the iron (Fe ) is chelated by haemoglobin. About the function of hemoglobin.
   

 A study published in the American Journal of Neuroradiology on 24 March 2016 using high powered 7 Tesla MRI reported that only patients with MS showed signs of "iron laden lesions" which contain a central vein that allows blood products, like iron, into brain tissue. The MS lesion has a very small, yet well-defined vein (venule) going through the center.  Lesions found in a control group of Non-MS Patients (people with Neuromyelitis Optica (NMO) lesions) do not. Microbleeds into brain tissue have been separately identified in MS.

When commenting upon these research outcomes MS advocate Joan Beal said ‘’the image shows that around this vein, in the MS patient, there is iron.  The researchers do not say that this is from blood leaking into tissue.  But this is the very obvious inference.  Blood, or heme, contains iron and here, once again, we have more proof”.
  Low Dose Iron Treatments induce DNA Damage
  In February 2016 scientists from Imperial College London suggested a need to look carefully at the amount of iron given in standard treatments, such as tablets and infusions, and the effects this could be having on the body. Dr Shovlin said “low dose iron treatments induce a DNA damage response in human endothelial cells within minutes. While it is known that iron could be damaging to cells in very high doses this study found that  the levels of iron found in the blood stream after taking an iron tablet, seemed to be able to trigger cell damage - cells seem more sensitive to iron than previously thought.”

 Dr Shovlin stressed that prescribed iron supplements are essential for many patients: “We’re not at the stage yet where we would advise doctors to change their approach to prescribing iron supplements.  This is very early stage research, and we need more work to confirm these findings and investigate what effects this may have on the body. We are still not sure how these laboratory findings translate to blood vessels in the body."
  Early Days
  It is well known that patients with MS tend to have abnormal iron deposition in and around the MS plaques, in the basal ganglia and the thalamus and that this imbalance become more dramatic over time. Iron accumulation in deep grey matter of MS patients is most strongly and independently associated with duration and severity of the disease. While the causes and consequences of these imbalances are now evolving , a genetic link, involving three separate genes has been established.
*
On 10 August 2012 BioMED Central reported "Whatever the mechanism causing brain iron deposition is, our study shows strong influence of gene variants in MS onset and disease course in terms of expectation of disability and severity. this opens new clinical concrete perspectives in monitoring iron accumulation as an underlying mechanism connected to the natural history of MS together with the prognostic value of iron trafficking genes".

"Further larger investigations on iron genes should become mandatory in MS. Understanding the exact mechanism by which iron acts in the brain causing MS and how the brain would be impacted by iron chelation/supplementation could potentially furnish precious prognostic information and novel insights for alternative personalized treatments (pharmacogenetics) aimed in preventing or counteracting neuron loss and degeneration"

 More about iron imbalances
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A Time for Change
Challenges A study published in the New England Journal of Medicine on 9 December 2011, involving the examination of 563 brain biopsies, challenges the the long-accepted theory that MS begins in the myelin on the inner layers of the brain, also known as white matter. However, the findings of this collaborative study show the opposite -- that the disease likely can move from the outer (cortical) layers of the brain toward the white matter, offering new insight into the progression of MS.
We have discovered an entirely new concept of how MS may start," said Richard Ransohoff, M.D., Director of the Neuroinflammation Research Center of the Department of Neurosciences at Cleveland Clinic's Lerner Research Institute.
 
* CHALLENGING LONG ACCEPTED THEORIES  REGARDING THE PROGRESSION OF MS

Lesions are thought to be critical to MS progression. Researchers found that the lesions are distinctly different than previously speculated, giving clues to better disease management. In autopsy tissues of MS patients, lesions in the cerebral cortex show demyelination without inflammation, raising a challenging issue: if cortical lesions form entirely without inflammation, then cortical demyelination would not be explainable by current theories of MS nor treatable by current MS therapies. "The next step in this research is to study the lesions to uncover new molecular targets for treatment. We also need to push forward to develop imaging techniques to view these cortical lesions," said Dr. Lucchinetti. "In that way, effects of treatment can more easily be measured." - read more about this study
 
* BEYOND THE MS AUTOIMMUNITY MODEL

A 2005 paper published in Journal of the Royal Society of Medicine observed that "the definition of MS as a T-cell-specific autoimmune demyelinative disease is in our view too narrow. First, nearly 60 years of EAE-based research yielded not a single MS-halting therapy. This in itself should be an important reason to consider a shift in research direction

Although the existing disease-modifying therapies reduce relapse rates in some patients by up to one-third there is little evidence that the common features of fatigue, pain, depression and cognitive decline are positively influenced. There is also a concern, theoretical at present, that early benefit of reduced relapse rates may later be offset by accelerated brain atrophy" - access this report.

Given subsequent developments, whereby these "common features" are now being shown to be significantly and positively influenced by vascular interventions, little wonder about the frustrations and extreme concerns being expressed by the MS community because of barriers that prevent ready access to effective vascular screening and treatment.
 
SOME FREQUENT TALKING POINTS
Discussion Feedback from the MS community provides an important patient-centered focus to exploring many aspects of these new medical understandings. Details of frequent questions/answers follow.
 
 
  Does CCSVI exist?

In December 2014 researchers across seven Italian Universities and Institutions reported on an investigation, by Echo-Color-Doppler, of 552 MS patients (333 females and 219 males) following Zamboni’s criteria. The identification of CCSVI was by ECD examination. The ECD data were analysed by the new online MEM-net software which identified 83% of these patients as CCSVI positive and 17% as CCSVI negative

By February 2015 this research had extended to more than 1000 MS patients from four of seven testing centres with 84% tested as CCSVI positive - further illustrating the importance of the consistent
MEM-net protocol across a diverse range of centres.


Further Afield

 
Also in December 2014 researchers at SunYatSen University when reporting on the first Chronic cerebrospinal venous insufficiency investigation in China said ''this study confirmed CCSVI in some MS and NMO patients involved in pathogenetic mechanisms of multiple sclerosis (MS) and other inflammatory demyelinating diseases. (CCSVI) in ten MS patients and nine NMO (and NMOSD) patients. Extracranial venous ultrasonography revealed that backstreaming in IJVs and vertebral vein (VVs) were significantly associated with MS and NMO, and this association was much more significant in MS than NMO. Extracranial venous ultrasonography was taken in all patients.


 Observation indexes included venous reflux, cross sectional area (CSA) of internal jugular veins (IJVs), and changes in IJVs CSA. Some of the patients underwent angiography to detect stenosis of IJVs and azygous vein. Extracranial venous ultrasonography was also taken in 20 age-matched healthy controls. Results CSA of IJVs were obvious compared with controls. Narrowing in VVs and collateral circulation were seen in MS and NMO patients using ultrasonography and DSA.
 
* In October 2011 the International CCSVI Alliance published details of a meta analysis of the research published to date against a rigorous criteria. The aim of the analysis was to answer the questions "does CCSVI exist" and "is it linked to MS?'.  It highlighted two of the largest studies which included by far the largest number of patients, together with the data validating their diagnostic technique. The overall weight of the trends is that CCSVI exists and is associated with MS. - read more
 
* Are CCSVI Conditions caused by Multiple Sclerosis?

In February 2015 the Royal Society of Medicine Journal Phlebology reported that age, disease duration, sex, subtypes of multiple sclerosis and expanded disability status scale score (EDSS) are not considered predictors of CCSVI conditions. Also In February 2015 PLOS ONE reported the outcomes of a significant study, that found in people with MS it takes double the time (transit time) for blood to flow in and out of the head, when compared with normal people. This blood flow slowdown is independent of MS duration or disability level. They illustrated that this slowed blood flow is NOT due to MS progression

In August 2012 the Journal  of the Royal Society of Medicine reported on a statistical analysis of 353 people with multiple sclerosis treated for CCSVI conditions. The analysis related to the correlations between the duration of multiple sclerosis and the degree and number of venous lesions revealed using catheter venography. The conclusions were that "the results of our survey indicated that venous malformations are most likely congenital, and multiple sclerosis had no significant impact on the development of venous pathology". Researchers went on to say "this analysis did not yield any data supporting the idea that MS is the cause of venous lesions" -  read more

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* Do People with MS have irregular/diminished Blood Flow?

For a 'post'' 2012 update regarding the slowed blood flow experienced by people with multiple sclerosis click here.

 
* In April 2012 VascularWeb, the prime source for all vascular health and disease information, reported on the first angiographic study to quantitatively analyze the impact of percutaneous balloon angioplasty (PTA) on blood flow dynamics across the Internal Jugular veins (IJV) and the Azygous veins of people with MS and CCSVI related conditions. The results of this prospective pilot study suggest an association between MS and CCSVI, which results in abnormally elevated flow through the IJV. Furthermore, following balloon angioplasty the hemodynamic parameters that are comparable to healthy non-MS patients  - more about this research
 
* On 22 September 2011, Pubmed reported on an Italian study, involving 79 subjects, that evaluated via Colour-Doppler-Sonography, whether there is a statistically significant difference of cerebral venous outflow between healthy subjects and people with Multiple Sclerosis. The findings are that people with Multiple Sclerosis have an abnormal return blood flow to the heart. When compared to the normal population more blood travels through veins when MS patients are upright and their is a reduced venous blood flow when supine. Researchers said "this is the exact opposite of normal controls. This seems to be a pathologic condition. In MS patients, a vascular dysregulation resulting from involvement of the autonomic nervous system may be supposed" - find out more about this study
 
* On 7 March 2011 Dr. Paolo Zamboni and his team published a long awaited research paper on CCSVI, titled ” Hypoperfusion of brain parenchyma is associated with the severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a cross-sectional preliminary report”. Dr Bill Code subsequently described this process in the following terms "it takes 2 to 3 times longer for blood to pass through the brain of MS patients than the non MS population. This results in poorer oxygen delivery to brain tissue and the venous blood leaving the brain system is lower in oxygen and higher in carbon dioxide than normal". This confirms the findings of Dr Ivo Petrov in Bulgaria who has shown this pattern in MS patients and also a marked improvement following venoplasty - read more about oxygen deficiency/hypoxia and fatigue.
 
* For subsequent updates on the topic of slowed blood flow and multiple sclerosis click here
 
  Why is IVUS important in Evaluating Potential CCSVI Conditions?
* In June 2012 Pubmed reported on the multiple imaging modalities used for the evaluation of chronic cerebrospinal venous insufficiency (CCSVI). These include Doppler ultrasound, magnetic resonance venography, computed tomographic venography, and catheter venography. Each modality has deficiencies, which can impact treatment. Intravascular ultrasound (IVUS) has a role in this evaluation owing to its ability to accurately assess vessel circumference and cross-sectional area in real time. IVUS can also identify potential complications of angioplasty. As a result, IVUS is an important part of an evaluation for CCSVI and, when available, should be used to identify patients who may benefit from endovascular treatment - read Dr Scaflani's detailed comments on each of these modalities.
 
* Is the Autonomic Nervous System Involved?

On 1 July 2012, and supported by some 'must watch' video presentations, Dr.Michael Arata discussed the outcomes of treating more than 1,000 MS patients for CCSVI conditions. He identifies the majority of the most frequently reported improvements as related to Dysautonomia - impaired functioning of the autonomic nervous system. He attributes improvements in conditions such as fatigue, temperature intolerance, brain fog/cognitive issues, speech, sleep, headache on awakening, bladder/bowel function and cardiovascular function to a better functioning autonomic nervous system following venoplasty. 95% of patients presenting with these conditions experienced sustainable improvements following venoplasty.

He highlights the role of  the hypothalamus and vagus nerve in regulating these symptoms and hypothesises why venoplasty improves the functioning of the autonomic nervous system. To the extent that there is currently no known cure for Dysautonomia this appears to be is a significant medical association in its own right.  Dr Aranta
identifies potential, and significant, medical benefits across a range of conditions - well beyond multiple sclerosis .

Evaluating  Potential Autonomic Nervous System Disorders

In offering venoplasty Dr Arata's practice now seeks to pre-identify patients with 3 or more of the aforementioned autonomic nervous system conditions in association with an ECG based clinical diagnosis of Dysautonomia (as related to blood flow). Doppler ultrasound is now only called upon to eliminate the possibility of blood clots. View an earlier (May 2012) short graphic representation of Dr Arata's presentation. It is of significance that this approach involves offering a specific medical intervention for a specific range of medical conditions

In June 2014 Dr Arata published details of his approach in the Journal of Endovascular Therapy vi
a a study titled “Transvascular Autonomic Modulation: A Modified Balloon Angioplasty Technique for the Treatment of Autonomic Dysfunction (ANS) in Multiple Sclerosis Patients”. The study concluded "the combination of balloon angioplasty of anatomically normal veins coupled with external compression during dilation of these veins can improve indicators of ANS dysfunction. The safety and efficacy of TVAM in MS patients observed in this pilot study is encouraging, paving the way for the treatment of dysautonomia in pathological states other than MS" - more about this study.

 
In October 2015 Pubmed reported, via a study titled ''Genetic, Epigenetic, and Environmental Factors Influencing Neurovisceral Integration of Cardiovascular Modulation: Focus on Multiple Sclerosis'' that ANS dysfunction could not only enhance MS inflammatory and neurodegenerative processes, but can also lead to clinical symptoms such as depression, fatigue, sleep disorder, migraine, osteoporosis, and cerebral hemodynamic impairments. Therefore, factors influencing ANS functional activities, in one way or another, will have a significant impact on MS disease course.

More about Autonomic Disorders CCSVI and MS
 
* What about Fatigue?

During the period October 2011 to December 2011 details of the prevalence of vascular irregularities in pwMS also began to appear in the literature. Collectively, studies are showing that more than 80% of the overall MS population identify extreme fatigue as one of their major issues and that the same population percentage has vascular irregularities. The cause of MS fatigue, while not previously well understood, was frequently believed to have neurological/immune system associations. The role of the vascular system in this process is challenging this belief. This challenge is compounded by the fact that, in a significant percentage of patients treated for these irregularities, improvements in fatigue related conditions occur simultaneously with the restoration of normal blood flow.

 
More about MS fatigue and related issues.
 
 
WHAT IS THE PREVALENCE OF CARDIOVASCULAR (INCLUDING CCSVI) CONDITIONS IN PEOPLE WITH MS?
There is a rapidly evolving body of knowledge regarding the high incidence of cardiovascular disorders in multiple sclerosis and the impact this has on common MS related symptoms and disability progression. Seriously impaired vein irregularities, known as CCSVI conditions (giving rise to irregular blood flow) are at the forefront of this problem.
 In July 2016 the American Journal of Neuroradiology published details of a comprehensive model to validate screening (using MR imaging and echo-color Doppler ultrasound) for extracranial blood flow obstructions in humans

Researchers concluded ''The good agreement between simulated and experimental results means that the model can correctly reproduce the main factors affecting the extracranial circulation and could be used to study other types of stenotic conditions not represented by the experimental data''. Great to see collaboration on effective methods of identifying and measuring the variety of abnormalities that affect the flow of blood in and and out of the brain. - a very significant development. Download the full text of this study.

WHAT IS BEING LEARNT?
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In general terms, and given proper operator training and proven diagnostic modalities, early doppler ultrasound findings indicated a CCSVI prevalence in the range 70% to 86% amongst MS populations and 10% to 14% in the general community. Subsequent research, especially that supported by the newly developed MEM-net process, is seeing prevalence levels (via non-invasive techniques) at around 84%. Invasive techniques including the use of IVUS further extend the prevalence parameters. Details of a range of studies and developing insights follow:
 
A need for more comprehensive operator training and over reliance upon the use of Echo-Color-Doppler ultrasound (ECD) as the primary diagnostic tool have been cited as important factors in explaining some dramatic 'early days' fluctuations in outcomes across different testing centres. Also, while doppler ultrasound can provide an important 'baseline' for identifying jugular related problems it is important to be aware that CCSVI can occur elsewhere in the vascular system requiring more extensive testing.
 
In July 2014 the potential for greater consistency in the use of ultrasound (ECD) to detect CCSVI conditions became available via a web accessible computer based global database called MEM-net. Developed by the National Epidemiological Observatory on CCSVI for data collection around protocols agreed with national vascular scientific societies. Described as a heritage to humanity the developers said "the MEM-net algorithm acts as a blind control for the ECD report eliminating another source of possible human error and subjective interpretation of the examination. We hope that in the future, everyone will use this data collection tool for all scientific work on this topic"
The prevalence of venous anomalies and developmental variants, indicative of CCSVI is even higher, when investigated with sophisticated invasive imaging techniques. An overview of increased understandings was published in Biomedcentral (Zivadinov et al) on 27 June 2013 emphasising the urgent need for a multimodal approach for better understanding of the venous abnormalities and developmental variants being considered in CCSVI. There is ongoing fact finding about the prevalence of CCSVI conditions in pwMS as compared to the general community.
In January 2017 Professor Zamboni highlighted the further  progress being made in the CCSVI diagnostic process via a new non-invasive diagnostic method that provides a precise picture of the heart-brain axis. This will help end the diagnostic controversy regarding  CCSVI. It will also help to clarify who should be looked at further by venogram. It can also be used as a follow-up method for patients after venoplasty treatment.
Click here for details of the benefits in treating CCSVI conditions.
MEM-net CCSVI DIAGNOSTIC and RESEARCH DATABASE - "A Heritage to Humanity"
In July 2014 the potential for greater consistency in the use of ultrasound (ECD) to detect CCSVI conditions became available via a web accessible computer based global database called MEM-net. Developed by the National Epidemiological Observatory on CCSVI for data collection around protocols agreed with national vascular scientific societies
Described as a heritage to humanity the developers said "the MEM-net algorithm acts as a blind control for the ECD report eliminating another source of possible human error and subjective interpretation of the examination. We hope that in the future, everyone will use this data collection tool for all scientific work on this topic"
The MEM-net database represents a quantum advance in multiple sclerosis multi-disciplined patient centred diagnostic medical technology. Globally accessible it is equipped with powerful real time data analysis tools.  It is a free shared resource available to medical professionals that enables the standardised storage, retrieval and analysis of patient medical data relating to all aspects of CCSVI examinations and treatments. Included are the outcomes of past and present procedures and examinations including Neurological, MRI, CT Scans, Phlebography, Surgical, Echo Doppler Ultrasound (ECD), MRV, Angioplasty and other Therapies. Confidential patient data is protected through random codes.

For example, in a few seconds it creates a map of individual examinations of the ECD veins of the neck and intracranial area. An automatic report describes the injuries found and treated, and an assessment of the percentage change in lesion score after the procedure. The printing of the examination of ECD map allows an easy and immediate visual presentation to the patient about the results of an examination. Read more about this potentially game changing resource or watch a demonstration video. To register to access the program itself  click here.


 
  Beyond Uncertainty - MEM-net protocol facilitates consistency
 
In December 2014 researchers across seven Italian Universities and Institutions commenced reporting on CCSVI investigations, by Echo-Color-Doppler, whereby ECD data is analysed by the new online MEM-net software. First reported is a study of 552 MS patients (333 females and 219 males) following Zamboni’s criteria which identified 83% of these patients as CCSVI positive - caused by blockage inside AND outside of veins  - and 17% as CCSVI negative.
  External compression can be caused by a variety of situations including muscles in the neck or shoulder, blocking off the vein - some examples involving the omohyoid muscle. This may also help explain restenosis issues for some people.

The research classified CCSVI in three different types by identifying a new hemodynamic parameter the “venous compression”. Type-1 with intravenous block (17%), type-2 with extravenous compression (4%) and type-3 with both conditions (79%). The results provide the hemodynamic basis for a new CCSVI classification, which may lead to a better optimization of individual treatment. More about MEM-net.

By February 2015 this research had extended to more than 1000 MS patients from four of seven testing centres with 84% tested as CCSVI positive - further illustrating the importance of the consistent MEM-net protocol across a diverse range of centres

Importance of Consistent Guidelines

On 29 June 2015 the journal Veins and Lymphatics
published the outcomes of an analysis of four earlier studies (with a cohort of 559 MS patients). Strengths and limitations of each study are discussed providing insight into conflicting reports. Guidelines for data acquisition and analysis for future studies related to extra-cranial structure and flow, both arterial and venous, are discussed..The lack of agreement between studies is likely due to inconsistent data acquisition and incomplete data analysis.

 Researchers said ''Our own work over four independent sites shows good agreement, indicating that there is a high incidence of stenosis and structural venous abnormalities in the MS population and that this change results in reduced outflow of the IJVs and increased collateralization of venous return to the heart compared to healthy controls''
 
In July 2016 the American Journal of Neuroradiology published details of a comprehensive model to validate screening (using MR imaging and echo-color Doppler ultrasound) for extracranial blood flow obstructions in humans

  Understanding Divergent Outcomes
 

On 26 June 2014 Multiple Sclerosis Research Australia (MSRA) selectively referenced the outcomes of a range of CCSVI prevalence studies which it described as "New studies from key international research groups question the validity of the CCSVI diagnosis and its usefulness in MS" subsequently retitled "New evidence on the rates of CCSVI in people with MS". On 9 March 2017 MSRA revisited this theme under the title "Trial Shows Unblocking Veins not beneficial for MS". Curiously details of this incomplete trial conducted at the University of British Columbia are yet to be formally published (to enable peer review) with no reference to the long term studies (first published in October 2015) that clearly demonstrate the benefits of Angioplasty in relieving most of the common symptoms of MS.

 

The outcomes of these earlier studies were primarily reported around October 2013, the latest in June 2014 It should be noted that the outcomes of the studies selected by MSRA, with one notable exception, do not primarily relate to actually treating people for CCSVI conditions via balloon venography - they largely focus on the merits of relying on non invasive diagnostic techniques, primarily doppler ultrasound, to identify potential CCSVI conditions. This is despite long standing knowledge that doppler ultrasound is far removed from a "gold diagnostic standard".

 

MSRA qualified the scope of its original selection process as follows 'please note that very small studies, review articles, conference abstracts and public media or online coverage are not included in this summary''. Not referenced was a significant meta analysis (3 March 2014) by Dr Simka (encompassing the majority of the aforementioned prevalence studies).

 

Studies were not looking for the same Pathology

 

When referring to studies, such as PREMiSe and CoSMo, Dr Simka said ‘considering the many faces of CCSVI, it becomes more comprehensible why the results of prevalence studies have been so discordant. Not only were the authors using different diagnostic modalities and distinct protocols, but (probably more importantly) they were not looking for the same pathology''.

 

''Since these abnormalities were indeed differently prevalent in patients and healthy controls, the results inevitably became conflicting'' - he went on to suggest how future research, preferably using a multimodal approach, should be directed - including the need to achieve far greater levels of consistency/competence in doppler ultrasound screening for CCSVI conditions''. The outcomes of the limited number of studies cited by MSRA do no more than reinforce this need. See now details of the very significant MEM-net diagnostic advances (reported in December 2014) that go a long way to addressing many of these shortfalls.

 

Severe extracranial venous anomalies

 

One of the authors of the MSRA selected studies, Robert Zivadinov, also encapsulated these points with the following comment "This pilot study shows that both a non-invasive and invasive multimodal imaging diagnostic approach should be recommended to depict a range of extracranial venous anomalies indicative of CCSVI. The findings from the 2 invasive techniques confirmed the existence of severe extracranial venous anomalies that significantly impaired normal blood outflow from the brain in this group of MS patients".

 

Dr Simka's research similarly observed ''catheter venography studies gave a regular picture, with the majority of patients with multiple sclerosis presenting with demonstrable outflow abnormalities in the veins draining the central nervous system. The prevalence of these lesions was over 50%, and even higher (about 90%) when more liberal definition of an abnormality or intravascular sonography was used.''

 

Notwithstanding the comprehensive nature of these, and other related outcomes there continue to be instances whereby ''divergent outcomes'' are cited as conclusive evidence to support differing agendas -.thereby creating ongoing uncertainty in the minds of some. Fortunately in Australia we have a range of independent resources to call upon including the Alfred trial which is currently reporting an 80% CCSVI prevalence rate for people with MS.

  Meta Analyses Stress Need for Consistency
In a March 2014 paper titled "Chronic Cerebrospinal Venous Insufficiency - Current Perspectives" (referencing 122 studies), Dr Mariam Simka said "considering these many faces of CCSVI, it becomes more comprehensible why the results of prevalence studies have been so discordant. Not only were the authors using different diagnostic modalities and distinct protocols, but (probably more importantly) they were not actually looking for the same pathology. Since these abnormalities were indeed differently prevalent between patients and healthy controls the results were inevitably conflicting - read this paper.
 
  The Need for a Multimodal Approach
* An overview of prevalence issues was published in Biomedcentral (Zivadinov et al) on 27 June 2013.  Having reviewed 150 studies researchers commented "The dramatic difference in prevalence findings between different studies using non-invasive and invasive imaging techniques (ranging from 0% to 100%) emphasises the urgent need for a multimodal approach for better understanding of the venous abnormalities and developmental variants being considered in CCSVI".

Researchers went on to say "In a number of recent studies, noninvasive and invasive imaging techniques were applied and compared. The findings of these studies are extremely important to understand the true prevalence of CCSVI and the comparison of invasive vs noninvasive imaging findings is especially important.  It is emerging that the prevalence of venous anomalies and developmental variants, indicative of CCSVI is even higher, when investigated with sophisticated invasive imaging techniques"
 
* By June 2013 in excess of 350 research papers relating to CCSVI prevalence were available with, at times, dramatic differences between individual studies. Many studies did not seek to address key issues including the question advanced by Australia’s peak Health Policy Advisory Committee on Technology (HealthPACT) viz "Does Percutaneous Venoplasty make a difference in relieving the symptoms of multiple sclerosis by improving cerebrospinal venous drainage"?

These issues were  however broadly addressed by three meta analyses all of which confirmed a significant prevalence of CCSVI in MS. Only six out of 19 comparable studies denied the association between CCSVI and multiple sclerosis - more about these analyses.
 
* On 22 February 2012 a study published in the journal of the Royal Society of Medicine reported on the incidence of CCSVI conditions in pwMS as detected via Doppler ultrasound examination of the internal jugular veins (IJV) and vertebral veins (VVs). The presence of outflow disturbances and morphological abnormalities were evaluated. Pathological changes in the extracranial jugular veins were diagnosed in 148/181 MS patients (82%) and 7/50 control group volunteers (14%) - read this research
 
* In November 2011 participants at the 2011 Veith Symposium discussed how often internal jugular venous stenoses occur in the community. Professor Zamboni reported a prevalence of 70% for CCSVI in multiple sclerosis patients versus 10% in control patients. These findings represent the combined results from 14 studies. These findings build upon and confirm earlier published research on this topic. Participants also heard that the most frequently noted intraluminal defects or abnormalities inside internal jugular veins, such as malformed or fixed valves, septa and webs may be detected in a high resolution B-mode ultrasound. Michael Drake, chief of Interventional Radiology at Stanford University California, USA reminded participants “the localisation of the extracranial venous obstruction is not specific and can occur everywhere” -.find out more.
 
* On 26 October 2011, the journal BMC Neurology reported on a multi centre study of 710 people with MS whereby CCSVI was diagnosed in 86% of the patients, but the frequency varied greatly between the centres. Even greater differences were found when considering singly the five diagnostic criteria proposed by Zamboni et al. Despite these differences, significant associations with clinical data were found, the most striking being age at disease onset (about five years greater in CCSVI-positive patients) and clinical severity (mean EDSS score about one point higher in CCSVI-positive patients). Patients with progressive MS were more likely to have CCSVI than those with relapsing-remitting MS - read more.
 
*

On 3 October 2011 a meta analysis (Andreas Laupacis et al) published in the Canadian Medical Association Journal confirmed significant associations between CCSVI and Multiple Sclerosis. The research team tracked 471 references to CCSVI and identified 10 as meeting its rigorous research criteria –  read the analysis. An executive overview of this important meta-analysis is also available  - click here

 

Researchers also observed "The methods for diagnosing CCSVI need to be refined, as the between-centre differences, particularly in single criteria, were excessively high. Despite these discrepancies, the strong associations between CCSVI and MS phenotype suggest that the presence of CCSVI may favour a later development of MS in patients with a lower susceptibility to autoimmune diseases and may increase its severity - read more about this research

 

 
* Early days. The aforementioned outcomes amplify earlier findings on this topic - find out more.
 
WHAT ARE THE SAFETY ISSUES REGARDING  PERCUTANEOS VENOPLASTY IN RELATION TO CCSVI?
Safety On 28 March 2011, researchers at the Society of Interventional Radiology’s 36th Annual Scientific Meeting in Chicago, in releasing details of a study of 231 multiple sclerosis patients treated for CCSVI conditions, said "Angioplasty, the nonsurgical procedure of threading a thin tube into a vein or artery to open blocked or narrowed blood vessels, is a safe treatment.
Our study will provide researchers the confidence to study it as an MS treatment option for the future and encourage additional studies for its use as a treatment option for individuals with multiple sclerosis. Angioplasty is a process used by Interventional radiologists to widen the veins in the neck and chest to improve blood flow" - read the study or watch a video about this research. These findings build upon and confirm related research some examples of which follow.
Part 1 - Research relating primarily to Safety Issues
 
 
* During November 2011 HealthPACT (Australia’s peak Health Policy Advisory Committee on Technology) released a Brief relating to the role of Percutaneous Venoplasty in treating vascular irregularities experienced by people with multiple sclerosis. In doing this it observed that "percutaneous venoplasty (per se) is an established, routine procedure, with a proven safety and efficacy" and went on to highlight the importance of randomised, controlled, clinical trials, to formally assess Percutaneous Venoplasty in the treatment of CCSVI in patients with MS, before the procedure can be widely adopted.  - find out more
 
* On 18 June 2011 Pubmed reported on a study whereby in a 1-year period, 461 MS patients with CCSVI underwent endovascular treatment of 1012 venous lesions during 495 procedures. Complication rates were compared to published data for similar endovascular methods. There were no deaths, major bleeding events, or clinical deterioration of MS. Access site complications included limited groin hematoma (5, 1.0%); there were no arteriovenous fistulas or puncture site infections. Researchers concluded "endovascular therapy appears to be a safe and reliable method for treating CCSVI. Innovations such as purpose-specific materials and devices are needed, as are case-controlled and randomized data to establish efficacy in ameliorating MS symptoms".  find out more about this research
 
* In March 2011 the Journal of  Vascular and Interventional Radiology reported on a retrospective analysis of 231 MS patients with CCSVI undergoing endovascular treatment of the internal jugular and/or azygos veins that identified  and described any adverse events occurring within 30 days of treatment.  Conclusions included "endovascular treatment of CCSVI in MS patients is a safe procedure when performed on an outpatient basis. Cardiac monitoring is essential to permit detection and rapid treatment of patients with procedure-induced arrhythmias" - read this research
In December 2010 Pubmed reported on a study whereby a total of 564 endovascular procedures (balloon angioplasty or, if this procedure failed, stenting) were performed during 344 interventions in 331 CCSVI patients with associated multiple sclerosis. There were no major complications (severe bleeding, venous thrombosis, stent migration or injury to the nerves) related to the procedure, except for thrombotic occlusion of the stent in two cases (1.2% of stenting procedures) and surgical opening of femoral vein to remove angioplastic balloon in one case (0.3% of procedures). Researchers concluded "the procedures appeared to be safe and well tolerated by the patients, regardless of the actual impact of the endovascular treatments for venous pathology on the clinical course of multiple sclerosis, which warrants long-term follow-up" - more about this research 
* The issue of safety is also addressed by researchers when addressing the benefits in treating CCSVI conditions -  see later
 
WHAT ARE THE REPORTED BENEFITS OF VENOPLASTY IN TREATING CCSVI CONDITIONS?
Benefits Salvatore JA Sclafani MD, the Medical Director for the CCSVI service line for American Access Care describes (2012) the inter-relationships between MS and CCSVI in the following terms. "Firstly recognize that MS is a neurodegenerative disease with neuronal loss. That will result in disability. This disability is unlikely to heal itself; at least in the short term. CCSVI, an associated condition, with outflow obstructions of the veins draining the cerebrospinal venous circulation, results in altered drainage that may affect cerebrospinal arterial inflow and arterial pulsatile flow, and decreased drainage of cerebrospinal fluid with resultant hydrocephalus
Relief of this obstruction affects some neurological symptoms such as chronic fatigue, temperature intolerance, memory and cognition disturbances and vision disturbance, often quickly. Sometimes other symptoms such as spasticity, ataxia, motor and sensory abnormalities also improve, usually not so quickly. Opening a vein can be done with precision and safety but what result you get from venoplasty likely depends to a large degree on the degree of neurodegenerative neuronal death that is present" – More about Dr Sclafani
 
 

In November 2017 the Journal of Vascular Surgery reported on a study involving 797 consecutive patients with venous outflow anomalies who underwent standardized, operator-independent catheter venography and angioplasty (PTA) of the internal jugular veins.  The aim of the study was to investigate the anatomic factors and patient characteristics that might influence the efficacy of such interventions. PTA resulted in an increased outflow through the IJVs in most patients. However, younger individuals with transverse endoluminal defects and higher pre-PTA flows are more likely to respond well to PTA compared with those who exhibit hypoplasia, stenosis, or longitudinal endoluminal defects.  Researchers observed ''the earlier patients receive CCSVI angioplasty the better''. The study also teased out which types of blood flow problems will respond best.

 
* On 2 October 2015 the Journal Veins and Lymphatics published details of a four year independent follow up of 366 persons treated with venoplasty (PTA) for CCSVI conditions - comprising 264 relapsing remitting, 62 secondary progressive and 40 primary progressive. Outcomes were evaluated against 11 commonly reported MS symptoms.  Results for the relapsing remitting group were described as ''significantly good''. Greatest improvements related to blurred vision 99.2%, concentration 98.6%, fatigue 98.5%, headache 98.6%,  sleep 93.2%, vertigo 90.9%, balance 88.5%, numbness and mobility 83.3%, temperature intolerance 75%, bladder control 66.6%. While the progressive experiences are different they are statistically significant. Researchers observed ''the overwhelming PTA results in the RR group lead us to say the sooner the better''.
 
* On 5 December 2014 the Austin Journal of Multiple Sclerosis and Neuroimmunology reported on the 12 month follow up of 72 patients treated with venoplasty for CCSVI conditions - 20 with RR and 52 with SP-PP. The group of RR patients was significantly younger, duration of disease was shorter and the degree of disability lower than in SP and PP patients. In the relapsing-remitting group of patients an improvement of disability was observed, whereas in patients with the progressive course of the disease a stable clinical status was noticed. Both patient groups showed a significant improvement of fatigue. Cognitive and psychosocial impact on the quality of life showed better outcome in patients with advanced course of the disease than in less affected patients. Important amelioration of bladder dysfunction was achieved in both groups.
 
* In May 2014 the Alfred Hospital (Melbourne, Australia) confirmed that 27 of 34 participants (80%), in Australia's first CCSVI clinical trial, who had the baseline venogram have CCSVI. 26 of these 34 have continued on to the treatment phase. In other words, in this random sample of 34 people with Multiple Sclerosis, 4 out of 5 have identifiable venous abnormalities in either the jugular and/or azygos veins. Whilst these are encouraging numbers, the study requires further funding to enrol a total of 160 participants and provide statistically significant results
 
* During 2013 CCSVI Australia initiated a process to enable those treated in Australia to provide testimonials regarding their reasons for seeking treatment for CCSVI related conditions and the outcomes thereof. Click here to access this information, along with snapshots of global developments. While this ‘qualitative evidence’ may lack the scientific rigour of, for instance, randomised controlled trials, it provides a body of knowledge that not only complements  other forms of evidence, but also enables a greater understanding of the decision-making processes, both on the part of practitioners and that of service users and carers. 
 
* On 28 August 2012 the Journal of Vascular and Interventional Radiology reported on a study led by Dr. David Hubbard that confirms that treatment for CCSVI is safe and effective. Two hundred fifty-nine patients with MS were followed with the Multiple Sclerosis Impact Scale (MSIS-29) before and for 1 and 6 months after treatment of extracranial internal jugular vein and azygos vein stenoses and occlusions using venous angioplasty, as well as stent placement in 2.5% of patients. Before treatment, the patients were tested with magnetic resonance (MR) venography and flow quantification. The study concluded "treatment of CCSVI in patients with MS appears to be a safe procedure resulting in significant clinical improvement" - read more
 
* On 26 March 2012 Medscape reported on proceedings at the Society of Interventional Radiology 37th Annual Scientific Meeting held in San Francisco. "This is the first wave of CCSVI research that has been presented that is beyond just the observational," said Michael Drake, MD, professor of cardiothoracic surgery at Stanford University in Palo Alto, California. He went on to say "It's a nice experience with a large group (297) of patients.
 
* In relation to one of the studies, involving 192 patients, Kenneth Mandato, MD, an interventional radiologist at the Albany Medical Center said "Results were quite exciting and promising". The greatest improvement was in those with relapsing remitting disease — 77% reported a physical improvement and 74% reported a mental improvement. Of those with secondary progressive disease, 59% improved on the physical index and 50% improved on the mental index. Of those with primary progressive disease, 77% had a physical and 70% had a mental improvement. These changes were all statistically significant (P < .05) - find out more
 
* The second retrospective review that examined the results of 105 procedures performed in 94 patients with MS was led by Hector Ferral, MD, an interventional radiologist at North Shore University Health System in Evanston, Illinois. Researchers said, these early results show that performing angioplasty on azygos and jugular vein lesions may have a positive impact on the symptoms of those individuals with MS and also could be an effective palliative treatment geared toward improving their quality of life. “Our experience showed that 95% of the individuals we evaluated had venous obstructions, supporting the concept that venous lesions are common in individuals with MS,”
 
* Dr. Ferral’s team reported symptomatic improvement in 55% of the individuals treated, and 38% reported no improvement. Seven percent of patients did not comply with their follow-up visits and were considered to be lost to follow-up. Close to 60% of those with relapsing-remitting MS reported improvement in symptoms, the highest of all the subgroups in this study. “These important results revealed that for people with MS who experience debilitating symptoms, minimally invasive interventional radiology treatments can be an effective, palliative treatment that also may improve their quality of life,” said Dr. Ferral - find out more
 
* In November 2011 Australia’s peak Health Policy Advisory Committee on Technology (HealthPACT) referenced research "that the reestablishment of a normal cerebrospinal venous return through percutaneous venoplasty significantly reduced chronic fatigue perception at 12 months follow-up, and improved the rate of relapse-free patients, quality of life, and neurological function at 18 months follow-up, in MS patients diagnosed with CCSVI". In doing this it emphasised that at this stage the research is limited to low level case series studies and that outcomes over longer term studies are not yet available.
 
* In August 2011 the European Journal of Vascular & Endovascular Surgery reported on a case control study involving Professor Zamboni, the objective of which was to see if percutaneous transluminal angioplasty (PTA) of duplex-detected lesions, of the internal jugular and/or azygous veins, was safe, burdened by a significant restenosis rate, and whether there was any evidence that treatment reduced MS disease activity. This study further confirms the safety of PTA treatment in patients with CCSVI associated with MS. The results, despite the significant rate of restenosis (27%), are encouraging and warrant a larger multicentre double-blinded, randomised study.- more about this study
* Click here to scan all affiliated Network Sites regarding Benefits and Efficacy of Venoplasty for CCSVI conditions, including Australian patient testimonials
 
WHAT ARE THE BENEFITS OF BEING TESTED FROM AN INDIVIDUAL'S PERSPECTIVE?
Screening By September 2012 it is reported that more than 30,000 pwMS across the globe have been treated by vascular specialists for CCSVI related conditions. It is estimated that around 4,000 of these are being regularly monitored - giving rise to much of the aforementioned statistical data.  Several hundred have been treated in Australia - primarily those with access to private insurance or who may otherwise be able to pay 'up front'.
In July 2014 the potential for greater consistency in the use of ultrasound (ECD) to detect CCSVI conditions became available via a web accessible computer based global database called MEM-net. Developed by the National Epidemiological Observatory on CCSVI for data collection around protocols agreed with national vascular scientific societies
Unfortunately Australia has no national monitoring system in place to comprehensively learn from Australian experiences. This is a major weakness.  There are also growing numbers of Australians being diagnosed with CCSVI conditions who are unable to access treatment and/or essential follow up  treatments. About subsequent Australian developments.
For pwMS who become involved in CCSVI testing there can be clarity, at an individual level, about the nature of any blood flow irregularities and a possible options to redress such irregularities. In an ideal world participation should also fundamental to the overall research effort. It is reported that around two thirds of those treated experience improvements in some MS symptoms - some immediate and some over time. While there is, as yet, little significant long term evidence to properly understand the overall relationship, if any, between CCSVI and MS, the available evidence is that "venous malformations are most likely congenital, and multiple sclerosis had no significant impact on the development of venous pathology". Researchers said  "this analysis did not yield any data supporting the idea that MS is the cause of venous lesions" -  read more While a percentage of jugular veins angioplasty procedures may need repeating, research is ongoing about ways that this may be minimised. Many of Australia's ' early adopters' seeking vascular screening since the beginning of 2010 report doing so to:
 
* Clarify, at an individual level, the nature of any blood flow irregularities
* Understand the possible consequences any such irregularities
* Identify possible treatment options and associated risks
* Make decisions about redressing any identified irregularities
 
  Click here to hear from some of Australia's Early Adopters  
Other factors reported as influencing treatment outcomes include the nature, extent and location of possible vascular irregularities, the types of MS symptoms being experienced, and the extent to which neurologically based issues may also be associated with impaired functioning. Discuss these issues with your GP/Vascular specialist. Details of a range of Australian based medical practitioner who, since 2010 are reported as becoming involved in CCSVI scanning and treatment are available from the web site of CCSVI Australia click here for these details. The list is not exhaustive and is based on feed back from members of the MS community based upon 'first hand' experiences. Let us know of other practitioners whose details you would like to see referenced.
WHAT WERE THE ''Early Days'' GLOBAL CCSVI TURNING POINTS - ADAPTING TO CHANGE - from an Australian Perspective?
Milestones Click here for further snapshots of post 2012 Australian turning points including the recognition of CCSVI Australia as a Charity in its own right and the commencement of Australia's first CCSVI Clinical Trial
 
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CCSVI ''From the Lab to the Clinic to Parliament'' Kirsty Duncan

 

Dr Kirsty Duncan is a medical research scientist and a member of the Canadian Parliament. Kirsty is also a powerful advocate for the rights of people with Multiple Sclerosis - watch a video (March 2011)

 

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First elected as a Member of the Canadian Parliament in 2008 and re-elected in 2011 and 2015 on 21 September 2011 Kirsty introduced a (at that time unsuccessful) bill in the Canadian Parliament seeking independent research and a registry of CCSVI in people with MS - which made waves across the world - watch a short video. A second reading of this bill on 8 December 2011 is also good reading as well as good viewing.

In 2014 Kirsty tabled a new bill to be debated in the next parliament.  She said  “the best science should be done so we can get the best answers… via a strategy ''from the lab to the clinic to parliament''. Watch a related video in October 2014 - powerful stuff.

 

On 24 July 2015 CCSVI Australia and the Australian MS Network of Care jointly made representations to the Australian Parliament that pretty much mirror the legislation originally proposed by Kirsty  - click here to access this submission.

 

Following the successful election of a Liberal parliamentary majority in 2015, and on November 4, 2015, the incoming Prime Minister (Justin Trudeau) appointed Kirsty to his Cabinet as Minister of Science.

 

More about Kirsty and MS


* On 23 August 2012 Australia's highly regarded ABC Science program, Catalyst, featured Dr Paul Thibault, an Australian CCSVI researcher who has hypothesised an association between Chlamydia pneumoniaecm and vascular effects associated with CCSVI related conditions - a must watch presentation.
 
* On 16 August 2012 MS Australia and CCSVI Australia provided a United Statement to the Parliament that said, inter alia, "as covered at the Parliamentary briefing (25 June 2012), while the diagnosis of CCSVI by Doppler ultrasound can be accessed under the Medicare Benefits Scheme, the most common form of treatment – balloon angioplasty – cannot. Angioplasty is available under the scheme for various conditions involving venous abnormalities, but it is not available for treatment of venous abnormalities if patients have multiple sclerosis".
 
* The statement went on to say "we will be working with representatives of the phlebological community to progress a campaign to rectify this issue, and would warmly welcome any advice or support from our Parliamentary friends. In addition to these two pressing matters, we will endeavour to raise awareness of this important issue and will shortly be seeking briefing meetings with the Department of Health and Ageing to appraise them of our activities and the latest research"
 
* For nearly 2 years CCSVI Australia advocated for the Alfred trial in respect of which $95,700 (August 2012) had been donated by the MS community with a further $335,000 required to complete the trial. The United Statement addressed this issue as follows "MS Australia will actively work with the Alfred Hospital to engage funds to complete this vital research. In addition we ask for your (Australian Parliament) support in advocating for funding support of the trial to the National Health and Medical Research Council and the Minister for Health to ensure the future of this vital research' '- read the full statement
 
* A briefing was conducted at Parliament House, Canberra on Monday 25 June 2012 with the aim of building common ground. Organised by MS Australia, in collaboration with CCSVI Australia, and under the auspices of Senator Kate Lundy, it was agreed to progress this issue on a bi-partisan basis. Laura Smyth MP committed to meet with Janelle Saffin MP on what to present to the Parliament's Health Committee with the aim of obtaining agreement from the Health Minister and NHRMC to fast track appropriate action. MSA and CCSVI Australia agreed to produce a 'united statement' for them to use in their work. MS Australia was represented by their President, Rob Hubbard and Robert Pask. CCSVI Australia was represented by Kerri Cassidy and Helena Webb. An excellent clinical overview of CCSVI and MS was provided by Doctor Paul Thibault. All in all an important step forward

The overall aim is to translate the new and significant knowledge about vascular irregularities into Australian Government "policies, programs and practices to support the advancement of CCSVI medical knowledge while, at the same time, addressing the ongoing CCSVI needs of Australians living with MS". Clinical trials are only one part of this process. Ensuring that the 'Voice of People Affected by MS' is heard and respected is fundamental..
 
* In February 2012 the Multiple Sclerosis International Federation (MSIF) published the results of a survey (involving 10,090 people in 101 countries) about the incidence and impact of fatigue experienced by pwMS. The survey outcomes replicate and expand upon 2001 research by the (then) Multiple Sclerosis Society of NSW, Australia involving 2618 pwMS in NSW. The continued highlighting of extreme fatigue (with flow on consequences to cognitive issues etc) is consistent with the health improvements being reported by the estimated 30,000 pwMS across the globe treated for CCSVI vascular irregularities - find out more
 
* In February 2012 Australia’s first comprehensive CCSVI trial at the Alfred in Melbourne received ethics committee approval and will shortly commence recruiting - with additional such trials understood to be in the pipeline. The Alfred is the trial in support of which CCSVI Australia were catalystic in rasing $95,700 (August 2012) in donations from the MS community. More about the Alfred trial.  While these are very important developments more is needed.

Apart from the Alfred trial access to CCSVI procedures in Australia is currently limited. Where it is available it is largely restricted to those with private insurance or otherwise able to meet the full cost of the treatment.  To the extent that there is no nationally recognised registry reporting system to capture data arising from these treatments an extremely valuable body of knowledge is at risk of being under utilised and potentially lost - find out more.
 
* The 28 December 2011 edition of the ABC Australia 7.30 report relating to CCSVI developments in Australia is well worth watching. Subsequent coverage by the Channel 7 Sunday Show reinforces this message - watch the Channel 7 coverage. Participants in these programs, (and consequential feedback) identified significant improvements in both function and psychological well being following angioplasty in Australia to treat CCSVI conditions.
 
* During the period October 2011 to December 2011 the results of ongoing fact finding about the prevalence of CCSVI conditions in pwMS as compared to the general community began to appear in the literature. In summary, these findings (that primarily relate to screening of jugular veins via doppler ultrasound) identify a CCSVI prevalence in the range 70% to 86% amongst MS populations and 10% to 14% in the general community. A need for more comprehensive operator training was cited as an important factor in the fluctuations across a range of testing centres. While these findings provide a very important 'baseline' it is important to remember that CCSVI can occur elsewhere in the vascular system requiring more extensive testing - see earlier
 
*

During November 2011 HealthPACT(Australia’s peak Health Policy Advisory Committee on Technology) confirmed that Percutaneous Venoplasty is an established, routine procedure, with a proven safety and efficacy" and highlighted research that this procedure "significantly reduced chronic fatigue perception at 12 months follow-up, and improved the rate of relapse-free patients, quality of life, and neurological function at 18 months follow-up, in MS patients diagnosed with CCSVI". Both NHMRC and HealthPACT stressed the importance of properly designed clinical trials. The development of a national monitoring system, to capture information to help identify disease patterns and track CCSVI treatments and long-term outcomes for people living with MS was also referenced - find out more.

 
*

On 3 November 2011 the Canadian CCSVI Coalition announced the composition of its Scientific Advisory Board (SAB). The Board comprises a group of diagnostic, treatment and pathology experts with extraordinary insight into CCSVI and MS and a wealth of practical experience in assessing and treating people with CCSVI. They have been assembled to be an expert resource for researchers and government on these issues and to facilitate a balanced and open dialogue regarding CCSVI and MS. The Board is Chaired by Dr. Michael E. Shannon, an acknowledged expert in designing and running large clinical trials. He is well known to government and medical experts in Canada through his past positions as Deputy Surgeon General, Director General of The Laboratory Centers for Disease Control and Senior Medical Advisor to the Canadian Public Health Agency  - find out more about this development.

 
* On 22 September 2011 the MS Network of Care, Australia provided a Briefing Note to all of Australia's Federal Parliamentary representatives requesting that "the Australian Parliament put in place policies, programs and practices that support the advancement of CCSVI medical knowledge while, at the same time, addressing the ongoing CCSVI needs of Australians living with MS". In May 2011, in conjunction with World Multiple Sclerosis Day, Janelle Saffin MP ,the Federal Member for Page in the Northern Rivers region of NSW, addressed the Australian House of Representatives regarding this issue.  Since that time many families living with MS across Australia have approached their parliamentary representatives, both State and Federal, about a range issues associated with these new developments - Read the Briefing Note.
 
* On 24 August 2011 the UK National Institute for Health and Clinical Excellence (Nice) announced that it is changing its guidelines to enable CCSVI procedures to be used in the context of research only, so further evidence on its safety and clinical efficacy can be developed. Professor Bruce Campbell, chairman of the independent committee that develops Nice's interventional procedures guidance, said: "Multiple sclerosis can be a distressing and disabling condition with a lack of effective treatments. This means that it is really important to find out whether percutaneous venoplasty is clinically effective and safe for use in the NHS. Based on the existing evidence, we believe that clinicians should only consider offering percutaneous venoplasty as a treatment option for people with MS who fit the diagnostic criteria for CCSVI, as part of structured clinical trials" - find out more
 
* On 29 June 2011, Canada's Health Minister, Leone Aglukkag announced that Canada, on the advice of an expert panel, is extending its existing level of CCSVI support for Canadians with MS by funding CCSVI clinical trials across Canada. The scientists who advised the federal government to go ahead with clinical trials said it was new evidence — not public pressure — that changed their minds. Dr. Aaron Field, an associate professor of neuro-radiology at the University of Wisconsin, said he went into the meeting with an open mind but was still surprised by what he learned. Even when you took a very conservative approach to the meta-analysis, it still came out looking like there was an association between CCSVI and MS. The panel stressed that there is still not enough evidence to suggest cause and effect - click here for details
 
* On 28 March 2011, researchers at the Society of Interventional Radiology’s 36th Annual Scientific Meeting in Chicago, in releasing details of a study of 231 patients treated for CCSVI conditions, said "Angioplasty, the nonsurgical procedure of threading a thin tube into a vein or artery to open blocked or narrowed blood vessels, is a safe treatment.  Our study will provide researchers the confidence to study it as an MS treatment option for the future and encourage additional studies for its use as a treatment option for individuals with multiple sclerosis. Angioplasty is a process used by Interventional radiologists to widen the veins in the neck and chest to improve blood flow" - read the study or watch a video about this research. These findings build upon and confirm earlier research by Dr Simka from Poland in a study involving 347 patients..

* On 26 March 2011, there was an official apology by the Alberta Chapter of Canadian MS Society to the MS community in the following terms "we should have listened to the successful stories patients have had when getting the treatment done. "We are sorry," said Darrel Gregory  "I think we came down too heavily on the side of research and not enough empathy for patients and what they're going through. The organization will focus more on addressing those who went overseas to get the controversial treatment, and to see that patients who haven't can get treated right here at home".
 
* On 23 March 2011 the federal government of Canada announced that it will provide funding through the Public Health Agency of Canada to support development of a national monitoring system that will capture information to help identify disease patterns and track treatments and long-term outcomes for people living with MS. The system will be developed by the Canadian Institute for Health Information (CIHI) in close collaboration with the Canadian Network of MS Clinics and the MS Society of Canada. The monitoring system will be able to track Canadians with MS who have chosen to have the Zamboni procedure abroad and monitor MS symptom changes over time and any complications - read more.
 
* On 15 March 2011  Dr Kirsty Duncan a medical research scientist (and a member of the Canadian Parliament) addressed the First International Venous Endoplastic Forum in Poland on the history, politics and science of the CCSVI debate from a Canadian perspective. Canada has one of the highest rates of MS in the world. Perhaps more than any other country, CCSVI issues have been subject to vigorous political debate from which many valuable lessons can be learnt - most of the issues Dr Duncan spoke about have a high degree of relevance in Australasia -  watch Dr Duncan's presentations
 
* April 2010 to February 2011 saw an intense groundswell of interest, research and treatment of CCSVI across the globe. Dr Sclafani (former head of Interventional Radiology, SUNY University, New York described the environment as being an 'Age of Discovery' in which maintaining and improving the Quality of Life of people living with MS, while at the same time, enhancing medical knowledge through 'hands on experiences', have become cornerstones for MS management - watch this interview
 
* In November 2010 the ethics committee of the San Anna  hospital in Ferrara  (Italy) approved Prof Zamboni proposed two year randomised double blinded CCSVI clinical trial (known as Brave Dreams) involving over 650 pwMS in 20 centres across Italy. The study (results published November 2016) included two phases comprising an assessment of the procedure itself and a therapeutic assessment of the outcome of the treatment, There is also an objective measurement that includes measuring motor activity, balance, and neural activity.  >
 
* In March 2010 Kerri Cassidy, amongst the first of several hundred people to receive CCSVI treatment in Australia, underwent Balloon Angioplasty (in Melbourne) to open up two blocked jugular veins. Since that time Kerri's experiences have provided important insights into the CCSVI debate, both in Australia and globally.  Read more about Kerri's experiences and/or watch a video about the outcomes of Kerri's first treatment. An interview with Kerri, two years after her treatment, is also available - click here
 
* In December 2009 the International Union of Phlebology released a consensus document relating to the diagnosis and treatment of venous malformations including those relevant to the drainage of blood from the brain and spinal cord. In January 2010 the Union recognised CCSVI as a congenital vascular malformation in its own right and outlined guidelines for its diagnosis and treatment.
 
* In December 2008 the Journal of Neurology, Neurosurgery and Psychiatry published details of research by Dr.Zamboni who made the startling find that in more than 90 per cent of people with multiple sclerosis, including his spouse, the veins draining blood from the brain were malformed or blocked. In people without MS, they were not. He hypothesized that iron was damaging the blood vessels and allowing the heavy metal, along with other unwelcome cells, to cross the crucial brain-blood barrier - read more.
 
WHAT ELSE IS BEING LEARNT? EMERGING KNOWLEDGE - More Snapshots in an Age of Discovery
Further Afield The environment is being described as an 'Age of Discovery' in which maintaining and improving the Quality of Life of people living with MS, while at the same time, enhancing medical knowledge through 'hands on experiences', have become cornerstones for MS management. Some of the developments attracting the attention of MS communities follow. In some cases the emerging knowledge is 'ms specific' - in others the implications are broader.
 
* MISDIAGNOSIS MORE COMMON THAN PREVIOUSLY THOUGHT

Running in parallel with this new knowledge are strengthened understandings about other chronic conditions
sometimes mistaken for, or associated with, MS.
A study published on 10 May 2012 in Neurology (the medical journal of the American Academy of Neurology) found that it is relatively common for doctors to diagnose someone with multiple sclerosis when the patient doesn't have the disease — a misdiagnosis that not only causes patients potential harm (example) but costs health care systems untold millions of dollars a year. The study is based on a survey of 122 multiple sclerosis specialists across America.  Dennis Bourdette, M.D., the senior author of the study, said the misdiagnoses not only meant patients were getting expensive and potentially harmful treatments they didn't need, but they were also not getting the appropriate treatment for the diseases they may have had - read much more about misdiagnosis, under diagnosis and misinformation.

* POTENTIAL FOR PERCEIVED CONFLICTS OF INTEREST

On 16 January 2012, the New York Times highlighted pending legislation to require drug companies to disclose the payments they make to doctors for research, consulting, speaking, travel and entertainment. Many researchers found evidence that such payments can influence doctors’ treatment decisions and contribute to higher costs by encouraging the use of more expensive drugs and medical devices. The legislation does not define the difference between proper and improper payments. It says simply that public reporting of the financial ties between doctors and drug and device companies “will permit patients to make better-informed decisions when choosing health care professionals and making treatment decisions" read more

On 5 July 2012 the Age Newspaper reported on associated developments in Australia. Subsequently Medicines Australia announced the establishment of a Transparency Working Group,
chaired by Medicines Australia Board member Dr Dominic Barnes, to develop new measures to increase transparency of pharmaceutical company payments and other transfers of value to healthcare professionals. The AMA, the Royal Australian College of Physicians, the Consumers Health Forum and other key healthcare and consumer organisations have been invited to this group. This is a significant issue for the Australian MS community. The working group's terms of reference appear to be sufficiently broad to address pharmaceutical company payments/influence (either publicly disclosed or undisclosed) channelled through "third party" organisations and/or individuals perceived as being in positions to significantly influence consumer medical decisions, i.e for participation on Advisory Boards, provision of consultancy services, and sponsorships for attending educational meetings - more about this development.

On 6 December 2013 the Journal of Law, Medicine & Ethics, under the heading "Institutional Corruption and the Pharmaceutical Policy", referenced a series of discussion papers whereby the goals of pharmaceutical policy and medical practice are often undermined due to institutional corruption that is, widespread or systemic practices, usually legal, that undermine an institution’s objectives or integrity. As a result, practitioners may think they are using reliable information to engage in sound medical practice while actually relying on misleading information and therefore prescribe drugs that are unnecessary or harmful to patients, or more costly than equivalent medications. At the same time, patients and the public may believe that patient advocacy organizations effectively represent their interests while these organizations actually neglect their interests.-
read more.
 
* BETA INTERFERONS DO NOT DELAY MS PROGRESSION

On 17 July 2012 the Canadian press reported on a study involving 2,656 patients with MS (published in the Journal of the American Medical Association) that found that exposure to a group of drugs known as the beta interferons was not strongly associated with a reduction in progression of long-term disability in people with multiple sclerosis. Researchers said "Our main finding suggests the drugs aren't preventing the progression of disability" .Dr. Helen Tremlett, one of the study's authors, says the finding is just coming to light because in the past, not enough time had elapsed from when the drugs were approved to treat the disease. However, the researchers warn that the study's results weren't meant to suggest that MS patients stop taking the drugs as the medications are still effective at reducing relapse rates - related research on this topic.
 
  CONSIDERING MS AS A METABOLIC DISEASE
* Multiple sclerosis, long viewed as primarily an autoimmune disease, is not actually a disease of the immune system, a U.S. researcher says. Dr. Angelique of the John Jay College of Criminal Justice in New York suggests (January 2012) instead that MS is caused by faulty lipid metabolism -- in many ways more similar to coronary atherosclerosis -- hardening of the arteries -- than to other autoimmune diseases. Considering MS as a metabolic disorder helps to explain many puzzling aspects of the disease, particularly why it strikes women more than men and why cases are on the rise worldwide. Multiple sclerosis is mainly characterized by inflammation followed by scarring of tissue called myelin, which insulates nerve tissue in the brain and spinal cord. Over time, this scarring can lead to profound neurological damage, but medical researchers have theorized that a runaway immune system is at fault, but no one has been able to fully explain what triggers the onset of the disease - find out more
 
* GENETIC BRAIN DISORDERS MISDIAGNOSED AS MS

 Neurologist Zbigniew K. Wszolek, M.D. reported (ScienceDaily December 25, 2011) on research relating to an abnormal gene that leads to the development of hereditary diffuse leukoencephalopathy with spheroids (HDLS). The study found that a significant number of people who tested positive in this study had been diagnosed with a wide range of other conditions. "Because the symptoms of HDLS vary so widely -- everything from behaviour and personality changes to seizures and movement problems -- these patients were misdiagnosed as having either schizo phrenia, epilepsy, frontotemporal dementia, Parkinson's disease, multiple sclerosis, stroke, or other disorders," says Dr. Wszolek. "Many of these patients were therefore treated with drugs that offered only toxic side effects. "Given this finding, we may soon have a blood test that can help doctors diagnose HDLS, and I predict we will find it is much more common than anyone could have imagined," he says. The gene was found using a combination of traditional genetic linkage studies and recently developed state-of-the art sequencing methods, - read more.
 
  AEROBIC EXERCISE, BLOOD  FLOW and HEALTHY ARTERIES
* In June 2010 the journal of the American Society of Haematology reported on research that illustrates that disturbances in the patterns of blood flow in an artery determine where atherosclerosis will later appear. Atherosclerosis describes a process where the arterial walls thicken and harden, because of a gradual build-up of white blood cells, lipids and cholesterol. This process can lead to plaque formation, and eventually to heart attacks and strokes. This research could provide insight into how aerobic exercise, known to provide protection against atherosclerosis, improves the patterns of blood flow and encourages protective genes to turn on in blood vessels. Scientists have previously observed that atherosclerosis occurs preferentially in branched or curved regions of arteries, because of the "disturbed flow" branches and curves create. Constant, regular flow of blood appears to promote healthy blood vessels, while low or erratic flow can lead to disease.

It is reported that the common amino acid arginine can help (some say in a surprising way) to maintain the health and optimal functioning of our circulatory system - veins as well as arteries. Arginine is well known for its beneficial roles in many physiological processes, such as increasing muscle tone and improving immune function - find out more about arginine and related research.
 
  PULSE PRESSURE ASSOCIATED WITH MS PROGRESSION
* People with multiple sclerosis have reduced gait performance which is associated with disability and disease progression. A study (August 2011) by researchers at Syracuse University, New York of 33 individuals with MS and 33 age/sex matched controls supported the hypothesis that higher than normal pulse pressures contribute to increased arterial stiffness and pressure which, in turn, may contribute to the deterioration of physical functions in people with MS. In the study, central blood pressure (BP) was assessed via applanation tonometry. Brachial BP was measured using an automated oscillometric cuff. PP was defined as systolic BP - diastolic BP. Researchers observed "PP is a predictor of gait performance in persons with MS" - find out more about this stud
 
  BACTERIUM LINKED TO MULTIPLE SCLEROSIS
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The organism, Chlamydia pneumoniae (CPN), is a relatively recent addition to the list of bacteria known to affect humans. It is now recognized as a cause of pneumonia, pharyngitis, bronchitis, and several chronic diseases. More importantly, Chlamydia pneumoniae is recognized as playing at least some causative role in reactive arthritis and coronary artery disease--medical conditions which, like MS, are characterized by ongoing inflammation. Convincing data relating infection with a specific organism to Multiple sclerosis was reported in 1999 and is borne out by subsequent events.

 

Researchers said  "The evidence of Chlamydia pneumoniae in both progressive MS and relapsing-remitting patients suggests that the infection of the central nervous system with Chlamydia pneumoniae occurs early and persists perhaps throughout the course of the disease and does not differentiate between different clinical subtypes of the disease." read more about this research. In 2011 the Australian CCSVI researcher Dr Paul Thibault hypothesised an association between Chlamydia pneumoniaecm and the vascular effects associated with CCSVI related conditions - read Dr Thibault's hypothesis. In August 2012 the ABC Catalyst program also featured the work of Dr Thibault in relation to associations between Chlamydia pneumoniae and CCSVI - a must watch.

 

 Cpnhelp.org have provided a handbook that organises and pulls together information on Chlamydia pneumoniae, it's impact on human diseases, and it's treatment via combined antibiotic protocols in an easily accessible, organized and up to date format. access this handbook. There is also a very useful facebook site at https://www.facebook.com/ChlamydiaPneumoniae

 

Click here to scan all affiliated Network Sites regarding Chlamydia pneumoniae

 
* LYME DISEASE CONTINUES TO ATTRACT INTEREST

Lyme disease is an illness caused by the organism Borrelia burgdorferi, a bacterium known as a spirochete believed to be carried by a deer tick. The spirochete can be transmitted to people or animals by the bite of a tick. Some of the neurologic symptoms of Lyme disease are similar to those of MS. The first signs of Lyme disease develop within days or months of the tick bite - watch a video. Sixty to 80% of those infected with Lyme disease get a large, reddish rash sometimes described as a bulls-eye. Other symptoms include a flu-like illness with fever, headache, stiff neck, and muscle and joint pains. Testing to confirm its presence can be complex - read more.

Lyme disease can cause delayed neurologic symptoms similar to those seen in MS, such as weakness, blurred vision caused by optic neuritis, dysesthesias (sensations of itching, burning, stabbing pain, or “pins and needles”), confusion and cognitive dysfunction, and fatigue. Lyme disease symptoms may also have a relapsing-remitting course - read more. There is also evidence about inter-relationships between Lyme Disease and Chlamydia pneuoniae.

Recent research in the UK challenges many preconceived notions about the potential for the spread of this disease - read a recent U.K case history involving Julia Marshall-Wessendorf,
 Ticks that can transmit Lyme disease may be more prevalent in the UK than realised, say researchers who have found out how many dogs harbour them. Experts have suspected for some time that the UK has a growing problem with these tiny pests - rates of the disease have been creeping up in recent years. Of the 3,534 pet dogs inspected at veterinary clinics in the UK between March and October 2009, 14.9% had ticks.  Researchers said "Without considerably better surveillance and routine diagnostic testing, Lyme disease is only likely to become more prevalent” - read more


For many years it was believed by many that Lyme Disease was not present in Australia. However, this is contradicted by a December 2011 study by the Australian doctor, Peter Mayne MD. Natalie Young from Coffs Harbour in Australia is one many of Australia's tireless campaigners for the proper diagnosis and early treatment of Lyme Disease.  Read Nat's story. In July 2013 Australian television highlighted the deep despair and tragedy experienced by growing numbers of Australians who have contracted Lyme disease despite long standing medical assertions that it cannot be contracted in this country.
 
In March 2013 the Australian Government Chief Medical Officer, Professor Chris Baggoley,  established a Clinical Advisory Committee on Lyme disease to provide advice on the evidence for Lyme disease in Australia, diagnostic testing, treatment and research requirements. The Committee will also provide advice on the most appropriate ways to disseminate information to health professionals and the general public.
- more about this important development.

In setting up this Advisory Committee
Professor Baggoley said  "There are a lot of distressed people, it's a matter of controversy, and it's a matter where people are having very strongly held views, and they are polarised, Where there is controversy, and where I can get people together to look at and consider evidence, and even ask questions of what else might need to be done to help settle this, that woulE d be of useful thing to do. And hence I'm doing it."

It is reported that Australian Biologics is the only Australian based organisation with the capability to effectively test for Lyme. Overseas sites include Infectolab in Europe and IGeneX in California.  The web site of the Lyme Disease Association of Australia is also a valuable source of information.
LYME DISEASE MICROBE ASSOCIATED WITH ALZHEIMERS
  In June 2014 Dr Alan MacDonald reported on the role of spirochaetes across a broad spectrum of chronic diseases. Dr MacDonald describes his stunning findings of Borrelia bacteria in brain tissue of Alzheimer victims. Incredibly seven out of ten brain specimens were positive for the specific DNA of Borrelia, a microbe which causes Lyme Disease. He goes on to postulate associations with other diseases including Parkinsons and Multiple Sclerosis. Watch this May 2014 video

Click here to scan all affiliated Network Sites regarding Lyme Disease.
 
* ALZHEIMERS AND PARKINSONS DISEASE LINKED TO VASCULAR  IRREGULARITIES

A growing body of research indicates that Alzheimer's disease is the result of deficient blood supply to the brain over time. Scientists and clinicians have long known that cardiovascular conditions predisposing patients to heart attack and stroke also significantly increase the likelihood of developing Alzheimer's disease. Investigators are recognizing that it is the reduced cerebral blood flow that may be the first step in the pathologic evolution leading to the disease.

The 2011 International Conference of the AD/PD (Alzheimer's Disease/Parkinson's Disease) Conference held in Barcelona on March 9 heard about new developments, by Clarimex Inc, aimed at increasing blood flow, reducing inflammation and triggering gene expression changes in the brain. This non invasive approach is claimed as groundbreaking not only because it may effectively treat Alzheimer's disease symptoms, but also because it represents paradigm-shift advantages over traditional drug approaches. This 'shift in emphasis' has parallels with emerging understandings about relationships between vascular irregularities and multiple sclerosis. Find out more about the Clarimex approach.

A September 2011 study of brain MRI scans suggests a potentially treatable blood vessel abnormality may be associated with Parkinson's Disease in some patients. The research is published in the journal Neurology International by a team of physicians and neuroscientists at Allegheny General Hospital in Pittsburgh. The very idea that a manageable vascular abnormality in the brain may be a critical factor in disease onset and manifestation for some Parkinson’s patients is an extremely exciting possibility,” said Dr. Peter Jannetta who is recognized worldwide as one of the pre-eminent authorities on diseases associated with vascular compression of cranial nerves -  find out more

Dr Mark Haacke reported at the 2012 ISNVD Conference (February 2012) on 29 patients studied with Parkinson's disease. Of the 29 cases, 18 of them have potentially missing left transverse sinus or slow flow in the left transverse sinus. These 18 cases have abnormal flow in the left internal jugular vein. Dr Haacke observed that these results indicate that CCSVI conditions are prominent in patients with
Parkinson's disease and that abnormal blood flow is a strong marker for these conditions. He went on to say "this gives credence and credibility to everything we thought about multiple sclerosis and raises the question about the extent to which these irregularities may be treatable and with good results" - watch a video
 
Scan affiliated Sites regarding Parkinson's and Alzheimer's diseases


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WHERE IT BEGAN - EARLY DAYS - VEIN ABNORMALITIES BELIEVED TO CONTRIBUTE TO MS SYMPTOMS - CCSVI
Early Days Vascular issues and MS were the subject of research (June 2009), by Professor Zamboni, about a significant association between blood not draining properly from veins and multiple sclerosis - a condition referred to in the literature as chronic cerebrospinal venous insufficiency (CCSVI)
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CCSVI In what is a rapidly emerging phenomena a significant percentage of pwMS are being identified as having this problem. While It is thought to be a congenital condition further research is needed.  It involves vein abnormalities inhibiting the flow of deoxygenated blood back to the heart -  watch a short video.  In many cases it is possible to correct this condition, using an established day surgery vascular procedure known as balloon angioplasty
   

It is reported that the reestablishment of normal blood flow can result in inhibiting MS progress and may also result in progressive, and at times significant, improvements in many MS symptoms as well as a reduction in lesions. CCSVI is primarily manifested in the jugular veins followed closely by the azygos vein. Less common, though not infrequent, abnormalities have been found in the lumbar, vertebral, renal, and deep cerebrospinal veins. The azygos vein is the central drainage vein responsible for carrying deoxygenated blood from areas of the chest and abdomen to the heart, along the spine. Abnormalities in the azygos vein can contribute to a range of problems and are also thought to be associated with progressive forms of MS

A STARTLING FIND
Dr. Zamboni made the startling find that in more than 90 per cent of people with multiple sclerosis, including his spouse, the veins draining blood from the brain were malformed or blocked. In people without MS, they were not. He hypothesized that iron was damaging the blood vessels and allowing the heavy metal, along with other unwelcome cells, to cross the crucial brain-blood barrier.
Professor Zamboni The barrier keeps blood and cerebrospinal fluid separate. In MS, immune cells cross the blood-brain barrier, where they destroy myelin, a crucial sheathing on nerves. More striking still was that, when Dr. Zamboni performed an established day surgery procedure (known as angioplasty) to unclog veins and get blood flowing normally again, many of the symptoms of MS disappeared. In the group of patients who underwent the surgery the number of active lesions fell rapidly.
Two years after surgery 73% of patients had no lesions. It is understood that in 47% of participants the internal jugular veins subsequently returned to having restricted blood flows - possibly suggesting the need for repeat or varied procedures - biodegradable stents may possibly address aspects of the restenosis issue in the future. Also, in March 2012 researchers from the Fraunhofer Institute for Manufacturing Engineering and Automation IPA in Stuttgart announced the development of valve implants - this is an interesting development that may also have CCSVI implications.

In describing the benefits (see below) Dr Zamboni advocated for additional research to build on what has been learnt so far.
 The identified benefits
 
* a significant reduction in relapses,
* a significant reduction in active lesions,
* improved functionality based upon the MS Function Composition measure (MSFC),
* improved Quality of Life, and 
* a significant decrease in chronic fatigue.
 
A NEUROLOGICAL PERSPECTIVE
In an interview in July 2010, the neurologist Dr. Fabrizio Salvi, PhD, discusses how he initially disregarded CCSVI but how, by working with Dr. Zamboni to rigorously test CCSVI diagnosis and treatment, he was eventually persuaded to become the worlds first neurologist focusing on CCSVI and MS. In this wide ranging interview, Dr. Salvi also discusses CCSVI treatment and safety, emerging research, and future directions in CCSVI investigation. - read a transcript of this interview. A further neurological perspective was provided recently by Dr David Hubbard - watch a video that highlights Dr Hubbard's insight into the CCSVI phenomena based upon his first hand experiences and professional background. This association between vascular problems and MS is not new - see earlier about a substantially increased risk of disability progression where pwMS also have vascular comorbidities.
MS STUDY DESIGN UNIQUE IN THE HISTORY OF MEDICINE
On 12 August 2011 the European Journal of Vascular & Endovascular Surgery published details of a pilot case-control study of 15 patients with relapsing–remitting MS and duplex-detected CCSVI. The objective of the study was to see if percutaneous transluminal angioplasty (PTA) of duplex-detected lesions, of the internal jugular and/or azygous veins, was safe, burdened by a significant restenosis rate, and whether there was any evidence that treatment reduced MS disease activity.
All patients were on disease modifying drugs before, during and after, for consistency in treatment. The study outcomes confirmed that Angioplasty for CCSVI reduced lesions, improved MS symptoms and reduced relapses, when compared to those in the delayed group on the drugs alone. Researchers said that despite the significant rate of restenosis (27%), the results are encouraging and warrant a larger multicentre double-blinded, randomised study
In commenting on the study outcomes Professor Zamboni MD, Director of the Vascular Diseases Centre at the University of Ferrara, Italy said "the study design is unique in the history of medicine - it also eliminates many of the criticisms associated with earlier (2009) published research on this topic". He went on " to say, after these two positive studies, that epidemiological studies have to wait is not sustainable" - click here to read more about this important development.
OTHER EXAMPLES OF WHAT IS BEING LEARNT
Good examples of what is being learnt are reflected in 'must see' presentations by Dr Tariq Sinan from Kuwait and Dr. Mark Haacke a neuro-imaging scientist at McMaster University and Wayne State University in Detroit. Dr Haacke is a driving force behind the development of MRI technology and has become a focal point for exploring ways that this technology can best be exploited in relation to CCSVI. Other examples follow
RELATED DEVELOPMENTS - CONFIRMATION BY PEERS
On 10 February 2010 Dr Robert Zivadinov, who directs the University of Buffalo's Neuroimaging Analysis Center said that  he is "cautiously optimistic and excited" about the preliminary data from a subsequent study involving 500 participants, 290 of whom have MS and 210 who do not. Between 56% and 62% of those with MS showed narrowing of the veins compared to 22% of healthy subjects. He went on to say that the data show that narrowing of the extracranial veins, at the very least, is an important association with multiple sclerosis - see later
In August 2010 Dr. Marian Simka from Poland released data that identified 97.1% of 381 pwMS evaluated using catheter venography as having vein irregularities. He observed a correlation between severity and the location of lesions with MS presentation but no correlation between the duration of MS and severity of venous pathologies. The data indicated that venous abnormalities are probably congenital, slowly progress, but are unlikely to be caused by multiple sclerosis. In earlier reports Dr Simka said that 80 to 90 per cent of 347 patients treated for CCSVI, at his hospital in Katowice -- including those with progressive MS, for whom there are no drug treatments, reported improvements in one to two-month follow-up studies. 
A presentation at the American Academy of Neurology in April 2010, by Doctors Zamboni, Zivadinov, Common and Miller reported on four studies, each of which showed a significant incidence of CCSVI in people with MS (pwMS) as compared to non MS populations. While the CCSVI phenomena is apparent across all types of MS the Zivadinov study was that its presence may be more significant in those with progressive forms of MS. Catheter venography was highlighted as the gold standard for confirming the presence of CCSVI and percuteneous transluminal angioplasty as the treatment process. Read a forum overviewwatch a video, or read a forum transcript. A snapshot of incidence rates in these four studies, and subsequent studies, follows. The presentations subsequently provided by Dr Simka (study 4 - June 2010) and Dr Tariq Sinan (study 5 - September 2010 ) are excellent and 'must sees' for both clinicians and pwMS.

 

Percentage of MS population exhibiting CCSVI Percentage of non MS population exhibiting CCSVI
Study 1 - Dr. Zamboni et al. 100% 0%
Study 2 - Dr Zivadinov et al 56% To 62%  22%
Study 3 - Dr Mamoon Al-Omari et al 84%  0%
Study 4 - Dr Simka et al - Poland 90% To 97% not stated
Study 5 - Dr Tariq Sinan - Kuwait 87% To 96% 7%
 There are a growing number of  additional studies relating to aspects of this hypothesis - click here for details

Some of those that build upon the foregoing research are also referenced later in this overview
 
THE NEED FOR MULTI TESTING and TRAINING
The Zamboni study involved a combination of colour doppler scanning and venography whereas the Zivadinov study did not involve venography (described by Dr Zamboni as the 'gold standard').  In commenting on the lower percentages reflected by Study 2, Dr Zivadinov said "we believe strongly that the type of the machine you are using is very important for determining certain structures -- if not, with specific technology that Dr. Zamboni developed. We believe that this is one of the reasons why our prevalence in certain criteria was definitely lower than in Dr. Zamboni's work. We have some experience by using this new technology that has been developed in the meantime and we see substantially different results." 
 
See now about Mem-net In July 2014 the potential for greater consistency in the use of ultrasound (ECD) to detect CCSVI conditions became available via a web accessible computer based global database called MEM-net. Developed by the National Epidemiological Observatory on CCSVI for data collection around protocols agreed with national vascular scientific societies.
 
Dr Zivadinov went on to say "I also want to point out that the training and the reproducibility of scan tests in Doppler will be essential because that definitely may alter the prevalence of the disease, and that's why I strongly believe that only multi tests will be able to show whether there is certain confidence that the diagnosis is met"' - read the forum transcript for more details. Details of this study were not published in the journal Neurology until 14 April 2011 - some 14 months after the outcomes first became available - unfortunately Dr Zivadinov's reservations about the relevance of the study outcomes (i.e when compared to studies 1,3,4 and 5 and others) were not included in the published report - click here to read the comments of Dr Ashton Embry on 20 April 2011 about the reliability of the conclusions in the published information.

Also in June 2010 Dr Simka discussed the experiences of his team in working with some 400 pwMS receiving CCSVI examination. His comments provide a 'down to earth'  guide to those who may be contemplating this procedure and are recommended reading. In commenting upon the impact of the treatment for CCSVI on the clinical course of MS he observes that "Our data indicate that the things are far more complicated than it might be suspected".  He emphasises that all treatment modalities should be regarded as experimental, with still unknown efficacy and safety. The doctors always try to balance the risk and the efficacy factors, but the best solution is not always possible and is not always chosen - importantly, we don't have data on long term consequences of ballooning or stenting. 

THE IMPORTANCE OF SPECIALISED DOPPLER ULTRASOUND TESTING
The Doppler ultrasound scan referred to by Dr Zivadinov has been specially adapted. Professor Zamboni devised five specific protocols for the detection of CCSVI. He has also designed a sophisticated Premium Echo Doppler Scanner System programmed with the algorithms created to aid the analysis of these five protocols. The features of this equipment include QDP exclusive 3D Doppler technology for multiple directional flow, high sensitivity for venous low flows, CCSVI analysis protocol and scoring system, dedicated CCSVI measurements and reports. The combination of these special features recognises the needs of this type of scanning - and that existing scanners may struggle without the specific measurements required.  The importance of ultrasound technicians participating in specialist training facilitated by Professor Zamboni's team is regularly mentioned in the literature.
WHERE TO FROM HERE?
Dr Zivadinov, in discussing the results of his research (study 2) drew distinctions between the role researchers as compared to the role of medical practitioners involved directly in patient care. Research needs to continue, not only in relation to CCSVI and MS but to its significance for other diseases. The point was made that ongoing CCSVI research funding depends upon the priorities of funding agencies and that the attitudes of MS organisations are important in this process. These priorities, in turn, are influenced by the needs, aspirations and expectations of pwMS who are encouraged to become involved in recognised CCSVI trials. Circumstances were also envisaged whereby practitioners would offer the service to patients to address specific situations. 
DEVELOPMENTS IN AUSTRALIA

During May 2011 many members of the Australian MS community commenced the process of seeking the support of their State and Federal parliamentary representatives relating to frustrations in obtaining medical advice and treatment for this condition. Access to CCSVI procedures in Australia is currently very limited. Where it is available it is largely restricted to those with private insurance. Leadership by the Australian Government is needed to support a range of initiatives that, collectively, will enable all Australians with MS to find out if they are affected by CCSVI and what treatment options may be available. 

In consequence, and in conjunction with World MS Day 2011, Janelle Saffin, the Federal Member for Page in the Northern Rivers region of NSW, addressed the Australian Parliament on CCSVI and its association to Multiple Sclerosis. Prior to her presentation Janelle drew upon the advise, experiences and expertise of many people with MS across Australia to complement her own background in health care
Janelle advocated on behalf of Australia's MS community for leadership by the Australian Parliament in bringing into being six national initiatives to enable people with MS, who also may have vascular irregularities, to receive appropriate medical treatment. In noting differences between the positions of MS Australia and the MS Network of Care, Janelle went on to say "But this is certainly an emerging issue that we will have to turn our minds to". In this regard Janelle commended a discussion paper   'CCSVI in Australia - A Strategic Overview from the Perspective of those with MS'   - read about subsequent developments.
CCSVI ASSESSMENT, TREATMENT, SAFETY and CASE MANAGEMENT - A CONDENSED SNAPSHOT - July 2011 
The following table depicts the various processes that may be involved cross referenced to further information in what is a rapidly evolving environment.
ASSESSMENT
 To identify possible problem areas
Non invasive screening procedures, primarily involving doppler ultrasound and magnetic resonance venography are used to help to in identifying the location of abnormalities in the jugular vein as precursors to catheter venography. In the work undertaken by Dr. Zamboni (see later) he stated that the only truly reliable method of locating these problems is via catheter venography – which he describes as the ‘gold standard’. The literature emphasises that a reliable assessment of the azygos system can only be done using  catheter venography - read more about diagnosis. 
TREATMENT
 To re-establish normal blood flow
Vascular Specialists in several countries are treating an increasing number of pwMS with endovascular procedures either as part of recognised trials, registry based reporting or to address the specific needs of individual patients. This procedure, involving the use of balloon venography, has been found to be effective in re-establishing normal blood flow in the jugular and azygos veins provided that other compromising factors do not exist. Watch a video of the procedure carried out at the Alfred Hospital in Melbourne. There is a percentage of cases, perhaps up to 20% but yet to be clarified, whereby the nature of the restriction is such that it may not be possible to rectify it by this procedure - this is a subject under ongoing exploration by medical specialists involved with CCSVI treatment and research. 
SAFETY ISSUES
 Associated with CCSVI endovascular procedure
In October 2010 Dr. Simka from Poland released a report about safety and complications related to endovascular treatment for CCSVI for a total of 587 endovascular procedures: 414 balloon angioplasties and 173 stent implantations performed during 361 interventions in 347 CCSVI patients with associated multiple sclerosis. The aim of this report is to assess the safety of endovascular treatment for CCSVI. The report observes "although balloon angioplasty and stenting in other vascular territories are already accepted and seem to be safe procedures, there are currently no data on such treatments of a large group of patients with compromised venous outflow in the internal jugular (IJV) and/or the azygous vein (AV)". The report concludes "Regardless of the actual impact of the endovascular treatments for venous pathology on the clinical course of multiple sclerosis, which warrants more clinical studies and long term follow ups, these procedures appeared to be safe and well tolerated by the patient 
  On 28 March 2011 researchers at the Society of Interventional Radiology’s 36th Annual Scientific Meeting in Chicago, in releasing details of a study of 231 patients said "Angioplasty, the nonsurgical procedure of threading a thin tube into a vein or artery to open blocked or narrowed blood vessels, is a safe treatment.  Our study will provide researchers the confidence to study it as an MS treatment option for the future and encourage additional studies for its use as a treatment option for individuals with multiple sclerosis -  read the study.
CASE MANAGEMENT
Post procedure
The need for ongoing and accessible assessment programs subsequent to endovascular procedures is highlighted in the literature. MS Australia expresses this need as follows 'If the person with MS and their specialist do decide that CCSVI treatment is appropriate for them, it is recommended that procedures be performed in Australian hospitals where ongoing care can be provided". Such programs to monitor overall well being including restenosis issues, the potential for blood clots developing (as has been reported for some cases involving the use of stents) and to track, over time, variations in function associated with re-establishing normal blood flow. It is important to note that, while stents are reported as 'appearing to be safe and well tolerated where they are used ', they are not used in several countries including Australia. Professor Zamboni is reported as not supporting the use of stents
SOME COMMON TERMS
Doppler ultrasound Venous Doppler Ultrasound is reported as the most important non invasive measure for assessing CCSVI. Doppler is a  dynamic study, capable of venous assessment in both upright and supine positions. Professor Zamboni devised five specific protocols for the detection of CCSVI complemented by specialised CCSVI scanning equipment. More Video
Magnetic resonance venography (MRV) MRV stands for magnetic resonance venography. MRVs are primarily non invasive and are used to assess abnormalities in blood vessels. An MRI scan may be undertaken concurrently with an MRV scan -  pwMS  have greater IJV flattening and a trend toward more non-IJV collaterals than healthy subjects - find out more More  

The aforementioned imaging techniques have been shown to not always be reliable, in isolation, in detecting CCSVI.  MRV is not the best way to show CCSVI, which is a condition of intraluminal abnormalities within the vein, and MRV is better at showing the structure of the vein and collaterals but not what's inside the vein. Research published on 7 April 2011 is that Conventional MRV has limited value for assessing IJV anomalies for both diagnostic and post treatment purposes. - See later for details of the pioneering work being undertaken by Dr Haake in relation to the role of MRI in CCSVI exploration.

Assessment of cerebral venous return by a novel plethysmography method

Magnetic resonance imaging and echo colour Doppler (ECD) scan techniques do not accurately assess the cerebral venous return. Studies suggest that  cervical plethysmography has great potential as an inexpensive screening device and as a postoperative monitoring tool. More  
IVUS

IVUS is a state of the art imaging technology which uses a miniature ultrasound probe and gives a 3D image from within the vein. This not only magnifies the imaging of the CCSVI lesions but also allows direct examination of the internal jugular valves. As valvular lesions are crucially important in CCSVI and may well be the primary cause of jugular venous flow problems, it is vital to have good imaging of the valves to ensure the best treatment outcomes. Catheter venography used during the angioplasty procedure gives a one dimensional view of the vein and does not allow such close and direct imaging of venous valves.

More  
Catheter venography   Catheter Venography has thus far proven to be the gold standard in finding blockages in the veins associated CCSVI. The literature emphasises that a reliable assessment of the azygos system can only be done using catheter venography.  More  
Find out more about diagnosis The CCSVI Alliance is an organisation dedicated to educating about CCSVI with research-based information that includes a comprehensive overview of the diagnostic processes. More  
Percuteneous transluminal Angioplasty Where abnormalities are detected they are addressed by balloon angioplasty, which has been shown to be an extremely safe procedure when done by experienced physicians, This procedure is sometimes referred to as the Liberation Procedure.  Video  
Find out more  The CCSVI Alliance is an organisation dedicated to educating about CCSVI  with research-based information that includes an extensive glossary of terms More  

   
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