Addressing REM Sleep Behavior Disorder in Parkinson’s

While most people are dreaming, the action taking place in their mind never quite reaches their body, which is essentially paralyzed during sleep. Those with the parasomnia REM sleep behavior disorder (RBD), however, physically act out their dreams in ways that can be dangerous to themselves and those around them.

“Normally, during REM sleep, reduced serotonergic activity in the brain leads to atonia or loss of muscle tone through action in a network involving brainstem nuclei including the locus subcoeruleus and magnocellularis nucleus,” Benjamin L. Walter, MD, associate professor of neurology and director of the Parkinson’s and Movement Disorders Center at University Hospitals Case Medical Center, told Neurology Advisor. “In RBD, this mechanism is dysfunctional, possibly due to pathology in this circuit, and there is not loss of tone during REM sleep.”

This results in dreams that are often violent and, when enacted, can lead to falls from the bed, collisions with various objects, or physical harm toward bed partners.

RBD and Neurodegenerative Disorders

Up to 60% of Parkinson’s disease (PD) patients have RBD, as do 80 to 100% of patients with dementia with Lewy bodies and multisystem atrophy.

“What these diseases all have in common is that they are synucleinopathies, and they have pathology that involves specific subcortical and brainstem areas, including those involved in the regulation of atonia during REM sleep,” said Walter.

A prospective cohort study published in the August 2015 issue of JAMA Neurology found that RBD may be a marker indicating more aggressive progression of PD.¹ The authors concluded with a recommendation that patients with PD be screened for RBD at baseline visits, as it identifies a “diffuse/malignant subgroup of patients with PD for whom the most rapid progression rate could be expected.”¹

Additionally, idiopathic RBS “is thought to be a precursor to neurodegenerative disease due to a synucleinopathy,” said Liza H. Ashbrook, MD, a clinical fellow at the Stanford Sleep Medicine Center, who has a background in neurology and is now focusing on treatment of sleep disorders. Increasing data shows that the majority of “patients with idiopathic RBS will develop a neurodegenerative synucleinopathy, whether it is three or 20 years between the diagnoses.”

A 2013 study published in Sleep Medicine² by researchers at the Minnesota Regional Sleep Disorders Center at the University of Minnesota Medical School, found that 80% of patients with idiopathic RBD had developed a parkinsonian disorder or dementia 16 years later. Another study published in 2013 found that 82% of patients with idiopathic RBD eventually developed a neurodegenerative syndrome by the follow-up assessment years later, leading the authors to conclude that idiopathic RBD “represents the prodromal phase of a Lewy body disorder.”³

Treating RBD

In cases of suspected RBD, patients should first attempt to reduce behavioral and environmental factors that might influence symptoms, primarily through practicing good sleep hygiene.

“Avoid triggers like caffeine and alcohol, and any disruptive influence on sleep–shiftwork, eating before bed, noise, and light,” Karl Doghramji, MD, a professor of psychiatry and neurology at Thomas Jefferson University, and medical director of the Jefferson Sleep Disorders Center, told Neurology Advisor. Meanwhile, practical measures to increase safety might include padding the walls, removing sharp objects from the bedroom, and moving the mattress to the floor to reduce the distance in case falls occur. It may also be necessary for partners to sleep in separate beds or rooms. If problems persist, a sleep study should be conducted to rule out other disorders, such as sleep apnea and periodic limb movement disorder.

“When we treat these, we often see a resolution of the RBD.” In other cases, correcting chemical imbalances – such as low or high blood sugar – or medical co-morbidities can lead to resolution. Finally, once all of those conditions are ruled out, medication will typically be prescribed. There are no double-blind randomized controlled trials regarding treatment options for RBD, but in clinical practice, clonazepam has been commonly found to decrease the motor behavior and the propensity toward nightmares associated with RBD. 

Research also suggests that melatonin may be helpful⁴, possibly “because of its general sedative effect, and anecdotal studies show that it decreases electromyographic activity,” said Doghramji. A 2015 review⁴ by researchers at the Mayo Clinic College of Medicine noted that “melatonin appears to be beneficial for the management of RBD with reductions in clinical behavioral outcomes and decrease in muscle tonicity during REM sleep.” In refractory cases, certain antidepressants and benzodiazepines may be used.

References

1. Fereshtehnejad SM et al. New Clinical Subtypes of Parkinson Disease and Their Longitudinal Progression: A Prospective Cohort Comparison With Other Phenotypes. JAMA Neurology. 2015; 72(8):863-73.
2. Schenck CH et al. Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. Sleep Medicine. 2013; 14(8):744-8.
3. Iranzo A et al. Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study. The Lancet Neurology. 2013; 12(5):443-53.
4. McGrane IR et al. Melatonin therapy for REM sleep behavior disorder: a critical review of evidence. Sleep Medicine. 2015; 16(1):19-26.