REM behavior disorder associated with sleep

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RBD and sleep disordered breathing
REVIEW ARTICLE
REM behavior disorder associated with sleep
disordered breathing
Transtorno comportamental do sono REM associado com distúrbio respiratório
do sono
Maria Isabel Montes 1,3, Rosa Hasan2, Stella Tavares2, Geraldo Lorenzi Filho3
ABSTRACT
REM behavior disorder (RBD) is a parasomnia characterized
by muscle tonus during REM sleep and presence of vigorous
movements which can be potentially harmful. RDB is mostly
prevalent in men between 40 and 70 years and it is usually
associated with neurodegerative disease. Obstructive Sleep Apnea
(OSA) is a common disorder in the general population and may
present multiple clinical manifestations that include disrupted sleep.
Arousals with vigorous movements may be present in patients with
OSA and may express a clinical manifestation known as pseudo
RBD. Using the keywords “Obstructive sleep apnea” and “REM
behavior disorder” in the main data bases we found a total of
99 articles, but 94 articles were excluded because they did not
specifically approached the relationship between the 2 diseases.
Therefore, 5 articles were initially evaluated and we included 2 more
relevant studies that were quoted by the initially selected articles.
The articles reviewed consisted mainly of case reports or small
case series. Pseudo RDB is usually associated with severe OSA and
severe oxyhemoglobyn desaturations. The small number of reports
may indicate a low awareness of this condition.
Keywords: electromiography, obstructive sleep apnea, polysomnography, REM behavior disorder.
RESUMO
Transtorno comportamental do sono REM (TCSREM) é uma
parasomnia caracterizada por persistência do tônus muscular
durante o sono REM e presença de movimentos que podem ser
vigorosos e potencialmente prejudiciais. TCSREM é principalmente
prevalente em homens entre 40 e 70 anos e é geralmente associado
à doença neurodegerativa. Apneia obstrutiva do sono (AOS) é
um distúrbio comum na população geral, e que pode ter várias
manifestações clínicas que incluem sono agitado. Quando a AOS leva
a despertares com movimentos vigorosos, o distúrbio é conhecido
como “pseudotranstorno comportamental do sono REM”. Usando
as palavras chaves “apneia obstrutiva do sono” e “transtorno
comportamental do sono REM” achamos 99 artigos, dos quais 94
foram excluídos porque especificamente não abordavam a relação
entre as duas doenças. Portanto, 5 artigos foram inicialmente
avaliados e foram adicionados 2 artigos relevantes citados pelos
artigos selecionados. Os artigos incluídos na presente revisão são
relatos de casos ou pequenas séries de casos. “Pseudo transtorno
comportamental do sono REM” está associado com AOS grave e
dessaturações de oxihemoglobina importantes. O pequeno número
de relatos descritos na literatura pode indicar um reconhecimento
ainda insuficiente dessa associação.
Descritores: apneia obstrutiva do sono, polissonografia, transtorno do
comportamento do sono REM.
INTRODUCTION
REM behavior disorder (RBD) is a parasomnia characterized
by behavioral release during rapid eye movement sleep (REM)
caused by the loss of normal muscle atonia during REM. The
behavior manisfestation is variable, ranging from talking, singing,
to complex episodes of vigorous movements that are related
to unpleasant and combative dreams that can be potentially
harmful to patient and bedfellow(1,2). The overall prevalence
of RBD in the general population ranges from 0.38% in Hong
Kong(3) to 0.5% in the United States(4). RDB may be associated
with extrapyramidal disorders and often precede the clinical
onset of Parkinson disease, Lewy body dementia or multiple
system atrophy. Any evidence for RBD should be as it may have
major clinical implications. Neuroimaging studies have revealed
that RDB may affect several levels of cerebral organization,
from neurotransmission (presynaptic striatal dopaminergic) to
neuroanatomical integrity (lesions in mesopontinetegmentum)
and brain function (frontal, temporoparietal and cingulate cortex
dysfunctions)(5).
Obstructive sleep apnea (OSA) is distinguished by
recurrent obstruction of the upper airway leading to repeated
episodes of either complete (apnea) or partial (hypopnea)
reductions of airway flow. OSA is characterized by intermittent
hypoxia and increased negative intrathoracic pressure during
breathing effort against an occluded upper airway. The obstructive
episodes are typically terminated by an arousal or awakening
from sleep that restores the upper airway muscle tone to the
awake level and allows the patient to breath(6). The typical clinical
Study carried out at Sleep Laboratory, Pulmonary Division of the Heart Institute (InCor) - Medical School, Universidade de Sao Paulo.
1
Department of Neurology, University of Antioquia, Medellin, Colombia.
2
Psiquiatric Institute, Hospital das Clínicas, Medical School, Universidade de São Paulo.
3
Sleep Laboratory, Pulmonary Division of the Heart Institute (InCor), Medical School, Universidade de São Paulo.
Corresponding author: Geraldo Lorenzi Filho. Pulmonary Division of the Heart Institute (InCor) - Medical School, Universidade de São Paulo. Av. Dr. Eneas
Carvalho de Aguiar, nº 44. Cerqueira César. São Paulo - SP. Brazil. CEP: 05403-000. E-mail: [email protected]
Received: August 01, 2012; Accepted: October 22, 2012.
Sleep Sci. 2013;6(1):32-35
Montes MI, Hasan R, Tavares S, Filho GL
manifestation of OSA are loud and irregular snoring, disrupted
and non-restorative sleep and excessive daytime sleepiness. In
contrast to RDB, OSA is extremely common in the general
population. For instance, a recent large epidemiological study
at the city of São Paulo, Brazil estimated that 33% of the adult
population present OSA syndrome, as characterized by more
than 5 events per hour of sleep plus symptoms or more than 15
events/hour of sleep, independent of symptoms(7).
OSA and RBD have different pathophysiologic substrates.
While OSA is caused by repetitive obstruction of the upper
airway during sleep, RBD is thought to reflect dysfunction
of the brainstem structures that modulate REM sleep(8).
The clinical manifestations of OSA and RDB are also considered
fundamentally different. However, it must be stressed that
patients with OSA present a fragmented sleep and may show
movements during sleep. Dream-enacting behaviors can also
occur among patients with OSA during arousals from NREM
sleep and REM sleep, a clinical situation termed pseudo RBD(2).
Given the fact that OSA is extremely common in the
general population, it is therefore possible that several patients
with clinical manifestations of RDB may in reality present OSA
and therefore should be classified as pseudo-RDB. It is also
possible that some patients will present both RDB and OSA.
The aim of the present study was to review all articles that
reported on pseudo RDB.
METHODS
We used the following data base Pubmed, Scielo, Cochrane,
Bireme, Lilacs, and we searched for articles with the relationship
between RBD and OSA or with the term Pseudo RBD. We used
the following keywords: “Obstructive sleep apnea” and “REM
behavior disorder”. We also included older relevant articles that
were quoted by the selected articles.
RESULTS
We found 99 articles in Pubmed, and only one article in Scielo,
Cochrane, Bireme and Lilacs, respectively. The articles published
in Scielo, Cochrane, Bireme and Lilacs were also present in
Pubmed. Ninety four articles were excluded because they did not
specifically approached the relationship between the 2 diseases.
Therefore, 5 articles were initially evaluated. In addition, we
included 2 more articles that were not found in the search(9,10),
but were quoted by all the selected articles Figure 1. A summary
of articles with RBD and OSA evaluated with year and journal
of publication, study design, number and characteristics of the
patients and conclusions are described in Table 1. The reports
consisted mainly of case reports or case series. The main
findings are discussed below.
DISCUSSION
The present review found only 7 relevant articles and highlights
the small number of studies that have evaluated the relationship
between RDB and OSA. In addition, the reports included in
the present review are represented by case reports or small
case series. This may reflect the low awareness of the potential
Figure 1. Flowchart of the articles that were revised, excluded and finally included
in the review.
importance of pseudo RDB. Despite these limitations, several
important conclusions can be drawn from this review. First,
pseudo RDB is usually associated with severe OSA and severe
oxyhemoglobyn desaturations. The apnea-hypopnea index
(AHI) of the patients with OSA that were reported to have
pseudo RDB ranged from 31 to 124 events/hour of sleep(8-10).
One paper also reported on severe oxygen dessaturations
in these patients(8). Second, the physiopathology of pseudo
RBD is not completely understood. It has been reported that
OSA induced arousals detected in NREM and REM sleep or
only in the REM sleep, with dream-related complex and violent
behaviors occurred just at the end of obstructive sleep apneic
events(8).
Some authors speculated that pseudo RBD is a form of a
confusional arousal secondary to a combination of severe levels
of oxyhemoglobin desaturations during the apneic events(8,9).
RBD may be associated incidentally with OSA, one study found
OSA in patients with previous diagnostic of RBD presumed
that OSA is extremely frequent in older people making the
chance association of OSA with RBD possible(11).
In the other hand, RBD has been proposed to be
protective against OSA(10). Supporting this theory, Huang et al.
reported that patients with RBD and OSA presented shorter
duration of apneas and hypopneas during REM than NREM
sleep. Therefore, excessive EMG activity associated with RBD
probably protected from long apneas resulting in shorter
respiratory events, less REM sleep-related exacerbation, and
probably a lower frequency of apneas and hypopneas(12).
The diagnosis of RDB must be made with
video-polysomnography (VPSG). This is the only test that can
simultaneously diagnosis OSA and RDB and also clearly observe
if the abnormal motor and vocal behaviors occur at the end of an
obstructive events during sleep(8). One study aimed to distinguish
patients with the independent association of idiopathic RBD
and OSA (that can be present in the same patient) vs. patients
with moderate to severe OSA with pseudo RBD(13). The
Sleep Sci. 2013;6(1):32-35
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RBD and sleep disordered breathing
Table 1. Articles with RBD and OSA evaluated in the review.
Publication
Design
Patients
Conclusions
Huang J, Sleep, 2011;34(7):909-15.
Case-control Study
71 RBD patients
28 RBD-OSA cases
27 OSA controls
Excessive EMG activity in RBD might
protect patients against severe OSA
Cross-sectional Study
23 idiopathic RBD without OSA patients
9 idiopathic RBD with OSA mild patients
15 idiopathic RBD with moderate to severe
OSA patients
16 moderade to severe OSA patients without RBD
(123) I-MIBG cardiac scintigraphy
has the potential to distinguish true
RBD from pseudo-RBD associated
with OSA
Miyamoto T, Sleep Med. 2009;10(5):577-80
Henriques-Filho PS, Arq Neuropsiquiatr.
2008;66(2B):344-9.
Cross-sectional
103 patients with Chiari malformations
The high rate of RBD suggests that
this parassomnia and the increased
frequency of central sleep apnea
episodes, may be considered as a
marker of progressive brain stem
dysfunction
Iranzo A, Sleep.2005;28(2):203-6
Cross-sectional
16 patients with OSA and Pseudo RBD
20 patients controls
16 patients with idiopathic RBD
RBD may be associated incidentally
with OSAH, and only VPSG can
detect both conditions when occurring
in the same patient
Schuld A, J Sleep Res.1999;8(4):321-2
Case Report
1 patients with RBD
Patients treated with clonazepam
should be monitored for the possible
development of OSAS
Nalamalapu U, Sleep Res 1996;25:311
Case Series
5 patients with OSA and Pseudo RBD
OSA may be associated with behaviors
that simulate RBD
Case Series
14 patients with RBD and OSA
10 patients with Obstructive breathing-related
arousals with minimal O2 desaturations
72 patients with normal respiration
OSA when present in RBD is
usually mild
Schenck CH, Sleep Res 1992;21:257
authors used cardiac (123)I-metaiodobenzylguanidine (MIBG)
scintigraphicthat. MIBG is taken up and accumulates in cardiac
sympathetic nerve postganglionic fibers. Marked reduction of
cardiac MIBG uptake seems to be a specific marker of Lewy
bodies, that in turn have been found in patients idiopathic RBD.
However, in this study MIBG was reduced both in patients with
RBD and pseudo RDB. Therefore, this study did not provide a
mechanism to explain why MIBG was low in all forms of RDB
and was not able to distinguish RDB and pseudo RDB.
One study found the association between Chiari, central
sleep apnea and RDB(1). The authors speculated that the
proximity in the brain stem of neuronal groups responsible for
the control of breathing and the control of REM sleep may
help to explain this association. REM sleep control centers and
some of the respiratory control centers are situated between the
caudal region of the facial nucleus and the ambiguous nucleus
located in the lateral tegument of the giganto-celular region of
the medulla. The respiratory system during REM sleep when
damaged would therefore be responsible for central apneas.
CONCLUSION
We conclude that it is important to distinguish RBD from
OSA because they have different clinical connotations and
outcomes. Moreover, OSA and RBD require very different
treatments. Clonazepam is the treatment of choice for RBD
and may worsen coexisting OSA(8) or may induce OSA in some
predisposed patients(14).
Diagnosis of RBD in a subject with no evidence of underlying
neurodegenerative disease must be accurate since idiopathic RBD
Sleep Sci. 2013;6(1):32-35
frequently precedes the onset of a parkinsonian or cognitive disorder.
On the other hand, OSA is a risk factor for cardiovascular disease
and the treatment of choice is the use of continuous positive airway
pressure. If we consider that OSA is highly prevalent in the general
population, pseudoRBD could be more common than currently
recognized. Pseudo RBD must become a differential diagnosis of
RBD. The reasons why only some patients with severe OSA present
pseudo RBD remains not established.
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