Breaches in the Barrier
The last article reported that Younger speculated that people with chronic fatigue syndrome (ME/CFS) have an immune-triggered metabolic disorder. The widespread neuroinflammation found in ME/CFS patients provides a clue, he thinks, to what’s going on. It suggests that immune cells are breaching the blood-brain barrier in multiple areas; like a flood overwhelming a dike, they’re essentially pouring through gaps across the brain. In some diseases, the breach is local, but given his findings in ME/CFS, it’s probably blood-brain barrier wide.
Breaches of the blood-brain barrier appear to be common in neurodegenerative diseases. Studies suggest, for instance, that massive immune cell infiltrations into the brain precede the appearance of lesions in multiple sclerosis (MS).
From the beginning of his stint with ME/CFS, Avindra Nath – who specializes in these kinds of diseases – suggested this may be occurring in ME/CFS.
Wrong Cells – Wrong Place
It turns out that having immune cells from the body show up in the brain is not a trivial thing. The microglia, which are derived from macrophages, are uniquely adapted to work in the brain, but B and T-cells are not. In fact, they’re like a “bull in a china shop”. Once they get into the brain, they can cause a lot of damage. It’s entirely possible that immune cells from the body are major culprits in diseases like MS, Parkinson’s Disease and HIV encephalitis.
Younger believes an immune cell invasion of the brain may be behind ME/CFS.
If T and B-cells can cause so much damage, why would they ever show up in the brain? Younger reported it’s possible that the microglia are actually asking them in. Ordinarily, this would only happen in the most extreme of circumstances – if the brain is in danger from an infection or a tumor which the microglia can’t handle. In that situation, calling in these A A A carpet bombers may be the only way to save the brain.
Another possibility is that hypersensitized microglia are opening the door for the T and B cells. A strong immune insult, a series of illnesses, a massive infection like Lyme disease, exposure to environmental toxins (diesel can do it), even obesity through its production of leptin, can lead to hypersensitized microglia and a traumatized, sensitized immune response in the brain. With the microglia responding to every little stressor, they simply go into overwhelm and call the big guns in. This may be the most likely model for chronic fatigue syndrome (ME/CFS).
A check through the literature found that recent studies also indicate that inflammation in the body can open a pathway through the blood-brain barrier (BBB). Liver inflammation triggers the microglia to produce CCL2, a chemical which attracts immune cells called monocytes in the brain. When CCL2 is blocked, the immune cells fail to enter the brain.
A recent Parkinson’s Disease finding, shows another pathway. It indicates that our genetic makeup can interact with an infection to cause disease. It found that T and B-cells with a mutation – in combination with an infection – can create such a cytokine storm that the BBB is overwhelmed, and the cells in the brain that govern movement are destroyed.
Finally, Dr. Theorharides believes activated mast cells in the hypothalamus are opening the BBB in ME/CFS. A blog on that is coming up shortly.
The Study
Proving that immune cells from the body are making it into ME/CFS patients’ or anyone else’s brains has, however, not been easy. PET tracers which lock onto immune cells have been used, but have a flaw. Since it takes about three days for an immune cell in the body to get into the brain, the tracers need to last four or five days to be effective. Most poop out before that but the one Younger is using lasts for seven days.
Younger’s going to pull ME/CFS patients’ blood, isolate their T and B-cells and then incubate them with a new Zirconium 89 tracer which slides through the cell membranes but does not damage them. He fully expects ME/CFS patients’ brains to light up like candles. Similarly, he doesn’t expect to see any light shows coming from the healthy controls.
If Younger can show that ME/CFS patients’ brains have been invaded by immune cells from the body he’ll have evidence that ME/CFS is an immune disease which attacks the central nervous system. His heat map /spectroscopy study already suggests that ME/CFS is an encephalomyelitis – an inflammatory brain condition with metabolic issues. The PET scan study showing how the inflammation is occurring is the next step.
This one-two punch – showing that neuroinflammation and the immune cells that may be causing it are present in the brain -would clearly make it much harder not to take this condition seriously. These are the same general processes, after all, that are occurring in some of our most devastating neurodegenerative diseases.
Two Similar But Different Diseases
MS, with its high rates of fatigue, its link to infectious mononucleosis, the female predominance and the possibility that Epstein-Barr virus plays a role, has always seemed like a possible second cousin to ME/CFS. Younger agrees. He hypothesizes that T and B-cell infiltration play a key role in both diseases. The difference is that the T and B-cells in MS are primed to attack the myelin on the nerves, while, thankfully, the T and B cells in ME/CFS patients’ brains are simply producing inflammation.
The difference between ME/CFS and multiple sclerosis may be that one disease produces inflammation while the other directly attacks the nerves.
A ton of money has been poured into MS. More money, in fact, is spent every year on MS than has been spent in almost twenty years in ME/CFS. On the face of it, that’s disappointing. If MS can’t get solved in thirty years, is it going to take us a hundred?
As Younger pointed out, though, MS is different: it produces lesions (neuronal damage) that, at least as of yet, there’s no recovering from. There’s only the hope of slowing down the process of further neurodegeneration.
Because the ME/CFS field, thankfully, doesn’t have to tackle the problem of frank neuronal damage, it may be a much easier disease to figure out and treat. Let’s hope so.
The Multiple Sclerosis Project
Younger has also been funded to use the same PET scan technique in multiple sclerosis. If everything turns out as Younger hopes, our ME/CFS/FM researcher may be on the precipice of making an indelible mark on one of our most feared diseases. (The same is occurring with Dr. Klimas and Parkinson’s Disease.)
MS, at least in its initial stages, is a waxing and waning disease that’s characterized by sudden attacks, subsequent neuronal deterioration and loss of functioning. Younger believes those attacks are preceded by sudden breaches in the blood-brain barrier. If he can catch those breaches as they’re happening, he may be able to determine: a) where in the brain the next lesion is likely to occur, and more importantly; b) when to hit the immune system with enough corticosteroids to temporarily turn those T and B-cells off and stop the infiltration before permanent damage occurs. If he can do that, he’s found a way that may be able to keep that dread disease at bay.
MERUK Steps Forward
We don’t know what Younger will find when he peers into the brains of ME/CFS patients, but we do know he has the possibility of producing a major finding which, one would think, could produce a turning point for this disease. For that we can thank MERUK, a Scottish research based ME/CFS non-profit whose motto is “Energizing Research”. MERUK, a small organization, dug deep to give Younger $160K to get his pilot data. It’s an expensive study – the PET scans run at $5K an hour – but if it works out, Younger’s study could produce results that will make those costs trivial.
This study, however it turns out, demonstrates again how important even small non-profit foundations are to growth in this field. You need pilot data to get a big NIH grant and these non-profits – from the OMF to the SMCI to Simmaron to MERUK and others – are filling a crucial gap.
Your Support Is Requested
Health Rising’s East coast trip provided a wealth of information inspiring the article you just read and the ones below. Several more articles will come from the Younger stop, plus Dr. Klimas’s exercise study, a possible new treatment for fibromyalgia, an Avindra Nath interview, and – on the return home – the folks at the Bateman-Horne Center. Next up on the travel agenda is the Stanford Symposium.
Travel provides many opportunities but travel to the East Coast, in particular, is expensive for a small organization like Health Rising which is still working on recouping its trip costs. If you find conference reports and other travel related blogs helpful and want to see these in the future, please support Health Rising.
Articles From the East Coast Trip
The Jarred Younger Series
- Widespread Neuroinflammation Found in Chronic Fatigue Syndrome (ME/CFS)
- Invasion – The Source of Neuroinflammation in Chronic Fatigue Syndrome (ME/CFS)
The IVIG Series
- An IVIG Chronic Fatigue Syndrome (ME/CFS) / POTS Treatment Success Story: IVIG#1
- Are Chronic Fatigue Syndrome, POTS and Fibromyalgia Autoimmune Dysautonomias? IVIG #2
- The Case for IVIG Treatment in Chronic Fatigue Syndrome (ME/CFS), Fibromyalgia, Small Fiber Neuropathy, and POTS: IVIG#3
- Winning the Lottery: “Novel” Treatments Return Severely Ill POTS Patient to Near Health: IVIG #4
Advocacy
From the Dysautonomia Conference
- 2018 Dysautonomia International Conference I: Small Fiber Neuropathy, POTS, MCAS and Vagus Nerve Stimulation
- The 2018 Dysautonomia Conference Pt. II: Could You Have a Spinal Fluid Leak? An ME/CFS, POTS, FM Perspective
- Dysautonomia International Conference Pt III: The Autoimmunity Revolution in POTS
- “Sticky Blood” – Antiphospholipid Syndrome, POTS, Chronic Fatigue Syndrome and Fibromyalgia – The Dysautonomia Conference #4
- Stagnant Hypoxia – Where Chronic Fatigue Syndrome and Hyperadrenergic POTS Meet?
- Promise Fulfilled – A New Chronic Fatigue Syndrome / Fibromyalgia Practitioner Steps Forth
Hi Cort,
Saw this last night – along the same line?
https://www.npr.org/sections/health-shots/2018/09/05/636860122/inspired-by-her-own-pain-a-researcher-explores-alternatives-to-opioid-treatments
I don’t know if it fits or doesn’t fit but it is inspiring. Thanks for the link. That’s some thing to keep an eye on. Isn’t it great when patients take the initiative like that?
THANK YOU YOUNGER!!! I think he is onto something..
Also… I noticed this: b) ‘WHEN’ to hit the immune system with enough corticosteroids to temporarily turn those T and B-cells off and stop the infiltration before permanent damage occurs.
Part of the ‘WHEN’ may involve the act of triggering a crash. This would explain why an immuno-suppressant dose of corticosteroids right before exertion can stop a crash. I’ve definitely tested this to its limits.
Hi Cort,
Very interesting and encouraging advances being made by Younger. Curious. Does this theory harmonize with the Cortene findings and (hopeful) treatment?
Also, does it coordinate in any way with the LDN therapy (which evidently has some moderating effect on T and B cells–think)
Jim
Cortene, as I remember, believes stressors such as inflammation knock the CRF2 receptor for a look. Younger believes the LDN therapy tamps down the microglial cells – which he thinks may be calling the T and B-cells into the brain – so yes, my guess is that they mesh.
Hi Cort – has the study been published..?
The study is just getting underway. We’ll see what happens! Neither this one or the brain inflammation one has been published.
Exciting stuff, but I do wonder if younger will find any differences between very severe and the patients he is dealing with now in terms of damage. I know many ME/CFS patients do have small white blobs in their brain MRI’s but they’re always told we don’t know the significance but we know they are dangerous. Not exactly a passifying statement. I do wonder if severity plays a role.
It’s always facinating reading about parkinsons and MS to me, I am sure in the early days they were not treated well at all but it’s interesting how they do not have a clear biomarker and most diagnoses for them seem to be based on scans, history and clinical exams… at least from what I have read. It kind of gives me hope that we’ll be taken more seriously. It’d be great if the research into our condition helped other illnesses, if we flag on the same new tech they do then we have more evidence for us.
Sorry that should say “also”… it’d be amazing to see more research for other neuro diseases bulstered with new treatments but also that it indirectly still could help us.
Using his new technique Younger is able to pick up much lower levels of inflammation than before. So now instead of seeing scattered lesions which it’s hard to understand – he’s seeing signs of inflammation across the brain. The problem with the lesions is that they’re in different parts of the brain in different patients and healthy controls also tend to have some lesions.
This makes a lot of sense to me ased on my personal experiences. I was dx with CFS 2 years after selling my woodworking company where I had been exposed almost daily to serious industrial solvents and finishes. Along with the pattern of sympotoms I’ve experienced for the past 15 years is a primary complaint of intense sensation of inflammatory headaches (debilitating) that can last for days regardless of treatment, along with periods of deep fatigue (brain, not so much physical).
I have been realizing the most help turning this around in the last two years using homeopathy whereas nothing else ever touched it. Still got a ways to go.
Dr. Ron Davis has mentioned he believes he has found the Cause of ME/CFS further work is needed & he says it is the East Africa Sleeping Sickness Parasite & Yes it is already known to cross the blood Brain barrier & causes inflammation in the Brain including Encephalitis & the reason why Suramin could be the medicine used to Cure the illness…If caught early this infection can be Cured 100% & if Chronic in later
stages the Cure rate drops to 95% I think he already knows more about this but because he has not Published yet or done some more work he is not saying more at this point, he did say the symptoms of ME/CFS is
100% identical to East Africa Sleeping Sickness…If true it would also push this Research above further as I am sure numerous Neuro testing has already been Published on this Parasite, so lets hope he is right
he also said the West blood test is easier to find the parasite but the East one is difficult in a blood test & I know Microscopic findings & spinal fluids are other diagnostic tools so he likely already sees this
parasite already in samples. I still feel this illness is still Alpha Gal Meat Allergy IgE under-diagnosed unless ME/CFS is East African & Lyme is AG or some have both conditions combined…
Whoa! Ron is talking later. Looking forward to hearing more…
Aidan — I watched that video too and he mentioned that the parasite is just one of three theories they have for the cause of ME/CFS. Further testing still needs to be conducted to verify or debunk any of these three theories.
Has he found any evidence of that particular parasite? African Sleeping Sickness (parasite from the Tse Tse fly) is a fatal illness if untreated, in most cases, and clearly if it is involved in ME/CFS, something is very different about the version we have. I expect there is more to discover here before anyone can say what is causing this inflammation. For example, the similarities may be due to a common end-state pathology of neuro-inflammation, and not due to a common cause. Or perhaps another, similar parasite is involved, there are so many bugs to choose from … and this parasite is Trypanosoma brucei, a protazoa. How many species of protazoa are there that could create a similar pathology? I don’t think we know them all.
Also – ME/CFS is seen all over the world. If it was caused by a protozoa would we expect to see it in some continents but not others?
I don’t know anything about the protozoa; this is the first time I’ve heard about it but studies indicated that ME/CFS can be triggered by all sorts of pathogens – from EBV to Ross River Virus to Giardia. Talking to Neil McGregor from Australia – who has an encyclopedic knowledge of ME/CFS 🙂 – he states that mutations in the receptors which our cells use to grab onto pathogens probably play a significant role in some people becoming ill. Since different people have different mutations – you might be at risk of having trouble handling one virus while I have trouble handling another. Interesting stuff!
He mentioned the East Africa type both can kill but the West type is the deadlier one & the East one is harder to find in blood samples I believe he has already found it in his lab it
is also found with a microscope & in spinal fluids or tissue as well & the Autistic drug used by Naveaux is the drug of choice…He feels this is the Cause & says Doctors do not check for it because they think it is only in Africa
Thank you so much Cort for your diligent efforts in keeping our community up to date and informed of all this information! It is so appreciated.
We are very lucky to have Dr. Younger in our field – I feel like he is definitely on to something. Fingers crossed that he continues to make inroads!
One really hopeful thing is that Younger is a younger researcher who has targeted ME/CFS/FM and he’s being successful, he’s getting grants, hes getting good findings and his lab is growing.
I hope others are watching and taking note…
I think Youngers perspective give a lot of scence! No way the brain is not envolved:) And earlier neuroinflammation seem to correlate affected areas in brain with spesific sympthoms (fatigue, pain, autonomic ns, depression).
But can Youngers approach also explain the lactatelevels, and why the muscles have extreemly reduced capasity?
That’s my big question as well. What is the connection between the lactate and anaerobic problems in the brain and in the muscles? It seems like there are energy production problems everywhere. What is the link?
“But can Youngers approach also explain the lactatelevels, and why the muscles have extreemly reduced capasity?” and “What is the connection between the lactate and anaerobic problems in the brain and in the muscles?”
IMO local lactate accumulation is a three-way result of massive inflammation levels in the body.
1) Inflammation is linked with high levels of oxidative stress and immune activity. Both consume lots of glutathione (requiring NADPH for regeneration) and NADPH. This IMO turns down NAD/ATP production in favor for NADPH production (production of both requires partly same resources).
When one eats a normal meal, even a supposedly healthy one, it is very easy to have more combined glucose and fructose in the blood then desired. Both can be converted to glycogen. When the liver glycogen stores are full or that conversion is not quick enough, triglycerides are produced. Unfortunately that requires a lot of NADPH. People with extensive oxidatave stress and immune problems are short of it. For a healthy person about 25% of fructose consumption is turned to lactate. When one is short on NADPH, it is very likely IMO that producing a lot more lactate is the only way out to reduce blood sugar levels.
2) There is still debate around it, but consensus is going to the idea that lactate acid can be used as an aerobic fuel for the hart and brain (and other muscles?) to some extend. Having ME and being able to do very few both physically as mentally lactic acid consumption (and thus clearance) will be reduced.
3) ATP production through the Krebbs cycle is a very oxidative process, generating plenty of oxidative stress. When that is already rampant and NADPH/glutathione is low then producing NADH/ATP through Krebbs cycle must be reduced. At a vital place where inflammation is already high but ATP production cannot be reduced sufficiently, producing it anaerobically is the near-only way out. That means producing a lot more lactic acid at that place.
1) Means more lactic acid production by the liver.
2) Means less lactic acid clearance by using it for ATP production.
Combining 1) and 2) means higher body wide blood lactate levels. Higher blood lactate levels mean that it will clear slower out of all places including problematic places (areas in the brain in ME).
3) Means more production in problematic areas in the brain.
Combining all 3 means increased lactate production and decreased clearance in problematic areas. That logically leads to local accumulation of lactic acid.
As to the question about extremely reduced muscle capacity, I believe the answer is in 1): strong shortness in NADPH (due to inflammation/oxidative stress/strong immune response) must shut down NADH production as much as possible because NADH production (for ATP) is a highly oxidative process and having depleted NADPH/glutathione means defenses against oxidative stress are faltering big time. Basically I think the brain deliberately shutting down all non vital energy expenses as much as possible (and making one feel a wreck when one wants to push true exhaustion and pain) is a vital (last line?) safety mechanism.
Note: keto patients could “disrupt” research findings if included IMO.
I can’t help but wonder if cataplexy and narcolepsy may somehow be tied in, with orexin involvement. I have been a passive reader, mostly out of necessity. My diagnosis is murky. I am working full time, barely. Adderall keeps me from collapsing. My sleep doctor wants to evaluate me for Narcolepsy. I am diagnosed with fibromyalgia, a diagnosis I somewhat resist. Treatment for sleep apnea turned the so-called fibromyalgia from a tiger into a kitten, so I feel it is sleep-related and have spoken with other apnea patients who had fibro-like symptoms prior to treatment for apnea. Perhaps we are a subset. I am still dragging myself around daily and my sleep neurologist prescribed the Adderall, which seems to make it “Safe” (I rarely feel like I will collapse and pass out/sleep? in the street somewhere). I had heard for awhile about similarities between narcolepsy and fibromyalgia (when Xyrem was investigated as a treatment for fibromyalgia). If I am understanding some comments and posts, it seems like orexin might be an interesting avenue for investigation. With narcolepsy, many patients also experience cataplexy which causes sudden muscle weakness. I find it odd that I have recognized that emotions take energy.
I wonder if there are any links in brain chemistry, brain areas affected by narcolepsy and ME. I seem to be seeing things in what you write that ring a vague bell for me in things I read. I am a curious person but my mind doesn’t make the connections it used to. Hypoxia and orexin… HPA axis… lactic acid… I just wish I could make connections in a meaningful way but I feel there are patterns between what I have read on narcolepsy and some comments and writings here. Wishful thinking, perhaps.
Ha. Dr. Klimas says that about 50% of her ME/CFS patients have sleep apnea – it’s a major concern.
Narcolepsy is interesting. I don’t know if there’s a connection or not but it’s an interesting idea 🙂
@Heather: I believe what you describe is related to ME/FM patients not regenerating during the night but during the day.
It is not a reversal of sleep patterns IMO, but base metabolism dropping dangerously low during the night. As the night progresses basic life support falters causing increasing damage/problems accumulating during the night.
I was able to turn a nasty vicious circle into a slow upward spiral by getting up and doing some breathing and circulation exercises every time I woke at night. In the beginning it was devastating my sleep, but yet I felt better then when I tried to sleep enough. Over months both sleep and energy improved remarkably. I’ll put it on my to-do list to write about it on the forum coming month.
‘Silent Migraines’ could also be a Cause of ME/CFS & diagnosis is crucial & also diet & the right medicines to be tried on is key from a Migraine
Medicines & headache Pain ones…Silent Migraines are ones that can
totally incapacitate anyone just by themselves or a combination of what I just posted above. There is one Guy diagnosed with ME/CFS treated for Silent Migraines he is totally well 5 years out & numerous thing can
trigger (SM) & even peanuts, coffee, loud noises etc. the list is long
The migraine connection in fibromyalgia and ME/CFS has just gotten stronger and stronger over time. It’s possible that some people with these diseases have migraines without knowing it. Check out the below blog on the possible connection between migraine, lactate and oxygen and questionnaires for self tests to assess the possibility you might have a migraine. If you do some hot new drugs are coming on the market that may be helpful. Dr. Baraniuk has also found that some migraine drugs work in people with ME/CFS who do NOT have migraines. Its a good area to keep an eye on.
https://www.healthrising.org/blog/2016/04/11/migraine-me-cfs-fibromyalgia-oxygen-lactate-triad/
and questionnaires on this page for
https://www.healthrising.org/forums/resources/categories/pain-diagnosing-and-assessing.176/
That is the trick with Silent Migraines some get occasional headaches & with Silent ones they are there all of the time & triggers are everywhere I react to Coffee or Peanuts but not
always but Walnuts destroy me…We would have to do elimination diets puls evidence if stimuli & try numerous migraine medicines, maybe the Diamox low dose could help but
minute doses only…Go on Youtube the latest Video on Ron Davis open it up to about 30 minute mark it will come on there-there is a test in the UK at Medichecks it cost about
221.00 Pounds to run but still not sure if it tests for both
Wouldn’t it be wonderful if – after all this drama – the most appropriate name actually proved to be “myalgic encephalomyelitis”? (Or some type of encephalomyelitis.)
That would be a lesson for the history books!
Yes, indeed…
or Younger’s Disease ;o)
@MarthaLauren – Yesss!
Just what I was thinking. The brilliance of Younger was the use of thermometry and subsequent discovery of lactate where the inflammation was. I hope someone will replicate his result independently before we go too far down in that path, but I have a strong feeling that CFS will be renamed ME eventually. The independent finding by the Japanese researchers using PET scan is certainly encouraging. If this thing pans out, they all deserve a Nobel.
I’m really looking forward to finding out just how much of a mistake it was for all so-called “CFS researchers” to arrogantly think “We don’t need to talk to the members of the original CFS outbreak. We’ll just study anyone we please”
And throw the Lake Tahoe outbreak off the cliff.
We already know it was a huge mistake that has caused much suffering
and cost many lives.
The question is now whether this will be recorded as the worst “medical EPIC FAIL” of all time.
McGregor talked at dinner last night about a flavivirus outbreak. The first patient Dr. Peterson saw, he said, was an infected Chinese man from out of the area who may have gotten bit by a mosquito – transmitting a flavivirus – to the mosquito which then spread hitting others in the area – if I got that right.
Hi Cort
Will regulary PETscans show signs of inflammation in me-patiens considering Younger or is the special prosedure described requiered, do you know?
Thank you for being both so fulll of knowlegde, and providing hope!
All I know is that a PET scan with specific tracer is used. I imagine that it is not readily available in doctors offices.
I found your answer here now (sorry for posting same question twice).
I recond this means that the normal PET-procedure , will be unnessesary.
Can Yonger be reached?
I’d love to have a (paid) consultation, asking if there are availeble tracers to be found, but I cannot find his website/lab anywhere.
Younger runs the Neuroinflammation, Pain and Fatigue Lab at the Univ of Alabama at Birmingham – https://cas.uab.edu/younger/. There’s a contact form on the website. Good luck in your search 🙂
From a CCSVI page, might be worth including in Dr Younger’s scanning “”The role of the extracranial veins in the pathogenesis of inflammatory neurological/neurodegenerative diseases remains largely unknown and under-investigated.
A condition named chronic cerebrospinal venous insufficiency (CCSVI) strikes the main extracranial veins and determines a slight increase in pressure up to the brain venules.
The condition is linked with a recently-described chain of pathophysiologic events. Impaired CSF diffusion into the brain parenchyma between the peri-arterial and the perivenous spaces contributes to a worsened protein clearance.
Furthermore, restricted venous outflow through the jugular veins reduces perfusion and the energy available to oligodendrocytes for myelin synthesis. Both peptide waste and myelin debris represent a strong chemotactic signalling.
Increased transmural pressure in the CCSVI condition may also facilitate blood-brain barrier leakage and red blood cells extravasation. Consequently, iron stores are increased and likely linked to inflammation and degeneration.
The contribution of the impaired venous function to neuroinflammation/degeneration warrants further studies in this direction.”
The research continues…”
https://www.sciencedirect.com/science/article/pii/B9780128117095000363
Wow…The theme I keep seeing coming up – problems with oxygen delivery. Systrom, from what I can tell, finds the same thing in the body – venous insufficiency – reduced blood flows from the veins leading up to the heart. Really interesting…
Nice info I’ll have to look deeper into when my head is clearer.
For now let me add: poor venous flow also has a very direct link to the local “brain overheating” found in the thermographic imaging Cort reported on recently.
The brain after all is the only part of the body that hasn’t low temperature even in hypothermia patients. With the brain consuming such a big portion of total energy whilst (the head) having low surface area means: big needs for cooling besides losing heat by the head itself. That means: through using “coolant” and run it through the brain. The only coolant that runs through the brain sufficiently is blood.
In fact, that may help explain why so many of us are hypothermic: it makes the temperature of the blood going into the head lower as the rest of the body is so cold, cooling the blood very well. Colder blood going to the head means better cooling capacity per liter of blood flow going to the brain. Doing gentle neck mobilization exercises (likely increasing blood flow to the brain through reducing artery compression by tense neck muscle) was one of the first things that improved when I was in ME hell. Always ask therapist advice for doing neck exercises as it can block important nerves if done wrong.
Hyperventilating helps in losing a bit more heat by air taking it away from just beneath the brain. Not that I recommend doing more so ;-). But not drinking and eating too hot stuff is a smallish help that also helps reduce heat shock protein formation so it reduces mouth inflammation too. Easy and cheap one!
Hi! Tried to post yesterday, sorry if same questions appears twice”)
I am waiting for a PET-scan at the hospital, these days. Is it possible to see signs of inflammation on regular PET- procedure, or is the method Yonger uses required.
I dont think the hospital has eigther the technique or the competence to mark the b/t-cells as described.
But I have read before (in your blog), that neutoinflammation is descovered in other studies as well. Has it then been practised “regular” PET-scan methods?
Thank you so much for all the work you do, and the knowlegde you provide!
They wouldn’t. Both of these -heat mapping neuroinflammation project and immune cell infiltration studies are research projects using what I gather are a new techniques. The PET scan using a tracer might be a possibility but I think it too may be rather new. My understanding is that just over the last few years has it been possible to pick up lower levels of inflammation. That suggests only researchers may have access to it but I don’t know.
good luck anyway! (tried to get one too but guess it was too expensive for a mere MUPS-patient)
Younger’s approach is careful and empirical, the way things should proceed. Maybe the reason the brain invites the immune cells in is because there’s a virus in the brain that it’s fighting.
A virus attacking the central nervous system is definitely one of the possibilities.
One of the more crazy ideas that struck me tonight was that there seems to be a resemblance between the common blood blister (the 5mm wide painful red blood filled thing when you hit with a hammer on your fingers) and the thousands of tiny red burning spots I get on my pale skin when I am utterly exhausted.
I know it seems far fetched but some of my far fetched ideas have helped me well. The common blood blister is one big extracellular accumulation of blood, lasting for days to weeks and being very painful. I guess all sort of bad stuff happens to the blood being trapped there for so long, like coagulation, infection, turning sour or rancid… …so I guess ultimately it is the immune system that cleans up this mess.
Now with, according to much info on Corts blogs, chances of auto-immunity against the blood vessel walls, weakened cell walls, connective tissue disorders… I can easily see many of us having thousands of “micro blood blister” just from having such damaged “hardware” as we have. Now if that were true, imagine the thousands of red dots appearing on the skin are just a small part of the total amount. So much more would be just beneath the skin and in organs, out of sight. Over the total body volume that would mean hundreds of thousands little painful long(er) lasting sources of nasty chemicals, infection and inflammation. As they are smaller then a mm in diameter, clearance would be hours to days rather then days to weeks. With rest, that’s about the time it takes them to disappear and coincidentally it is in line with the duration of PEM.
I know histamine/mast cells would be a far more conventional explanation of these thousands of red dots. But that only says something is initiating a histamine/mast cell based attack, not what it might be against. Maybe the attack isn’t that wrong after all. And maybe the equivalent happens in the brain. It certainly would require strong action to clear it out of the brain.
I’d love any thoughts on this one ;-).
Hi Dejurgen, Could you contact me? I would like to talk to you about fibromyalgia. contact@fibrocentrum.nl
Thanks!
Cort, it’s still not clear to me why Younger is suspecting BBB breach. What he found with his thermometry was the lactate buildup and inflammation. And it seems more likely that the lactate is causing the inflammation, not the immune cells breaching BBB. Here is a paper about lacate’s role in modulation of inflammatory immune reponse: https://www.ncbi.nlm.nih.gov/pubmed/27883186
And here is an interesting article about increased lactate uptake by injured brains: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868386/
Post-TBI/concussion fatigue is quite common, btw, present in 50-80% cases. They are probably caused by increased lactate uptake by the brain.
https://www.nytimes.com/2017/11/27/well/new-recognition-for-chronic-fatigue.html
Cort,
Thanks for posting this. It is interesting to see new ideas and new researchers come to the table.
Could orexin be involved somehow?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155688/
As a patient and an intellectual, I deeply appreciate the efforts and the challenges. As a less important comment I causally submit that at $5k/hr for scans, something could be wrong with that economic system somewhere. It’s difficult to imaging hardware cost, maintenance, and operation, etc actually be ‘worth’ that much without someone getting rich somewhere. A pretty good comp can be to see if the same is done in other countries, and what the costs are there. Anyone who thinks American drug and device industry is not completely broken economically is incorrect.
Agreed!
Spot On..?
It’s an interesting hypothesis, but I don’t think it fits with the rapidity of fall and rise of symptoms during the times I had temporary remission. I switched state from baseline ME symptoms to healthy and energetic over the space of minutes, and back to feeling lousy over the space of minutes. To me that more likely indicates a chemical reaction inside cells: perhaps DNA or RNA transcription.
Dejurgen asked about lactate levels and muscle impairment. Not all ME victims have muscle impairment or obvious signs of lactate issues. I suffer from mental lethargy and other neurological symptoms, but my physical capability has been unaffected by ME. Strenuous physical effort can trigger PEM, but my muscles are fully capable of hours of hard labour. I’m not the only member of this subgroup of ME. I believe that the muscle impairment and lactate issues–and most of the other physical symptoms–are secondary medical problems caused by ME, and that the core dysfunction of ME is in the brain, probably in the microglial cells.
Cort,
I was diagnosed with CFS in 1994. My symptoms go up and down, depending on lifestyle. If I’m sleeping my life away (physically inactive and not stressing myself mentally), symptoms are low. If I’m attempting to function like a 52 year old healthy woman, my symptoms are blaring. I recently found Health Rising and greatly appreciate the information. Like everyone else, I’m frustrated because without a specific cause, there is no specific treatment. Different doctors treat differebt symptoms, which is difficult for someone with brain fog to manage (appointments, medications, insurance).
Are there local support groups – I live in NJ, USA? I noticed that there are comments after each of these emails. How can I connect with someone in my area to share info on medical practitioners, etc?
Thank you.
Sue Mazzeo
This is spot on about the brain barrier blood and there is a hole..
I want to thank all the researchers that are listening to us..?and Nurses…
Shooting for the moon?