ISNVD 29-30th April 2016
Kerri Cassidy had the privilege to attend the 6th Annual Meeting of the International Society of Neurovascular Diseases last month.
There were presentations from 49 scientists and doctors specifically looking at vascular aspects of neurological diseases including Multiple Sclerosis, Alzheimer’s, Parkinson’s, Ménière’s disease, etc.
One frustration that was mentioned several times was that current theories of MS have tunnelled vision – that MS is purely an auto-immune disease. Increasingly we see that MS has multiple factors with many unanswered questions. Certainly over the weekend we heard that people with MS have a higher incidence of cerebral micro bleeds and that cardiovascular co-morbidities are associated with neurological disease progression. This was not believed to be due to a sedentary lifestyle as Dr Zivandinov mentioned, these are seen in people with clinically isolated syndrome (early MS).
There was discussion about the impact of impaired venous flow on the endothelium and how sheer stress is required to keep the veins healthy. Perhaps this is what makes the blood brain barrier permeable to immune cells? Several researchers are using the latest MR technology to study both the arterial and venous micro vessels in the brain, their density and flow. Never before have we had such a clear picture of oxygen concentration within the vessels of the brain. There was an incredible image shown of areas of hypo-perfusion, or low levels of oxygen in the blood, in the areas of the brain where MS lesions are seen. There’s interest in Dr Mark Haacke’s group of imaging the venous walls and getting a better understanding of what they look like in people with MS compared with healthy controls.
Keynote speaker was Jonathon Kipnis from Virginia University. His first comment was that the belief that there should not be any immune cells present in the brain is bad and needs to change. He discussed how immune cells move in and out of the brain and the role of lymphatics. Dr Kipnis explained that arteries are like water pipes bringing in blood, veins act like the sewerage system and the lymphatics cleanse waste products from the tissue and drains them to the lymph nodes. Cerebrospinal fluid is constantly cleansing and being replaced. Any disruption to this process, called glymphatics, is bad news for brain health. Kipnis was able to image the pathways of lymphatics by injecting two different coloured dyes into the blood vessels and the lymph of mice to show quite nicely that the T cells move in a vessel like structure next to the sinus and nowhere else. Incidentally It is not new news that the brain has lymphatic vessels as there were papers in 1966 and 1979, however, this is the first time they have been able to image them. A deeply encouraging statement from Kipnis was that he is moving to study MS specifically as in his words, “MS is a condition close to his heart.”
On day two we heard from several researchers from Zamboni’s lab. Some interesting discussion on imaging, models of the mechanical system to measure jugular blood flow including venous pressure in both the brain and the heart, the velocity of blood flow and movement of pressure waves in the jugular veins. Interestingly they found that 22% of people with MS studied showed reflux, reversal of flow in the jugular vein and that the amount of time blood remains in the brain (wash out rate) is correlated to EDSS. They have also found that in sections of the jugular vein where there is increased pressure (like behind a narrowed valve) there is reduced endothelial cells. This endothelial layer is damaged in people with CCSVI because veins are exposed to turbulent flow. They have also been studying situations where there is a muscle compressing the vein and open vein surgery as angioplasty is not successful for these abnormalities.
There were complex presentations on cerebral spinal fluid and how it moves though the brain and that if jugular flow is impeded there is a rise in venous pressure. There were mathematical models of flow for fluids in the brain, discussion on intra-cranial compliance – what the brain does to adjust to pulsation of cerebrospinal fluid.
Several researchers are looking specifically at angioplasty treatment of CCSVI. Petrov in Bulgaria is utterly convinced after seeing over 1300 people with MS that venous abnormalities precede MS and he is seeing on average an improvement in EDSS and that 62% had functional improvements in those successfully treated.
Dr Helen Kavnoudias presented on Australia’s venous angioplasty treatment of CCSVI in Multiple Sclerosis study. They have not disproved CCSVI, it does exist and was found in 80% of people tested. These 80% (n=30) went on to the treatment arm, half to placebo group and half to treatment group. Those in the placebo group crossed over to treatment group at the one year point giving 30 people treated. Some people have shown considerable functional improvement and on average the increase in EDSS is approaching significance. More participants would need to be studied to find statistical significance. Interestingly, no placebo effect has been detected, in other words, no one who received placebo have shown any improvements. We look forward to seeing further enrolment of people with MS in this study in the near future.
It is clear that people with MS have a higher incidence of cardiovascular co-morbidities than healthy controls. It would be beneficial for people with MS to have cardiovascular assessment when they are first diagnosed and throughout their lives as these appear to be associated with disease progression. We currently have a petition in Australia asking for cardiovascular screening to be available for all people with MS http://ccsviaustralia.com.au/make_a_difference/. Please sign if you have not yet done so. Finally, the Alfred study still requires funding to see it completed, again, people can give a tax deductible donation via our website or, if you are in Melbourne, join us and run, walk or roll with us at Run Melbourne on July 24th http://ccsviaustralia.com.au/run-melbourne-2016/.
Thanks for your ongoing support.