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The GIST 

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(The GIST is about halfway down the page on the right)

Health Rising’s series of “What’s Up Doc?” Zoom videos asks chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID and related diseases experts “What’s up? What’s exciting you now?” The first talk features Lauren Stiles, the leader of Dysautonomia International.

The Zoom Interview is below and below that is an overview of the interview that includes some added content.

I am new to this and for some reason the video starts about halfway through. Please use the scroll bar at the bottom to return it to the beginning. 

Lauren’s Story 

We will get to the “What’s Up” part but first, I had to ask her about Lauren about the illness that led her to found Dysautonomia International. A healthy, energetic 31-year-old environmental law attorney, Lauren suddenly developed postural orthostatic tachycardia syndrome (POTS) following a ski accident that produced a concussion and intracranial hypertension. Bringing up thoughts of craniocervical instability and a compressed brainstem in my mind, anyway, she described a spine that had been compressed together not by lax tendons but by an accident.

The injury damaged her autonomic nervous system, which then tweaked her immune system, which then apparently destroyed many of the small nerve fibers in her body. She described a harrowing trip through the medical profession that took her several years, but she finally self-diagnosed POTS from her hospital bed and got a neurologist – who had apparently never heard of POTS – to agree that’s what she had.

After another convoluted journey, she ultimately came to find that Sjogren’s Syndrome – a disease she believes is greatly underdiagnosed in these diseases – had triggered her POTS. IVIG treatment – which came with its own set of serious issues – helped greatly. At no time, over the first couple of years, did Lauren have an easy ride through our medical system.

In 2012, Lauren, who had been engaged in non-profit work before, founded Dysautonomia International (DI) – a non-profit organization that quickly became the leader in the dysautonomia field. Dysautonomia International produces yearly international conferences, educates patients, provides information on doctors, and has dysautonomia, POTS and long-COVID research funds).

A Big Family…With Lots of Cousins

connections

Lauren believes that ME/CFS, FM, POTS, long COVID and others are more alike than different.

Because dysautonomia is the one factor that shows up in ME/CFS, FM, POTS, Long COVID, etc., Lauren may be the most centrally located person I will talk to.

As a dysautonomia expert, Lauren has her eyes on everything from more obscure autonomic conditions like baroreflex failure and Autoimmune Autonomic Ganglionopathy to conditions like chronic fatigue syndrome (ME/CFS), fibromyalgia, and long COVID. Noting that POTS was the most common, and ME/CFS the second most common, comorbid diagnosis in a long-COVID study, she called them “cousins”.

She believes these diseases are more alike than different. Things like small fiber neuropathy, antibodies that disrupt the autonomic and sensory nerves, inflammation, and metabolic abnormalities appear to pervade all these diseases. Her assertion that if we find something in one disease, it will likely show up in the other diseases, brought to mind Avindra Nath’s belief that if we solve one, we will solve them all.

Lauren was a case in point. Through her healthcare journey, she met the criteria for chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), POTS, and mast cell activation syndrome (MCAS) before she was finally diagnosed with Sjogren’s Syndrome.

That made me think of fibromyalgia (FM). Few people associate FM with orthostatic intolerance or POTS, yet multiple studies suggest OI may be common in FM. That makes sense given the evidence that autonomic nervous system problems could be contributing to the pain, sleep, digestive, exercise, and standing problems. At least 8 studies suggest that orthostatic intolerance is present in FM, yet the OI issue is virtually ignored. A 2018 Health Rising poll (n=457) found that 83% of FM patients said their doctors had never recommended a tilt table test.

Is the Entire Autonomic Nervous System Messed Up in Fibromyalgia?

Even if the FM patients had taken a tilt table test, it’s likely that many of them would have still been misdiagnosed, which is why I thought DI’s decision to provide transcranial doppler equipment to several doctors/research groups was simply brilliant. As Lauren explained, ME/CFS and POTS have near identical symptoms, but if you don’t show a high heart rate on tilt table testing, you’ll likely be told that everything is fine.

Visser, Van Campen and Rowe have shown, though, that virtually everyone with ME/CFS – whether they have increased heart rates while standing or not – has reduced blood flows to the brain. That is the core problem with these diseases – not increased heart rates. With this equipment, doctors can show that everything is not fine after all, and that brought up one thing Lauren is really excited about: the STAT earpiece.

Low Brain Blood Flows and Orthostatic Intolerance Ubiquitous in Chronic Fatigue Syndrome (ME/CFS)

The Exciting STAT…err Lumia Earpiece 

Lauren said she’s “genuinely excited” about the potential of the STAT earpiece (recently rebranded to Lumia) which can measure blood flows to the brain. (She’s not the only one. I recently talked to ME/CFS expert Theresa Dowell, who is really excited about the device’s potential to assess treatment effectiveness, pacing, etc. We thought the earpiece would be available by now but I was told November is now the expected release date.)

Could the New STAT Earpiece Bring Instant Credibility to ME/CFS, POTS and Long COVID?

THE GIST

  • The first of Health Rising’s “What’s Up Doc?” Zoom interviews with ME/CFS, FM, long COVID, etc,. experts features Lauren Stiles, the founder of Dysautonomia International. The “What’s Up Doc?” interviews focus on what’s exciting these experts right now, but I first had to ask Lauren about the illness story which led her to create Dysautonomia International. (See the video at the top of the blog.)
  • Lauren was a healthy, athletic, environmental lawyer when a ski accident caused a compression of her spine and intracranial hypertension (high pressure in her brain). It took Lauren two years before she diagnosed herself with postural orthostatic tachycardia (POTS) from her hospital bed.
  • Her ski accident damaged her autonomic nervous system, which tweaked her immune system, which then destroyed most of the small nerve fibers in her body. After another convoluted journey, she ultimately came to find that Sjogren’s Syndrome – a disease she believes is greatly underdiagnosed – had triggered her POTS. IVIG treatment – which came with its own set of serious issues – helped greatly. Check out Lauren’s full story here. 
  • In 2012, Lauren founded Dysautonomia International the leading non-profit researching, educating and advocating about autonomic nervous system conditions. Because dysautonomia is the one factor that shows up in ME/CFS, FM, POTS, long COVID, etc., Lauren has her eyes on things happening in all these diseases.
  • She believes these diseases are more alike than different. Things like small fiber neuropathy, antibodies that disrupt the autonomic and sensory nerves, inflammation, and metabolic abnormalities appear to pervade all these diseases. Her assertion that if we find something in one disease, it will likely show up in the other diseases, brought to mind Avindra Nath’s belief that if we solve one, we will solve them all.
  • Tying all these strange and mostly neglected diseases (ME/CFS, FM, POTS, long COVID) together, Lauren asserted that “chronic autonomic dysfunction is going to lead to chronic immune dysfunction“. That made sense, as the autonomic nervous system is a major regulator of the immune system. The tie that binds all these diseases together is some sort of autonomic impairment.
  • That made me think of fibromyalgia. Studies indicate that dysautonomia could be contributing to everything from pain to sleep to problems standing (orthostatic intolerance), yet few FM patients are ever tested for orthostatic intolerance, and FM is rarely studied in conjunction with its close relatives.
  • Lauren noted that very early in the course of their illness, people with rheumatoid arthritis and Crohn’s disease already exhibit autonomic dysfunction. She explained that during an infection, the autonomic nervous system explodes into action – sometimes to the point of no return – which brings us to a possible ANS tamer – vagus nerve stimulation (VNS).
  • Dysautonomia International has funded three successful VNS trials in autonomic nervous system diseases and Lauren is excited about the potential VNS holds for POTS, long COVID, ME/CFS, FM, etc. Parasym, a European VNS company, is attempting to obtain approval for its device in the US this year.
  • Turning to the $1.6 billion NIH Recover initiative for long COVID, Lauren, who has sat on several RECOVER committees, described a mostly out-of-touch effort that never took patient engagement, or experts from the ME/CFS or other post-infectious illnesses, seriously. She said, “When you give nearly 2 billion dollars to people with no experience in post-viral syndromes, don’t be surprised when what you get is something that’s disconnected with what the patients actually need”, and does not believe that RECOVER is improving.
  • Remarkably, POTS did not have an ICD code that enabled doctors to electronically document its existence until Oct. 2022. Having one now makes it possible to understand how prevalent POTS is, the cost of treating it, helps with disability, and has prompted pharmaceutical companies to start digging into POTS for the first time.
  • Lauren was excited about Stanford research showing that insulin resistance may be contributing to POTS and vice versa, and the new STAT (now called Lumia) earpiece that measures blood flows to the brain. That device should help validate these diseases in the eyes of doctors and give patients and doctors a way to evaluate treatments and improve pacing. It should be available in November.
  • Another subject of great potential for these illnesses is something called ganglionitis which refers to immune-triggered damage to the nerve bundles that relay autonomic and sensory signals to the brain. Ganglionitis could explain many of the strange sensory, as well as the autonomic nervous system, problems in these diseases.
  • Lauren is much better now, but after being bedridden for years, she knows how tough this illness can be and how hard it can be to keep going. She said, though, that “so much research” is going on she that felt “strongly confident” we will see better treatments soon.
  • Health Rising’s Quickie Summer Donation Drive is underway. You can support us by using the donation widget at the bottom of this blog, or with a check, Amazon Gift card or bitcoin gift.
Lumia is presenting new research at their conference showing that blood flow to the head is a better predictor of dysautonomia symptoms than heart rate in POTS. That’s no surprise! Getting a device like this embedded in health care would be a huge win for everyone struggling to get validation for these diseases. (Could any doctor dismiss data showing reduced blood flows to the brain?)

Sjogren’s Syndrome – a Majorly Underdiagnosed Illness in the ME/CFS, POTS, FM, Long-COVID Sphere?

Lauren suggested whatever condition we get diagnosed with first will tend to swallow up all our subsequent symptoms. With our search effectively over, we get stuck with the treatments available for that condition while possibly missing the treatments available for other conditions – which brings up Lauren’s Sjogren’s Syndrome story.

Lauren believes that, absent her Sjogren’s Syndrome diagnosis and the door it opened to IVIG, she could have been bedridden for life. Her POTS, mast cell problems, migraines, and post-exertional malaise all got much better on IVIG.

Check out Health Rising’s IVIG Series

She believes that Sjogren’s Syndrome is widely underdiagnosed in the ME/CFS, POTS, fibromyalgia and long-COVID communities. The Sjogren’s diagnostic criteria is something of a mess. For one, the diagnostic criteria used by doctors is research-based, not clinically based; i.e. it’s highly restrictive, so much so that Lauren herself, because she does not have the antibodies to Sjogren’s (about 40 percent of SS patients do not) would not meet it.

Lauren pointed out a study which showed Sjogren’s patients with a more neuropathic presentation (like those with ME/CFS for fibromyalgia) are more likely not to have SS antibodies. While no drugs have been FDA-approved, off-label drugs are available and clinical trials are underway. As noted above, Lauren’s ability to get IVIG was critical to her improvement. (Note that she highly recommends getting intramuscular IVIG shots over the infusions).

  • She recommended following the Sjogren’s Advocate blog
  • Check out Trish’s ME/CFS/FM/myasthenia gravis story for another story about how a different diagnosis opened up new treatment options

From a Spinal Injury to POTS, ME/CFS/FM and Sjogren’s Syndrome

Concussion Anatomy

Concussions trigger short-term and sometimes long-term autonomic nervous system dysregulation and immune dysfunction. (Image by Max Andrews, CC BY-SA 3.0 Wikimedia Commons)

How Lauren’s spinal injury led the development of SS is unclear, but Lauren noted that a study showed that concussions send the autonomic nervous system into a tizzy. Immediately after a concussion, both symptomatically and at the biological level, everyone after a concussion looks like they have POTS (!) Most people, of course, recover, but a subset get diagnosed with a chronic illness.

She believes that the reason that people who have experienced a concussion have a lifetime increased risk of all-cause mortality is inflammation.

Tying all these strange and mostly neglected diseases (ME/CFS, FM, POTS, long COVID) together, she asserted that “chronic autonomic dysfunction is going to lead to chronic immune dysfunction“. That made sense, as the autonomic nervous system is a major regulator of the immune system. The tie that binds all these diseases together is some sort of autonomic impairment.

Could autonomic nervous system dysregulation set the stage for trigger these and more diseases? She noted that very early in the course of their illness, people with rheumatoid arthritis and Crohn’s disease already exhibit autonomic dysfunction. Lauren explained that during an infection, the autonomic nervous system explodes into action – sometimes to the point of no return – which brings us to a possible ANS tamer – vagus nerve stimulation.

Vagus Nerve Stimulation

Vagus Nerve Stimulation

Dysautonomia International’s trials suggest VNS could be one tool in the complex chronic illness toolkit.  (Manu5, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons)

Dysautonomia International recognized the autonomic implications of COVID-19 very early in the COVID pandemic and attempted to get a vagus nerve stimulation (VNS) study going that would crank up the parasympathetic tone and down-regulate inflammation during acute COVID.

(Interestingly, Lauren noted that benzodiazepines (Ativan, Xanax, Klonopin, Valium) can do the same thing! It’s their ability to stabilize mast cells and tone down sympathetic nervous system activity (and not their ability to reduce anxiety) that makes them so helpful at times in these diseases.)

A presentation at the upcoming Dysautonomia Conference will show that vagus nerve stimulation helped pediatric POTS patients with Ehlers-Danlos Syndrome (EDS). Another study found that NEMOS – a European vagus nerve stimulator – reduced symptom severity and functionality. In all, three different Dysautonomia International-funded trials have shown efficacy in 3 different groups with POTS – a nice track record. If Parasym, a European VNS company, gets approval for its device in the US, people in the US will have more options. Parasym will be presenting at the DI’s international Conference this year (June 28-30, 2024).

When I suggested that wouldn’t it have been great if the RECOVER Initiative for Long COVID had funded a vagus nerve stimulation (VNS) trial, Lauren, (her voice rising a bit (:)) said RECOVER turned down a VNS application because it hadn’t done its homework. It rejected the application because the VNS would not lower the heart rate in POTS. 

Vagus nerve stimulation (VNS), however, is not used in POTS to lower the heart rate. (You’d have to stimulate all day long for it to do that). Instead, it’s used – for a few minutes a day – to lower the inflammation. That episode highlighted a big hole in the RECOVER program: somehow, despite the very early evidence that POTS was a problem in long COVID, it lacked experts in POTS.

Lauren believes that VNS is a benign, safe possibility for people with all these diseases. Because the field is dominated by small companies, it’s taking a while for the devices to take hold. Check out some recent VNS trials.

The RECOVER Initiative Flops Again

“When you give nearly 2 billion dollars to people with no experience in post-viral syndromes, don’t be surprised when what you get is something that’s disconnected with what the patients actually need”. Lauren

RECOVER Initiative Flops Again

RECOVER misses again. Will we ever get good news from the RECOVER Initiative?

Lauren was on multiple planning committees for RECOVER and described a mostly out-of-touch effort. Lauren felt that for the most part, RECOVER never took the patient input aspect of RECOVER – which RECOVER has lauded again and again – seriously. While some individual investigators did involve patients, she felt it was given lip service at the highest levels of the RECOVER leadership.

Dysautonomia International’s request that researchers with decades of experience studying these diseases be included at the leadership level was ignored. She said:

“When you give nearly 2 billion dollars to people with no experience in post-viral syndromes, don’t be surprised when what you get is something that’s disconnected with what the patients actually need”.

Ouch! When asked if RECOVER was adjusting to the many critiques and bad press it’s received, the answer was “absolutely not”. (Double ouch!) Instead of acknowledging that changes need to be made, instead she’s seen more “defensiveness” and an effort to close the ranks on RECOVER’s part. In short, RECOVER feels they’re doing just fine.

Researchers from prestigious institutions like Harvard, Yale, and Stanford all urged RECOVER to do functional autonomic testing in a subset of its patients, yet 3 years later, it is still not doing that. The consequences – no data on functional autonomic dysfunction associated with long COVID from the biggest long-COVID effort on the planet – leaving doctors clueless. Meanwhile, research outside of RECOVER has shown that 70-80% of long-COVID patients have dysautonomia.

(Note that RECOVER is doing tilt table testing in its Tier III patients but isn’t employing the functional autonomic nervous system tests recommended. It is also funding two autonomic nervous system clinical trials – one using IVIG and one using Ivabradine.)

Lisa McCorkell, the founder of the Patient-Led Research Collaborative, feels much the same way about the RECOVER Initiative.

The RECOVER Initiative – Not the Solution for Long COVID (Or Anyone Else)? The Lisa McCorkell Interview

POTS Gets an ICD Code – and Interest from Drug Companies

ICD-10

Getting an ICD code for POTS was huge.

Early RECOVER Initiative studies relied on electronic health records which, because there no ICD code for POTS existed concluded there was no POTS in long COVID.  (The researchers apparently missed the fact that because no code for POTS existed it couldn’t have shown up in their studies.) Outside RECOVER, of course, studies found not only that was POTS common in long COVID but that it was associated with significantly more disability.

Getting the ICD code (G90.A) for POTS in Oct. 2022 was a signature achievement of Dysautonomia International. Despite the fact that POTS is not a disease of the heart or an arrhythmia (it’s a tachycardia), it used to land under ICD code I49.8 “Other specified cardiac arrhythmias”. That code included numerous other medical conditions like Brugada syndrome, re-entrant atrioventricular tachycardia, ectopic rhythm disorder, and other arrhythmias – none of which have anything to do with POTS (POTS is not an arrythmia condition).

Dysautonomia International presented evidence for a change to the US Center for Disease Control committee, which approved the new ICD code (G90.A) Instead of being shunted in under heart conditions, POTS is now found in the autonomic diseases section.

Getting an ICD code may seem like a small thing, but it has big consequences. It makes it possible to understand how prevalent POTS is, the cost of treating it, helps with disability, and of course – electronic health data studies will now pick it up. Interestingly, Lauren said the implementation of the ICD code has also prompted pharmaceutical companies to start digging into POTS for the first time.

The goal now is to make doctors aware of the code change so that they can put it in POTS patients’ medical records. Check out Dysautonomia International’s letter that patients can give to doctors that helps explain what the ICD code and POTS are all about. (ME/CFS’s ICD code, by the way, is G93.32)

The Insulin Resistance Dysautonomia Connection

Insulin Resistance

Could insulin resistance be causing dysautonomia and vice versa? (Image from public domain: Wikimedia Commons)

When asked what else excites her now, she noted that Cyndya A. Shibao at Stanford recently published a paper, “Worsening Postural Tachycardia Syndrome is Associated with Increased Glucose Dependent Insulinotropic Polypeptide Secretion“. After Dr. Shibao noticed that may POTS patients feel worse after a high carbohydrate meal, she showed that POTS patients eating these meals release a peptide called GIP which tells the pancreas to release insulin, potentially increasing the risk of insulin resistance; i.e. pre-pre diabetes. My first thought was, “Finally someone is exploring this very common reaction”.

Plus, sympathetic nervous system activation – a common finding in POTS – stimulates GIP. (She noted that normal blood norepinephrine levels may not reflect high intraneural norepinephrine levels). Insulin sensitivity, in turn, can cause sensory and autonomic nerve damage: a new pathway to POTS shows up! Plus, the finding lends itself to possible treatments. (Note that insulin resistance may predispose one to fibromyalgia as well.)

The other silver lining is the huge funding that diabetes and associated conditions gets, which Dr. Shibao has been able to tap into. (Dr. Shibao recommends that POTS patients try a low carb diet.)

An NIH Center for Post-Infectious Diseases

Lauren said she was 100% behind the effort to build a Center for these diseases at the NIH, helped to draft the legislation, and explained why. She talked about a failed attempt by a well-known and well-funded researcher at a major university to get a multidisciplinary genetics/immune/dysautonomia-funded long-COVID study at the NIH. The researcher was told by the various institutes that they couldn’t fund it because other institutes were responsible for different parts of the study. The application was rejected without even being reviewed.

Right now, ME/CFS researchers are not talking to or collaborating with FM researchers, POTS researchers are not talking to ME/CFS researchers, etc. An NIH Center that prioritized subjects of interest, that had these diseases be studied together, that was intent on showing commonalities between them, etc., would allow all these diseases to move together so much more quickly.

Could the Ganglia Have it?

Take post-exertional malaise (PEM), the signature symptom of ME/CFS. Is it found in POTS and, if so, in what percentage of people with POTS? Right now, we have no idea. After I brought up the recent Gulf War Illness (GWI) study showing no PEM in GWI, Lauren pointed out that a GWI study found damage to the autonomic and sensory nerves (ganglionitis). Might autonomic and sensory nerve damage be the tie that binds all these diseases together? (In an upcoming interview, FM researcher Daniel Clauw will highlight how important he believes damage to sensory processing plays in FM.)

Dorsal Root Ganglia - from Wikimedia

A dorsal root ganglia. (Image DP Wikimedia- Commons – https://commons.wikimedia.org/wiki/File:DRG_Chicken_e7.jpg)

Unfortunately, there are no tests right now for ganglionitis but Lauren (again showing how much she is up on all these diseases) noted that autopsy studies have shown damage to the ganglia in ME/CFS. Ganglia problems have also shown up in post-treatment Lyme disease, and animal data indicates that COVID-19 can damage the autonomic ganglia.

Dr. Martinez-Lavin has proposed that the buck may stop at the dorsal root ganglia in fibromyalgia. Plus, the fibromyalgia study that transferred serum from FM patients to mice found that the mice suffered from damage to the autonomic ganglia. (A POTS serum study is underway…).

Immune Disease? Neutrophils on the Attack in Fibromyalgia

Small fiber neuropathy testing can pick up damage to the sensory nerves, but most labs do not assess the autonomic nerves that are just under them. Note that many things (ischemia, metabolic problems, insulin resistance, infection) can cause damage to these nerves and small fiber neuropathy can be found in many diseases. The good news is that these small nerve fibers can grow back. Lauren lost 85% of small nerve fibers. After IVIG, her small nerves weren’t completely back to par, but they all grew back.

Study Suggests Something in the Blood is Causing Fibromyalgia

Thanks to Dysautonomia International’s input, RECOVER’s autopsy study is going to assess the autonomic ganglia in long COVID. One wonders what role damaged autonomic and sensory nerves will, in the end, play in these diseases. They could explain a lot.

Lauren ended the interview by emphasizing the need to explore the overlaps between all these different, yet similar, fields. Creating an Office at the NIH would be a major step forward.

Lauren Stiles

Lauren says: “hang on!”. She believes better treatments are coming.

Better Treatments Coming

Lauren is much better now, but after being bedridden for years, she knows how tough this illness can be and how hard it can be to keep going. She said, though, that “so much research” is going on she that felt “strongly confident” we will see better treatments soon.

Health Rising’s Quickie Donation Drive Blasts Off!

Rocket Piggy

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