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Awakening the Mysteries of an Abnormal Sleep Disorder

It’s been featured in many magazines, most major newspapers, and on TV: a good night’s sleep plays a crucial role in our overall health.

In addition to fostering muscle growth, protein synthesis, and tissue repair, sleep is vital in helping manage our stress and emotions1,2. While these rejuvenating functions can occur throughout sleep, the most restorative sleep occurs during the deep stages of slow-wave sleep (SWS) and during rapid eye movement (REM) sleep.

What is REM Sleep Behavior Disorder?

REM sleep is the stage of sleep where all dreaming happens. During the 4-6 periods of REM sleep that typically occur per night, the brain wave pattern suddenly shifts from a slow rhythmic tempo to one that appears “awake.” Aside from some twitching eye movements, the body is still “asleep” due to a chemically induced muscle paralysis that prevents people from acting out the content of their dreams.  However, in REM sleep behavior disorder (RBD) the chemical signal that keeps the motor system offline is incomplete or absent, causing people to physically and/or vocally act out their dreams, such as kicking, punching, thrashing, yelling, and jumping3. Why RBD is associated with such violent and dramatic behaviors is poorly understood, but it can lead to personal injury and injury to bed partners in up to 65% of cases4. Frequently reported injuries include bruises, abrasions, and lacerations, whereas more serious injuries, such as subdural hematomas, are reported less commonly5. RBD is not insomnia or a feeling of restlessness or fidgeting in the legs. People often do not know when they are experiencing behaviors, so they are unable to prevent unwanted harm. While RBD-related injuries may pose a threat to patients and their bed partners, a more scientifically intriguing issue is that people with a specific type of brain disorders can develop RBD.

How is RBD related to Dementia?

The association of RBD to a group of neurodegenerative diseases known as Lewy body diseases has been well documented. Lewy body diseases include dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD). Lewy bodies are microscopic protein aggregates that clog up brain cells and often accumulate in the brain region that controls REM sleep. Studies show that up to 80% of patients with DLB and 60% of patients with PD have coexisting RBD6. Recognizing RBD early may be very useful for the future of research in brain disorders as well as for avoiding unwanted injuries and complications that could be prevented by appropriate care.

How is RBD treated? 

There are currently no FDA-approved treatments for RBD. Physicians use off-label treatments to reduce the number of RBD episodes and associated injuries; however, these medications have significant limitations and can often be more harmful in patients with other existing conditions. Clonazepam is commonly used to treat patients with RBD, and several case studies show that it may reduce or resolve RBD behaviors. Nonetheless, clonazepam can cause sedation, memory impairment, and falling which are particularly concerning in patients who either have or are at risk for developing a neurodegenerative disease. Melatonin has also had success in limiting RBD episodes with doses ranging from 3-12 mg though large doses have been associated with daytime delusions and hallucinations7. Protective measures such as bed rails and customized bed alarms may be effective in reducing sleep related injuries, but they have no effect on RBD behaviors8.

New Research for RBD in DLB and PDD: A Nationwide Clinical Study

RBD was formally identified in 19863, yet decades later, no drug therapies have been developed and approved for its treatment. Now, researchers are enrolling people in a nationwide clinical study evaluating an investigational medication, called nelotanserin, as a potential treatment for RBD in people who have DLB or PDD. Nelotanserin is thought to work by selectively blocking a certain protein receptor in the brain whose excess activity has been associated with sleep disturbances in patients with brain disorders of the Lewy-body type9,10. In a previous study of nelotanserin in patients with primary insomnia, nelotanserin appeared to improve sleep consolidation and reduce nighttime arousals11. If awakenings from sleep trigger disruptive REM sleep behaviors, nelotanserin’s selective blocking of the receptor might help ameliorate RBD in people with DLB and PDD.

The study of nelotanserin as a potential treatment for RBD in people with DLB or PDD is currently enrolling participants nationwide. Learn more about the study Contact CCHC Atlantic Neurology or Giga Smith, RN, Research Coordinator at 252-639-5984

References:

  1. Dattilo M, Antunes HK, Medeiros A, et al. Sleep and muscle recovery: endocrinological and molecular basis for a new and promising hypothesis. Med Hypotheses. 2011;77(2):220-2.
  2. Beattie L, Kyle SD, Espie CA, Biello SM. Social interactions, emotion and sleep: A systematic review and research agenda. Sleep Med Rev. 2015;24:83-100.
  3. Schenck CH, Mahowald MW. REM sleep behavior disorder: clinical, developmental, and neuroscience perspectives 16 years after its formal identification in SLEEP. Sleep. 2002;25:120–38.
  4. Boeve BF, Silber MH, Ferman TJ, et al. REM sleep behavior disorder and degenerative dementia: An association likely reflecting Lewy body disease. Neurology. 1998;51:363–70.
  5. Aurora RN, Zak RS, Maganti RK, et al. Best practice guide for the treatment of REM sleep behavior disorder (RBD). J Clin Sleep Med 2010;6:85–95.
  6. Boeve BF, Silber MH, Saper CB, et al. Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain. 2007;130, 2770-88. 10.1093/brain/awm056
  7. Boeve BF, Silber MH, Ferman TJ. Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep Med. 2003;4(4):281-4
  8. Howell MJ, Ameson PA, Schenck CH. A novel therapy for REM sleep behavior disorder (RBD). J Clin Sleep Med. 2011;7(6):639-44
  9. Ballanger B, Strafella AP, van Eimeren T, et al. Serotonin 2A receptors and visual hallucinations in Parkinson disease. Arch Neurol. 2010;67(4):416-21
  10. Yasue I, Matsunaga S, Kishi T, et al. Serotonin 2A Receptor Inverse Agonist as a Treatment for Parkinson’s Disease Psychosis: A Systematic Review and Meta-analysis of Serotonin 2A Receptor Negative Modulators. J Alzheimers Dis. 2016;50(3):733-40
  11. Rosenberg R, Seiden DJ, Hull SG, et al. APD125, a selective serotonin 5-HT(2A) receptor inverse agonist, significantly improves sleep maintenance in primary insomnia. Sleep. 2008;31:1663-71