Editorial: Autonomic markers, chronic fatigue syndrome, and post-exertion states, 2019, Friedberg

[Andy]

A large body of evidence suggests that autonomic imbalance, i.e., hyperactive sympathetic nervous system and hypoactive parasympathetic nervous system, is associated with a number of pathological conditions and diseases, and may be a final common pathway to increased morbidity and mortality [1]. Heart rate variability (HRV), a measure of inter-beat interval fluctuations and more broadly of parasympathetic (vagal) activity has been successfully used to index autonomic imbalances [1]. HRV provides a conveniently assessed, non-invasive window onto the autonomic system. It should be noted that HRV is an indirect measure of autonomic output, as it measures the end organ response to the autonomic nervous system. Reduced HRV is associated with autonomic impairments that precede changes in the heart rate (HR) itself or other physiological measures of distress [2]. In addition to HRV, other cardiac measures including HR and time-to-recovery of resting HR after exposure to a stressor provide valid indices of centrally-mediated vagal inhibition of sympatho-excitatory circuits [3].

Paywall, https://www.sciencedirect.com/science/article/abs/pii/S0022399919309055
Scihub, https://sci-hub.se/10.1016/j.jpsychores.2019.109845

 

[Marco]

This editorial argues for the conduct of new autonomic studies in
CFS focused on post-exertion states as they may generate findings unique
to this illness that ultimately could lead to a biomarker

Seems like a reasonable idea although I doubt there's anything unique to find.

 

[Snow Leopard]

The problem with measures of HRV is they are quite non-specific. A lack of fitness in general is a strong predictor of lower HRV. Sleep disruption and other factors can also alter HRV as discussed in the editorial.

The findings (across more than a handful of studies I have seen) tend to show lower HF, rather than a reduction in LF influence, which suggests lower parasympathetic activity, rather than increased sympathetic activity which lends further weight to the hypothesis that the HRV findings are primarily due to lower fitness/activity levels.

Seems like a reasonable idea although I doubt there's anything unique to find.

I agree. There have been a small number of studies already that have not found anything specific, likely due to significant within-group variation.

Friedburg cites the 'sustained arousal' model, but fails to note that the findings of higher catecholamines has only been found in adolescents by one research group and may reflect the social context of the testing (of ill adolescents), rather than be a generalised finding. Notably, this finding has not been replicated in adults.

 

[MSEsperanza]

Not sure how the editorial is related to the two studies announced here:

https://reporter.nih.gov/search/MFkYFqJYG0-YuVKog5mE5Q/projects

Some details could be relevant for discussions on research methodology and hint to caveats that apply for ME research in particular. Not able to explain now or link to relevant discussions on other threads, so just leave the links to the study reports here:

https://clinicaltrials.gov/ct2/show/NCT02948556?id=NCT02948556&draw=2&rank=1&load=cart

https://clinicaltrials.gov/ct2/show/NCT03331419?id=NCT03331419&draw=2&rank=1&load=cart

 

[Mithriel]

hyperactive sympathetic nervous system and hypoactive parasympathetic nervous system

There may well be something wrong with these systems in ME but this is awfully close to ideas like central sensitisation and other BPS ideas.

If the sympathetic nervous system is hyperactive then you are anxious so CBT and mindfulness will cure you.

If they are going wrong in ME it is more likely that it is the result of the body being so physically damaged that we are like someone who is in cardiac failure not a healthy body reacting abnormally to the outside world.

Researchers need to be aware of the way their research could get abused and make sure they protect us.

 

[Hutan]

Some details could be relevant for discussions on research methodology and hint to caveats that apply for ME research in particular. Not able to explain now or link to relevant discussions on other threads, so just leave the links to the study reports here:

https://clinicaltrials.gov/ct2/show/NCT02948556?id=NCT02948556&draw=2&rank=1&load=cart

Research project with $400,000 of funding in 2016. Led by Fred Friedberg, expected completion date May 2020. No results posted to date.
Brief Summary:

The purpose of this study is to identify daily activity patterns, negative life events and autonomic abnormalities that may be related to non-improvement in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). For both naturalistic studies and behavioral intervention trials, roughly 50% of patients report worsening or unchanged illness. The proposed four year study would be the first to look at the relation between illness non-improvement, patient activities at home and autonomic function. Our long-range goal is to identify physiological signals and activity patterns that predict non-improvement and relapse and develop a self-management program that prescribes improvement-linked behaviors and discourages non-improvement activities.

Specific Aim 1: To assess the relation between non-improvement and prospectively assessed activity patterns and life events. Hypothesis 1: Non-improvement will be significantly associated with these dimensional variables: (a) illness-exacerbating activity patterns (e.g., "push-crash") reported on home web diaries; (b) daily hassles assessed in web diaries; and (c) negative life events reported in phone interviews.

Specific Aim 2: To assess the relation between improvement and prospectively assessed activity patterns and life events. Hypothesis 2: Improvement will be significantly associated with: (a) illness-moderating activity patterns (e.g., healthy pacing) reported on home web diaries; (b) daily uplifts assessed in web diaries; and (c) positive life events assessed in phone interviews.

Specific Aim 3: To assess the relation between activity patterns and symptoms. Hypothesis 3: (a) the "push-crash" pattern will predict greater actigraphy variability and symptom variability; (b) the "limiting activity" pattern will be associated with very low actigraphy counts and high symptom severity; and (c) a healthier "pacing" pattern will be associated with moderate variability of actigraphy and symptoms.

 

[Trish]

Specific Aim 3: To assess the relation between activity patterns and symptoms. Hypothesis 3: (a) the "push-crash" pattern will predict greater actigraphy variability and symptom variability; (b) the "limiting activity" pattern will be associated with very low actigraphy counts and high symptom severity; and (c) a healthier "pacing" pattern will be associated with moderate variability of actigraphy and symptoms.

Am I misreading this? That sounds like they are prejudging activity levels as good and bad. Specifically, the low actvity counts are predicted to be associated with high symptoms severity. Surely that's inevitable, since sicker patients are by definition less able to be active. It's the last one that bothers me particularly, following on from the severe one: 'a healthier pacing pattern...

So they seem to be judging those with moderate activity able to pace and still have some activity levels as showing 'healthier' behaviour than the very sick able to do less.

I think hypotheses like this, although they are careful to use association not causation as their word relating activity to symptoms, need to be more careful not to add any value laden hints to their wording and order of examples and order of sentences.

Here's what I would prefer as the wording, that includes no value judgements or implied directions of causation:

Specific Aim 3: To assess the relation between symptoms and activity patterns. Hypothesis 3: (a) there will be a direct association between activity variability and symptom variability; (b) there will be an inverse association between overall symptom severity level and mean actigraphy count.

 

[Hutan]

This is the inclusion criteria for that study:

Fukuda-based ME/CFS symptoms including:

• six months of unexplained, debilitating fatigue
• 4/8 secondary symptoms impaired memory or concentration unrefreshing sleep sore throats headache muscle pain joint pain tender lymph nodes post-exertional malaise

It's a bit sad when the President of the International Association of CFS/ME is not requiring participants in his ME/CFS research to have PEM.

 

[Mithriel]

Too many of these researchers think of CFS even if they now say ME. They have no idea of what our disease does to us.

Thinking about it, people with unexplained fatigue must outnumber those who specifically have ME especially as people with ME give up on the medical profession, so the ones they see the most are similar to each other and do not have PEM but more of a post exertional fatigue.

PEM is so nonspecific that the 6 months of fatigue could then seem to cover it as the cardinal symptom.

I can't see why they do it otherwise.