AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Rapid eye movement (REM) sleep behavior disorder (RBD) is a newly described disorder, recognized as a distinct clinical entity following a series of reports in 1986 of adults with RBD. RBD is the best-studied REM sleep parasomnia. Clinically, RBD is characterized by loss of normal voluntary muscle atonia during REM sleep associated with complex behavior while dreaming. According to the International Classification of Sleep Disorders, the minimal diagnostic criteria include movements of the body or limbs associated with dreaming and at least one of the following criteria: potentially harmful sleep behavior, dreams that appear to be acted out, and sleep behavior that disrupts sleep continuity (American Sleep Disorders Association, 1997). In 1965, experimental models showed that cats with bilateral pontine lesions adjacent to the locus ceruleus act out their dreams.

Pathophysiology

Normally, generalized atonia of muscles occurs during REM sleep. This atonia results from active inhibition of motor activity by pontine centers (ie, perilocus ceruleus) that exert an excitatory influence on the medulla (ie, magnocellularis neurons) via the lateral tegmentoreticular tract. These neuronal groups, in turn, hyperpolarize the spinal motor neuron postsynaptic membranes via the ventrolateral reticulospinal tract. In RBD, the brainstem mechanisms generating the muscle atonia normally seen in REM sleep may be interfered with.

Studies by Eisensehr et al using iodine 123 (¹²³I) immunoperoxidase technique (IPT) single photon-emission computed tomography (SPECT) demonstrated that striatal presynaptic dopamine transporters are reduced in idiopathic RBD. Recent studies by Fantini et al demonstrated impairment of cortical activity in idiopathic RBD, particularly in the occipital region during both wakefulness and REM sleep compared with controls. Results were similar to the functional studies such as perfusion and metabolic impairment pattern observed in diffuse Lewy body (DLB) disease and to some extent in Parkinson disease. Similar cortical activity in the frontal and temporal regions was impaired only during wakefulness.

The subcortical structures involved in the pathophysiology of RBD provide dopaminergic (nigrostriatal neurons), noradrenergic (locus coeruleus), and cholinergic innervation (pedunculopontine tegmental nucleus) of the cerebral cortex and play a role in cortical activation during wakefulness and REM sleep.

In essence, RBD may be the prodrome of neurodegenerative disease, such as DLB or Parkinson disease. In experimental studies in cats, bilateral pontine lesions resulted in a persistent absence of REM atonia associated with prominent motor activity during REM sleep similar to that observed in RBD in humans.

Frequency

United States

The exact incidence and prevalence of RBD are unknown because of inadequate reporting and misdiagnosis. However, a recent telephone survey indicated a 2% overall prevalence of violent behaviors during sleep, 25% of which were likely to be due to RBD. This gives a prevalence of 0.5% of RBD in the general population.

International

No difference in the frequency of RBD exists internationally.

Mortality/Morbidity

The morbidity and mortality rates of RBD depend on the etiology.

• No death has been reported in idiopathic cases; however, patients and bed partners may experience serious injury. In the reported cases, 32% of patients had injured themselves and 64% had assaulted their spouses. Subdural hematomas occurred in 2 patients.
• In secondary cases, the morbidity and mortality rates depend on the specific underlying disease itself.

Race

Racial differences in incidence and prevalence of RBD have not been reported.

Sex

RBD occurs predominantly in males. In a recent report by Olson et al, of 93 patients with RBD, only 12 (13%) were females.

Age

Typically, RBD is a disease of elderly persons. The risk increases after the sixth decade, although the disease may occur at all ages, including childhood.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• The presenting complaint is violent dream-enacting behaviors during REM sleep, often causing self-injury or injury to the bed partner. The dream-enacting behaviors are usually nondirected and may include punching, kicking, leaping, or running from bed while still in REM sleep.
• Directed behavior, such as homicide, has not been reported.
• The patient may be wakened or may wake spontaneously during the attack and recall vividly the dream that corresponds to the physical action.
• In some cases, an extended prodrome of prominent limb and body movements occurs before the development of RBD.

Physical

The neurologic examination findings are unremarkable in idiopathic cases; in secondary cases, the physical findings depend on the underlying disorder.

Causes

In a recent study, Nightingale et al suggested that 36% of persons with narcolepsy experience symptoms of RBD. This link has lead to the identification of a strong association of RBD with HLA class II genes.

• RBD may be idiopathic, or it may occur in association with various neurological conditions, such as brainstem neoplasm, multiple sclerosis affecting the brainstem, olivopontocerebellar atrophy (OPCA), DLB disease, Alzheimer dementia, progressive supranuclear palsy (PSP), or Shy-Drager syndrome.
• The incidence of RBD is increased in Parkinson disease, and RBD may precede the development of parkinsonism by several years. The relationship between RBD and Parkinson disease is complex, however, as not all patients with RBD develop parkinsonism.
• Additional degeneration of brainstem neurons is postulated to play a significant role in the control of this condition.
• Various neuroimaging and pharmacologic studies suggest involvement of dopaminergic systems in both restless legs syndrome (RLS) and RBD.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Primary disorders of arousal
Sleep terrors
Sleep walking
Confusional arousals

Secondary disorders of arousal
Obstructive sleep apnea (OSA)
Periodic limb movements in sleep (PLMS)
Gastroesophageal reflux (GERD)
Nocturnal seizure (eg, frontal lobe epilepsy)

Other possibilities
Posttraumatic stress disorder (PTSD)
Psychogenic dissociative disease
Malingering
Frightening hypnagogic or hypnopompic hallucinations

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Routine medical history should include questions that screen for abnormal sleep movements and altered dreams. Routine laboratory tests are usually not helpful.

Imaging Studies

• Imaging studies are not indicated in idiopathic cases. They are indicated if neurological dysfunction is suggested by history and neurologic examination. However, a recent study demonstrated that IPT-SPECT might be a useful tool in the diagnosis of RBD.

Other Tests

• The most important diagnostic studies include the following:
• • Polysomnographic (PSG) video recording: This is the most important diagnostic test in RBD. On PSG, at least some tonic or phasic abnormalities of muscle tone are observed during REM sleep accompanying the attack, though usually patients have both.
  • Monitoring electro-oculogram (EOG)
  • EEG
  • ECG
  • Nasal flow
  • Multiple electromyography (EMG) channels utilizing chin, bilateral extensor digitorum, and tibialis anterior muscles

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• RBD is treated symptomatically by various medications; however, the response varies in individual cases. Therefore, all available medications should be tried before considering the patient's RBD as intractable.
• The other important aspect of management of patients with RBD is environmental safety. Potentially dangerous objects should be removed from the bedroom, and the mattress should be placed on the floor or a cushion should be put around the bed.

Consultations

The neurologist may consult a sleep specialist for proper diagnosis and treatment of RBD.

Diet

No special recommendations or restrictions of diet exist for RBD.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The treatment of RBD can be challenging in some patients with underlying neurodegenerative conditions. Clonazepam is highly effective in the treatment of RBD. It is effective in nearly 90% of patients (complete benefit in 79% of patients and partial benefit in another 11% of patients), with little evidence of tolerance or abuse. The response usually begins within the first week, often on the first night.

The initial dose is 0.5 mg at bedtime. If this is ineffective, doses can be increased to 1-2 mg. With continued treatment for years, moderate limb twitching with sleep talking and more complex behaviors may reemerge. Nevertheless, control of the violent behaviors persists. The treatment should be continued indefinitely, as violent behaviors and nightmares relapse promptly with discontinuation of medications in almost all patients. The specific mechanism of action of clonazepam in RBD is unknown but may reflect in part to its serotonergic properties. In a minority of patients, particularly in elderly persons, clonazepam may increase the risk of confusion or falls and may worsen obstructive sleep apnea. Clonazepam is ineffective in approximately 10% of patients.

Several studies demonstrated the beneficial effect of melatonin on RBD. The effective dose of melatonin was 3-6 mg PO qhs; only 36% experienced adverse effects, which resolved with decreased dosing. The dosage may be increased every 5-7 days to 12 mg/d in some cases, if tolerated. The mechanism of melatonin is unclear; Kunz and Bes suggested that melatonin restored RBD-related desynchronization of the circadian rhythms. PSG studies showed possible direct restoration of the mechanisms producing REM sleep muscle atonia.

Other medications, such as tricyclic antidepressants, may be effective in some patients. However, tricyclics are known to precipitate RBD.

Levodopa may be very effective in patients in whom RBD is the harbinger of Parkinson disease.

In addition, anecdotal reports exist of responses to carbamazepine, clonidine, and L-tryptophan.

Drug Category: Benzodiazepines

By binding to specific receptor sites, these agents appear to potentiate the effects of GABA and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.

Drug Category: Tricyclic antidepressants

This is a complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects.

Drug Category: Antiparkinsonian agents

These agents often are indicated for patients with Parkinson disease.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• As RBD has strong relationships with many neurodegenerative disorders, such as Parkinson disease, multiple system atrophy, and dementia, the neurologist always should explore the possibility of RBD in these conditions. RBD symptoms may be the first manifestations of these disorders; therefore, careful follow-up is needed.

In/Out Patient Meds

• Symptoms relapse promptly on discontinuation of medications in almost all patients; therefore, the drug should be continued indefinitely.

Prognosis

• The prognosis of RBD depends on etiology. In idiopathic cases, the symptoms are controlled with medications. In secondary cases, the prognosis depends on the primary disease.

Patient Education

• Educate the patient and the bed partner for environmental safety.
• Potentially dangerous objects should be removed from the bedroom, and the mattress should be placed on the floor or a cushion placed around the bed.
• For excellent patient education resources, visit eMedicine's Sleep Disorders Center. Also, see eMedicine's patient education articles REM Sleep Behavior Disorder, Disorders That Disrupt Sleep (Parasomnias), and Sleep Disorders and Aging.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• RBD is a treatable condition. However, misdiagnosis and treatment may result in potential medicolegal problems. Commonly, violent behaviors of RBD involve patients' responses to some form of perceived threat. For example, the patient may dream that he is rescuing his wife from attacks, though at that time he actually is striking his wife. Some patients may strangle their bed partners. Appropriate recognition and treatment can avoid these dangerous injuries and their medicolegal consequences.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Jan 11, 2007