Research Funded in 1995

Sleep, Immune and Endocrine Function in FMS

Principal Investigator: Harvey Moldofsky, M.D.
University of Toronto Centre for Sleep
Toronto, Ontario, Canada
Award: $29,770 - June 1995

As the brain goes through its sleep-wake cycles, it continually communicates with the immune and neuroendocrine systems (processes that produce serotonin, growth hormone and cytokines like interleukin-1). Moldofsky and co-workers theorize that FMS symptoms result from a disruption of sleep, immune and endocrine functions. In this study, Moldofsky hypothesizes that alterations of the immune and neuroendocrine systems are associated with "alpha" brain wave intrusions during deep level sleep. The "alpha" brain waves indicate an awake-like state and are thought to be associated with the production of symptoms in people with FMS and CFS. They can occur the moment you close your eyes during a boring lecture--you are not fully alert, but you certainly aren't asleep.

A number of studies using healthy males have shown various immune changes associated with sleep. For example, interleukin-1 is increased and natural killer cells are decreased. These changes occur at about the same time of night as the "alpha" brain waves in FMS patients. Moldofsky is studying the interleukin-1 and natural killer cell differences in healthy women and FMS women to determine if "alpha" brain wave intrusion is associated with these immune changes. He is studying these women at times in their menstrual cycle when progesterone is high and low. This study will further our understanding on the interactions between these substances with sleep and clinical symptoms. It may also influence the development of therapeutic interventions specifically targeted for women during various stages of their menstrual cycle.

Dr. Moldofsky was the first researcher to point out that non-refreshing sleep was a problem in both FMS and CFS patients (e.g., waking up feeling tired).

Preliminary Results -- Presented at the 1998 ACR

Moldofsky has shown that the rhythm or chronobiology of how FMS/CFS patients feel throughout a 24-hour period is dramatically different from that of healthy people. He presented preliminary findings at the 1998 ACR meeting on FMS. Patients showed an overall decline in natural killer cell activity during the day and night, as well as alterations in prolactin and cortisol. Moldofsky hypothesizes that the rhythmic patterning of immune and endocrine substances will be distinctly different in patients when compared to healthy controls. The study is now completed and the rest of Dr. Moldofsky's data are being analyzed for submission to a medical journal. We will continue to report on Dr. Moldofsky's progress in the AFSA Update.

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Autonomic Function in FMS and CFS

Principal Investigator: Daniel J. Clauw, M.D.
Georgetown University Medical Center
Washington, DC
Award: $29,650 - June 1995

Has received NIH funding to further his investigation.

The autonomic nervous system is responsible for controlling functions of internal organs and tissues. It enables you to breathe without having to consciously think about it. It also plays an important role in your body's stress responses, getting your heart pumping, your adrenaline flowing, and your muscles charged should the situation warrant it (i.e., when faced with stressful challenges).

Several studies have suggested that autonomic function may be abnormal in FMS and CFS patients. For this project, Clauw performed (1) tilt-table testing which involved tilting a person from a horizontal position to a 60 degree angle with their head above their feet, (2) Holter monitoring of the heart responses to the tilting process, and (3) serum collection to measure various levels of autonomic hormones and transmitting substances in 40 FMS patients and 20 controls. In addition, symptomatology, which may be caused by dysautonomic function, was assessed.

Study Results - Presented at 1996 ACR

(1) Tilt-table testing: Twenty percent of the patients tilted had dizziness along with a significant drop in blood pressure.

(2) Holter monitoring: With the Holter monitor, it is possible to measure the strength of the nerve transmissions going to the heart as well as roughly identify whether the signals are coming from the sympathetic and related neurohormonal systems, or the parasympathetic system. Clauw found that the sympathetic and neurohormonal transmission to the heart was significantly reduced in patients. Under this situation, the autonomic nervous system might be partially crippled in its ability to respond to stressful challenges, such as physical trauma, exertion, or infections.

(3) Neuropeptide Y: This compound functions as a long acting form of norepinephrine (meaning that neuropeptide Y is more stable and easier to analyze). Norepinephrine is one of the transmitting substances involved in the sympathetic part of the autonomic nervous system. Levels of neuropeptide Y in the blood before and during the tilt-table test appeared to be low in the patient group, but there was too much variation in the healthy controls to draw any conclusions. In 1997, Dr. Clauw received NIH funding to further explore his dysautonomic findings in relationship to allergic rhinitis in CFS/FMS patients.