What does this mean for MS/treatment?
The presence of lymphatics I suspect very little. I hope some nutter doesn't start trying to sell the idea of lymph gland removal.....they are there for a reason.As for the glymphatics an interesting bit of biology that is surely part of brain health
It means that the little drawing in the advertisement leaflet they give for lemtrada or tysabri (maybe in both) is wrong, false and misguiding. An MS relapse is not due to the crossing the blood/brain barrier (BBB) by immune cells simply because they are always free to come and go in the brain as they like. Is it right?
A relapse is due to immune cells crossing the blood/brain barrier (in large numbers). The normal traffic of immune cells into the CNS is very low (I used to work in this area many years ago). Thing is you do need some immune cell traffic into the brain to detect possible pathogens, which is why stopping all immune cells enering the brain can cause problems such as PML.
You just restated what the field thought, no? This article (BTW this not the one making the discovery, it appeared in a much less sexy journal but before: see http://jem.rupress.org/content/212/7/991.abstract) so, this article seems to reshuffle the cards quite heavily about this theory.
Would this support the stress related theory ?Also what implications does this have for trrarment, would it give weight to any of the existing cause theories or would it present a possible new cause of Ms?Reading the articles the authors and scientists involved seem to state this is a huge breakthrough for treatment of ms
Support stress theory........no ideaTreatment see above....Cause theories......no different as the ideas of antigens draining into lymph glands was already known, this just shows a pathway, which was already knownReading the article.....yep I agree about claims of break through Just look at the abstract but this is the comic Nature and so it helps if you 'big-up' the story.....However just like to say congrats to Johnathan and the team, it certainly made a splashYep it has changed my neuroimmunology as it gives a drain for T cells to leave the brain, I didn't think much of this concept until yesterday but it is clear that once inflammatory processes are halted they soon get emptied out of the CNS, this should be easy to show if this is the case using fluorescent cells and microscopy. Do cervical lymph nodes fill up with cells from the brain, it would be even better if they only started to glow once they have reached the CNS. When you get a primary immune response in the draining lymph node you get blast cells (Large pyroninophilic cells) the ear skin drains into the auricular lymph glands and then also downstream into the cervical glands where this can be seen with a skin sensitizer. So if epitope spread occurs in a sequential fashion as claimed by some, due to this route, then one would expect to see T cell expansion in the para cortex during CNS inflammation....however I bet this doesn't happen, maybe it does has anyone looked?.
There is no new thing under the sun. Dawsons central observation and subsequent thesis of MS cause was the involvement of the lymphatic system of the CNS, and that famous and celebrated publication is 100 years old in 2016! By the way, Wellers papers were some time afterMM Esiri and D Gay. Immunological and neuropathological significance of the Virchow-Robin space. J neuro Sci 100,1990,3-8. You should read it and learn. See also, Gay F. Activated Microglia in Primary MS Lesions: Defenders or Aggressors. Int MS J. 14,2007,78-83....and learn even more.
Thanks DerekMaybe i have read and learned.Yes the virchow.....very important do we want a post on that peeps.
What is the relevance of these in relation to Ms treatment, I know they support the lymphatic discovery but do they give any new options for treatment? From reading the article released they say it could be looked at mechanistically, can this be explained, how can there be a mechanistic approach to what is a viral or immured mediated issue?
To a non-medical eye, the most immediate possible applications could be in searching for MS biomarkers in places other than CSF, avoiding lumber punctures. I have no idea whether sampling the lymph glands in the neck is any easier, but I suspect it may be.
interesting but not so sure. Analysing fluids is easier than analysing solid tissue. Also i wonder how you would guide needle in the neck. Removing a lymph gland can cause swelling
Assuming that this new information is correct, does it improve or reduce the likelihood of success of anything being studied or used in the MS community now? (getting at it another way, if we know about this now, what will we want to have done looking back 10 years from now - abandon XX approach or drug; study YY in more detail; or it explains why ZZ only works for 50% of people. . .)
nothing changed at all I would suspect. So all the altmetrics for what.....intersting bit of science for us and not much therapeutic output i suspect
Does this discovery minimize the importance of the blood brain barrier integrity in neuro-degeneration? During periods of inflammation the BBB would become a pathway for lymphocyte movement into the CNS. Are reactive t-cells coming from leaky blood vessels or from the lymphatic vessels? And does it really matter how they get into the CNS as long as they are present and causing damage?
noblood in lymphatics out
From your comment: "Clearance of soluble proteins, waste products, and excess extracellular fluid is accomplished through convective bulk flow of the ISF, facilitated by astrocytic aquaporin 4(AQP4) water channels." Is this the same aquaporing 4 which is implicated in NMO?
Yep so I wonder what this means for their brain flushing.....an obvious study to do if you are interested in NMO.....Based on profGs question about whether anyone with NMO reads this blog...I think we got no positive responses so the only releveant of those posts are for docs reading the blog.
Does this implicate and or support the ccsvi theory and explain why many have seen success from this treatment
Absolutely not and the "success" of this treatment is highly dubious as recent clinical data has confirmed.
perhaps rather a lot of textbooks need to be rewritten - then perhaps patients will come to understand CCSVI in the context of the underlying venous pathology of MS http://ccsviinms.blogspot.co.uk/2015/06/rewrite-textbooks.html?showComment=1435436197474
The discovery of were brain lymphatics will require updates in text books but I really doubtthat this will be seen in the CCSVI debacle, as the two are in my opinion unrelated one phenonomon appears no to exist the other appears no to.
I know this won't be posted but I'll write it anyway--This study confirms how important mechanical drainage of the brain is, supporting the importance of venous angioplasty for CCSVI--so of course the loudest naysayers feel the need to dismiss it! I'm just glad there are some researchers with real scientific curiosity out there--the MouseDoctor can't shut them all up by deleting them!
Wrong on both counts...comment posted and does nothing to support importance of CCSVI, and if you actually read why the American group did the study, it was because they are interested in immunology....something the CCSVIers would have us believe is a waste of time...so yes it is good that researchers are curious but it is misguide to think that we have any influence on their thought process or their ability to do such work
If the CSF is removing waste to the lymph system that has been 'found' does that mean that the flow of CSF is crucial to neurological health?If for instance there is slow blood flow and a decrease in oxygen that is symptomatic, if there is slow CSF flow is that symptomatic?If the arterial flow 'powers' the CSF pulsations then aren't the CCSVI decreased flow findings also directly linked to the lymph system's ability to clear the brain, you can't have good CSF and poor blood flows? Your comment that CCSVI is not related to the lymph system findings doesn't appear to be at all correct, or even could be biased against CCSVI being a factor in MS.Regards Nigel
Thanks for the reading, i've been following the developments about lymphatic drainage of CNS by a few months. Glymphatic system has been known for some years, but papers goes back to 1992 was something new for me. i am so pleased to find out your comments and i will be following your blog.
Thanks for this - does it mean that manual lymphatic drainage could be a helpful treatment for MS?
I wouldn't think so and it certainly does not support the CCSVI theory.
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