The loss of normal rapid eye movement (REM) atonia observed during REM sleep, results in RBD. The diagnosis can be made with a history of dream enactment or complex motor behaviours occurring from sleep.
In normal rapid eye movement (REM) sleep, a descending, glutaminergic signal from the brainstem inhibits the motor neurons present in the spinal cord resulting in muscle atonia, which refers to the loss of muscle tone. In REM sleep behaviour disorder (RBD), progressive neurodegeneration of the inhibitory brainstem control results in the loss of normal REM atonia observed during REM sleep, resulting in dream enactment behavior alongside vivid and often violent dream content.
COMMONLY OBSERVED BEHAVIOURS
Behaviours commonly observed include shouting, kicking and punching, which reflect dream content. These events are typically violent, but a range of milder behaviours are also recognised1. RBD typically occurs in the second half of the night as the proportion of REM sleep increases with longer sleep duration.
This is in stark contrast to other sleep disorders such as restless legs syndrome and the non-REM (NREM) parasomnias, which tend to occur in the first half of the night when NREM sleep predominates.
Thus, enquiring about the approximate time the nocturnal behavioural events occur can help to narrow down the differential diagnoses of the events.
Up to 70% of patients will cause injury to themselves or their bed partner. It is common for patients to report falling out of the bed and sustaining fractures, or bed partners complaining of being bruised or hit by their unknowing partners at night. Bed partners may have also recognised RBD earlier, and have chosen to sleep in separate rooms but did not report these events to medical practitioners.
CAUSES OF RBD
The condition predominantly affects older men with a reported prevalence of at least 1%
2-3. RBD was first described in 1986 from a small series of elderly men by Schenck4. However, RBD was in fact recognised much earlier in animals in 1967 as there were reports of selective brain stem lesions in cats causing oneiric or dreamlike behaviours5.
RBD is traditionally classified into idiopathic or secondary forms.
Secondary RBD
Secondary RBD can be caused by a neurodegenerative disorder, particularly the synucleinopathies which include:
- Parkinson’s Disease
- Dementia with Lewy Bodies
- Multiple System Atrophy
Idiopathic RBD
Other causes include :
- Structural lesion in the brain
- Antidepressants, in particular the selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs)
- Beta-blockers
- Alcohol withdrawal.
Highly serotonergic SSRIs such as mirtazapine can worsen existing RBD. Discontinuation of the antidepressant may result in clinical and polysomnographic resolution of RBD. However, in others, RBD has also been reported to persist and antidepressants may simply unmask individuals with a latent neurodegeneration.
There is increasing debate whether true idiopathic RBD exists with an increasing recognition of the strong association between RBD and the subsequent development of neurodegenerative disease, with 91% developing one of these conditions over 14 years of follow up6. As currently published longitudinal studies on RBD have been only of limited duration due to the relative recent discovery of RBD, it is anticipated that future published studies with even longer durations of follow up would show near 100% phenoconversion of RBD into another neurodegenerative disorder.
As such, long-term follow up of these patients is important to detect incipient development of neurodegenerative disease.
RBD is now commonly regarded as a prodromal phase of the alpha-synucleinopathies including Parkinson’s Disease.
ASSESSMENT
The diagnosis of probable RBD can be made with a positive history of dream enactment or complex motor behaviours occurring from sleep. Patients are often unaware of these behaviours unless injury has occurred, so a complete history is essential for thorough understanding of the extent.
In RBD, sleep behaviours usually begin gradually and infrequently such as limb jerks and sleep talking, before progressing to become nightly or near nightly violent events.
A number of validated screening questionnaires are available to allow diagnosis of probable RBD. However, these questionnaires are unable to distinguish RBD from other NREM parasomnias, sleep apnoea and nocturnal confusion. Occasionally, severe obstructive sleep apnoea (OSA) can cause strikingly vivid dreams and agitated arousals termed as ‘pseudo-RBD’.
Hence a diagnostic polysomnography should be performed in patients who have other features to suggest OSA. To make a definite diagnosis of RBD, polysomnography is required to identify the excessive electromyography (EMG) activity that occurs in REM sleep.
TREATMENT
There is debate as to how and when patients with idiopathic RBD should be counselled on their future risk of developing a neurodegenerative disorder.
Immediate treatment measures:
1. Behavioural interventions to ensure a safe sleeping environment should be implemented to prevent injury to the patient or their bed partner.
2. If comorbid OSA is present, treatment of OSA often improves RBD.
3. Medications known to worsen RBD should be discontinued where possible.
Clonazepam
There are no licensed therapies for RBD but clonazepam has been regarded as the first-line treatment for RBD. This drug should be used cautiously as common side effects like sedation, falls, confusion, cognitive impairment and respiratory depression often limit dose escalation. A lack of response to the drug should prompt the clinician to reevaluate the diagnosis of RBD. Clonazepam should not be used in co-morbid OSA.
Melatonin
Melatonin has been used as a second-line therapy and was demonstrated to be effective when evaluated in one small randomised blinded cross-over trial7. Unlike clonazepam, melatonin is able to restore normal REM atonia. Melatonin also tends to be better tolerated with less adverse effects than clonazepam, with similar efficacy although there are no head-to-head trials8.
The effective dose ranges between 2 and 12mg, with a recent large case series showing benefit at an average of 6mg8. It is common for patients not to achieve complete remission with melatonin, and supplementary clonazepam use is required to manage the symptoms.
In patients for whom RBD remains unmanageable, occasional case reports have described that rivastigmine and sodium oxybate may be effective9-10.
Where To Seek Treatment at SingHealth This condition is treated at the SingHealth Duke- NUS Sleep Centre. The Centre sees patients at six SingHealth institutions. - Singapore General Hospital
- Changi General Hospital
- Sengkang General Hospital
- KK Women’s and Children’s Hospital
- National Dental Centre Singapore
- National Neuroscience Institute
It is staffed by a multidisciplinary team of specialists from ENT, Surgery, Respiratory Medicine, Neurology, Psychiatry, Psychology and Dentistry who have all undergone further specialised training in the field of Sleep Medicine locally and abroad. |
GPs can call for appointments through the GP Appointment Hotline at 6330 6363 for more information.
By: Dr Xu Zheyu is a Consultant Neurologist at the National Neuroscience Institute.
She subspecialises in both Movement Disorders and Sleep Neurology. Her practice
locations include Tan Tock Seng Hospital and Changi General Hospital. RBD
awareness is poor in Singapore and she is keen to manage these patients in her clinic
and build up a RBD research clinic in future.
REFERENCES
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2. CHIU, H. F., WING, Y. K., LAM, L. C., LI, S. W., LUM, C. M., LEUNG, T. & HO, C. K. 2000. Sleep-related injury in the elderly--an epidemiological study in Hong Kong. Sleep, 23, 513-7
3. KANG, S. H., YOON, I. Y., LEE, S. D., HAN, J. W., KIM, T. H. & KIM, K. W. 2013. REM sleep behavior disorder in the Korean elderly population: prevalence and clinical characteristics. Sleep, 36, 1147-52.
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5. MOURET, J., DELORME, F. & JOUVET, M. 1967. [Lesions of the pontine tegmentum and sleep in rats]. C R Seances Soc Biol Fil, 161, 1603-6.
6. IRANZO, A., TOLOSA, E., GELPI, E., MOLINUEVO, J. L., VALLDEORIOLA, F., SERRADELL, M., SANCHEZ-VALLE, R., VILASECA, I., LOMENA, F., VILAS, D., LLADO, A., GAIG, C. & SANTAMARIA, J. 2013. Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study. Lancet Neurol, 12, 443-53.
7. KUNZ, D. & MAHLBERG, R. 2010. A two-part, double-blind, placebo-controlled trial of exogenous melatonin in REM sleep behaviour disorder. J Sleep Res, 19, 591-6.
8. MCCARTER, S. J., BOSWELL, C. L., ST LOUIS, E. K., DUEFFERT, L. G., SLOCUMB, N., BOEVE, B. F., SILBER, M. H., OLSON, E. J. & TIPPMANN-PEIKERT, M. 2013. Treatment outcomes in REM sleep behavior disorder. Sleep Med, 14, 237-42.
9. DI GIACOPO, R., FASANO, A., QUARANTA, D., DELLA MARCA, G., BOVE, F. & BENTIVOGLIO, A. R. 2012. Rivastigmine as alternative treatment for refractory REM behavior disorder in Parkinson’s disease. Mov Disord, 27, 559-61.
10.MOGHADAM, K. K., PIZZA, F., PRIMAVERA, A., FERRI, R. & PLAZZI, G. 2017. Sodium oxybate for idiopathic REM sleep behavior disorder: a report on two patients. Sleep Med, 32, 16-21.
