Brain on Fire: Widespread Neuroinflammation Found in ME/CFS by Jarred Younger

[stiffler]

My health issue is definitely inflammation. Some things that have helped are a low inflammation diet (Keto), cannabis and a Rife machine. Cannabis works to reduce inflammation at the cellular level. It seems to last 2-6 hours. The Rife machine works longer term (I've had relief for a week or two at a time) but then I relapse and start feeling chitty again. Every month with a Zyto scan I fight what I describe as a co-infection. I've been able to clear all pathogens (EBV, CMV, Rikketsia, Strepp, mytobacterium, etc) detected in about 2-3 weeks, feeling amazingly better. Rikketsia took 2 months and was brutal. Co-infections to what? After chelating metals for about 18 months (with some improvement), I think it's an undetectable pathogen such as retro-virus. There is definitely something else that I fight. I sweep frequencies for two hours at night sometimes and usually produce a herx-like reaction in the morning. The sweeps generally make me feel much better but so far I cannot get lasting effect. I'm definitely in the camp that believes something resides in my CNS and acts upon the CNS as well as the brain.

 

[Marylib]

Before Youngers research on the 'Hot Head' thing going on in cfsers, i think there was a post that was quite long where many of us were talking about brain fog and if it worsened it felt like our brain was on fire or going through a bad run of insomnia and our brain would feel on fire. Interesting to see the research showing this.

Now how do we get ice to cross the bbb . Maybe the ice bucket challenge will be an actual treatment??

I wonder if cannabis crosses the blood-brain barrier? It really helps me - with sleep, pain, over-stimulation, and I am actually able to carry on a conversation with much less suffering.

 

[FMMM1]

I wonder if cannabis crosses the blood-brain barrier? It really helps me - with sleep, pain, over-stimulation, and I am actually able to carry on a conversation with much less suffering.

Google something like cannabis blood-brain barrier

 

[RYO]

It would be interesting if Jarred Younger could perform thermal brain imaging of patients with active viral infection (such as influenza) and compare images to ME/CFS patients.

 

[Jackb23]

Thanks for posting this, it's good to have some evidence we're experiencing brain inflammation as that's how it feels for us, albeit fluctuating in severity of course.

I told a neurologist about Jarred Younger's work on brain temperature and they dismissed it, saying if Lumbar Puncture was normal and MRI is normal, this is proof inflammation is not present.

It's so frustrating that neurologists don't want to accept new ideas, and new technologist when it comes to our specific illness.

The problem that I find arises half the time with doctors is not always that they are completely ignorant and dismissive, but I find they work from a very cookbook esque paradigm. A lot of my doctors at least (I realize this isn't everyones case) sometimes won't progress further or warrant any more inquisition towards a problem because they know that even if they were to find something, they wouldn't know how to go about it. For instance, if there is a large and ubiquitous inflammation in the brain, no one really knows a golden standard means of treating it just yet. There of course are ways and medications that cross the BBB/plasma proteins to enter the CNS, but many of these drugs are either: 1. Used for something such as depression (ssris might help, etc.) Or 2. Haven't been studied extensively for any condition in the CNS such as minocycline.

I personally have been through a litany of treatments and some have provided "significant" improvement and others have really perturbed my brain (such as rTMS). I have found that almost all antidepressants help my brain fog to a particular degree. These include your SSRI's, SNRI's, Wellbutrin, Remeron, etc. (All of these do have some positive cytokine activity). I have found that while Ketamine infusions can be extremely helpful, they give me severe insomnia and induce a certain kind of glutamate hyperdrive. This insomnia has taken my bedtime from being naturally lulled to sleep at 2-3 AM to having to take 12.5 mg CR Ambien, 1 mg of Klonopin, and 6 Benadryl just to ensure I knock myself out before the sun comes up. I don't know why, but rTMS really fucked up my brain to the point where I couldn't tolerate any antidepressants, neuroleptics, or mood stabilizers, and induced a dystonic like twitch in my neck (cervical dystonia) that has just now begun to settle. Not that anyone on here is probably thinking about trying rTMS, but at one point I thought that what was truly wrong with my brain was a result of treatment resistant depression.

Below are just a few studies that show how rTMS can change the genetic expression in your brain for quite some time depending on how many sessions you do (months to years). While glutamate and other neuro-communicators (transmitters and cells) may already run errant in many of our brains, it has been shown that rTMS can significantly alter glutamate activity not just in the PFC, but also in the Basal Ganglia. It can also significantly unregulated the D2 dopamine receptor that is found primarily in the limbic system (Striatum, Caudate, Putamen, Globus Pallidus, etc.).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653621/
Repetitive transcranial magnetic stimulation induces long-lasting changes in protein expression and histone acetylation

https://www.ncbi.nlm.nih.gov/pubmed/12814378
Metabolic changes after repetitive transcranial magnetic stimulation (rTMS) of the left prefrontal cortex: a sham-controlled proton magnetic resonance spectroscopy (1H MRS) study of healthy brain.

 

[lenin]

My health issue is definitely inflammation. Some things that have helped are a low inflammation diet (Keto), cannabis and a Rife machine. Cannabis works to reduce inflammation at the cellular level. It seems to last 2-6 hours. The Rife machine works longer term (I've had relief for a week or two at a time) but then I relapse and start feeling chitty again. Every month with a Zyto scan I fight what I describe as a co-infection. I've been able to clear all pathogens (EBV, CMV, Rikketsia, Strepp, mytobacterium, etc) detected in about 2-3 weeks, feeling amazingly better. Rikketsia took 2 months and was brutal. Co-infections to what? After chelating metals for about 18 months (with some improvement), I think it's an undetectable pathogen such as retro-virus. There is definitely something else that I fight. I sweep frequencies for two hours at night sometimes and usually produce a herx-like reaction in the morning. The sweeps generally make me feel much better but so far I cannot get lasting effect. I'm definitely in the camp that believes something resides in my CNS and acts upon the CNS as well as the brain.

How do you take cannabis? do you smoke it? I made a tea with milk and cannabis. First time I Got really high, second time I did it, i used less cannabis and I managed to sleep better and reduce the pain in my legs. It worked, however it still had some side effects, digestives for instance. Im thinking about giving a second try bc I cannot sleep at all.

 

[stiffler]

How do you take cannabis? do you smoke it? I made a tea with milk and cannabis. First time I Got really high, second time I did it, i used less cannabis and I managed to sleep better and reduce the pain in my legs. It worked, however it still had some side effects, digestives for instance. Im thinking about giving a second try bc I cannot sleep at all.

I smoke it, vape it, eat it, drink it, grow it... lol, I live in Colorado, very cannabis friendly. I've never had canna-tea, I'll have to put that on my list. It can be definitely a sleep aid but be sure to know what strain you have. Indica's are the goto strain for sleep, sativa's are way to energizing, Hybrids are both. Try to find a strain high in CBN... N for Nightime. THC naturally changes over time to CBN with exposure to air, light and heat. The best sleep aid I ever had was a bag of weed that was a year old.

I like to vape or smoke the best but sometimes for deep sleep, that would definitely be an edible from an Indica. Edibles most definitely last longer. 20 mg is good for me but finding the right dose in an edible can be difficult. I make a coconut oil that I'll just take a spoon, dip in and try to estimate a dose

My latest batch of oil will come from a 2:1 CBD/THC strain called Pure Love. Trying to dial down the psychoactive effects with CBD. The CBD also helps a bunch with pain. CBD alone isn't enough for my pain.

https://www.leafly.com/start-exploring/good-night-sleep

https://www.medicaljane.com/2013/08/19/cannabinol-cbn-will-put-you-to-bed/

 

[halcyon]

I agree that I ‘feel’ it is a brain problem. But how does all this tie in with PEM? Why delayed? And how do the mitochondria tie in?

I think this disease is 100% a brain problem. It ties in with PEM because it’s impossible to exert your body in any way without using your brain. Maybe a few of your organs can function without brain input, but everything else you do requires activating sensory, autonomic, vestibular, neuromuscular, and cognitive nerve pathways.

The primary pathology of the disease is activated by increasing the metabolic activity of these nerve pathways (exertion), the response to which is inflammation local to the actived nerves in the brain. It’s delayed because it takes time for the affected tissue to start the inflammatory cascade, which includes recruitment of inflammatory cells which take time to reach the tissue and peak the response.

The mitochondria don’t tie in. The fatigue of this disease is central, and the muscle weakness is neuromuscular, not due to an energy problem in the muscle itself.

 

[pamojja]

Don't know how accurate this list it, found it somewhere made by someone else:

Some Antioxidants Which Cross the Blood-Brain Barrier:
——————————————————————————————————————————————————————————————————
Astaxanthin 12 mg · · · · · Half life: 52 hours · Crosses BBB: Yes, easily
Vitamin C 1000 mg · · · · · Half life: 30 mins· · Crosses BBB: Oxidized form does
Vitamin E 400 mg· · · · · · Half life: 2 days · · Crosses BBB: Yes, to a degree
Grape seed extract 500 mg · Half life: 3 days · · Crosses BBB: Yes
Q10 200 mg· · · · · · · · · Half life: 1.4 days · Crosses BBB: Yes
Fisetin 100 mg· · · · · · · Half life: 3 hours· · Crosses BBB: Yes
Rutin 500 mg· · · · · · · · Half life: ?? days· · Crosses BBB: Possibly
Lutein 10 mg· · · · · · · · Half life: 15 days· · Crosses BBB: Yes
Zeaxanthin 4 mg · · · · · · Half life: 12 days· · Crosses BBB: Yes
N-acetyl-carnitine 500 mg · Half life: 4 hours· · Crosses BBB: Yes, easily
Alpha lipoic acid 200 mg· · Half life: 30 mins· · Crosses BBB: Yes, easily
Lycopene 25 mg· · · · · · · Half life: 3 days · · Crosses BBB: Yes
N-acetyl-cysteine 400 mg· · Half life: 2 hours· · Crosses BBB: Yes

Just realized how inaccurate this list I posted earlier probably is, in that it's author most probably had access to petri-dish studies only. For example vitamin C indeed has a half life of about 1/2 an hour in water, though in biological systems it might look completely different. And in vitamin C deficiency the half-life of vitamin C in serum allegedly prolongs to weeks.

In a recent study (https://isom.ca/article/the-levels-...ion-taken-without-and-with-iv-hydrocortisone/) the serum concentrations of 1 dose of 5g ascorbic acid and 5g liposomal vitamin C after a 5 day washout period was measured:

Additionally the intercellular content of vitamin C in white blood cells:

It looks like to take about 2 hours to reach highest serum, and 4 hours to reach highest intercellular levels. A faster half-life of 2 hours of non-encapsulated ordinary ascorbic acid, but then surprisingly leveling out at the halved level for an other 2 hours. Therefore to assume linear half-lifes of substances in biological systems is in itself very inaccurate.

It is of course also very individual. The first graphs non-encapsulated curve is actually the mean of 5 individuals:

Where it appears with 2 individuals that after 2 hours of halving, the levels are even rising again. And the 1 individual with the highest rise, first half-life was reached after 4 hours only.

edit:

1 dose of 5g ascorbic acid

My mistake. The non-encapsulated vitamin C was actually sodium ascorbate, not ascorbic acid.

 

[Wishful]

I notice that the list shows that vitamin C crosses the BBB in the oxidised form, which I assume means that it can no longer works as an antioxidant. You need adequate supplies of another antioxidant, such as glutathione or other thiols to reduce the oxidised vitC so that it can work again. So, if you're trying to deal with ROS in your brain, you'll need to take more than just VitC.

 

[pamojja]

I notice that the list shows that vitamin C crosses the BBB in the oxidised form, which I assume means that it can no longer works as an antioxidant.

Where its reduced to ascorbic acid again. Otherwise the brain wouldn't contain 10 times higher concentrations of ascorbic acid than blood:

Vitamin C crosses the blood-brain barrier in the oxidized form through the glucose transporters.

Abstract:
Vitamin C concentrations in the brain exceed those in blood by 10-fold. In both tissues, the vitamin is present primarily in the reduced form, ascorbic acid. We identified the chemical form of vitamin C that readily crosses the blood-brain barrier, and the mechanism of this process. Ascorbic acid was not able to cross the blood-brain barrier in our studies. In contrast, the oxidized form of vitamin C, dehydroascorbic acid (oxidized ascorbic acid), readily entered the brain and was retained in the brain tissue in the form of ascorbic acid. Transport of dehydroascorbic acid into the brain was inhibited by d-glucose, but not by l-glucose. The facilitative glucose transporter, GLUT1, is expressed on endothelial cells at the blood-brain barrier, and is responsible for glucose entry into the brain. This study provides evidence showing that GLUT1 also transports dehydroascorbic acid into the brain. The findings define the transport of dehydroascorbic acid by GLUT1 as a mechanism by which the brain acquires vitamin C, and point to the oxidation of ascorbic acid as a potentially important regulatory step in accumulation of the vitamin by the brain. These results have implications for increasing antioxidant potential in the central nervous system.

 

[Wishful]

Yes, but does taking VitC decrease overall ROS, or is it an important (critical?) resource for other antioxidants? Is it actually glutathione or other molecules that donate the electron that ultimately reduces the ROS molecule? It's like hydrogen-fueled cars: unless you have a source of molecular hydrogen, it's not an energy source, but an energy storage medium.

I'm just vaguely curious about whether taking ViC reduces overall ROS by itself, or if it's only a mediator. It's a vital nutrient either way.

 

[Rufous McKinney]

Cannabis works to reduce inflammation at the cellular level. It seems to last 2-6 hours.

Yup. I see this as a key indicator/ hint hint. If you can get this brain inflammation and histamine reactions to subside, plus a bit of pain relief: I can actually almost Kinda Function. Mitochrondria wake up some.

I love 11 at night.

 

[FMMM1]

I think this disease is 100% a brain problem. It ties in with PEM because it’s impossible to exert your body in any way without using your brain. Maybe a few of your organs can function without brain input, but everything else you do requires activating sensory, autonomic, vestibular, neuromuscular, and cognitive nerve pathways.

The primary pathology of the disease is activated by increasing the metabolic activity of these nerve pathways (exertion), the response to which is inflammation local to the actived nerves in the brain. It’s delayed because it takes time for the affected tissue to start the inflammatory cascade, which includes recruitment of inflammatory cells which take time to reach the tissue and peak the response.

The mitochondria don’t tie in. The fatigue of this disease is central, and the muscle weakness is neuromuscular, not due to an energy problem in the muscle itself.

Whatever, your theory (bottom up/top down - Phair) you have to be able to explain the plasma switching reversal in cellular energy/mitochondria morphology (Prusty - the mitochondria change shape/it's reversible) and yes central nervous system problems (brain). Exosomes, seem to me to provide the "signalling" to explain this cascade - fatigue --. Fluge and Mella suggested a signalling problem in 2006: "ME/CFS is caused by immune interference with an unidentified target, potentially a signaling factor, which ultimately causes metabolic dysfunction and in" [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161229/ ].

I posted this in another place [https://www.s4me.info/threads/blog-...lood-by-simon-mcgrath.9168/page-2#post-162329 ].
"I came across this after posting/before reading your replies and yes it refers to something new to me (at least) i.e. prions. From:
https://www.frontiersin.org/articles/10.3389/fnins.2017.00026/full


"Multiple Sclerosis and Inflammation

Inflammation is a central player in most neurodegenerative diseases. Neuroinflammatory processes exert profound changes not only in the vicinity but beyond the local environment of cells. In addition to the propagation of toxic proteins, exosomes also carry important inflammatory modulators, such as mRNAs, miRNAs, and cytokines (Gupta and Pulliam, 2014). Microglia, the resident macrophages of the CNS, can shed exosomes loaded with pro-inflammatory molecules such as IL-1β (Bianco et al., 2005) and other cytokines. Their scavenging functions are also crucial in the clearance of toxic seeds such as Aβ (Yuyama et al., 2012). Furthermore, endocrine signals from hematopoietic cells directed to the brain can be transported by exosomes, a phenomenon that is augmented in a context of inflammation (Ridder et al., 2014). It is interesting to note that extracellular vesicles can readily cross the blood brain barrier, adding a communication channel by which systemic inflammation can modulate physiological processes in the CNS."

Second extract:
"As many other proteins are present in exosomes, recent initiatives have used large-scale methodologies to analyze exosome content. Using mass-spectrometry to analyze circulating microvesicles, it was identified that PD patient fibroblasts are enriched in syntenin 1, a regulator of exosome biogenesis (Tomlinson et al., 2015). Similarly, a set of nine miRNAs have been shown to be distinct in exosomes purified from control and prion-infected cells (Bellingham et al., 2012a), defining a molecular “signature” that can identify a pathological process. Although the relevance of such hits in the disease is not established yet, these approaches suggest that establishing a “bar-code” from the exosomal profile of patients might be a more valuable diagnostic tool than quantifying specific disease-related proteins, which are often mixed at early disease stages." "

ME Action are lobbying for the delivery of a diagnostic test
https://www.meaction.net/2019/02/26/announcing-millionsmissing-2019-join-us/

@JaimeS

 

[Rufous McKinney]

This article is interesting and focuses on exosome studies generally, and how to isolate and potentially sort them (so you can study them) (and diagnose things).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5327650/

 

[Rufous McKinney]

https://www.ncbi.nlm.nih.gov/pubmed/24068616

This study from 2014 is regarding autoimmune issues in MECFS. (Morris, et al.)

So a theory for the moment: here they describe that there is more cell death in MECFS:

"Low ATP production and mitochondrial dysfunction is a source of autoimmunity by inhibiting apoptosis and stimulating necrotic cell death."

So its possible that our blood contains a high density of exosomes containing the waste products from cell death processes. Maybe this contributes to the experience that our blood is rather stagnent. Not flowing properly. Qi not flowing properly either. Here, lymph ain't flowing well either. All systems may contain exosomes.

So if they could sort them, separate them out, identify our specific types and incapacitate them...if if if lets Dream a Fix.

 

[Rufous McKinney]

I

I wonder if cannabis crosses the blood-brain barrier? It really helps me -

It has to be....in my humble opinion

 

[Rufous McKinney]

I wonder if Hecannabis crosses the blood-brain barrier? It really helps me - with sleep, pain, over-stimulation, and I am actually able to carry on a conversation with much less suffering.

Here: reference describes the many areas of the brain and spinal chord which contain cannibanoid receptors....

https://www.ncbi.nlm.nih.gov/pubmed/9472392

"These results show that cannabinoid receptor binding sites in the human brain are localized mainly in: forebrain areas associated with higher cognitive functions; forebrain, midbrain and hindbrain areas associated with the control of movement; and in hindbrain areas associated with the control of motor and sensory functions of the autonomic nervous system."

I presume cannibanoids can cross the BBB to reach these receptors. (but have not tied that knot up yet)

 

[Rufous McKinney]

Here: a Not a Science Study : indicates we have about 3 times the THC concentrations within the brain, compared with the blood, indicating THC is crossing the BBB.

http://profofpot.com/thc-blood-brain-barrier/