A person starting to awake with their eyes closed is in an alpha rhythm, or “relaxed wakefulness.” These are recorded as “waves” on electrical monitoring devices such as electroencephalographs (EEG) that show the alpha rhythms to have “cycles” that oscillate at about 7 to 13 cycles per second. In stage 1 sleep, the alpha rhythm starts to be replaced by theta and delta wave rhythms which are seen as slower cycles on the EEG. These cycles are termed “slow waves” as they oscillate at about 2 to 3 cycles per second.
Stage 2 sleep shows more of these slow waves and something new – intermittent sleep spindles. These are important and we’ll mention them later. Stage 3 sleep is defined by more than 20% but less than 50% of slow delta waves and stage 4 sleep is greater than 50% delta waves. Stages 3 and 4 are also known as delta wave or slow wave sleep. Stages 1, 2, 3 and 4 constitute a non-rapid eye movement (NREM) sleep episode. Sleep stages occur in 4 to 5 sleep cycles where a cycle is a period composed of a NREM sleep episode and a subsequent REM sleep episode, the combination of which lasts about 90 minutes.
The REM stage increases in length as the night progresses. Delta wave sleep occurs primarily early in sleep and is usually not present after the second sleep cycle. An individual awakened during an early morning REM stage can usually recall dreaming. On average, individuals spend about 40% to 55% of the night in stage 2 sleep, 20% to 25% of the night in REM sleep, 10% to 15% in stage 4 sleep, and the remaining time in stages 1 and 3. That’s what a normal sleep pattern is like.
Along with pain and fatigue, difficulties with sleep are one of the top three complaints in patients with FMS. Up to 60% to 90% of patients with FMS will report subjective complaints of sleep disturbances, both difficulty falling asleep and staying asleep. FMS patients may report that poor sleep can dominate their lives, affecting levels of pain and fatigue with the most profound difficulty being able to fall back asleep after a night-time awakening. If you’ve taken the Fibromyalgia Impact Questionnaire you’ve been asked to rate your sleep on a scale of 0 to 10 with this question, “How have you felt when you get up in the morning?” The question was scored with 0 being “Awoke very tired” and 10 being, “Awoke well rested.”
A prospective study, meaning patients were selected and then followed forward in time using sleep diaries, confirmed that nights of worse sleep are followed by days of increased pain and daily measures of pain predicted poorer subsequent sleep. Sleep impairments also have much more long-term consequences. A study that followed 492 patients with FMS over 1 year found that baseline sleep, meaning the type of sleep at the beginning of the study, predicted 1-year pain. When base-line pain was measured it predicted 1-year physical functioning. When base-line physical functioning was measured it was found to predict 1-year depression. In other words, sleep started the ball rolling. If someone did not have good sleep, they did not have good pain control, and if they did not have good pain control they couldn’t function, and if they couldn’t function they ended up being depressed.
As mentioned in the short report on fatigue and FMS, sleep tends to match fatigue in that patients with FMS also experience the most sleep disturbances from November to March and the most improvement from May to August.
The sleep dysfunction in FMS is not simple insomnia. The general findings are decreases in the total time someone is able to sleep, decreases in time spent in slow wave sleep (delta or stage 3 or 4 sleep), decreases in REM sleep, a higher number of awakenings, longer time needed to return to sleep, and a longer time needed to fall asleep. The longer time needed to fall asleep is medically termed, a longer sleep latency.
The more precise term for FMS is nonrestorative sleep (NRS) – awakening non-refreshed. Given how long FMS has been in the medical world, and how long the unique sleep characteristics of FMS have been known (since about 1975) it was surprising, and actually somewhat sad, that it was not until 2008 that an actual operational definition for nonrestorative sleep was finally published. NRS was considered, “persistently feeling unrefreshed upon awakening in the presence of a normal sleep duration, occurring in the absence of a sleep disorder.” Sounds simple, but that’s the “official” definition.
The first mention of the sleep disturbances in FMS was published in a chapter in a well-known Rheumatology textbook in 1972 written by two physicians who would continue to make significant contributions to the field of FMS. At that time, FMS was known as “fibrositis.” The second author of the chapter was Harold Moldofsky. Dr. Moldofsky is considered the “father” of sleep studies in FMS.
In a sleep electroencephalography study of 10 FMS patients (7 female, 3 male), using an EEG, the electrical monitoring device that records brain waves, he found near absent stage 3 sleep and absent stage 4. He also noted something very unusual that has since become the hallmark of sleep in nearly all patients with FMS. The NREM delta wave sleep (slow wave stages 3 and 4), that normally continues undisturbed, kept being interrupted by alpha-wave rhythm sleep patterns.
This intrigued Dr. Moldofsky. Being very bright, he tried something unique. He recruited six healthy males and had them sleep in his sleep laboratory connected to the monitoring equipment. When they began to enter NREM delta wave sleep his technicians would wake them up. This continued over three consecutive nights. By the fourth day they developed complaints of stiffness, achy pain, fatigue, and mood disturbances.
Dr. Moldofsky essentially re-created the symptoms of FMS by sleep deprivation! A second study by Moldofsky one year later where he deprived for three nights six subjects of stage 4 sleep and seven subjects of REM sleep found increases in muscle tenderness only in subjects in whom stage 4 sleep was disrupted. That’s how specific the sleep interruption needed to be.
In the ensuing 35 years this sleep abnormality has been termed, “alpha intrusion on delta wave sleep,” “alpha-delta sleep EEG pattern,” and, the “alpha NREM sleep anomaly.” and alpha intrusion has been broadened to include intrusion into all stages of NREM sleep. Although this particular characteristic has been suggested to be a defining characteristic of both FMS and chronic fatigue syndrome it does not occur in all patients with FMS and it is seen in other diseases as well. Also, other researchers who have tried to replicate Dr. Moldofsky’s sleep interruption experiment have not been that successful.
As the study of FMS has progressed, more interesting findings regarding sleep have emerged and other sleep abnormalities have been noted in patients with FMS. One of these abnormalities is called cyclic alternating patterns, CAPs, that are observed only in non-REM sleep. When CAPs are present in sleep it means that the brain is still being vigilant and “watching out for things,” it has not been able to quiet itself down. CAPs have been correlated to the duration of FMS and the number of tender points. The increased occurrence of CAPs may be associated with a second sleep characteristic noted in FMS patients: decreased sleep spindles in stage 2 sleep.
The decreased number of sleep spindles suggest the same thing in that the brain is still being hypervigilant, but the sleep spindles are a little more specific and indicate activity that is occurring in the thalamus. The thalamus is a structure in the brain that can be termed a “sensory gate.” When it is closed, sensory information is prevented from reaching the “feeling” parts of the brain and an individual does not actually “sense” discomfort. If the “sensory gate” is open, then an individual will be able to feel and localize discomfort. The presence of CAPs are thought to suggest that in a chronic pain state like FMS, the thalamic sensory gate loses the ability to close all the way during sleep and the brain is constantly being nudged a bit, so it isn’t able to fall into a restful sleep.
As most people with FMS know, the most common primary sleep disorder in patients with FMS is restless legs disorder (RLS) which was first named in 1945 by the Swedish Neurologist Karl Ekbom. It was originally known as Ekbom’s Syndrome. However, the first descriptions can be found in a book written by a very famous English anatomist, Sir Thomas Willis, called De Anima Brutorum, concerned with the mental processes of the brain and their derangement, published in 1672.
As an independent disease RLS has a significant economic cost and a substantial impact on quality of life. RLS is not an insignificant disorder. There is actually an International Restless Leg Society that keeps reviewing treatments and publishes the symptoms necessary for a patient to be given a diagnosis of RLS. The clinical diagnostic criteria for RLS were reviewed in 2003 by the International Restless Leg Study Group as well as by the U.S. National Institute of Health. Here is what they have decided: “An urge to move the legs due to uncomfortable sensations which worsen during inactivity and at night with symptoms being relieved partially or totally by movement.”
The sensations may be described as being itchy or electrical in nature and may seem to come from deep in the bones, usually the shin bones, between the knee and ankle. As the disease progresses symptoms may occur earlier in the day and can begin to move further up the leg. In a 2009 study of 3302 European women with FMS, 64% were found to have RLS. However, this study was conducted at a specialty clinic and the percentage most likely has over-estimated that which would be found in the general population.
There is some interesting science being uncovered that is beginning to connect RLS and FMS and explain why RLS so frequently accompanies FMS. RLS is a dysfunction of a particular chemical system in the brain, or more specifically, a neurotransmitter system in the brain, called the dopaminergic system. Some of the newer scientific findings have also found that the dopaminergic system contributes to other symptoms of FMS than just RLS. Using an advanced imaging tool called positron emission tomography, researchers have shown that the brains of FMS patients do not handle dopamine the way people without FMS do, to the point where it is actually dysfunctional. In short, the problem seems to be regions of the brains of FMS patients do not have enough dopamine. Some parts of their brains have now tried to become accustomed to low levels of dopamine but certain dopamine receptors still cannot function normally; receptors are the “keyhole” like molecules on the surfaces of nerve cells to which dopamine will bind and then cause changes.
FMS patients without RLS, who have been treated in research settings with a particular drug called pramipexole, showed significant improvement in measures of pain, fatigue, function and global status. This drug is able to act similar to dopamine and bind to the dopamine receptors. Consequently, some new medication options are being suggested for the treatment of FMS patients. Another correlation between dopamine and FMS was just reported in a 2010 study that found a high frequency of a history of childhood ADHD (attention deficit hyperactivity disorder) in women with FMS. ADHD is also a medical condition in which the brain does not have enough dopamine.
RLS is treated with medications that act at the dopamine receptors, termed dopamine agonists. Some patients note that if they have been diagnosed with RLS, begin treatment with a dopamine agonist, and find their RLS symptoms resolve their sleep noticeably improves as does their corresponding daily level of pain. If a dose of their RLS medication is missed, especially the medication ropinirole, which is noted to have a higher incidence of rebound effects, their sleep is profoundly disturbed leading to even greater pain complaints. In effect, what has happened is that by waking up so frequently they have reproduced the sleep experiments described earlier, where Dr. Moldofsky woke up people every time they started to fall into a deep sleep.
Future short reports will talk about the available treatments for RLS as well as how some other neuro-chemical systems in the brain may have changed in FMS as a result of disturbed sleep and, most importantly, how these systems have affected the brain’s ability to control pain. There are even more fascinating connections coming up.
