Autonomic Dysfunction in ME/CFS: Findings from the Multi-Site Clinical Assessment of ME/CFS (MCAM) Study in the USA, 2025, Unger et al

[John Mac]

Abstract​

Background/Objectives: Symptoms of autonomic dysfunction are common in infection-associated chronic conditions and illnesses (IACCIs), including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This study aimed to evaluate autonomic symptoms and their impact on ME/CFS illness severity.

Methods: Data came from a multi-site study conducted in seven ME/CFS specialty clinics during 2012–2020. Autonomic dysfunction was assessed using the Composite Autonomic Symptom Scale 31 (COMPASS-31), medical history, and a lean test originally described by the National Aeronautics and Space Administration (NASA). Illness severity was assessed using Patient-Reported Outcomes Measurement Information System measures, the 36-item short-form, as well as the CDC Symptom Inventory. This analysis included 442 participants who completed the baseline COMPASS-31 assessment, comprising 301 individuals with ME/CFS and 141 healthy controls (HC).

Results: ME/CFS participants reported higher autonomic symptom burden than HC across three assessment tools (all p < 0.0001), including the COMPASS-31 total score (34.1 vs. 6.8) and medical history indicators [dizziness or vertigo (42.6% vs. 2.8%), cold extremities (38.6% vs. 5.7%), and orthostatic intolerance (OI, 33.9% vs. 0.7%)]. Among ME/CFS participants, 97% had at least one autonomic symptom. Those with symptoms in the OI, gastrointestinal, and pupillomotor domains had significantly higher illness severity than those without these symptoms.

Conclusions: ME/CFS patients exhibit a substantial autonomic symptom burden that correlates with greater illness severity. Individualized care strategies targeting dysautonomia assessment and intervention may offer meaningful improvements in symptom management and quality of life for those with ME/CFS and similar chronic conditions.

https://www.mdpi.com/2077-0383/14/17/6269

 

[ME/CFS Science Blog]

Not sure if the term 'autonomic symptoms' is a useful category. For at least some of the symptoms it seems that the problem could lie elsewhere than in the autonomic nervous system?

 

[Jonathan Edwards]

Not sure if the term 'autonomic symptoms' is a useful category. For at least some of the symptoms it seems that the problem could lie elsewhere than in the autonomic nervous system?

Agreed.

 

[Sasha]

Recruiting PwME from clinics means that the housebound, who are likely to have the worst OI, won't have been included, so the study's results will be an underestimate of the problem. It's good that they're looking, though.

However:

Individualized care strategies targeting dysautonomia assessment and intervention may offer meaningful improvements in symptom management and quality of life for those with ME/CFS and similar chronic conditions.

The standard interventions have had zero effect on my OI. I'm not sure we even know that OI in PwME is the same as OI in other people.

 

[Mij]

I don't have unstable BP. It's still unclear whether the relationship between the cardiovascular system and cognitive impairment is causal or simply correlative,

 

[Kitty]

I'm not sure we even know that OI in PwME is the same as OI in other people.

As soon who had it before ME/CS (it started in early childhood), I'd say the symptoms aren't the same even if the underlying cause is.

My mam and I had a type of OI that included a tendency to black out, but it took the best part of half a school assembly to get to the risk of collapse stage. The warning symptoms were feeling nauseous and woozy, not a deafening alarm bell going off in my brain.

The only experience I can compare the ME/CFS version to was free diving training in the deep pit at an indoor pool. When I was running low on air as I ascended from a dive there'd be the same blaring, panicky alarm going off. Being less than three feet from the surface made no more difference than being less than three feet from a chair—the noise didn't stop till I got there.

The difference was that in diving, getting accustomed to it eventually switched off the panic alarm. Never happened in ME/CFS.

[Slightly edited for clarity]

 

[Simon M]

Autonomic dysfunction was assessed using the Composite Autonomic Symptom Scale 31 (COMPASS-31), medical history, and a lean test originally described by the National Aeronautics and Space Administration (NASA).

I'm sure I read that the compass – 32 questionnaire was shown to be a poor measure of objectively measured autonomic problems. But that report came out after this work would've been done. @ME/CFS Science Blog – 00 I misremembering something you posted?

Recruiting PwME from clinics means that the housebound, who are likely to have the worst OI, won't have been included, so the study's results will be an underestimate of the problem. It's good that they're looking, though.

These are the small number of very specialist clinics in the US. I would expect they would see some housebound patients who might well make a huge efforts to get to such a place.. The definition of housebound is usually that you can't leave the house without assistance. But I doubt they saw any bedbound ones. Probably some of their data eg SF 36 physical function would help clarify the level of severity of these patients.

 

[Yann04]

These are the small number of very specialist clinics in the US. I would expect they would see some housebound patients who might well make a huge efforts to get to such a place.. The definition of housebound is usually that you can't leave the house without assistance. But I doubt they saw any bedbound ones. Probably some of their data eg SF 36 physical function would help clarify the level of severity of these patients.

Still leaves out quite a chunk of severe people. Who can’t leave their beds and such and such.

 

[Simon M]

Still leaves out quite a chunk of severe people. Who can’t leave their beds and such and such.

Of course, and that's true of a large majority of ME/CFS studies, with DecodeME as a spectacular exception. Representative samples are rare in this field.

 

[dave30th]

Of course, and that's true of a large majority of ME/CFS studies

They found the funding to assess the BPS approach to homebound with the failed FINE study, the "sister trial" to PACE. There needs to be similar funding for biomedical studies, so they have the bandwidth to collect samples etc from homebound.

 

[ME/CFS Science Blog]

I'm sure I read that the compass – 32 questionnaire was shown to be a poor measure of objectively measured autonomic problems. But that report came out after this work would've been done. @ME/CFS Science Blog – 00 I misremembering something you posted?

Probably this study by Peter Novak:

Mismatch between subjective and objective dysautonomia - Scientific Reports

Autonomic symptom questionnaires are frequently used to assess dysautonomia. It is unknown whether subjective dysautonomia obtained from autonomic questionnaires correlates with objective dysautonomia measured by quantitative autonomic testing. The objective of our study was to determine...

www.nature.com

The lack of correlation between subjective and objective instruments highlights the limitations of the commonly used questionnaires with some patients overestimating and some underestimating true autonomic deficit [...] At this time, the use of autonomic questionnaires as a replacement of autonomic testing cannot be recommended.

 

[ME/CFS Science Blog]

Seems like there is an inflation of the term autonomic dysfunction or dysautonomia. In this paper they report that "38% of the healthy controls had autonomic abnormalities". If it is so common, it's probably not an abnormality anymore?

Using the lean test (not tilt table) the study found that 10.6% of ME/CFS patients had POTS compared to 4.8% in controls. 6.2% had orthostatic hypotension compared to 3.1% in controls.

 

[Nightsong]

Probably not worth its own thread, but may be of some additional interest - there was a recent study reported in JACC (a well-known cardiology journal) of Long COVID patients which found only a small minority met POTS criteria on autonomic function testing:

Link