You are here: Simmaron ResearchME/CFS“Medical Game-Changer” To Shed New Light on Neuroimmune Diseases

“Medical Game-Changer” To Shed New Light on Neuroimmune Diseases

“The discovery of the central nervous system lymphatic system 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.”

In what’s being touted as a “medical game-changer” researchers at the University of Virginia have uncovered a new way the brain interacts with the immune system.

The researchers were looking for ways immune cells recirculate within the meninges – the protective membranes that envelop the brain – when they stumbled upon an amazing finding in this day and age – a major new anatomical feature of the brain.

Structural and functional features of central nervous system lymphatic vessels. Antoine LouveauIgor SmirnovTimothy J. KeyesJacob D. EcclesSherin J. Rouhani, J. David PeskeNoel C. DereckiDavid CastleJames W. MandellKevin S. Lee, Tajie H. Harris, Jonathan Kipnis. Naturedoi:10.1038/nature14432

lymph system brain

The lymph system and the brain: before and after: from Univ of Virginia

First, they found high concentrations of immune cells around the dural sinuses – veins that drain blood and cerebral spinal fluid from the brain and empty into the jugular vein. A closer look revealed that high numbers of  T-cells were aligned linearly along endothelial cell structures along the sinuses.  That finding piqued their interest: endothelial cells line the two major transportation venues in the body – the blood vessels and the lymphatic system. Could they have stumbled on an undiscovered pathway between the body and the brain?

Further testing revealed the structures were part of a undiscovered section of lymphatic  system in the brain.  That was a shocker. The anatomy of the brain, they thought, had been fully mapped years ago.

“I really did not believe there are structures in the body that we are not aware of. I thought the body was mapped,” said Dr. Jonathan Kipnis, who runs the University of Virginia lab where the discovery was made. “I thought that these discoveries ended somewhere around the middle of the last century. But apparently they have not.”

Then again, the lymph system has historically been a bit of an odd man out.  First described by Hippocrates in 400 BC, it was rediscovered as the “milky veins in the gut of a well fed dog” in the 17th century but then was virtually ignored until 1937 when Howard Florey showed that lymph nodes become enlarged in inflammation.

Getting the Garbage Out

The finding helps to solve a longstanding mystery.  The brain is a busy place. That almost by definition means its going to produce a lot of byproducts.  But where did they go? Absent knowledge of any means of getting rid of toxins, the prevailing hypothesis for many years was that the brain broke down the toxins to their essential elements and then reused them.  That hardly passed the smell test but it wasn’t until 2012 that one part of the brains waste removal system – the glymphatic system – was identified.

Now we know that a traditional – and presumably much more efficient – lymphatic system also exists in the brain. (If I got it right, the authors believe the glymphatic fluids probably drain into the new lymphatic system.)

The location of this part of the lymphatic system – situated alongside a major blood vessel – was difficult to see.  Unless it was dissected in just right manner it was invisible.

The lymphatic network  found that runs from the eyes to over the olfactory lobe to the sinuses.

Filtration System

The lymphatic system transports immune cells to lymph nodes – central immune staging areas  packed with immune cells. Lymph nodes are also responsible for filtering out foreign particles and cancer cells. Disturb the lymphatic system and you can get a bollixed up immune response and a toxin laden system.

Two different types of lymphatic vessels exist: vessels with valves that collect fluid and vessels without valves which fluid passes through. The lymphatic vessels found in this study are valveless- they’re designed to let the lymph fluid pass right though the meninges into the neural sinuses and into the lymph nodes.

High Potential

The filtration part of the lymph system appears to be getting the most play right now.

garbage truck

How’s your filtration system doing?

The potential this system – or rather the potential a dysfunction of this system – could have on disease is large.  In fact one of the researchers went so far as to say that it was hard to imagine a neuro-immune disorder that was not impacted by this pathway.

“We believe that for every neurological disease that has an immune component to it, these vessels may play a major role. Hard to imagine that these vessels would not be involved in a [neurological] disease with an immune component.”

He hadn’t been drinking too much bubbly. Maiken Nedergaard, director of the University of Rochester Center for Translational Neuromedicine agreed saying that “Essentially all neurodegenerative diseases are associated with the accumulation of cellular waste products. Understanding and ultimately discovering how to modulate the brain’s system for removing toxic waste could point to new ways to treat these diseases.”

Picture central nervous system inflammation. Free radicals are punching holes in membranes. Cells are dying. Pathogens are wreaking havoc.  The  “garbage” that all this activity produces in the form of dead and damaged cells and pathogens needs to be flushed out of the system before more damage results.

The classic example of a bollixed up CNS lymphatic system causing disease could be Alzheimer’s with it’s accumulations of amyloid proteins. One researcher studying Alzheimer’s said

“Understanding how the brain copes with waste is critical. In every organ, waste clearance is as basic an issue as how nutrients are delivered. In the brain, it’s an especially interesting subject, because in essentially all neurodegenerative diseases, including Alzheimer’s disease, protein waste accumulates and eventually suffocates and kills the neuronal network of the brain.”


Chronic fatigue syndrome could fit in that picture. The high brain lactate levels and low glutathione levels Shungu found in ME/CFS patient brains suggest high rates of anaerobic energy production and its accompanying toxic by-products could be present.  The recent Japanese study suggested inflammation was present. Low blood flows to the brain could easily be producing high levels of “garbage”.   (Stroke is another condition the new findings could illuminate.)


The finding will provide new insights into neuro-immune disorders

Studies indicate that most of the glymphatic flushing that occurs in the brain occurs during sleep – a problematic time for many people with ME/CFS and fibromyalgia. Then there’s Dr. Perrin who swears that his lymphatic drainage techniques help people with chronic fatigue syndrome.  He believes the cognitive and other problems found in ME/CFS are due to too much sludge in the system.

It’s not clear how researchers will use this new knowledge but  it is clear that tools are present that can exploit this new finding and provide better understanding of neuro-immune disorders – perhaps at some point even ME/CFS.

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  • Ken Holmes

    June 4, 2015 at 1:01 am - Reply

    Cort, you have a gift for explaining medical findings and their relevance for the layperson. Thanks for doing this. Question is, for us, what causes the restriction of blood flow to the brain in the first place?

    • Cort Johnson

      June 4, 2015 at 1:41 pm - Reply

      Thanks. In one of Doctor Newton’s studies she found that increased acid levels in the muscles and lactate spillover into the blood reduced blood flows to the brain.

  • Alicia Butcher Ehrhardt

    June 4, 2015 at 2:39 am - Reply

    This is probably why rest – 3-5 half-hour naps a day, one during every three hour period – works for me. It doesn’t make me well, but I call it ‘mental dialysis’ because I know when sleeping the spaces between cells get bigger, and the fluid washes away the debris from thinking – at the same time I’m not creating more.

    The vision system takes a lot of energy to maintain. While I’m resting, there is no visual processing of outside information.

    I had seen an article in Science News about the washing out effect; I make effective use of the time between naps because I know it is precious.

    • Danielle

      June 4, 2015 at 8:43 pm - Reply

      Interesting. I have recently been reading up on a protocol that suggests we NOT nap, but in my experience I can turn a flair around if I go lie down within 30 minutes of my first signs. Usually after a few hours in bed I’m able to rally, at least enough to make dinner for my kid and get him put to bed (basically the bare minimum). I think I might try this more often. Thanks for commenting.

      • Danielle

        June 4, 2015 at 8:49 pm - Reply

        Replying to clarify, I can “sometimes” turn a flair around if I’m in semi-remission. If I’m in a mega flair lasting more than a few weeks than I’m only ok for about 2 hours first thing in the morning, regardless of how long I nap or attempt to nap

    • Iain

      June 23, 2015 at 11:08 pm - Reply

      Thanks for the reminder. I must start doing this type of pacing again 😉

  • Donna

    June 4, 2015 at 10:07 am - Reply

    This is very exciting information! Periodically I get sinus pressure, pain behind my eyes and sometimes even the roof of my mouth goes numb. An episode can last weeks. Some of these episodes will be on and off again for months at a time. I’ve been to an eye specialist who has done many tests only to find no diagnosis. We did this testing several times over a period of several years. Family doctor had always prescribed antibiotics for the last 7 years as they present like sinus infection (minus any mucus). Finally last year (2014) I went to an ENT at the end of one of these episodes. He did an in office CT scan that didn’t show anything. But the pain and pressure is very real. This would make total sense as to what is going on with me.

  • Iain

    June 4, 2015 at 10:20 am - Reply

    Does anyone else experience pain or discomfort around left eye, ear and neck? Or recurring left ear infection

    • Cort Johnson

      June 4, 2015 at 1:39 pm - Reply

      I experience pain in my sinus areas – particularly when I press on them – and in my neck frequently. I don’t know if that’s related to this finding or not.

    • Kate Autry

      June 5, 2015 at 5:38 am - Reply

      Yes, I experienced all my migraines over and behind the left eye for years (when I used to have migraine). I also had recurrent ear infections and sinus pain (both sides I think, but definitely the left….pain in my left eye and vision worse on the left, and yes, especially, the base of my skull down my neck on left side especially has had chronic pain, stiffness, and swelling for 20+ years.

    • Maisie

      June 9, 2015 at 11:59 pm - Reply

      I have had recurrent brown waxy discharge from my left ear along with itchiness and pain since coming down with ME. Also had a tonsillectomy because of pain in left tonsil only. Curious why this should be – is it something to do with our heart being on our left hand side?

  • Dionysia

    June 4, 2015 at 10:36 am - Reply

    Thanks for sharing this, exciting and informative. I’ve been sharing with my GP the experience of ‘feeling viral activity’ under the roof of the skull; not s headache but a feeling of heat and infinflammation.The GP looked perplexed and seemed to think this impossible. I habe a hunch the findings shared in this article are highly relevant, and look forward to more insights in order to translate from research to treatment. Life feels to precious to waste being unwell and sludged-up !

    • Nathan

      June 7, 2015 at 6:48 pm - Reply

      I have noticed this was well. Do you think your CFS started with a viral infection? Have you tried any anti-virals? Also if you don’t mind, what are your other symptoms? Sore throat?

      You are the first person I have seen who has shared this symptom with me.

      • Dionysia

        June 7, 2015 at 11:55 pm - Reply

        Most interesting, Nathan. Yes, my CFS started 26 years ago with mono (overnight), soon followed by 2 lots of viral pneumonia. Yes, sore throat plus recurrent flu-type illness, painful lymph nodes, neuropathic pain, pronounced pem from even slight breach of energy envelope, gritty sore eyes,cognitive effects (feeling knocked on the head), extreme sensitivity etc. Currently severe, bedbound last 6 months, yet previously ‘recovered’ and high functioning for 7 years. One aspect I haven’t so far read-of
        (as quite newly surveying the research literature) is impact of childhood infections on later immune functioning, for example in my case I had severe mumps and recurrent tonsilitis as a child. Another ‘odd’ feature is hypersensitivity to fumes, especially cigarette smoke (though I’ve been a non-smiker all my life. I’ve been known to detect someone smoking at the bottom of the garden from my 1s1st floor room, with the window shut, purely because my neck lymph glands swell sizeably and quickly. Any of this chime with your experience?

      • Dionysia

        June 8, 2015 at 12:19 am - Reply

        Ps I asked my md for anti-virals this year but here in the UK they are not licensed. How about yourself?

  • Linda

    June 4, 2015 at 10:42 am - Reply

    I agree, Donna, nice to understand what’s going on. Because the nurse pushed the back of my head as I was being born, my skull and jaw were permanently misshaped. I have been told I have low blood flow to the brain from this.

    • Cort Johnson

      June 4, 2015 at 1:37 pm - Reply


  • Linda

    June 4, 2015 at 10:49 am - Reply

    I would bet that not only the head and sinus pain, but the accompanying sore throat, has the same cause. The pain around the eyes gets so severe it leads to bad migraines. More sleep helps, so the correlation looks valid to me. ME sufferers will be happy for any info on this horrible disease. Thank you Simmaron Research for this article and insight.

  • Sharon

    June 4, 2015 at 10:53 am - Reply

    How does this translate into cure? Are there any supplements to make this system work better?

    • Linda

      June 4, 2015 at 11:31 am - Reply

      Sharon here is an article on glutathione that may help: Just be sure to use real raw vitamin C as in Vitamin Code by Garden of Life. Most vitamin C on the market is synthetic and does little good.

    • Cort Johnson

      June 4, 2015 at 1:37 pm - Reply

      It’s just at the research stage now -but it should new ways to under neuro-immune disorders – something that’s greatly needed and that should ultimately help.

    • Kitty

      June 4, 2015 at 4:00 pm - Reply

      Dear Sharon,

      I have found that cranial sacral work has helped to relieve some of what I can only describe as “pressure in the brain”. This horrible ” headache” is distinctly different in onset and experience than what the medical profession calls a migraine. No drug on this earth has relieved it either. It is definetly related to the rest of my CFS/Fibro symptoms. Have had this “head” thing for 35 years…as long as the CFS. Been doing the cranial sacral for the past 18 months and it helps reduce the severity and frequency of these episodes. Maybe worth a try for other sufferers too…

  • Flavio

    June 4, 2015 at 5:01 pm - Reply

    Hi Donna ! Your post is exactly my story ,on the sinuses simptome ,even in the part where that was nothing showing for sinuses but the pain was as if it was . thanks for sharing .

  • leelaplay

    June 4, 2015 at 8:27 pm - Reply

    Hi Cort, I can’t see the link to the study anywhere. If I’m having ME-brain, excuse me. If not and it’s not there, could you edit to add it? thanks

  • Danielle

    June 4, 2015 at 8:40 pm - Reply

    “The lymphatic network found that runs from the eyes to over the olfactory lobe to the sinuses.”
    Hmm. . . I’ve had sinus surgery 3 times for the removal of nasal polyps. My symptoms didn’t start until a few years after the 1st surgery, and got progressively worse after the 2nd and 3rd. It just makes me wonder if there is some physical damage that could have been caused. But then again, you don’t see rates of CFS in patients with chronic sinusitis/nasal polyps. I’m an anomaly (not the norm) at my ENT and my Allergist/Asthma doc.

  • Chris Boyt-Cullis

    June 4, 2015 at 10:57 pm - Reply

    I have ME?Fibromyalgia, plus hydrocephalis, Graves Disease, osteoporosis and MCS. I get a lot of mucus in my respiratory system including sinuses, with exposure to perfumes, cigarette smoke, etc, etc. I’d put it down to the immune system screaming “Repel boarders!” and pouring out the mucus indescriminately as a defence mechanism against the fumes. It might work with large particles like pollun or dust, it does nothing helpful with fumes though. This info is very interesting. Odd that nobody has discovered it before, but for everything they know about the brain, there are a thousand things they don’t know yet.

  • Chris Boyt-Cullis

    June 4, 2015 at 10:59 pm - Reply

    Butterfingers, that was supposed to be ME/fibromyalgia. Sorry!

  • Ray Kinney

    June 5, 2015 at 3:39 pm - Reply

    The blood brain barrier helps isolate harmful contaminants in the body from affecting the brain, as long as the bbb has good integrity. this bbb gets compromised by metals such as lead, that can slowly cause leaky membranes of the bbb. Is there an analogous bbb-like protection of the lymphatic system flow through the brain? Or, do contaminants like lead have easier access to the brain through the lymphatic system?. Lead exposures routes in the body usually result in the lead concentrating first in the erythrocytes which have an affinity for the metal. Most toxicology in the past assumed that this meant that the bbb was very protective from lead entering the brain unless the bbb became compromised by peroxidation or physical insult. Most toxicologists still do not understand that since ’94 there has been research on the percutaneous route of lead uptake, that had previously thought not to be a problem because the definitive lead uptake test (the blood lead test) did not register much increase via skin exposure. Stauber and Gulson, found that contrary to accepted thought, lead does fairly readily pass through skin, but for some reason does not then retain the affinity for the RBCs, and therefore does not show up as elevated in the Bloood Lead Test. After entering the body via skin exposure, lead does get circulated (possibly in the lymph?). If so, does an anologous barrier effectively protect the brain from this lymphatic system possible exposure route, at least as effectively as from the blood system route? Lead is known to have many neurodegenerative effects, and if this route is still very understudied because of the possibly false confidence of a generally low blood lead level… rulled out as to importance in medical causation of CNS diseases, is this lymphatic brain system needing much better assessment for lead potential for pathogenesis?

  • marcie myers

    June 7, 2015 at 5:17 am - Reply

    What exactly are Dr. Perrin’s lymphatic drainage techniques? Just wondering if you knew…. make my life easier. marcie

  • Genevieve

    June 9, 2015 at 11:05 pm - Reply

    Hello Marcie,

    You can start by watching this video on youtube :

    After a very bad infection in one breast, which followed the severe burns of radiation therapy a few months previous, the breast clinic where I am being treated arranged for lymphatic drainage therapy on a regular basis, as I had gone through a very large spectrum of antibiotics for over two months and the infection was obviously not completely cured, I have to admit that the treatments helped in draining the engorged lymphatic vessels towards healthy nodes in other parts of my body,. I also did daily drainage exercises. I’m happy to say that even though I will have to keep a close watch on that damaged breast, I’m not as wary of it getting infected as I was. The clinic offers that service mainly for women who develop lymphatic oedema in their arms, a very painful condition.

    My point is that the therapists who “worked” on me during my sessions were almost fanatic about these techniques and would have wanted me to do an hour daily of drainage exercises. NOT! One of them was also absolutely certain that when I came out of her sessions, my ME had subsided, at least temporarily. I did not have the heart to contradict her. But no matter how long the session was and how expert her hands were – and they were! – not only did it do nothing to perk my energy level, but just the trip to the hospital and everything that goes with it would tire me out just like any other outing does deplete my energy reserves.

    I can’t find the brochure I have been given, but I’m pretty sure that the exercises were Perrin’s. A few years ago, I also tried osteopathic treatments of the skull;, which are pretty close to Perrin’s drainage. The only benefit I got out of it was a bit of relaxation. So no, I do not believe that lymphatic drainage can help the flow of lymph nodes located under the skull.

    That does not mean you should not try. Who knows what can help whom?

    Thank you very much Cort, for that most interesting article.

  • marcie myers

    June 16, 2015 at 3:39 am - Reply

    Thank you so much, Genevieve. Sounds like you’ve been through it in addition to the ME. I own an “Inversion Table” that likely promotes lymphatic drainage as well though not in such an aggressive manner as was done for you. Much luck and happiness for your future. A spontaneous remission of all symptoms!!!! We wish. marcie

    • marcie myers

      June 16, 2015 at 5:43 pm - Reply

      Dear Genevieve, I watched the 6 part series last night. Quite interesting. As a nurse, I’d learned what he’d said: that the lymph system drains via muscle movement so it was news to me that it has it’s own drainage system. I’m going to watch the nutrition video later as it’s 2 hrs long. The P2P report comes out today. I gather you live in the UK based on how you spelled certain words like “oedema”. We spell it edema. Anyway, thanks again. Hope they assign some individuals to carry out the recommended tasks. I wrote President Obama a letter yesterday requesting more CFS/ME research money and attached his 2011 letter saying he would check into it. Hope to get a real response. Love your name. French. Best wishes to you. Marcie (Marcella)

      • J.A.

        July 4, 2015 at 10:49 pm - Reply

        Marcie, where did you get a copy of President Obama’s 2011 letter? I’d like to get a copy & write him too.

        • marcie myers

          July 10, 2015 at 9:11 pm - Reply

          Dear J.A.
          I had written him via email in 2011 requesting additional funding for CFS and received a form letter in return about how he is interested in the health of all Americans, blah ,blah,….. So this time I sent him a hand-written brief one page letter with a photo attached of a bluebird feeding his babies that I’d taken and a copy of his 2011 letter. I haven’t heard back yet but expect to. You can google the White House Correspondence address for letters to the President. I’d been told by someone that his staff gives him one emailed and one hand-written letter per day which they hand-pick. Don’t know if this is necessarily true but…. gotta keep trying. Marcie Myers,

        • marcie myers

          July 10, 2015 at 9:14 pm - Reply

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