Fibromyalgia in obstructive sleep apnea-hypopnea syndrome: a systematic review and meta-analysis, 2024, He et al.

[nataliezzz]

The reason I’m sceptical off the bat, is that we see hundreds of publication about ME/CFS, FM, LC, etc. every year by researcher and doctors that show some kind of correlation between two kinds of variables, and then try to make up an elaborate story about how they have to be connected somehow. Very few of them hold up under scrutiny.

I’m not saying you are wrong for that reason. But the default assumption has to be that there is no connection, and then it’s up to someone to disprove it and demonstrate that there actually is something there. Otherwise we’d spend all our time collectively chasing red herrings. That’s not to say that we don’t need people to have creative ideas and explore possible connections (we won’t get anywhere without it) - just that getting others to follow your particular path over something else will take some convincing.

That's why I also shared this:

It's definitely not just a random correlation considering the multiple case reports of fibromyalgia cures with treatment of OSA from different authors/countries (one with the objective finding of alpha-delta sleep [the only consistent objective finding associated with fibro] disappearing along with fibro symptoms), Dr. Gold's study showing that fibro patients had a more collapsible upper airway (and one fibro patient who was unemployed due to symptoms returned to full employment after getting on CPAP), other studies showing improvement in fibro symptoms with CPAP treatment over traditional medication therapy, etc... It's not just about one piece of evidence here, it's about all of it together (but apparently some people won't even consider it until there is a large RCT proving it; although at this point I think even if there were, most people might *still* ignore it lol)

Again, it's not just about one piece of data here, it's about the collective evidence (meta-analysis, small studies, case reports, etc.) and this clinical experience below from 2 sleep doctors not affiliated with Dr. Gold certainly doesn't hurt either:

However, most UARS patients do not have a primary complaint of sleepiness. Dr. Guilleminault (who was not affiliated with Dr. Gold, by the way; he passed away in 2019) said this in 2004: Today, the clinical picture of UARS is better defined. We have learned that patients usually seek treatment with a somatic functional syndrome rather than sleep-disordered breathing or even a disorder of excessive daytime sleepiness (Upper airway resistance syndrome--one decade later)

In addition, this from Dr. Denise Dewald (another sleep doctor not affiliated with Dr. Gold):

"I think of flow limitation as a really important thing to look at when you're looking at a PSG [polysomnogram] and deciding is this a normal study, or is it not? Spoiler alert: just about everyone who's referred for a sleep complaint does not have a normal study. After thousands of sleep studies, I have yet to see an actual normal study* in someone who was symptomatic. The only normal studies I've seen have been in people who are referred because they needed a sleep study for bariatric surgery or because they work in transportation. Oh, and there was one guy who was sent by his cardiologist because he developed atrial fibrillation, and so of course he needed a sleep study, but he had rheumatic valvular disease."

*i.e. no flow limitation during non-REM sleep; most people have some flow limitation during REM due to loss of muscle tone

Thank you for at least engaging with me on it.

 

[nataliezzz]

I thought the AI summary was pretty good.

You need to look at the case reports of fibromyalgia cures with treatment of OSA, the other smaller studies, etc. along with the meta-analysis (and take into account Dr. Gold's theory of how sleep-disordered breathing could be causing fibromyalgia: as he states in his thesis in Sleep Medicine Reviews: One can demonstrate associations in cross-sectional studies and treatment effects in sham-controlled longitudinal studies, but if one cannot provide a rationale, a paradigm, connecting SDB [sleep-disordered breathing] to pain, diarrhea or anxiety, one will have a difficult time convincing anyone about the truth of the relationship.)

I'm focusing on fibromyalgia and not ME/CFS now, because that's where most of the evidence is.

 

[nataliezzz]

And here is the AI summary of the UARS theory. One thing that didn't make it into that summary that I think is compelling is that it provides a very simple explanation for why people with hypermobility/EDS (many of whom had no significant issues other than occasional dislocating joints prior to an infection/other stressor) are more likely to develop ME/CFS, fibromyalgia, and other related disorders (more lax connective tissue = more collapsible upper airway). A meta-analysis (see below) found that "When directly compared to the general population, patients with EDS/MFS [Marfan syndrome] were on average six times more likely to have a diagnosis of OSA [obstructive sleep apnea]"

Prevalence of Obstructive Sleep Apnea in Joint Hypermobility Syndrome: A Systematic Review and Meta-Analysis

 

[SNT Gatchaman]

I'd love to hear from other people who haven't weighed in on UARS yet like @Sean, @Andy @rvallee, @Nightsong @SNT Gatchaman etc. and @ME/CFS Science Blog

And here is the AI summary of the UARS theory.

The AI summary concludes:

This hypothesis provides a unifying framework that can explain many puzzling aspects of ME/CFS and related illnesses.

• Diverse Triggers: It accounts for how any type of severe stressor—not just infections—can trigger an identical syndrome by focusing on HPA axis activation as the common pathway to sensitization.
• Post-Exertional Malaise (PEM): PEM can be understood as a manifestation of a dysfunctional CNS stress response. Exertion (physical, cognitive, or emotional) acts as an additional stressor on an already over-taxed system, leading to a crash. This aligns with observations that CNS depressants (e.g., benzodiazepines) can sometimes prevent or reduce PEM.
• Partial Efficacy of Treatment: It explains why treatments like CPAP/BiPAP often provide significant (~35-50%) but incomplete relief. While these therapies reduce IFL, the device itself (pressure, mask) can act as a new stressor on a highly sensitized nervous system, preventing full recovery. More curative treatments may involve surgery or, for some, nervous system regulation techniques that aim to desensitize the stress response itself.

The hypothesis depends on central sensitisation and we have too much evidence implicating peripheral pathology that needs investigating, before even needing to consider central sensitisation. The proposed treatment is brain/limbic/amygdala retraining, with extra steps.

Looking at GWI, how might this mechanism help explain the one third of deployed personnel in 1991 being affected not repeating in subsequent conflicts. The Gulf War was a short and "easy" conflict for Coalition forces. Afghanistan and Iraq were long, bloody, horrific and incredibly stressful. The evidence indicates GWI was due to our own forces blowing up enemy ammo dumps and dispersing organophosphate nerve gas over a wide area, at low level.

From my perspective I don't have any evidence of IFL - I've never snored and slept like the proverbial before becoming sick. I didn't have a stress event to blame when I did. In fact I initially got sick on an idyllic summer sailing cruise, drifting around in paradise with not a care in the world. I had no idea what was suddenly happening to me.

Spoiler: Example of a personal physical and emotional stress event involving death

Four years prior I responded to a close-by coastal Mayday for a cardiac arrest. I had to jump off our boat, swim across to the distressed vessel in 18 knots of wind and do CPR for 40 minutes till the helicopter arrived. The diver (my age, ex-military) died under my hands.

… I'm sure my HPA axis was quite activated - shouldn't I have developed this illness then?

 

[nataliezzz]

The hypothesis depends on central sensitisation and we have too much evidence implicating peripheral pathology that needs investigating, before even needing to consider central sensitisation. The proposed treatment is brain/limbic/amygdala retraining, with extra steps.

Well yes, that could be one approach to recovering from UARS (although I've never suggested everyone can recover this way); I've always focused my efforts on raising awareness on the sleep-disordered breathing treatment piece. I don't think a theory is bad simply because one proposed treatment approach for it is unpalatable to people.

Re: peripheral pathology, don't think UARS is incompatible with high rates of SFN, for ex. (SFN could be downstream of chronic ANS dysfunction/hypoperfusion caused by UARS).

Looking at GWI, how might this mechanism help explain the one third of deployed personnel in 1991 being affected not repeating in subsequent conflicts. The Gulf War was a short and "easy" conflict for Coalition forces. Afghanistan and Iraq were long, bloody, horrific and incredibly stressful. The evidence indicates GWI was due to our own forces blowing up enemy ammo dumps and dispersing organophosphate nerve gas over a wide area, at low level.

There's actually plenty of people coming back from other conflicts with "war-related illness" too. Although GWI may be more than one thing, the clinical presentation of GWI is often identical to ME/CFS and does not fit with the clinical picture of a toxic chemical injury (e.g. symptoms fluctuating by the day/hour, post-exertional malaise, etc.)

From my perspective I don't have any evidence of IFL - I've never snored and slept like the proverbial before becoming sick.

Many people with UARS do not audibly snore. You can't possibly know whether or not you have IFL unless you have a sleep study with pressure transducers used (thermistors don't cut it).

I didn't have a stress event to blame when I did. In fact I initially got sick on an idyllic summer sailing cruise, drifting around in paradise with not a care in the world. I had no idea what was suddenly happening to me.

Interesting that you had no apparent stressor as a trigger. Glad to hear from another non-infectious onset person (although maybe you suspect an asymptomatic infection?) I get pretty tired of the whole IACC/PAIS/etc. narrative when many of us had clear non-infectious triggers (and more rarely, as in your case, no apparent trigger at all; although many people with no clear trigger will report that they were going through some kind of period of increased stress of one kind or another when their illness started - obviously not the case for you though).

… I'm sure my HPA axis was quite activated - shouldn't I have developed this illness then?

We can ask the same question about why people can get a bunch of infections (including the same one that ultimately triggers their ME/CFS) without any problems; shouldn't the person have developed ME/CFS the 1st/2nd/3rd/etc. time they had the flu/COVID/etc.?

The trigger for my ME/CFS was a day of intense physical activity (and ongoing undiagnosed celiac disease with GI symptoms for >1.5 years was probably part of the picture too). Several months prior to that I had worked on a trail crew for a few months swinging pickaxes and sledgehammers for hours a day and did not develop ME/CFS. Why was the one day of intense physical activity months later the ultimate trigger? Who knows.

 

[SNT Gatchaman]

the clinical presentation of GWI is often identical to ME/CFS and does not fit with the clinical picture of a toxic chemical injury (e.g. symptoms fluctuating by the day/hour, post-exertional malaise, etc.)

From Evaluation of a Gene–Environment Interaction of PON1 and Low-Level Nerve Agent Exposure with Gulf War Illness: A Prevalence Case–Control Study Drawn from the U.S. Military Health Survey’s National Population Sample (2022) —

A similar body of epidemiologic and clinical evidence has demonstrated a neurocognitive syndrome and dysfunction of the central nervous system and postural instability similar to those in GWI in the Japanese survivors of sarin attacks (by the Aum Shinrikyo cult on a housing subdivision in Matsumoto, Japan, in 1994 and on the Tokyo subway in 1995) in whom the severity of the chronic illness increased with the documented dose of sublethal sarin exposure.

Interesting that you had no apparent stressor as a trigger. Glad to hear from another non-infectious onset person (although maybe you suspect an asymptomatic infection?) I get pretty tired of the whole IACC/PAIS/etc. narrative when many of us had clear non-infectious triggers (and more rarely, as in your case, no apparent trigger at all; although many people with no clear trigger will report that they were going through some kind of period of increased stress of one kind or another when their illness started - obviously not the case for you though).

I have good immunological evidence that I had an asymptomatic infection some months prior. I also have a close relative that developed LC/ME after their 3rd mild Covid infection.