You wake up….luxuriate in that feeling of early morning bliss, yawn, stretch your arms and extend your toes and with a satisfied sigh fall back into the pillows …hmmm…now that was a good nights sleep.

New sleep studies suggest the autonomic nervous system plays a role in poor sleep

Sleep studies have been pretty unrevealing in ME/CFS…until recently

Those were the days, huh? Now waking up is probably more along the lines of groaning as you try to lift your remarkably heavy feeling limbs. Something definitely went wrong in your big rest and rejuvenate time…

Unrefreshing sleep has been recognized as a major problem in chronic fatigue syndrome for decades; it is for, instance, one of the eight symptoms in the International Definition, but documenting its cause has been difficult to say the least. Some delta wave problems have been found but traditional sleep studies have generally found minor or inconsistent problems in chronic fatigue patients’ sleep and little that could account for the sleep issues found. Several recent reviews of sleep findings highlighted how paltry the findings have been.

A 2012 review concluded that “polysomnographic and other objective measures of sleep have observed few differences in sleep parameters between CFS/ME patients and healthy controls”. A 2011 sleep study reported “While classical sleep studies…. have shown varied, nonspecific changes in sleep structure and efficiency in a subgroup of patients with CFS, these studies have not revealed any substantive evidence indicative of a primary sleep disorder….”

Finally, a 2011 review concluded that Whilst complaints of non-restorative sleep persist.., there is no demonstrable neurophysiological correlate to substantiate a basic deficit in sleep function in CFS. Polysomnographic findings have not shown to be significantly different between subjects with CFS and normal controls.”

In the absence of significant laboratory findings these reviewers suggested that ‘pyschosocial factors’ caused the poor ‘perception’, but not the reality of poor sleep in ME/CFS. Sleep studies have been so unrevealing that it’s gotten to the point where one of the most enduring and common complaints in ME/CFS was being considered something of a mirage…simply a matter of ‘perception’….

Recently, though, some light began to appear at the end of the tunnel. A 2011 study found no differences in ‘classical’ sleep tests (sleep duration, sleep pattern, sleep activity) or cortisol levels but did find a significant difference in a decidedly non-classical sleep test – a measure of autonomic functioning called heart rate variability. Wyller’s 2011 pediatric study measuring other indices of ANS functioning (heart rates, blood pressure) suggested sympathetic nervous system (fight or flight) activation in chronic fatigue syndrome was occurring precisely when the body should be relaxing and recovering – during sleep.

These studies suggested a) sleep researchers may have been digging down the wrong hole for the 20 years and b) a measurable physiological problem was occurring and c) problems with ‘perception’ could not account for the sleep issues reported by ME/CFS.

The Study

In this small study researchers analyzed a variety of heart rate variability (HRV) measures during sleep to see if ME/CFS patients were different from controls. They looked at HRV measures during different stages of sleep and broke out sleepier patients from non-sleepier patients to see if they were different.


This study found no significant changes in sleep architecture (time spent in various stages of sleep) between ME/CFS patients and controls but found significant changes in all heart rate variability measures between the two groups during sleep.

They also found reduced sleep efficiency and reduced total sleep time in the chronic fatigue syndrome patients. When they looked deeper, they found that patients who felt sleepier had a ‘higher fractal scaling index’,, which is believed to indicate increased sympathetic nervous system activity, in Stages 1, 2 and 3 sleep compared to controls.


Heart rate variability tests are believed to provide a ‘mirror’ of the ‘cardiorespiratory control system’. Since the heart rate is a function of parasympathetic and sympathetic nervous system inputs, researchers can use HRV to see if the two are in balance. Increased sympathetic nervous system functioning or decreased parasympathetic nervous system functioning can cause increased heart rates and reduced heart rate variability. Reduced HRV has been associated with increased cardiac risk.

Micro-arousals Getting You Down? The researchers believe the higher fractal scaling indices they found in the sleepier ME/CFS patients suggest ‘micro-arousals’ undetected in traditional sleep studies may be hampering sleep in non-REM periods. With regards to treatment they mentioned Clonidine, an SNS inhibitor and PNS booster  (and glutamate inhibitor) as a possibility. Other options are available and we’ll be covering those in an upcoming post.

Stress is not causing the sleep problems in ME/CFS

One study suggested stress or pain wasn’t keeping ME/CFS patients from getting a good nights sleep; it wassimply sympathetic nervous system activation

In one of the earlier HRV sleep studies,Vollmer-Conna et al. stated they believed the heart rate profile found in ME/CFS was indicative of a ‘hyper-vigilant, inflexible physiological state’ probably caused by poor vagal nerve functioning. (The vagus nerve controls parasympathetic nervous system (‘rest and digest’ functioning.) Interestingly, neither stress nor pain – two commonly ascribed reasons for poor sleep – appeared to have any effect on sleep quality in their study. Instead, heart rate variability values indicating increased activation of the sympathetic nervous system had occurred did.

This suggests something that’s been a long time coming in ME/CFS; it’s not ‘stress’ but the ability of the system to tolerate stress. The SNS is activated by stress (and exercise and other events) but if you’re really sick you don’t need to be under a particular stressor to throw your HRV measures off; you simply need for your sympathetic nervous system to have become (and stay) activated.

Heart Rate Variability Explained (Don’t worry about the remark about ‘sudden cardiac death’; this refers to patients who’ve already had heart attacks, etc. Low HRV increases the risk of that in those patients )

Science worked pretty quickly in this case in some ways and in some ways it didn’t. . The first hint of HRV issues during sleep in ME/CFS showed up in 2011 and by 2013 Togo and Natelson had nailed the issue in a study. In other ways it didn’t; Natelson pointed out that as far back as 1998 researchers had suggested that non-EEG studies might be more effective in assessing sleep quality than EEG studies. By 1997 researchers had shown that ‘autonomic activation’ could induce sleepiness during the daytime yet despite all the positive HRV studies in ME/CFS (and negative sleep studies) only recently have researchers begun to look at autonomic nervous system functioning during sleep in this disorder.

Back to the Autonomic Nervous System

So we’re back to the autonomic nervous system again. This big homeostatic regulator pumps up our systems when we need to exert ourselves and then puts them into rest mode to rejuvenate us. One of two major axes of the stress response, the ANS controls our heart beat, blood pressure, blood flows and it regulates immune functioning. Keep the stress response on long enough and you’ll have pro-inflammatory cytokines flooding the body. Dr Klimas recently tagged the ANS as the system that initiates the pro-inflammatory cascade during exercise she believes causes post-exertional malaise.


  • Classical sleep studies have failed to find the cause for the sleep problems in ME/CFS
  • Several recent studies suggest low heart rate variability (HRV) could play a role
  • Low HRV suggests the ‘fight or flight’ system is turned on even during sleep in ME/CFS
  • This enhanced ‘fight or flight’ activity may produce microarousals that interrupt sleep
  • Sympathetic nervous system inhibitors such as Clonidine may be helpful

Now it appears that that darned system may be keep you and I from getting a good nights sleep. For all the talk on the ANS, though, what it’s doing in ME/CFS is something of a mystery.  HRV tests suggest  the fight or flight side of the sympathetic nervous system is turned on but other ANS tests are often normal.

That means there’s alot left of learn about the role the autonomic nervous system plays in ME/CFS and surprises are surely in store. For now heart rate variability testing consistently suggests a system that’s too wired for its own good is in play in this disorder.

Coming  up we take look at HRV in another fatiguing disorder and see what it tells us about that disorder and ours and we take a look at different options for reducing ‘fight or flight’ activation and increasing the ‘rest and digest’ mode.

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