Chapter 16. Rapid Eye Movement Sleep Behavior Disorder

264



Mahowald and Schenck



spinal motoneurons while being quite activated at higher levels of the neuraxis.

Multiple areas of the brainstem may influence muscle tone during REM sleep (10).

Experiments have shown that loss of REM sleep atonia alone is insufficient to

generate RBD. Presumably, there must also be disinhibition of motor pattern generators in the mesencephalic locomotor region to result in over-excitation of

phasic motor activity with behavioral release during REM sleep (11,12). Recent

studies in dogs by Lai and Siegel have revealed a colocalization of the atonia and

locomotor systems of REM sleep in the pons, providing an anatomic basis for the

simultaneous dysregulation of these two systems in RBD (13).

Neuroimaging studies indicate dopaminergic abnormalities in RBD. Studies

of single photon emission computed tomography (SPECT) have found reduced

striatal dopamine transporters (14,15), and also decreased striatal dopaminergic

innervation has been reported (16). Decreased blood flow in the upper portion of

the frontal lobe and pons has been reported (17), as has functional impairment of

brainstem neurons (18). Positron emission tomography (PET) and single photon

emission computed tomography (SPECT) studies have revealed decreased nigrostriatal dopaminergic projections in patients with multiple system atrophy (MSA)

and RBD (19). Decreased blood flow in the upper portion of the frontal lobe and

pons has been found in one MRI and SPECT study (20). Impaired cortical activation

as determined by electroencephalographic spectral analysis in patients with idiopathic RBD supports the relationship between RBD and neurodegenerative

disorders (21).

The overwhelming male predominance of RBD raises the intriguing question

of hormonal influences, as suggested in male-aggression studies in both animals

and humans (22 – 24). Another possible explanation for the male predominance

is sex differences in brain development and aging (25, 26). There is evidence for a

sex difference on the effects of sex steroids on the development of the locus coeruleus in rats (27). Spontaneous cases have occurred in dogs and cats (28).

CLINICAL MANIFESTATIONS

RBD is more common in people older than 50 years of age, but the disorder may

begin at any age. Eighty percent to 90% of affected patients are men (29 –31). The

disorder most frequently presents with the complaint of dramatic, violent, potentially injurious motor activity during sleep. These behaviors include talking,

yelling, swearing, grabbing, punching, kicking, jumping, or running out of the

bed. Injuries are not uncommon and include ecchymoses, lacerations, or fractures

involving the individual or bed partner. The violence of the sleep-related behavior

is often discordant with the waking personality. The increased aggressive dream

content experienced by patients with RBD is not associated with increased

daytime aggressiveness (32). The reported motor activity usually correlates with

remembered dream mentation, leading to the patient’s complaint of “acting out

my dreams.” Less frequently, the primary complaint is one of sleep interruption.

There is evidence that the presentation of RBD is different in males (violent

dream-enacting behaviors) than in females (less violent dream-enacting behaviors),

skewing the reported male predominance (33). In some cases, bruxism, somniloquy,

or periodic limb movements of sleep may be the heralding or primary manifestation of this disorder. The duration of behaviors is brief, and upon awakening

from an episode there is usually rapid return of alertness and orientation. Some

patients adopt extraordinary measures to prevent injury during sleep: they may



Rapid Eye Movement Sleep Behavior Disorder



265



tether themselves to the bed with a rope or belt, sleep in sleeping bags, or sleep on a

mattress on the floor in a room devoid of furniture.

Case Vignette

A 75-year-old female who reported having dream-enacting behavior since her early

50s, beginning with complex movements and talking during her sleep—often

accompanied by very comical dreams. This evolved into more violent dreams

involving attacking animals. These behaviors led to the acquisition of a kingsized bed so that her behavior was less disruptive to her husband. She and her

family regarded these behaviors as “amusing” until one night, when dreaming

she was jumping over a fence in a garden, she threw herself out of bed, denting

a door with her head, and sustained a cervical vertebral compression fracture

requiring surgical repair. She was on no medications known to trigger RBD, and

had no abnormalities on neurological examination. Her sleep study revealed prominent REM sleep without atonia (Fig. 1), associated with very frequent extremity

twitching and vocalization.

Due to its association with REM sleep, the timing of the behaviors during the

sleep period ranges from 90 minutes after sleep onset to the final awakening in

the morning. RBD rarely occurs during daytime naps, as REM sleep during naps

is exceptional. Often there is a prodromal period lasting years or decades of

progressively more prominent sleep talking, yelling, or limb jerking during sleep.

Many patients with RBD report that their dreams have become more vivid and

“action-packed” coincident with the onset of the dream-enacting behaviors.



FIGURE 1 An epoch of rapid eye movement sleep demonstrating dramatic release of both tonic

and phasic electromyographic activity during REM sleep in a patient with RBD. This was

associated with prominent extremity twitching and vocalization. Abbreviations: LOC/ROC, left/

right outer canthus; A1/A2, left/right ear; C3/C4, left/right central EEG; O1/O2, left/right occipital

EEG; Chin1- submental EMG; Arm, left/right extensor digitorum EMG; LEG, left/right anterior

tibialis EMG; ECG, electrocardiogram.



266



Mahowald and Schenck



The frequency of the episodes ranges from once every few weeks to multiple

nightly episodes (34). Acute transient RBD may last for one night or a few nights

and is usually associated with medication use or withdrawal.

Serious injuries, including subdural hematomas may result from dreamenacting behaviors, raising interesting and difficult forensic medicine issues (35–37).

Acute Rapid Eye Movement Sleep Behavior Disorder

Acute onset of RBD is almost always induced by medications (tricyclic antidepressants, monoamine oxidase inhibitors, serotonin-specific reuptake inhibitors, bisoprolol, or cholinergic treatment for Alzheimer’s disease) or associated with their

withdrawal (alcohol, barbiturate, or meprobamate) (38– 41). Caffeine and chocolate

abuse has been implicated in causing or unmasking RBD (42). RBD may be

triggered by selegiline, prescribed as treatment for Parkinson’s disease and by

cholinergic agents, prescribed for patients with Alzheimer’s disease (43– 45).

Drug-induced [particularly serotonin-specific reuptake inhibitors (SSRI) medication] RBD is becoming increasingly common.

Chronic Rapid Eye Movement Sleep Behavior Disorder

The chronic form of RBD is idiopathic in 25% to 60% of occurrences (29,30,46). The

remaining cases are associated with various degenerative neurologic disorders (discussed later). All PSG and behavioral features of RBD are indistinguishable across

subgroups, irrespective of gender, age, or the presence/absence of a neurological

disorder (47). This suggests the presence of a “final common pathway” in RBD

that can be accessed by a wide variety of pathologic states.

RBD behaviors occur within REM sleep, often without associated tachycardia, and not during arousals from REM sleep. Complex RBD behaviors are generally aggressive or exploratory and never appetitive (feeding, sexual). There is an

almost inextricable link between altered dreams and dream-enacting behaviors,

suggesting a mutual pathophysiology: patients do not enact their customary

dreams, but rather they enact distinctly altered dreams, usually involving confrontation, aggression, and violence.

CLINICAL AND LABORATORY EVALUATION

Laboratory evaluation of injurious or disruptive nocturnal behaviors consists of

the following:

1. Clinical sleep–wake interview, with review of physician referral information

and past medical records, and with review of a completed, structured, patient

questionnaire, covering sleep–wake, medical, psychiatric, and alcohol/

substance use history (including family history), and review of systems.

2. Psychiatric and neurologic interviews and examinations.

3. Extensive overnight PSG monitoring with continuous videotaping. A full

electroencephalographic montage is employed in addition to conventional

physiologic sleep parameters. Monitoring for sleep-disordered breathing is

mandatory, as obstructive sleep apnea may masquerade as RBD.

4. Daytime multiple sleep latency testing (MSLT), if there is a complaint or suspicion of daytime sleepiness or fatigue.



Rapid Eye Movement Sleep Behavior Disorder



267



5. If RBD is diagnosed, neuropsychometric testing should be performed due to the

close relationship between RBD and degenerative neurologic conditions discussed later. Also, a brain imaging study, preferably a magnetic resonance

scan, may be indicated, depending on findings elicited from the clinical

history and/or neurologic examination.

Minimum diagnostic criteria of RBD (4,48):

1. PSG abnormality during REM sleep: elevated submental electromyographic

(EMG) tone and/or excessive phasic submental and/or limb EMG twitching.

2. Documentation of abnormal REM sleep behaviors during PSG studies (prominent limb or truncal jerking, complex, vigorous, or violent behaviors), or a

history of injurious or disruptive sleep behaviors.

3. Absence of clinical or EEG evidence of epileptiform activity during REM sleep.

A single night of recording is generally sufficient to establish the diagnosis,

because REM sleep polysomnographic abnormalities are usually present even

when a behavioral episode does not occur. A polysomnographic scoring system

for RBD in neurodegenerative disorders has been developed (49).

PREVALENCE

A recent phone survey of over 4900 individuals between the ages of 15 and 100

years of age indicated an overall prevalence of violent behaviors, in general,

during sleep of 2%, one quarter of which were likely due to RBD, giving an

overall prevalence of RBD at 0.5% (50). Another survey estimated the prevalence

of REM sleep behavior to be 0.38% in elderly individuals (51).

ASSOCIATION WITH OTHER NEUROLOGICAL CONDITIONS

The literature now contains hundreds of cases of RBD (29,52). Increasingly, chronic

or “idiopathic” RBD is becoming associated with neurologic disorders, but there is

great diversity in category and location. Three pertinent comments are warranted:

first, neurodegenerative disorders and narcolepsy are the most common neurologic

disorders associated with RBD. Second, the pons is rarely grossly involved, as ascertained by clinical neuroanatomical and neurophysiologic testing, which stands in

contrast to the animal model of RBD. Third, a wide variety of neurologic conditions

can also manifest “REM sleep without atonia” and/or excessive phasic EMG twitching in REM sleep, as a polysomnographic observation but without the clinical emergence of RBD—in other words, various preclinical forms of RBD can be found in the

same neurologic disorders that are associated with RBD, but also in individuals

without any apparent neurologic disease (39,48,53 –55). Sleep bruxism, in one

case, has been reported to be a subclinical manifestation of RBD (56).

Association with Neurodegenerative Disorders

The chronic form of RBD is idiopathic in 25% to 60% of occurrences (29,30,46,57).

The remainder are associated with various degenerative neurologic disorders,

most notably with the synucleinopathies [Parkinson’s disease (including juvenile

Parkinson’s disease)], dementia with Lewy body disease, and MSA (Shy-Drager

syndrome, striatonigral degeneration, olivopontocerebellar degeneration) (58,59).



268



Mahowald and Schenck



A recent study found that 40% of patients with Parkinson’s disease had either RBD

(16%) or polysomnographic evidence of REM sleep without atonia (60), and 90% of

patients with MSA had REM sleep without atonia. In another study, all of the 19

patients with MSA had RBD (61). Surveys indicate a very high prevalence of RBD

in Parkinson’s disease (up to 47%) and MSA (up to 69%) (62 – 68). In 27% of patients

with both RBD and Parkinson’s disease, the RBD preceded the Parkinson’s disease.

There is evidence that Parkinson’s disease and RBD are physiologically and anatomically linked (69). This is supported by the fact that olfactory impairment is

common in both (70). The presence of RBD in patients with Parkinson’s disease

may be predictive of cognitive impairment (71). RBD is also seen in nonsynucleinopathy-related Parkinson’s disease and in progressive supranuclear palsy (a tauopathy) (72,73). The clinical features of RBD are identical in the idiopathic cases and in

those with Parkinson’s disease or MSA (74). Interestingly, there is a striking (77%)

male predominance in patients with Parkinson’s disease who display RBD (75).

In one series, more than two-thirds of males initially diagnosed with idiopathic RBD eventually developed symptoms of one of the synucleinopathies

(76,77), with the average interval between the onset of REM sleep behavior disorder

and the first of the other symptom of the underlying neurodegenerative disease

being over 10 years. The fact that the majority of patients with RBD may eventually

be found to have an underlying neurodegenerative or medication-induced etiology

has led to the suggestion of use of the term “cryptogenic RBD” rather than “idiopathic RBD” (78).

Other reported associations include: mitochondrial encephalomyopathy,

normal pressure hydrocephalus, Tourette’s syndrome, Machado-Joseph disease

(spinocerebellar ataxia type 3), cerebellopontine angle tumors, group A xeroderma,

multiple sclerosis, ischemic or hemorrhagic cerebrovascular disease, brainstem

´

neoplasms, autism, and Guillain-Barre syndrome (79 – 92).

Association with Narcolepsy

Since both RBD and narcolepsy may be considered conditions associated with

abnormalities of state boundary control, it would stand to reason that RBD may

be a manifestation of narcolepsy, and may be precipitated or worsened by the

administration of tricyclic antidepressants or serotonin-specific reuptake inhibitors,

prescribed for the symptom of cataplexy (93). One questionnaire survey found

that 36% of patients with narcolepsy had symptoms suggestive of RBD (94).

RBD-like behaviors have been reported arising from cataplexy in a patient with

narcolepsy (95).

TREATMENT

The acute form is self-limited following discontinuation of the offending

medication or completion of withdrawal. Clonazepam is a remarkably effective

treatment in human RBD, in controlling both the behavioral and the dreamdisordered components of RBD (47). Treatment is usually immediately effective

at a dose of 0.5 to 1.0 mg at bedtime (range: 0.25 –4.0 mg). Prompt relapse of RBD

occurs whenever the patient fails to take clonazepam on a given night. The mechanism of therapeutic action has been shown by Lapierre and Montplaisir to involve

suppression of phasic EMG activity during REM sleep rather than restoration of

REM sleep atonia (96). The long-term efficacy and safety of chronic, nightly



Rapid Eye Movement Sleep Behavior Disorder



269



clonazepam treatment of RBD and of other parasomnias at this center has recently

been reported (97). Underlying obstructive sleep apnea should be ruled out before

prescribing clonazepam (98). Adjunctive or alternative treatments, for the few RBD

patients who do not respond fully to clonazepam or who develop daytime somnolence from this agent, include the following: desipramine or imipramine, carbamazepine, clonidine, carbidopa/L-dopa, L-tryptophan, or gabapentin (48). Recently,

melatonin (in relatively high doses, i.e., 6 to 12 mg at bedtime) (99 –101) or pramipexole (102,103) have been reportedly effective.

The treatment of Parkinson’s disease-associated RBD and RBD associated

with narcolepsy is the same as for idiopathic RBD (76). Pallidotomy has been effective in one case of RBD associated with Parkinson’s disease, whereas chronic bilateral subthalamic stimulation has not been effective (104 –107).

Interestingly, there may be spontaneous improvement in RBD symptoms with

progression of the underlying neurodegenerative condition (108).

VARIATIONS

Parasomnia Overlap Syndrome

A subgroup of RBD patients have been identified with PSG-documented overlapping NREM – REM sleep motor parasomnias consisting of sleepwalking, sleep

terrors, and RBD (109). Two other “overlap” parasomnia cases have been reported

(110,111). These cases demonstrate motor –behavioral dyscontrol extending across

NREM and REM sleep.

Status Dissociatus

This is the most extreme form of RBD, and appears to represent the complete breakdown of state-determining boundaries (112,113). Clinically, these patients appear to

be either awake or “asleep”; however, their “sleep” is very atypical, characterized

by frequent muscle twitching, vocalization, and reports of dream-like mentation

upon spontaneous or forced awakening. Polygraphically, there are no features of

either conventional REM or NREM sleep. Rather, there is the simultaneous admixture of elements of wakefulness, REM sleep and NREM sleep. “Sleep” is often perceived as “normal” and restorative, despite the nearly continuous motor and verbal

behaviors and absence of PSG-defined REM or NREM sleep. Conditions associated

with status dissociatus include protracted withdrawal from alcohol abuse, narcolepsy, olivopontocerebellar degeneration, prior open heart surgery, or following

brainstem surgery (61,112). The abnormal motor and verbal nocturnal behaviors

of status dissociatus may respond to treatment with clonazepam.

Agrypnia Excitata

This recently described condition is characterized by generalized overactivity

associated with loss of slow-wave sleep, mental oneiricism (inability to initiate

and maintain sleep with wakeful dreaming), and marked motor and autonomic

sympathetic activation seen in such diverse conditions as delirium tremens,

Morvan’s fibrillary chorea, and fatal familial insomnia (81,114,115). Oneiric dementia is likely a related condition (116). Oneiric symptoms reminiscent of RBD in these

conditions should lead to closer scrutiny of sleep in other neurologic disorders

(80,114– 117).



270



Mahowald and Schenck



DIFFERENTIAL DIAGNOSIS

The differential diagnosis includes sleepwalking, sleep terrors, nocturnal seizures,

psychogenic dissociative states, post-traumatic stress disorder, nocturnal panic disorder, delirium, and malingering. Confusional arousals with behaviors that may

mimic RBD can occur with nocturnal seizures, obstructive sleep apnea, sleeprelated gastroesophageal reflux, or periodic limb movement disorder (118– 120).

Previously undiagnosed RBD occurring in a patient in the intensive care unit

may be particularly difficult to diagnose (121). A recently described additional

“overlap” syndrome of RBD behaviors arising from light NREM sleep raises the

question of disinhibition of motor pattern generators as an explanation for RBD

behaviors arising from either REM or NREM sleep (73). This broad differential diagnosis mandates formal sleep studies in suspected RBD.



SUMMARY AND DIRECTIONS FOR THE FUTURE

RBD is a fascinating experiment in nature predicted by animal studies. Initially felt

to be a medical curiosity, over time, the majority of individuals with RBD will eventually develop additional signs and symptoms of a number of neurodegenerative

disorders, notably one of the synucleinopathies—often after a prolonged interval.

This relationship should encourage continued close collaboration between clinical

and basic science sleep medicine.



REFERENCES

1. Mahowald MW, Ettinger MG. Things that go bump in the night—the parasomnias

revisited. J Clin Neurophysiol 1990; 7:119–143.

2. Schenck CH, Bundlie SR, Ettinger MG, Mahowald MW. Chronic behavioral disorders

of human REM sleep: a new category of parasomnia. Sleep 1986; 9:293– 308.

3. Schenck CH, Bundlie SR, Patterson AL, Mahowald MW. REM sleep behavior disorder:

a treatable parasomnia affecting older adults. J Am Med Assoc 1987; 257:1786– 1789.

4. American Sleep Disorders Association. The International Classification of Sleep

Disorders, Revised: Diagnostic and Coding Manual. Rochester, Minnesota: Am Sleep

Disord Assoc 1997.

5. American Academy of Sleep Medicine. ICSD-2—International Classification of Sleep

Disorders, 2nd ed. Diagnostic and coding manual. Am Acad Sleep Med, 2005.

6. Jouvet M, Delorme F. Locus coeruleus et sommeil paradoxal. CR Soc Biol. 1965;

159:895–899.

7. Sanford LD, Cheng CS, Silvestri AJ, et al. Sleep and behavior in rats with pontine

lesions producing REM without atonia. Sleep Res Online. 2001; 4:1– 5.

8. Pompeiano O. Mechanisms responsible for spinal inhibition during desynchronized

sleep: experimental study. In: Guilleminault C, Dement WC, Passouant P, eds.

Advances in Sleep Research Volume 3 Narcolepsy. New York: Spectrum Press,

1976:411.

9. Sakai K, Sastre J-P, Kanamori N, Jouvet M. State-specific neurons in the pontomedullary reticular formation with special reference to the postural atonia during paradoxical sleep in the cat. In: Pompeiano O, Ajmone Marsan C, eds. Brain Mechanisms

and Perceptual Awareness. New York: Raven Press, 1981:405– 429.

10. Mileykovskiy BY, Kiyashchenko LI, Kodama T, Lai Y-Y, Siegel JM. Activation of pontine

medullary motor inhibitory regions reduces discharge in neurons located in the locus

coeruleus and the anatomical equivalent of the midbrain locomotor region. J Neurosci

2000; 20:8551 –8558.



Rapid Eye Movement Sleep Behavior Disorder



271



11. Hendricks JC, Morrison AR, Mann GL. Different behaviors during paradoxical sleep

without atonia depend upon lesion site. Brain Res 1982; 239:81– 105.

12. Morrison AR. Brain-stem regulation of behavior during sleep and wakefulness. In:

Sprague JM, Epstein AN, eds. Progress in Psychobiology and Physiological

Psychology. New York: Academic Press, 1979:91.

13. Lai YY, Siegel JM. Muscle tone suppression and stepping produced by stimulation of

midbrain and rostral pontine reticular formation. J Neurosci 1990; 10:2727– 2734.

14. Eisensehr I, Linke R, Noachtar S, Schwartz J, Gildehaus FJ, Tatsch K. Reduced striatal

dopamine transporters in idiopathic rapid eye movement sleep behavior disorder.

Comparison with Parkinson’s disease and controls. Brain 2000; 123:1155– 1160.

15. Eisensehr I, Linke R, Tatsch K, et al. Increased muscle activity during rapid eye movement sleep correlates with decrease of striatal presynaptic dopamine transporters. IPT

and IBZM SPECT imaging in subclinical and clinically manifest idiopathic REM sleep

behavior disorder, Parkinson’s disease, and controls. Sleep 2003; 26:507– 512.

16. Albin RL, Koeppe RA, Chervin RD, et al. Decreased striatal dopaminergic innervation

in REM sleep behavior disorder. Neurology 2000; 55:1410– 1412.

17. Shirakawa S, Takeuchi N, Uchimura N, et al. Study of image findings in rapid

eye movement sleep behavioural disorder. Psychiat & Clin Neuroscis 2002;

56(3):291–292.

18. Miyamoto M, Miyamoto T, Kubo J, Yokota N, Hirata K, Sato T. Brainstem function in

rapid eye movement sleep behavior disorder: the evaluation of brainstem function

by proton MR spectroscopy (1H-MRS). Psychiat Clin Neuroscis 2000; 54:350 – 351.

19. Gilman S, Koeppe RA, Chervin R, et al. REM sleep behavior disorder is related to striatal monoaminergic deficit in MSA. Neurology 2003; 61:29– 34.

20. Shirakawa S-I, Takeuchi N, Uchimura N, et al. Study of image findings in rapid

eye movement sleep behavioral disorder. Psychiat Clin Neuroscis 2002; 56: 291 – 292.

21. Fantini ML, Gagnon JF, Petit D, et al. Slowing of electroencephalogram in rapid eye

movement sleep behavior disorder. Ann Neurol 2003; 53(6):774– 780.

22. Goldstein M. Brain research and violent behavior. Arch Neurol 1974; 30:1– 34.

23. Moyer KE. Kinds of aggression and their physiological basis. Comm Behav Biol 1968;

2(part A):65 –87.

24. Ramirez JM. Hormones and aggression in childhood and adolescence. Aggress and

Violent Beh 2003; 8:621–644.

25. Coffey CE, Licke JF, Saxton JA, et al. Sex differences in brain aging. A quantitative

magnetic resonance imaging study. Arch Neurol 1998; 55:169– 179.

26. Patwardhan AJ, Eliez S, Bender B, Linden MG, Reiss AL. Brian morphology in

Klinefelter syndrome. Neurology 2000; 54:2218–2223.

27. Guillamon A, de Blas MR, Segovia S. Effects of sex steroids on the development of the

locus coeruleus in rats. Dev Brain Res 1988; 40:306– 310.

28. Hendricks JC, Lager A, O’Brien D, Morrison AR. Movement disorders during sleep in

cats and dogs. J Am Vet Med Assoc 1989; 194:686– 689.

29. Olson EJ, Boeve BF, Silber MH. Rapid eye movement sleep behaviour disorder: demographic, clinical and laboratory findings in 93 cases. Brain 2000; 123:331– 339.

30. Schenck CH, Hurwitz TD, Mahowald MW. REM sleep behavior disorder: a report on

a series of 96 consecutive cases and a review of the literature. J Sleep Res 1993;

2:224–231.

31. Sheldon SH, Jacobsen J. REM-sleep motor disorder in children. J Child Neurol 1998;

13:257–260.

32. Fantini ML, Corona A, Clerici S, Ferini-Strambi L. Increased aggressive dream content

without increased daytime aggressiveness in REM sleep behavior disorder. Neurology

2005; 65:1010 –1015.

33. Tatman JE, Sind JM. REM behavior disorder manifests differently in women and men.

Sleep Res 1996; 25:380.

34. Mahowald MW. REM sleep behavior disorder. In: Gilman S, ed. Neurobase. San Diego:

Arbor, 1999:CD ROM.

35. Dyken ME, Lin-Dyken DC, Seaba P, Yamada T. Violent sleep-related behavior leading

to subdural hemorrhage. Arch Neurol 1995; 52:318– 321.



272



Mahowald and Schenck



36. Gross PT. REM sleep behavior disorder causing bilateral subdural hematomas. Sleep

Res 1992; 21:204.

37. Mahowald MW, Schenck CH. Violent parasomnias: forensic medicine issues.

In: Kryger MH, Roth T, Dement WC, ed. Principles and Practice of Sleep Medicine.

4th edn. Philadelphia: Elsevier/Saunders, 2005:960– 968.

38. Iranzo A, Santamaria J. Bisoprolol-induced rapid eye movement sleep behavior

disorder. Am J of Med 1999; 107:390–392.

39. Schenck CH, Mahowald MW, Kim SW, O’Connor KA, Hurwitz TD. Prominent eye

movements during NREM sleep and REM sleep behavior disorder associated with

fluoxetine treatment of depression and obsessive-compulsive disorder. Sleep 1992;

15:226–235.

40. Schutte S, Doghramji K. REM behavior disorder seen with venlafaxine (Effexor). Sleep

Res 1996; 25:364.

41. Silber MH. REM sleep behavior disorder associated with barbiturate withdrawal. Sleep

Res 1996; 25:371.

42. Stolz SE, Aldrich MS. REM sleep behavior disorder associated with caffeine abuse.

Sleep Res 1991; 20:341.

43. Carlander B, Touchon J, Ondze B, Billiard M. REM sleep behavior disorder induced by

cholinergic treatment in Alzheimer’s disease. J Sleep Res 1996; 5(suppl 1):28.

44. Louden MB, Morehead MA, Schmidt HS. Activation by selegiline (Eldepryle) of REM

sleep behavior disorder in parkinsonism. WV Med J 1995; 91:101.

45. Ross LL, Yu D, Kropla WC. Stereotyped behavior in developmentally delayed

or autistic populations. Rhythmic or nonrhythmic? Behav Modif 1998; 22(3): 321 – 334.

46. Sforza E, Krieger J, Petiau C. REM sleep behavior disorder: clinical and physiopathological findings. Sleep Med Rev 1997; 1:57–69.

47. Schenck CH, Mahowald MW. Polysomnographic, neurologic, psychiatric, and clinical

outcome report on 70 consecutive cases with REM sleep behavior disorder (RBD): sustained clonazepam efficacy in 89.5% of 57 treated patients. Cleveland Clinic J of Med

1990; 57(suppl):S9 –S23.

48. Mahowald MW, Schenck CH. REM sleep parasomnias. In: Kryger MH, Roth T, Dement

WC, eds. Principles and Practice of Sleep Medicine. 4th ed. Philadelphia: Elsevier/

Saunders, 2005:897–916.

49. Consens FB, Chervin RD, Koeppe RA, et al. Validation of a polysomnographic score for

REM sleep behavior disorder. Sleep 2005; 28:993– 997.

50. Ohayon MM, Caulet M, Priest RG. Violent behavior during sleep. J Clin Psychiat 1997;

58:369–376.

51. Chiu HFK, Wing YK, Lam LCW, et al. Sleep-related injury in the elderly—an

epidemiological study in Hong Kong. Sleep 2000; 23:513 – 517.

52. 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 –130.

53. Schenck CH, Mahowald MW. Pre-clinical tonic and phasic REM motor disturbances in

19 patients. Sleep Res 1991; 20:322.

54. Tachibana N, Kimura K, Kitajima K, Shidne A, Nagamine T. REM sleep motor

dysfunction in multiple system atrophy. Sleep Res 1995; 24A:415.

55. Taniguchi M, Sugita Y, Tachibana N, et al. Sleeptalking in REM sleep could be

the prodromal symptom of REM sleep behavior disorder. Sleep Res 1995; 24A:242.

56. Tachibana N, Yamanaka K, Kaji R, et al. Sleep bruxism as a manifestation of subclinical

rapid eye movement sleep behavior disorder. Sleep 1994; 17:555– 558.

57. Fantini ML, Ferini-Strambi L, Montplaisir J. Idiopathic REM sleep behavior disorder.

Toward a better nosologic definition. Neurology 2005; 64:780– 786.

58. Boeve BF, Silber MH, Ferman JT, Lucas JA, Parisi JE. Association of REM sleep behavior

disorder and neurodegenerative disease may reflect an underlying synucleinopathy.

Movement Disord 2001; 16:622 –630.

59. Boeve BF, Silber MH, Ferman TJ. REM sleep behavior disorder in Parkinson’s disease

and dementia with Lewy body disease. J Geriatr Psychiat Neurol 2004; 17:146– 157.



Rapid Eye Movement Sleep Behavior Disorder



273



60. Wetter TC, Trenkwalder C, Gershanik O, Hogl B. Polysomnographic measures in Parkinson’s disease: a comparison between patients with and without REM sleep

disturbances. Wien Klin Wochenschr 2001; 113(7– 8):249 –253.

61. Vetrugno R, Provini F, Cortelli P, et al. Sleep disorders in multiple system atrophy: a

correlative video-polysomnographic study. Sleep Med 2004; 5:21– 30.

62. Ghorayeb I, Yekhlef F, Chrysosotome V, Balestre E, Bioulac B, Tison F. Sleep disorders

and their determinants in multiple system atrophy. J Neurol, Neurosur Psychiat 2002;

72:798–800.

63. Oerlemans WGH, de Weerd AW. The prevalence of sleep disorders in patients with

Parkinson’s disease. A self-reported, community-based survey. Sleep Med 2002;

3:147–149.

64. Gagnon J-F, Bedard M-A, Fantini ML, et al. REM sleep behavior disorder and REM

sleep without atonia in Parkinson’s disease. Neurology 2002; 59:585– 589.

65. Comella CL, Nardine TM, Diederich NJ, Stebbins GT. Sleep-related violence, injury,

and REM sleep behavior disorder in Parkinson’s disease [comment]. Neurology

1998; 51(2):526–529.

66. Wetter TC, Hogl B, Trenkwalder C, Gershanik O. Frequency of REM sleep behavior

disorder in patients with Parkinson’s disease. Movement Disord 1998; 13 (suppl 2):55.

67. Plazzi G, Cortelli P, Montagna P, et al. REM sleep behavior disorder differentiates pure

autonomic failure from multiple system atrophy with autonomic failure. J Neurol,

Neurosur Psychiat 1998; 64.

68. Scaglione C, Vignatelli L, Plazzi G, et al. REM sleep behavior disorder in Parkinson’s

disease: a questionnaire-based study. Neurol Sci 2005; 25:316 –321.

69. Lai Y-Y, Siegel JM. Physiological and anatomical link between Parkinson-like disease

and REM sleep behavior disorder. Mol Neurobiol 2003; 27:137– 151.

70. Stiasny-Kolster K, Doerr Y, Moller JC, et al. Combination of “idiopathic” REM

sleep behavior disorder and olfactory dysfunction as possible indicator for alphasynucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. Brain 2005;

128:126–137.

71. Sinforiani E, Zangaglia R, Manni R, Christina S, et al. REM sleep behavior disorder,

hallucinations, and cognitive impairment in Parkinson’s disease. Movement Disord

2005; 21:462 –466.

72. Kumru H, Santamaria J, Tolosa E, et al. Rapid eye movement sleep behavior disorder in

Parkinsonism with PARKIN mutations. Ann Neurol 2004; 56:599– 603.

73. Arnulf I, Merino-Andreu M, Bloch F, et al. REM sleep behavior disorder and

REM without atonia in patients with progressive supranuclear palsy. Sleep 2005;

28:349–354.

74. Iranzo A, Santamaria J, Rye DB, et al. Characteristics of idiopathic REM sleep behavior

disorder and that associated with MSA and PD. Neurology 2005; 65:247– 252.

75. Ozekmekci S, Apaydin H, Kilic E. Clinical features of 35 patients with Parkinson’s

disease displaying REM sleep behavior disorder. Clin Neurol Neurosur 2005;

107:306–309.

76. Schenck CH, Bundlie SR, Mahowald MW. Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement

sleep behaviour disorder. [erratum appears in Neurology 1996 Jun; 46(6):1787]. Neurology 1996 Feb; 46(2):388–393.

77. Schenck CH, Bundlie SR, Mahowald MW. REM behavior disorder (RBD): delayed

emergence of parkinsonism and/or dementia in 65% of older men initially diagnosed

with idiopathic RBD, and analysis of the minimum and maximum tonic and/or phasic

electromyographic abnormalities found during REM sleep. Sleep 2003; 26(abstract

suppl):A316.

78. Ferini-Strambi L, DeGioia MR, Castronovo VE, Oldani A, Zucconi M, Cappa S.

Neuropsychological assessment in idiopathic REM sleep behavior disorder (RBD).

Does the idiopathic form of RBD really exist? Neurology. 2004; 62:41– 45.

79. Bianchin MM, Ferreira NP, Fernandes LNT, Rizzo GNV, Kleimann FAD. Dissociated

sleep components in a patient with a pontomesencephalic astrocytoma. Ann Neurol

1997; 42:470(abstract).



274



Mahowald and Schenck



80. Plazzi G, Montagna P. Remitting REM sleep behavior disorder as the initial sign of

multiple sclerosis. Sleep Med 2002; 3:437 –439.

81. Plazzi G, Montagna P, Meletti S, Lugaresi E. Polysomnographic study of sleeplessness

and onericisms in the alcohol withdrawal syndrome. Sleep Med 2002; 3:279–282.

82. Nozawa T, Sato Y, Cho T, Takeuchi T. Polygraphic findings in mitochondrial encephalomyopathy. Sleep Res 1995; 24A:403.

83. Uchiyama M, Tanaka K, Isse K, et al. REM sleep behavior disorder in a case with

normal pressure hydrocephalus. Jpn J Psychiat Neurol 1991; 45:935– 936.

84. Trajanovic NN, Shapiro CM, Sandor P. REM sleep behavior disorder in patients with

Tourette’s syndrome. Sleep Res 1997; 26:524.

85. Kohyama J, Shimohira M, Kondo S, et al. Motor disturbance during REM sleep in

group A xeroderma pigmentosum. Acta Neurol Scand 1995; 92:91 – 95.

86. Fukutake T, Shinotoh H, Nishino H, et al. Homozygous Machado-Joseph disease presenting as REM sleep behaviour disorder and prominent psychiatric symptoms. Eur J

Neurol 2002; 9(1):97 –100.

87. Zambelis T, Paparrigopoulos T, Soldatos CR. REM sleep behavior disorder associated

with a neurinoma of the left pontocerebellar angle. J Neurol Neurosur Psychiat 2002;

72:821–822.

88. Kimura K, Tachibana N, Kohyama J, Otsuka Y, Fukazawa S, Waki R. A discrete

pontine ischemic lesion could cause REM sleep behavior disorder. Neurology 2000;

55:894–895.

89. Thirumalai SS, Shubin RA, Robinson R. Rapid eye movement sleep behavior disorder

in children with autism. J Child Neurol 2002; 17(3):173– 178.

90. Syed BH, Rye DB, Singh G. REM sleep behavior disorder and SCA-3 (Machado-Joseph

disease). Neurology 2003; 60:148.

91. Friedman JH. Presumed rapid eye movement behavior disorder in Machado-Joseph

disease (spinocerebellar ataxia type 3). Movement Disord. 2002; 17(6):1350– 1353.

92. Iranzo A, Munoz E, Santamaria J, Vilaseca I, Mila M, Tolosa E. REM sleep behavior disorder and vocal cord paralysis in Machado-Joseph disease. Movement Disord 2003;

18:1179 –1183.

93. Schenck CH, Mahowald MW. Motor dyscontrol in narcolepsy: rapid-eye-movement

(REM) sleep without atonia and REM sleep behavior disorder. Ann Neurol 1992;

32:3 –10.

94. Nightingale S, Orgill JC, Ebrahim IO, de Lacy SF, Agrawal S, Williams AJ. The association between narcolepsy and REM behavior disorder (RBD). Sleep Med 2005; 6:

253 –258.

95. Attarian HP, Schenck CH, Mahowald MW. Presumed REM sleep behavior disorder

arising from cataplexy and wakeful dreaming. Sleep Med 2000; 1:131– 133.

96. Lapierre O, Montplaisir J. Polysomnographic features of REM sleep behavior disorder:

development of a scoring method. Neurology 1992; 42:1371– 1374.

97. Schenck CH, Mahowald MW. Long-term, nightly benzodiazepine treatment of injurious parasomnias and other disorders of disrupted nocturnal sleep in 170 adults.

Am J Med 1996; 100:333–337.

98. Schuld A, Kraus T, Haack M, Hinze-Selch D, Pollmacher T. Obstructive sleep apnea

syndrome induced by clonazepam in a narcoleptic patient with REM-sleep-behavior

disorder. J Sleep Res 1999; 8:321–322.

99. Kunz D, Bes F. Effects of exogenous melatonin on periodic limb movment disorder: an

open pilot study. Sleep 1999; 22:S162.

100. Boeve BF, Silber MH, Ferman JT. Melatonin for treatment of REM sleep behavior

disorder in neurologic disorders: results in 14 patients. Sleep Med 2003; 4:281– 284.

101. Takeuchi N, Uchimura N, Hashizume Y, et al. Melatonin therapy for REM sleep

behavior disorder. Psychiat & Clin Neurosci 2001 Jun; 55(3):267– 269.

102. Fantini ML, Gagnon J-F, Filipini D, Montplaisir J. The effects of pramipexole in REM

sleep behavior disorder. Neurology 2003; 61:1418– 1420.

103. Tan A, Salgado M, Fahn S. Rapid eye movement sleep behavior disorder preceding Parkinson’s disease with therapeutic response to levodopa. Movement Disord 1996;

11:214–216.