Sleep disorders: Mayo's deep experience

Image of polysomnography for patient in sleep lab After initial clinical evaluation, patients may be referred for polysomnography in the center's 24-bed sleep lab.
Image of staff monitoring patients in sleep lab Sleep center specialists and staff monitor patients in the sleep lab.

The Center for Sleep Medicine at Mayo Clinic in Rochester, Minn., has a comprehensive, multidisciplinary practice treating children and adults. With a strong clinical focus, the center has consultants with experience diagnosing and treating sleep disorders ranging from the rare to the well-known. After initial clinical evaluation, patients may be referred for polysomnography in the center's 24-bed sleep lab.

The center's 22 consultants include neurologists, psychiatrists, pediatricians and pulmonologists. The neurologists who treat adults at the center specialize in sleep medicine. Although Mayo's sleep medicine specialists treat the full spectrum of neurological sleep disorders, particular areas of interest include Willis-Ekbom disease, also known as restless legs syndrome, rapid eye movement (REM) sleep behavior disorder and narcolepsy.

Willis-Ekbom disease (restless legs syndrome)

Mayo Clinic has a national reputation in treatment for and research on Willis-Ekbom disease, the most common sleep-related movement disorder seen at Mayo. Michael H. Silber, M.B., Ch.B., co-director of the Center for Sleep Medicine in Minnesota, currently serves as chair of the medical advisory board of the Willis-Ekbom Disease Foundation, which is revising the national algorithm for treating the condition.

"At Mayo, we are very interested, and have experience, in the management of complex cases of Willis-Ekbom disease," Dr. Silber says. "We see lots of patients with treatment-related problems, in which there have been drug failures and drug side effects."

Although therapies, notably dopamine agonists, are available to treat Willis-Ekbom disease, managing the condition remains difficult. The results of a recent Mayo study of the long-term effects of treatment with the dopamine agonist pramipexole suggest that the drug's efficacy decreases over time, leading to increased dosages and adjunct therapies.

According to an article in the December 2012 issue of Sleep Medicine, augmentation developed in 42 percent of patients in the Mayo study over a mean follow-up period of eight years. Side effects, including daytime sleepiness and impulse control disorders, were reported by 74 percent of study participants.

For patients who experience difficulties with dopamine agonists, Mayo neurologists have experience prescribing alternatives, including gabapentin, pregabalin and opioids. Iron supplements may be prescribed for patients with iron deficiency, which has been associated with Willis-Ekbom disease.

REM sleep behavior disorder

Rapid eye movement sleep behavior disorder (RBD) is a parasomnia characterized by dream-enactment behavior and abnormal motor activity during REM sleep. RBD has been considered rare, but recent Mayo Clinic research suggests the incidence may be higher than previously thought, particularly in men older than age 70. "We have a lot of experience with REM sleep behavior disorder," Dr. Silber notes.

Clonazepam has been the most common first line treatment for RBD. But the medication's possible side effects — which include cognitive impairment, dizziness and unsteadiness — are of particular concern in elderly patients. A recent Mayo study compared longitudinal outcomes for RBD treated with clonazepam and melatonin.

According to an article in the March 2013 issue of Sleep Medicine, the results indicated that although both treatments reduced RBD behaviors and injuries, melatonin-treated patients reported fewer adverse effects. "We're starting to recommend that treatment start with melatonin and then move to clonazepam if it doesn't work," Dr. Silber says.

Mayo physicians have also been at the forefront of research linking RBD to neurodegenerative disorders. A recent collaborative study with researchers from the University of Minnesota, updating research begun in the 1990s, reported that the vast majority (81 percent) of men initially diagnosed with idiopathic RBD developed a parkinsonian disorder or dementia. The mean interval from onset of RBD to emergence of the neurodegenerative disorder was 14 years, with the range extending to 29 years.

"Unfortunately, at this point there are no medications that can prevent that progression from happening," Dr. Silber says. "But this predisposed group will be an excellent model for testing such drugs as soon as they become available."

Narcolepsy

Narcolepsy has been studied and treated at Mayo Clinic since at least the 1930s. Mayo researchers completed one of the first epidemiologic studies of the disease, defining its prevalence and incidence. As with other sleep disorders, Mayo physicians have experience treating complex cases of narcolepsy. A range of stimulant medications are available — the major challenge, establishing a dose that is effective while minimizing adverse side effects.

A Mayo study, according to an article in the June 2005 issue of Sleep, demonstrated a significantly higher occurrence of psychosis, substance misuse and psychiatric hospitalizations in patients with narcolepsy who used high-dose stimulant therapy compared with those using standard doses. Mayo physicians also have experience with the range of selective serotonin reuptake inhibitors and norepinephrine reuptake inhibitors prescribed for cataplexy, as well as sodium oxybate, which helps improve nighttime sleep and may help with daytime sleepiness.

Research on the progression of narcolepsy is yielding intriguing results that may ultimately improve treatment. Mayo participated in a recent international study on narcolepsy without cataplexy. Previous research has focused mostly on narcolepsy with cataplexy, which is associated with hypocretin deficiency and the presence of the HLA-DQB1*0602 gene; it is considered a lifelong condition requiring treatment with potentially addictive medications. Narcolepsy without cataplexy, in which hypocretin levels are often normal, is less common.

According to an article in the September 2012 issue of Sleep, in a retrospective study of 171 cases of narcolepsy without cataplexy, Mayo researchers and colleagues found that nearly one-fourth (24 percent) of the patients studied had hypocretin deficiency. All of these patients were HLA-DBQ1*0602 positive. Of the 127 patients the researchers were able to recontact, 33 percent with low hypocretin had developed typical cataplexy by 26 years after onset of narcolepsy, whereas only 1 percent of patients with normal hypocretin had developed cataplexy.

Although more research is needed, the study suggests that the presence of hypocretin deficiency in HLA-positive patients may allow physicians to better predict the lifelong evolution of narcolepsy and thus guide treatment.

For more information

Lipford MC, et al. Long-term use of pramipexole in the management of restless legs syndrome. Sleep Medicine. 2012;13:1280.

McCarter SJ, et al. Treatment outcomes in REM sleep behavior disorder. Sleep Medicine. 2013;14:237.

Schenck CH, et al. Delayed emergence of a parkinsonian disorder or dementia in 81% of older males initially diagnosed with idiopathic REM sleep behavior disorder (RBD): A 16 year update on a previously reported series. Sleep Medicine. 2013;14:744.

Auger RR, et al. Risks of high-dose stimulants in the treatment of disorders of excessive somnolence: A case-control study. Sleep. 2005;28:667.

Andlauer O, et al. Predictors of hypocretin (orexin) deficiency in narcolepsy without cataplexy. Sleep. 2012;35:1247.