Swedish study finds ~30% reduction in overall ME symptom scores from intranasal mechanical stimulation of the vagus nerve

[junkcrap50]

https://twitter.com/i/web/status/1231119338561732608

https://twitter.com/i/web/status/1231120250311184384

ABSTRACT: https://www.biorxiv.org/content/10.1101/2020.02.20.958249v1
FULL PAPER: https://www.biorxiv.org/content/10.1101/2020.02.20.958249v1.full.pdf

Achieving symptom relief in patients with Myalgic encephalomyelitis by targeting the neuro-immune interface and inducing disease tolerance
Lucie ST Rodriguez, Christian Pou, Lakshmikanth Tadepally, Jingdian Zhang, Constantin Habimana Mugabo, Jun Wang, Jaromir Mikes, Axel Olin, Yang Chen, Joanna Rorbach, Jan-Erik Juto, Tie-Qiang Li, Per Julin, View ORCID ProfilePetter Brodin
doi: https://doi.org/10.1101/2020.02.20.958249
Abstract
Myalgic encephalomyelitis, ME, previously also known as chronic fatigue syndrome (CFS) is a heterogeneous, debilitating syndrome of unknown etiology responsible for long-lasting disability in millions of patients worldwide. The most well-known symptom of ME is post-exertional malaise, but many patients also experience autonomic dysregulation, cranial nerve dysfunction and signs of immune system activation. Many patients also report a sudden onset of disease following an infection. The brainstem is a suspected focal point in ME pathogenesis and patients with structural impairment to the brainstem often show ME-like symptoms. The brainstem is also where the vagus nerve originates, a critical neuro-immune interface and mediator of the inflammatory reflex which regulate systemic inflammation. Here we report the results of a randomized, placebo-controlled trial using intranasal mechanical stimulation (INMEST) targeting the vagus nuclei, and higher centers in the brain of ME-patients and induce a sustainable, ~30% reduction in overall symptom scores after eight weeks of treatment. By performing longitudinal, systems-level monitoring of the blood immune system in these patients, we uncover chronic immune activation in ME, as well as immunological correlates of improvement that center around the IL-17 axis, gut-homing immune cells and reduced inflammation. The mechanisms of symptom relief remains to be determined, but transcriptional analyses suggest an upregulation of disease tolerance mechanisms. We wish for these results to bring some hope to patients suffering from ME and inspire researchers to help test our new hypothesis that ME is a condition caused by a failure of inducing disease tolerance upon infection and persistent immune activation.

(abstract link has cool twitter intregration listing all tweets mentioning paper)

 

[junkcrap50]

Called: Intranasal Mechanical Stimulation (INMEST) or Kinetic Oscillation Stimulation (KOS)

There is some research into this form of intranasal stimulation:
Effects of intranasal kinetic oscillation stimulation on heart rate variability
Intra-Nasal Mechanical Stimulation (INMEST) as a Treatment of Keratoconjunctivitis Sicca (Dry Eye Syndrome)
Treatment of idiopathic rhinitis with kinetic oscillations - a multi-centre randomized controlled study

And some medical devices on the market:

https://www.truetear.com/

https://chordate.com/
http://www.gds-medtech.com/kinetic-oscillation-stimulation-kos/

 

[Hipsman]

Is there a cheap and easy way to try this?

 

[Rufous McKinney]

Wondering about what are: Disease Tolerance Mechanisms?

 

[Rufous McKinney]

Is there a cheap and easy way to try this?

the waterpik?

 

[ljimbo423]

Wondering about what are: Disease Tolerance Mechanisms?

I was wondering that too.....

Tolerance to infections


From Wikipedia, the free encyclopedia




Jump to navigation Jump to search
Tolerance to infections, or disease tolerance, is one of the mechanisms host organisms can use to fight against parasites, pathogens or herbivores that attack the host. Tolerance to infections is defined as the ability of a host to limit the impact of parasites, pathogens or herbivores on host health, performance, and ultimately on fitness. Tolerance is not equivalent to resistance. Disease resistance is the host trait that prevents infection or reduces the number of pathogens, parasites and herbivores within or on a host.
Tolerance to infections can be illustrated as the reaction of host performance along with increasing pathogen, parasite or herbivore load. This is a reaction norm in which host performance (on y-axis) is regressed against an increasing pathogen, parasite or herbivore burden (on x-axis).[1] The slope of the reaction norm defines the degree of tolerance. High tolerance is indicated as a flat slope, i.e., host performance is not influenced by increasing number of pathogens, parasites or herbivores. Steep downward slope indicates low tolerance; host performance is strongly reduced with increasing pathogen burden. An upward slope indicates overcompensation; a host can increase its performance with increasing pathogen burden.

• 
  
  
  Tolerance to infections concept illustrated as the host performance response to an increasing pathogen load
  
  

In farm animal science, tolerance to infections is sometimes termed disease resilience.[2][3]

Source

I'm not sure this has a place in ME/CFS, except maybe to the "sensitized" microglia Jarred Younger suspects are involved.

 

[Rufous McKinney]

Disease Tolerance discussed here also:...tied to response in host tissues

https://www.annualreviews.org/doi/abs/10.1146/annurev-immunol-042718-041739

Disease Tolerance as an Inherent Component of Immunity
Annual Review of Immunology
Vol. 37:405-437 (Volume publication date April 2019)
First published as a Review in Advance on January 23, 2019
https://doi.org/10.1146/annurev-immunol-042718-041739

Abstract
Pathogenic organisms exert a negative impact on host health, revealed by the clinical signs of infectious diseases. Immunity limits the severity of infectious diseases through resistance mechanisms that sense and target pathogens for containment, killing, or expulsion. These resistance mechanisms are viewed as the prevailing function of immunity. Under pathophysiologic conditions, however, immunity arises in response to infections that carry health and fitness costs to the host. Therefore, additional defense mechanisms are required to limit these costs, before immunity becomes operational as well as thereafter to avoid immunopathology. These are tissue damage control mechanisms that adjust the metabolic output of host tissues to different forms of stress and damage associated with infection. Disease tolerance is the term used to define this defense strategy, which does not exert a direct impact on pathogens but is essential to limit the health and fitness costs of infection. Under this argument, we propose that disease tolerance is an inherent component of immunity.

 

[ljimbo423]

These are tissue damage control mechanisms that adjust the metabolic output of host tissues to different forms of stress and damage associated with infection. Disease tolerance is the term used to define this defense strategy, which does not exert a direct impact on pathogens but is essential to limit the health and fitness costs of infection. Under this argument, we propose that disease tolerance is an inherent component of immunity.

I don't know how they are specifically relating disease tolerance to ME/CFS. So I'm just going by how I understand ME/CFS. I don't think our bodies are having an unusual response to chronic immune activation from a toxin or perceived pathogen in our disease.

However, if they are talking about the changes that happen in the body and possibly the brain, from EBV or other viral triggers in ME/CFS, that seems like it might fall into poor disease tolerance.

 

[Hipsman]

the waterpik?

Sorry, I’m confused with what INMEST or KOS actually mean and how to replicate them. Is it just vibrator-for-nose or low voltage electricity that is stimulating something inside the nose?

 

[Hufsamor]

Sorry, I’m confused with what INMEST or KOS actually mean and how to replicate them. Is it just vibrator-for-nose or low voltage electricity that is stimulating something inside the nose?

https://www.abilion.com/inmest-intranasal-mechanical-stimulation/

 

[Hufsamor]

Sadly, the energy didn't improve.
Petter Borodin said in a comment that he doesn't know why, he's wondering if the extra stress for the participants was the reason.

 

[Hip]

From the full paper:

The INMEST device consists of a thin plastic probe placed in the nose that vibrates at a set frequency to mimic turbulent airflow within the nasal cavity and induces a nerve reflex transmitted to the vagus nerve nuclei in the brainstem and other higher centers (Fig. 1B).

It is important to note that the effect of INMEST on the vagus nerve is different from that of classic vagus nerve stimulation. INMEST shifts the balance of sympathetic and parasympathetic tone resulting in a reduction of heart rate variability.

Fig. 1B — The INMEST device is plastic probe placed in the nose that vibrates

So INMEST is based on the stimulation of a reflex action on the nose, which affects the vagal nucleus located in the medulla oblongata of the brainstem.


Since the INMEST device mimics turbulent airflow in the nose, this makes me wonder whether the yoga practice of kapalabhati (Breath of Fire), which involves repeated and rapid strong expirations of air through the nostrils, might have similar benefits. This video shows how to do kapalabhati.

 

[junkcrap50]

It would be possible to make your own DIY version of this. This is what you would need: an "encapsulated vibration motor." Other search terms that would help find the item may include: micro, mini, waterproof, cylinderical. Then just hook it up to some batteries.

https://www.ebay.com/itm/DC-3v-5v-W...-encapsulated-resistant-vibrator/191914344994
7mm diameter is the smallest I could find, but that should be plenty small to fit in your nostril. However, I would be very careful not to stick it too far up your nose or you may not be able to remove it. I wouldn't trust pulling on the wires to get it out.

However, most likely the paper has the INMEST/vibrator set to a particular frequency, so that it may be tune and stimulate with the vagus nerve. So, you would have to modulate the vibration motor to get the correct frequency (68 Hz, from their references).

 

[junkcrap50]

It is important to note that the effect of INMEST on the vagus nerve is different from that of classic vagus nerve stimulation. INMEST shifts the balance of sympathetic and parasympathetic tone resulting in a reduction of heart rate variability(23).

23. M. Jerling, I. Cygankiewicz, N. Al-Tawil, B. Darpo, A. Ljungström, W. Zareba, Effects of intranasalkinetic oscillation stimulation on heart rate variability, Ann Noninvas Electro23(2018), doi:10.1111/anec.12474

It doesn't say HOW the effect on the vagus nerve is different from classical VNS. (From looking at the paper, it's different because heart rate remained unchanged?)

 

[Diwi9]

Helpful Twitter response to this study by Amy Proal:

https://twitter.com/i/web/status/1231329009633505284

 

[Hoosierfans]

It doesn't say HOW the effect on the vagus nerve is different from classical VNS. (From looking at the paper, it's different because heart rate remained unchanged?)

That’s what I was wondering as well. I’ve tried VNS (ear) and it helped for a bit but then the effects faded. The biggest thing it did was take this weird burning sensation I have WAY down, and anxiety way down. It really felt like my body went back into parasympathetic mode, like its supposed to.

It would be interesting if someone got a hold of the researchers and asked HOW the effect is different. From all that I’ve seen, I really believe vagal nerve stimulation can hold the key to improving and / or curing a lot of chronic ailments.

 

[Tella]

Please let this be of some help to us!
When and how can patients access it or get on another trial?

 

[Hipsman]

When and how can patients access it or get on another trial?

It's quite complicated and expensive to access this right now. I'm interested in this too, but I have to opt out for alternative tVNS. We don't know the difference between INMEST/KOS and tVNS, if there is any. People have experimented with tVNT for ME/CFS since 2015 and some found it helpful.

I think we can try tVNS before going to INMEST/KOS. Hope we can figure out how to do INMEST/KOS with TENS unit soon

tVNS is cheap with TENS unit, some studies and Drs used TENS unit for tVNS. There is a tutorial here.
tVNS have been discussed here previously 1, 2, 3

 

[Tella]

That’s what I was wondering as well. I’ve tried VNS (ear) and it helped for a bit but then the effects faded. The biggest thing it did was take this weird burning sensation I have WAY down, and anxiety way down. It really felt like my body went back into parasympathetic mode, like its supposed to.

It would be interesting if someone got a hold of the researchers and asked HOW the effect is different. From all that I’ve seen, I really believe vagal nerve stimulation can hold the key to improving and / or curing a lot of chronic ailments.

Where did u buy the device please?

 

[Tella]

It's quite complicated and expensive to access this right now. I'm interested in this too, but I have to opt out for alternative tVNS. We don't know the difference between INMEST/KOS and tVNS, if there is any. People have experimented with tVNT for ME/CFS since 2015 and some found it helpful.

I think we can try tVNS before going to INMEST/KOS. Hope we can figure out how to do INMEST/KOS with TENS unit soon

tVNS is cheap with TENS unit, some studies and Drs used TENS unit for tVNS. There is a tutorial here.
tVNS have been discussed here previously 1, 2, 3

Where did u buy the device please?