Topic: Sleep Disorders in MS
By Kristin Jenkins

When your MS patient complains: “Doc, I’m fatigued all the time,” listen carefully and ask questions. “You need to find out what your patient really means because there are a lot of reasons to be tired,” said David Brandes, MD, Assistant Clinical Professor, UCLA, and Medical Director, Northridge MS Center, Northridge, CA.

While many patients assume that MS is causing their fatigue, in fact there could be any number of other reasons, ranging from anxiety and depression to occult urinary tract infection. Then again, the patient with MS may be experiencing a primary or secondary sleep disturbance as a result of leg spasms, pain, immobility or nocturia.

Since sleep disorders are common in patients with MS and may complicate the presentation of fatigue, “you may need a sleep consult to determine whether or not fatigue is an MS thing or a sleep thing,” said Rock Heyman MD, Director of the University of Pittsburgh MS Center and Chief, Division of Neuroimmunology, Department of Neurology.

Few physicians are actually trained to diagnose and treat sleep disorders, pointed out Dr. Brandes. Studies show that during the first four years of med school, the average amount of time devoted to sleep disorders is about 20 minutes. Similarly, the study of sleep disorders is a relatively new science, with the first classification of sleep disorders published in 1979.

“Nobody really knows why we need to sleep or why we dream although we do know that resting the body rejuvenates biological processes and resting the brain rejuvenates the central nervous system, including the reticular activating system in the brainstem,” said Dr. Brandes. Sleep efficiency, he added, “should be 95% with a patient being awake no more than 5% during the night.”

Ask your MS patient patients about sleep, whether or not they snore and whether they are experiencing daytime sleepiness,” said Dr. Heyman. Periodic Leg Movements (PLMs) are very common in patients with MS and a certain percentage will require treatment because it is interfering with restorative sleep. In addition, noted Dr. Heyman, neuropathic pain can lower sleep efficiency, leaving the MS patient feeling chronically exhausted.

Medications used to treat MS also may be to blame for a patient’s fatigue. Side effects associated with beta interferon therapy include a flu-like syndrome, which can disrupt sleep. Other MS drugs such as anti-epileptic drugs (AEDs), anti-depressants and anti-spasticity drugs may be causing fatigue. “Many patients assume that fatigue is due to MS when it’s actually caused by the drugs used to treat MS,” said Dr. Brandes. Fatigue could also be one of the side effects associated with non-MS drugs such as anti-histamines and anti-hypertensives.

Many patients with MS have fatigue plus daytime sleepiness (hypersomnia), which produces uncontrollable drowsiness. The patient may complain of having no energy and feeling physically exhausted with very little effort. This may be chronic, because of MS, or it may occur only during acute exacerbation of disease. If the MS patient is depressed, fatigue may be caused by a lack of psychic energy. On the other hand, if the patient has decreased pelvic sensation, an undiagnosed occult urinary tract infection could be the culprit. 

Some 65% of MS patients have periodic limb movements (PLMs) that affect the quality of sleep, said Dr. Brandes. This is defined as a repetitive extension of the big toe with ankle dorsiflexion. Occasionally, the hips and knees may be involved but not the arms. PLMs occurring more than five times during the night affects 5% of people with MS who are 30-49 years of age and 35% of people 50 years of age and older. “We estimate that 15-20% of MS patient with PLMs need treatment,” said Dr. Brandes, adding that the condition—which is associated with narcolepsy, a disorder of REM sleep—is usually diagnosed with the help of the patient’s bed partner and an overnight polysomnogram. Treatment with dopamine agonists used in Parkinson’s disease is quite effective at producing a dose-related response.

Restless Leg Syndrome, on the other hand, occurs only when the patient awake. A feeling of discomfort arises and the patient has to get up and walk around. Restless Leg Syndrome affects 2.5% of the population, said Dr. Brandes, and the incidence increases with age. “Restless Leg Syndrome can be seen in MS patients and it is probably more common than we recognize.” Restless Leg Syndrome, which can be the result of peripheral vascular disease and is made worse by rest, can be diagnosed by history and effectively treated with benzodiazepines such as Clonazepam. In pregnancy, Restless Leg Syndrome appears related to iron deficiency, especially in the third trimester, said Dr. Brandes.

Other possible causes of fatigue include:

* Obstructive Sleep Apnea (OAS), a common disease affecting 2.5 million Americans, occurs more often in men and in people who are obese. Five events/hour of apnea is acceptable; more than five is not, said Dr. Brandes. Treatment with Continuous Positive Airway Pressure (CPAP) is an effective treatment but 50% of people won’t use this without support.

* Central Sleep Apnea is a problem of the central nervous system, pointed out Dr. Brandes, which results in loss of muscular control.

* Narcolepsy appears to be an autoimmune disease involving the HLA-genotype. “We think there may be two kinds of narcolepsy and more than one cause,” said Dr. Brandes, adding, “classical narcolepsy may have an inherited factor. Modafinil (Provigil, Alertec in Canada) appears useful in both narcolepsy and MS.

* REM Sleep Behaviour Disorder (RBD) is heralded by dramatic and violent behaviour such as talking, yelling, swearing and grabbing or beating the bed partner. Many people who have RBD go on to develop Alzheimer’s, said Dr. Brandes.

* Insomnia affects about one-third of people seen in private practice. It is a symptom not a disease and there are many things which can produce it, including depression or anxiety, alcohol withdrawal and poor sleep hygiene. Some 2-10% of people worldwide use sleep agents to treat insomnia. The ideal sleep agent, he added, is effective throughout the night and leaves no daytime hangover.

* Other causes of fatigue in the MS patient include hypothyroidism, hepatic or renal dysfunction, anemia, and chronic fatigue/fibromyalgia.