Sleep research—challenges, findings, and future direction

Challenges in doing CFS and FM sleep research

Dr. Solet laid out a list of why doing sleep research especially with this patient population is difficult. Individuals must be found and be willing to sign on as study subjects.

Diagnostic categories can be difficult to define and the clinical criteria and severity can vary. Pooled data can obscure differences and standard scoring periods of 30 seconds in sleep studies may not detect changes in sleep micro-structure.

Adjustment to sleeping in the lab with equipment can be difficult, especially the first night. Subjects’ awareness that they will be videoed and watched can increase stress. Multiple nights of testing are expensive and stressful for subjects.

Primary sleep problems and other comorbid illnesses complicate conclusions. Dr. Solet said, “We tend to look for our lost keys under the street light because it is brighter there, but that doesn’t mean that’s where the keys are.” Her analogy made clear that although the medical professionals have the tools to study certain issues, patients don’t necessarily have a singular sleep issue to the exclusion of other issues.

Sleep changes in CFS and FM

Dr. Solet made the point that the research findings in studies are inconsistent, possibly due to the small number of people enrolled, a difference in study subjects, or that the study is so small it does not have the statistical power to be convincing.

Dr. Solet cited a study conducted by Melinda L. Jackson and Dorothy Bruck, “Sleep abnormalities in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Review”, J Clin Sleep Med 8, no. 6 (Dec. 15, 2012): 719-728, http://dx.doi.org/10.5664/jcsm.2276 showing there were alterations in sleep stage transitions and sleep instability in CFS and FM, but not a basic deficit in sleep function.

Based on EEG and Polysomnogram tests, there have been some demonstration of changes in sleep architecture in CFS and FM patients with abnormal findings such as:

• Abnormal sleep stage transitions
• Disruption of duration and distribution patterns
• More arousals and lower sleep efficiency (Time in Bed)
• Alpha waves of 8-12 HZ (cycles per seconds) intrusion in 01-4 HZ Delta sleep, abnormal pattern during non-rem sleep on EEG. This means when in deep (Delta) stage sleep, the Alpha (REM) stage intrudes into the deep sleep and interrupts the deep sleep stage, which suggests you are not getting the true benefit of deep sleep. This can be associated with daytime sleepiness, pain and depression.

In ME/CFS patients:
  - Shorter Total Sleep Time (TST)
  - Shorter total Rapid Eye Movement (REM) and more REM to waking (waking up after dreams instead of moving into a deeper sleep)
  - Shorter spindles* called S1, S2, more S1 to waking
  - Extended sleep latency (prolonged sleep onset)

In FM patients:
  - Decreased spindles* in stage 2 sleep. Spindles are a sign of stage 2 sleep and decreased spindle density in stage 2 mechanisms shows impairment. Spindles come from the thalamus through to the cortex. Currently, researchers are looking into the genetics of spindles.
  - Individuals with FM who had the best sleep in the laboratory, when exposed to noises, in Dr. Solet’s research were those who had the most spindles in stage 2 sleep.

* A spindle is a burst of oscillatory brain activity during stage 2 sleep and consists of 12-14 HZ waves, which occurs for at least 0.5 seconds.

The importance of biomarkers in CFS and FM

Dr. Solet asked, “Why are we looking for biomarkers and what good will they be to us?” If real biomarkers could be identified, it would help improve diagnostic ability as well as the following:

• Help to understand the pathways and mechanisms going forward for patients
• Help to increase funding because it would confirm an organizational treatment direction
• Lead to interventions
• Validate subjective experiences

If biomarkers were identified and available, getting a diagnosis would be easier and reached more quickly; thus, there would be less suffering by the patients. Subjective reports by patients are too easily rejected in the absence of an objective biomarker and many times patients feel invisible.

Role of Heart Rate Variability in CFS

A study recently published in Autonomic Neuroscience that looked at Heart Rate Variability (HRV) in CFS is very promising in Dr. Solet’s opinion. Solet explained that HRV refers to the variation in the time interval between heartbeats (presentation slide New Direction: Heart Rate Variability).

This study found that the parasympathetic component—the “fight or flight” mechanism of the autonomic nervous system—was not functioning properly in CFS patients. Instead, it left patients in a more aroused state than should be the case.

The normal changes in heart rate adjustments are not happening and patients end up feeling “wired but tired.” This was a consistent finding and one that Solet views as being very hopeful because there may be ways to modify it, with neuro-feedback or pharmaceutical interventions.

Study citation: Fumiharu Togo and Benjamin H. Natelson, “Heart rate variability during sleep and subsequent sleepiness in patients with chronic fatigue syndrome,” Autonomic Neuroscience 176, no. 1-2 (March 14, 2013): 85-90. doi: 10.1016/j.autneu.2013.02.015.