International Journal of Neuroscience, 122, 407412, 2012

Copyright 2012 Informa Healthcare USA, Inc.

ISSN: 0020-7454 print / 1543-5245 online
DOI: 10.3109/00207454.2012.677882
Sleep Disturbances in Parkinsons Disease With Emphasis
on Rapid Eye Movement Sleep Behavior Disorder
Anthony Barber and Khashayar Dashtipour

Department of Neurology, Loma Linda University, Loma Linda, California, CA, USA
ABSTRACT
Sleep disturbances are common in patients with Parkinsons disease (PD). These disturbances can primarily
affect the patients quality of life and may worsen the symptoms of PD. Among the multiple sleep disturbances
in PD patients, there has been a marked growing interest in rapid eye movement (REM) sleep behavior disorder
(RBD). This is likely due to the fact that RBD has been proven to precede the motor symptoms of PD by many
years. The aim of this article is to examine the sleep disturbances found in PD, with special attention to RBD as
a premotor symptom of PD, as well as to assess its proposed related pathophysiology. MEDLINE (1966March
2010), American Academy of Sleep Medicines, The International Classication of Sleep Disorders, and current
textbooks of sleep medicine were searched for relevant information. Search terms: RBD, sleep disturbances,
Parkinsons disease, and pre-motor were used. Excessive daytime sleepiness (EDS), sleep attack, insomnia,
restless leg syndrome (RLS), sleep-disordered breathing (SDB), and RBD are sleep disturbances commonly
found in the literature related to PD. Sleep beneft has been proven to lessen PD motor symptoms. RBD
has been described as a premotor symptom of PD in several prospective, retrospective, and cross-sectional
studies. Sleep disturbances in PD can result secondarily to natural disease progression, as a side effect of the
medications used in PD, or in result of pre-clinical pathology. Treatment of sleep disturbances in PD patients is
crucial, as what is termed as, sleep beneft effect has been shown to improve the symptoms of PD.
KEYWORDS: Parkinsons disease, premotor symptoms, RBD, REM sleep, sleep benet, sleep disturbances
INTRODUCTION
For nearly a century, research in the feld of Parkinsons
disease (PD) has focused on its motor symptoms, re-
sulting in improved diagnostic accuracy, development
of strong rating scales, and new symptomatic treat-
ment strategies [1]. James Parkinson described the mo-
tor symptoms of PD, and this portrayal is still used as
the major diagnostic criteria. Similarly, he described the
nonmotor symptoms of the disease [2]. Recently, the
nonmotor aspect of the disease has become the cen-
ter of focus for research studies. Strong evidence has
linked constipation, olfactory defcits, depression, and
various sleep disturbances as the most common nonmo-
tor symptoms of PD[1]. James Parkinson, in his original
monograph, described the sleep disturbances in PD as
follows:
Received 14 December 2011.
Paper has been read and approved by all authors.

Address correspondence to Khashayar Dashtipour, M.D., Ph.D., Department

of Neurology, Loma Linda University, 11370 Anderson Street, Suite 2400,
Loma Linda, California, CA 92782, USA. E-mail: kdashtipour@llu.edu
In this stage, the sleep becomes much disturbed. The
tremulous motion of the limbs occurs during sleep, and aug-
ment until they awaken the patient, and frequently with much
agitation and alarm [2]. Michael S. Aldrich quotes James
Parkinson in his textbook, Sleep Medicine, that sleep becomes
much disturbed, and that in the fnal stages of the disease,
there is constant sleepiness, with slight delirium and other
marks of extreme exhaustion. [2]
Recent studies estimate a 100% prevalence of sleep
disturbances in PD [3]. The sleep disorders classifed
based upon their relation to PD include excessive day-
time sleepiness (EDS), sleep attacks, insomnia, rest-
less legs syndrome (RLS), sleep-disordered breathing
(SDB), rapid eye movement (REM), and sleep behavior
disorder (RBD). Sleep disturbances can primarily occur
during the progression of the disease or as a side effect
to medications used in symptomatic therapy. Moreover,
sleep disorders are often presented as a preclinical symp-
tom of PD, which will be the emphasis of this review.
Disturbances of sleep have consequences for both
the patient and the caregiver, causing increased stress
and reduced quality of life [4]. For the patient, this can
407
408 A. Barber and K. Dashtipour
translate into a momentous impact on cognitive and
physical functioning, often times becoming associated
with depression [5]. The aimof this article is to examine
the sleep disturbances found in PD, specifcally RBD as
a premotor symptom of PD, and to assess the proposed,
related pathophysiology.
MATERIALS AND METHODS
MEDLINE (1966March 2010), American Academy
of Sleep Medicines, The International Classification of
Sleep Disorders, and current textbooks of sleep medicine
were searched for relevant information. Search terms:
RBD, sleep disturbances, Parkinsons disease, and pre-motor
were used.
RESULTS
Excessive Daytime Sleepiness (EDS)
EDS, primary versus secondary, is a disturbance of
wakefulness. Primary EDS is due to a presumed intrin-
sic central nervous system (CNS) disorder, with Nar-
colepsy being the prototypical diagnosis in this category.
Secondary, or extrinsic EDS, as its name suggests, is
caused by an outside infuence upon the CNS. This
would include sleep disorders, medications, or psychi-
atric illnesses. With all of these different causes, EDS
is a frequent complaint from PD patients. One study
showed that this occurred in 15.5%, or 37out of 239
PD patients, compared to 1%, or 1 out of 100 healthy
elderly control subjects [6].
Possible etiologies of EDS in PD include SDB, re-
versal of the sleep-wake cycle, the disease process itself,
sleep disruption due to motor and nonmotor symptoms
of PD, and the use of dopamine agonists. The use of
Pramipexole as monotherapy in PD was found to cause
somnolence in 18.3%of 164 patients compared to 8.8%
of the 171 in the placebo group (p value .015) [7]. In an-
other randomized placebo-controlled study of Ropini-
role, somnolence occurred in 36% (42/116) compared
to 4.8% (6/125) of the placebo group [8] However, a
narcolepsy-like phenotype (2 sleep-onset REM peri-
ods (SOREMPs)) was found in 39% of PD patients
in two recent studies using multiple sleep latency test
(MSLT) as an outcome [9, 10]. In addition, Arnulf,
et al. found that the PD patients with SOREMPs on
their MSLTs had a signifcant decrease in their mean
sleep onset latencies (SOL) compared to those without
SOREMPs. The narcolepsy-like group had an average
SOL of 4.6 0.9 minutes compared to 7.4 0.7 min-
utes [9]. This suggests that although PD patients can
have many secondary causes for their EDS, there may
be an over-riding primary CNS process at the root of
this complaint.
Sleep Attack
Sleep attack, an unintended sleep episode, is another ex-
ample of a potential disturbance in wakefulness seen in
PD. Sleep attack by defnition is a paroxysmal episode of
excessive sleepiness and occurs most of the time without
warning. In 1999, Frucht et al. described sleep attacks
in patients with PD while they were driving, illustrating
its potential danger [11]. A few studies have shown that
sleep attacks have occurred in 6% to 30.5% of PD pa-
tients [12, 13].
Montastruc and others found two factors contribut-
ing to sleep attacks in PD patients: autonomic failure
and antiparkinsonian medications. In their study, 72 out
of 236 PD patients had sleep attacks, 70% of which
also were found to have dysautonomia. The same study
estimated dysautonomia to be present in only 24% of
the total PD patients studied [12]. Of the antiparkin-
sonian medications implicated in sleep attacks, many
studies have shown dopamine agonists as the main cul-
prit. However, more recent studies indicate that other
dopaminergic medications, such as Levodopa, can cause
sleep attacks as well [14]. Hobson, et al. found the fre-
quency of sleep attacks in PD drivers was 26% (24/90)
in Ropinirole users, 10.5% (43/407) in patients taking
Levodopa, and 9% (13/143) in Pramipexole users [14].
In the United States, package inserts for Pramipexole
and Ropinirole advice that patients should be warned
about the potential development of excessive drowsiness
and sleep attacks prior to initiation of treatment. If a pa-
tient develops signifcant drowsiness, let alone sleep at-
tacks, it is recommended that the dopamine agonist be
discontinued [15, 16]. Aretrospective study showed that
6.6%of patients taking dopamine agonists suffered from
sleep attacks; this was independent of length of treat-
ment, drug dosage, or patient age [17].
Insomnia
Insomnia is a disturbance of sleep initiation, mainte-
nance, or continuity; it primarily occurs as a result of
the diseases natural progression. Most of the time,
insomnia is the result of the symptoms associated
with the off time condition, such as nighttime tremor,
rigidity, and nocturnal akinesia. In some instances,
insomnia may develop as a side effect of dopaminergic
medications such as monoamine oxidase B (MAO-B)
inhibitors, dopamine agonists and levodopa. Finally,
it can be secondary to the comorbidities seen with
PD including nocturia, degenerative joint disease, and
neuropathy [4, 18].
International Journal of Neuroscience
Parkinsons Disease and RBD 409
Restless Legs Syndrome (RLS)
RLS is a neurological disorder characterized by any sen-
sory discomfort in the legs that occurs at times of inac-
tivity or rest, usually beginning when lying down. These
unpleasant symptoms are either partially or completely
relieved with movement. When present, the dysesthesia
varies from an uncomfortable feeling to a very painful
sensation, which may be diffcult for some patients to
describe [19]. The prevalence of RLS in PD in one
study was 20.8% (63/303) [20]. This is much higher
than that found in the general population, thought to
be existent in 3% to 10%, with a population-based sur-
vey of the elderly (6583 years of age) showing a preva-
lence of 9.8% (36/369) [21]. One recent study showed
that the most important predictive factor for develop-
ment of RLS in PD is the duration of antiparkinsonian
therapy [22]. The relationship between RLS and PD re-
mains unclear; however, functional imaging studies sug-
gest reduced dopaminergic function in the striatum in
both RLS and PD [18].
Sleep-Disordered Breathing (SDB)
Multiple epidemiologic studies report the prevalence of
obstructive sleep apnea (OSA) in patients with PD dif-
ferently. Trottie, et al. showed that PD patients did not
have an increased prevalence or severity of OSA when
compared to published, normative, population-based
data from the Sleep Heart Health Study [23]. Their
study found that neither body mass index (BMI), the
Epworth Sleepiness Scale (ESS), nor antiparkinsonian
medications were able to predict the apnea/hypopnea
index (AHI) in these patients. Another recent study of
100 PD patients showed that 27% had OSA, whereas
40% of the 50 control subjects had OSA [24]. Yet some
studies estimate that 20% of patients may suffer from
OSA despite having a normal BMI [9]. While contro-
versy surrounds the relevance and prevalence of OSA
in PD, central sleep apnea is known to occur more
frequently in neurodegenerative disorders, including
PD [18].
Sleep apnea, central and obstructive, has a major ef-
fect on the quality of sleep. In patients with PD, sleep
beneft is defned by the positive infuence good sleep has
on the motor symptoms during wakefulness. This sleep
beneft phenomenon has been found in approximately
10%55% of patients with mild to moderate PD [25].
The reason for the existence of sleep beneft is unknown.
Nonetheless, it does suggest that by applying continu-
ous positive airway pressure (CPAP) or bilevel positive
airway pressure (BIPAP) for the treatment of sleep ap-
nea, thereby improving an individuals sleep, it may be
possible to decrease motor symptoms in parkinsonian
patients.
REM Sleep Behavior Disorder (RBD)
According to the International Classifcation of Sleep
Disorders (ICSD-R), RBD is characterized by, the in-
termittent loss of REM sleep electromyographic atonia
and by the appearance of complex motor activity asso-
ciated with dream mentation [19]. During REM sleep,
the bodys musculature exhibits atonia, rendering the
body outside of the eye muscles and diaphragm virtu-
ally paralyzed. In patients with RBD, there is a loss or
impairment of this musculature atonia. This enables pa-
tients to exhibit dream-enactment behaviors, often with
violent or injurious results to self or bed partner. The
behaviors include talking, yelling, swearing, grabbing,
punching, kicking, jumping, or running out of the bed.
Some have described a, Jekyll and Hyde, like syn-
drome, in which a calm individual during the day acts
out aggressively during REM sleep [26].
In 1965, RBD was frst induced in animal models
by Jouvet and Delorme [26]. They showed that bilat-
eral pontine lesions made in the region adjacent to the
locus coeruleus (LC) in cats eliminated the atonia of
REM sleep. As a result, the lesioned animal was able
to walk and perform other complex motor movements
during REM sleep. This experiment has been further
replicated in other animal models since. In the 1970s,
several reports described dream-enacting behaviors in
humans which mirrored the behaviors induced by Jou-
vet and Delorme. This polysomnographic and behav-
ioral condition was initially referred to as, stage 1 REM
with tonic electromyogram. Finally, in 1986, RBD was
recognized as a distinct clinical disorder [27].
REM sleep contains two stages: a tonic stage charac-
terized by musculature atonia and a phasic stage, which
comprises the rapid eye movement, middle ear muscle
activity and extremity twitches. During normal REM
sleep, though the body remains still, the motor cortex
is highly activated. However, this activity becomes in-
hibited at the level of the motor neurons of the spinal
cord. It has been shown that the peri LCarea of the pons
via the medullary reticularis magnocellularis nucleus ac-
tively inhibits the anterior horn cells of the spinal cord,
creating the tonic stage of REM sleep. Likely, this acts
as a protective measure, preventing the highly activated
motor cortex from accomplishing dream induced mo-
tor movements. The pontine inhibitory area (PIA) and
medial medulla are involved in RBD, whereas, the ven-
tral midbrain is the main affected area in PD [28]. Lai
and Siegel found with an animal study that a lesion to
the ventral mesopontine junction (VMPJ) resulted in an
increased amount of REM sleep and muscle activity, re-
sembling that seen in RBDpatients [29]. Another lesion
placed by injecting N-methyl-D-aspartic acid (NMDA)
into the rostral ventral midbrain (RVMD) adjacent to
the VMPJ, corresponding to neurodegenerative areas
C 2012 Informa Healthcare USA, Inc.
410 A. Barber and K. Dashtipour
of parkinsonism, produced insomnia secondary to
frequent awakenings. This lesion also induced a parkin-
sonian tremor, rigidity, and akinesia for one-week post-
NMDAinjection, disappearing by the second-week post
injection. Since both structures are anatomically adja-
cent to one another in the ventral midbrain, this could
provide an anatomical and physiological link between
parkinsonism and RBD.
RBD is commonly associated with the -synuclein
neurodegenerative disorders, including multiple sys-
tems atrophy (MSA), lewy body dementia (LBD), and
PD. Pathologically, Lewy bodies and -synuclein have
been found in many similar areas of the CNS in patients
with PD and RBD [30]. These include the substantia
nigra (SN), LC, median raphe (MR), pedunculopon-
tine nucleus (PPN), nucleus gigantocellularis (NGC),
and nucleus magnocellularis (NMC). In addition, re-
cent neuroimaging studies have shown reduced striatal
dopamine transporters and dopaminergic innervation in
patients with idiopathic RBD. These results are consis-
tent with fndings in patients with PD [31, 32].
Risk estimates of RBD patients going on to develop
PD and LBD range from 20% to 45% at 5 years and
40% to 65% at 10 years [33]. Other studies indicate
that more than half of those diagnosed with RBD will
develop PD or parkinsonism within 12 years of their ini-
tial diagnosis [18]. However, the length of time between
diagnoses is highly variable, ranging between 3 and
29 years [28]. Recent evidence shows that RBD could
be a predictor of PD, giving it many future implications.
The frequency of RBD in parkinsonian patients as-
sessed by questionnaires or interviews varied from 15%
to 47% [33]. Reports of the rate of RBD were almost
at 33% (11/33) of patients with PD when polysomno-
gram (PSG) was used [34]. In the same study, some pa-
tients showed no atonia during REM sleep recorded by
PSG without behavioral manifestation of RBD, which is
suggestive of a preclinical form of RBD. In comparison,
RBD is estimated to occur in only 0.38% of the general
population and 0.5% in the elderly [19].
Numerous nonmotor symptoms have been proposed
to precede diagnosis of PD. In addition to RBD, these
include dysosmia, constipation, depression, impaired
color vision discrimination, and autonomic dysfunction
[35]. The association between RBD and the rest of the
premotor symptoms has been estimated in a few stud-
ies. These studies showed evidence of dysosmia, color
vision discrimination, and autonomic dysfunction in id-
iopathic RBD similar to those that were discovered in
PD [36].
Although RBD and PD without RBD share many
of the same nonmotor symptoms, there are many clin-
ical differences found between PD with RBD than that
without. PD with RBD differs in comparison by show-
ing a lack of tremor, decreased response to medication,
more cognitive impairment, higher incidence of hallu-
cinations, increased frequency of falls, and more auto-
nomic dysfunction [30, 37]. There are several theories
concerning the pathophysiology of RBD and its connec-
tion with PD.
Clonazepam has been used as the frst line agent to
treat RBD since the original 1986 case series describ-
ing RBD by Schenck et al. [38, 39]. As a long acting
benzodiazepine, its mechanism of action in the treat-
ment of RBD remains to be completely understood.
It does not suppress REM sleep, nor normalize REM
atonia; however, it does reduce phasic muscle activity
[40]. Most studies have reported minimal side effects,
the most common being memory dysfunction [41],
morning sedation [42], impotence [42], and possibly
can be associated with a worsening of sleep apnea [43].
Supporting evidence for the use of melatonin in
RBD is not as strong as clonazepam, but it remains
a strong treatment choice. A multiple report review
showed 31 of 38 patients had improvement to com-
plete control with melatonin, with a dosage range of 3
to 12 mg [44]. Polysomnographic studies of melatonin
have shown an increase in the number of REM epochs
with atonia, a differing action from clonazepam [45].
All side effects were dose related and included morning
headache/sleepiness and delusions/hallucinations [46].
There is limited evidence for the use of other medica-
tions including Levodopa, Donepezil, and Pramipexole
for RBD [44, 47]. However, there is even less data on
the treatment of RBD in PD. All possible treatments
have been given a Level U (unknown) recommendation
by the American Academy of Neurology [48] Some
medications shown to induce or aggravate RBD include
selective serotonin reuptake inhibitors (SSRI) [49],
serotoninnorepinephrine reuptake inhibitor (SNRI),
tricyclic antidepressants [50], and MAO-B inhibitors
[51].
Studies have shown a clinical and anatomical rela-
tionship between RBDand other premotor symptoms of
PD. Since PD is a progressive process, there is a length
of time that degeneration is ongoing when the disease
remains clinically silent. Screening for these premotor
symptoms could open the window to any future use of
a neuroprotective agent, one that could halt the process
prior to the development of diagnosable PD.
CONCLUSIONS
The sleep disturbances seen in PD occur as a result of
multiple factors. First, they can result as a primary out-
come of the disease progression. Second, they can occur
as a side effect of the medications used for the treatment
of PD. And fnally, as often seen with RBD, sleep dis-
turbances may develop prior to the presentation of the
International Journal of Neuroscience
Parkinsons Disease and RBD 411
motor symptoms in PD. The preclinical presentation of
RBD is highly suggestive of a shared, neurodegenerative
process with PD.
The ability to diagnose PD through its premotor
symptoms, such as RBD, is crucial for the possible use
of any future neuroprotective agent before the develop-
ment of motor symptoms. Another important factor to
consider is the correlation between the duration of pre-
motor symptoms and the progression of PD. The pro-
gression within PD varies considerably from one patient
to another. Measuring the length of time from RBD
symptoms to the initiation of PD motor symptoms may
be a predictor of the progression of the disease. Un-
derstanding the mechanism of RBD and its relationship
with PDwill give us newinsight into the evolution of the
disease and may help us fnd a new model to predict its
progression.
Declaration of interest: Dr. Barber reports no con-
fict of interest. Dr. Dashtipour has received honorar-
ium for serving on the scientifc advisory board and
as speaker for Teva, Allergen, Merz, Ipsen, Solstice,
and Lundbeck pharmaceuticals. He has also received
an honorarium as a speaker for Glaxo SmithKline and
UCB pharmaceuticals. The authors alone are responsi-
ble for the content and writing of this paper.
REFERENCES
1. Chaudhuri KR, Healy DG, Schapira AHV. Non-motor symp-
toms of Parkinsons disease: diagnosis and management. Lancet
Neurol. 2006;5:235-45.
2. Parkinson J. An essay on the shaking palsy. London: Whitting-
ham and Rowland; 1817.
3. Poryazova RG, Zachariev ZI. REM sleep behavior disorder
in patients with Parkinsons disease. Folia Med (Plovdiv).
2005;47:5-10.
4. Comella C. Sleep disturbances in Parkinsons disease. Curr
Neurol Neurosci Rep. 2003;3:173-80.
5. Caap-Ahlgren M, Dehlin O. Insomnia and depressive symp-
toms in patients with Parkinsons disease. Relationship to
health-related quality of life: an interviewstudy of patients living
at home. Arch Gerontol Geriatr. 2001;32:23-33.
6. Tandberg E, Larsen J, Karlsen K. Excessive daytime sleepiness
and sleep beneft in Parkinsons disease: a community-based
study. Movement Disord.1999;6:922-27.
7. Shannon K, Bennett JP, Friedman JH. Effcacy of Pramipexole,
a novel dopamine agonist, as monotherapy in mild to moderate
Parkinsons disease. Neurology 1997;49:724-28.
8. Alder CH, Sethi KD, Hauser RA, Hammerstad JP, Bertoni J,
Taylor RL, Sanchez-Ramos J, OBrien CF. Ropinirole for the
treatment of early Parkinsons disease. Neurology 1997;49:393-
99.
9. Arnulf I, Konofal E, Merino-Amdreu M, Houeto JL, Mesnage
V, Welter ML, Lacomblez L, Golmard JL, Derenne JP, Agid
Y. Parkinsons disease and sleepiness. An integral part of PD.
Neurology 2002;58:1019-24.
10. Rye DB, Bliwise DL, Dihenia B, Gurecki P. Daytime sleepiness
in Parkinsons disease. J. Sleep Res. 2000;9:63-9.
11. Frucht S, Rogers JD, Greene PE, Gordon MF, Fahn S. Falling
asleep at the wheel: motor vehicle mishaps in persons taking
Pramipexole and Ropinirole. Neurology 1999;52:1908-10.
12. Montastruc JL, Brefel-Courbon C, Senard JM, Bagheri H, Fer-
reira J, Rascol O, Lapeyre-Mestre M. Sleep attacks and an-
tiparkinsonian drugs: a pilot prospective pharmacoepidemio-
logic study. Clin Neuropharmacol. 2001;24:181-3.
13. Paus S, Brecht HM, K oster J, Seeger G, Klockgether T, W ullner
U. Sleep attacks, daytime sleepiness, and dopamine agonists in
Parkinsons disease. Movement Disord. 2003;18:659-67.
14. Hobson DE, Lang AE, Martin WR, Razmy A, Rivest J, Flem-
ing J. Excessive daytime sleepiness and sudden onset sleep in
Parkinsons disease: survey by the Canadian Movement Disor-
ders Group. JAMA. 2002;287:455-63.
15. Requip [package insert]. Research Triangle Park, NC: Glaxo-
SmithKline; 2009 April.
16. Mirapex [package insert]. Ridgefeld, CT: Boehringer Ingel-
heim Pharmaceuticals, Inc.; May 2011.
17. Homann CN, Wenzel K, Suppan K, Ivanic G, Kriechbaum N,
Crevenna R, Ott E. Sleep attacks in patients taking dopamine
agonists: review. BMJ. 2002;324(7352):1483-7.
18. Jahan I, Hauser RA, Sullivan KL, Miller A, Zesiewicz TA. Sleep
disorders in Parkinsons disease. Neuropsychiatr Dis Treat.
2009;5:535-40.
19. American Academy of Sleep Medicine. The international classi-
fcation of sleep disorders, 2nd ed: diagnostic and coding man-
ual. Rochester, MN: American Academy of Sleep Medicine;
2005.
20. Ondo WG, Vuong KD, Jankovic J. Exploring the relationship
between Parkinson disease and restless legs syndrome. Arch
Neurol. 2002;59:421-4.
21. Rothdach AJ, Trenkwalder C, Haberstock J, Keil U, Berger K.
Prevalence and risk factors of RLS in an elderly population: the
MEMO study. Neurology 2002;54:1064-8.
22. Lee JE, Shin HW, Kim KS, Sohn YH. Factors contributing
to the development of restless legs syndrome in patients with
Parkinson disease. Movement Disord. 2009;24:579-82.
23. Trotti LM, Bilwise DL. No increased risk of obstruc-
tive sleep apnea in Parkinsons disease. Movement Disorde.
2010;13:2246-9.
24. Cochen De Cock V, Abouda M, Leu S, Oudiette D, Roze E,
Vidailhet M, Similowski T, Arnulf I. Is obstructive sleep apnea
a problem in Parkinsons disease? Sleep Med. 2010;11:247-52.
25. Parkes JD. Variability in Parkinsons disease: clinical aspects,
causes and treatment. Acta Neurol Scand. 1983;68:27-35.
26. Aldrich M. Sleep medicine. NewYork: Oxford University Press;
1999. 271 p.
27. Schenck CH, Bundlie SR, Ettinger MG, Mahowald MW.
Chronic behavioral disorders of human REM sleep: a new cat-
egory of parasomnia. Sleep. 1986;9:293-308.
28. Schenck C. Sleep: the mysteries, the problems, and the solution.
New York: Avery; 2007. 213 p..
29. Lai YY, Siegel JM. Physiological and Anatomical link between
Parkinson-like disease and REM sleep behavior disorder. Mol
Neurobiol. 2003;27:137-51.
30. Postuma RB, Gagnon JF, Vendette M, Montplaisir JY. Idio-
pathic REM sleep behavior disorder in the transition to degen-
erative disease. Movement Disord. 2009;24:2225-32.
31. Eisensehr I, Linke R, Noachtar S, Schwarz J, Gildehaus FJ,
Tatsch K. Reduced striatal dopamine transporters in idiopathic
rapid eye movement sleep behavior disorder: comparison with
Parkinsons disease and controls. Brain 2000;123:1155-60.
32. Albin RL, Koeppe RA, Chervin RD, Consens FB, Wernette K,
Frey KA, Aldrich MS. Decreased striatal dopaminergic innerva-
tion in REM sleep behavior disorder. Neurology 2000;55:1410-
2.
C 2012 Informa Healthcare USA, Inc.
412 A. Barber and K. Dashtipour
33. Scaglione C, Vignatelli L, Plazzi G, Marchese R, Negrotti A,
Rizzo G, Lopane G, Bassein L, Maestri M, Bernardini S,
Martinelli P, Abbruzzese G, Calzetti S, Bonuccelli U, Provini
F, Coccagna G. REM sleep behaviour disorder in Parkin-
sons disease: a questionnaire-based study. Neurol Sci. 2005;25:
316-21.
34. Gagnon JF, B edard MA, Fantini ML, Petit D, Panisset M,
Rompr e S, Carrier J, Montplaisir J. REM sleep behavior disor-
der and REM sleep without atonia in Parkinsons disease. Neu-
rology 2002;59:585-9.
35. Siderowf A, Stern M. Premotor Parkinsons Disease: clinical
features, detection and prospects for treatment. Ann Neurol.
2008;64(suppl): S139-47.
36. Postuma RB, Lang AE, Massicotte-Marquez J, Montplaisir J.
Potential early markers of Parkinson disease in idiopathic REM
sleep behavior disorder. Neurology 2006;66:845-51.
37. Postuma RB, Gagnon JF, Vendette M, Charland K, Montplaisir
J. REM sleep behavior disorder in Parkinsons disease is associ-
ated with specifc motor features. J Neurol Neurosurg Psychiat.
2008:10;1117-21.
38. Anderson, K, Shneerson, J. Drug treatment of REM sleep be-
havior disorder: the use of drug therapies other than Clon-
azepam. J. Clin Sleep Med. 2009;3:235-9.
39. Schenck CH, Bundlie SR, Ettinger MG, Mahowald MW.
Chronic behavioral disorders of human REM sleep: a new cat-
egory of parasomnia. Sleep 1986;9:293-308.
40. Lapierre O, Montplaisir J. Polysomnographic features of REM
sleep behavior disorder: development of a scoring method. Neu-
rology 1992;42:1371-4.
41. Schenck CH, Mahowald MW. Long-term, nightly benzodi-
azepine treatment of injurious parasomnias and other disor-
ders of disrupted nocturnal sleep in 170 adults. AM J Med.
1996;100:333-7.
42. Schenck CH, Mahowald MW. A polysomnographic, neuro-
logic, psychiatric, and clinical outcome report of 70 consecu-
tive cases with REM sleep behaivior disorder (RBD): sustained
clonazepam effcacy in 89.5% of 57 treated patients. Clev Clin
J Med. 1990;57(Suppl):S9-23.
43. Schuld A, Kraus T, Haack M, Hinze-Selch D, Pollm acher T.
Obstructive sleep apnea syndrome induced by clonazepam in a
narcoleptic patient with REM-sleep behavior disorder. J Sleep
Res. 1999;8:321-2.
44. Aurora RN, Zak RS, Maganti RK, Auerbach SH, Casey KR,
Chowdhuri S, Karippot A, Ramar K, Kristo DA, Morgenthaler
TI. Best practice guide for the treatment of REM sleep behavior
disorder (RBD). Journal of Clinical Sleep Medicine. 2010;6:85-
95.
45. Kunz D, Bes F. Melatonin as a therapy in REM sleep behav-
ior disorder patients: an open-labeled pilot study on the possi-
ble infuence of melatonin on REM-sleep regulation. Movement
Disorder 1999;14:507-11.
46. Boeve BF, Silber MH, Ferman TJ. Melatonin for treatment of
REM sleep behavior disorder in neurologic disorders: results in
14 patients. Sleep Medicine 2003;4:281-4.
47. Gugger J, Wagner M. Rapid eye movement sleep behavior dis-
order. Ann Pharmacotherapy 2007;41:1833-41.
48. Zesiewicz TA, Sullivan KL, Arnulf I, Chaudhuri KR, Morgan
JC, Gronseth GS, Miyasaki J, Iverson DJ, Weiner WJ. Practice
parameter: treatment of nonmotor symptoms of Parkinsons dis-
ease. Neurology 2010;74:924-31.
49. Schenck CH, Mahowald MW, Kim SW, OConnor KA, Hur-
witz TD. Prominent eye movements during NREM sleep and
REM sleep behavior disorder associated with fuoxetine treat-
ment of depression and obsessive-compulsive disorder. Sleep
1992;15:226-35.
50. Schenck CH, Mahowald MW. Motor dyscontrol in narcolepsy:
rapid-eye-movement (REM) sleep without atonia and REM
sleep behavior disorder. Ann Neurology 1992;32:3-10.
51. Garcia-Borreguero D, Larrosa O, Bravo M. Parkinsons disease
and sleep. Sleep Med Rev. 2003;7:115-29.
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