REM Sleep Behavior Disorder

Aleks Videnovic, MD, MSc

Massachusetts General Hospital

Harvard Medical School

Boston, USA

REM Sleep Behavior Disorder

• Dream-enactment behavior

associated with loss of muscle

atonia in REM sleep

• The parasomnia most commonly

associated with

neurodegenerative disease

REM Sleep Behavior Disorder

Diagnostic Criteria

A. Repeated episodes of sleep related vocalization and/or complex motor

behaviors.

B. These behaviors are documented by polysomnography to occur during

REM sleep or, based on clinical history of dream enactment, are

presumed to occur during REM sleep.

C. Polysomnographic recording demonstrates REM sleep without atonia

(RWA)

D. The disturbance is not better explained by another sleep disorder,

mental disorder, medication, or substance use.

American Academy of Sleep Medicine,

International Classification of Sleep Disorders, 3rd ed., 2014

RBD: Clinical characteristics

• Episodes usually occur after midnight or more than two hours after

sleep onset.

• Association of behavior or vocalizations with dreaming

• Elaborated dream content

• Apparent dream enactment: behavior seems to resemble dream

content

• Large variability of behaviors and vocalizations even in an individual

patient

RBD – dreams

• Vivid, intense, full of action, unpleasant

• Dreamer is being threatened or attacked by unfamiliar people,

animals, insects.

• Dreamer is rarely the primary aggressor.

• Fear and anger are predominant moods.

Questionnaires and interview-based

instruments to detect RBD

• REM Behavior disorder screening questionnaire (RBDSQ) (Stiasny-

Kolster 2007)

• REM Sleep Behavior Disorder questionnaire Hong Kong (RBDQ-

HK) (Li 2010)

• Mayo Sleep Questionnaire (MSQ) (Boeve 2011)

• RBD1Q (Postuma 2012)

• Innsbruck REM Sleep Behavior Disorder Inventory (RBDI) (Frauscher

2012)

Author Name Sens / Spec

Stiasny-Kolster et al., Mov Disord (2007) RBD Screening Questionnaire 96% / 56%

Li et al., Sleep Med (2010) RBDQ-HK 82% / 86%

Boeve et al., Sleep Med (2011) Mayo Sleep Questionnaire 98% / 74%

Postuma et al., Mov Disord (2012) Single-Question Screen for RBD 94% / 87%

Frauscher et al., Mov Disord (2012) Innsbruck RBD Inventory 91% / 85%

Sensitivity and specificity of

currently available RBD questionnaires

M mentalis

M deltoideus

M abductor pollicis brevis

M flexor digitorum superficialis

M biceps brachii

M rectus femoris

M sternocleidomastoideus

M tibialis anterior

M gastrocnemius

M extensor digitorum brevis

Paravertebral Th11/12

M. submentalis

Polysomnography - EMG Analysis

Normative EMG Values during REM Sleep for the Diagnosis of REM Sleep

Behavior Disorder

Frauscher, Iranzo and the SINBAR group Sleep (2012)

Analysis of EMG Activity

Tonic Scored only in the mentalis channel using 30-sec epochs.

Epoch scored as “tonic” when increased sustained EMG activity was present in more than 50%

of the total 30-sec with amplitude of at least twice the background EMG muscle tone or > 10

μV.

Phasic Epoch divided into 3-sec miniepochs.

Phasic EMG activity defined as any burst of EMG activity lasting between 0.1 and 5.0 sec

with an amplitude exceeding twice the background EMG activity irrespective of its morphology.

Each 3-sec miniepoch was scored as having or not having “phasic” EMG activity.

``Any`` To simplify and to include periods of phasic EMG activity between 5 and 15 sec,

each 3-sec miniepoch as having or not having “any” EMG activity, irrespective of whether it contained tonic, phasic, or a combination of both EMG activities.

Frauscher and Högl, in: Chokroverty, Allen, Walters, Montagna (eds).

Sleep and Movement Disorders, 2nd ed.

Polysomnography:- EMG Analysis

PHASIC EMG ACTIVITY

TONIC EMG ACTIVITY

Some cut-off values for RBD detection

Authors Investigated

EMG measures

Proposed

Cut-off scores

Investigated

muscles

Epoch

duration

Scoring system

Ferri 2008, 2010 REM atonia index

0.8 chin N/A semiautomatic

Montplaisir 2010

Phasic EMG activity

Tonic EMG activity

15%

30 %

chin

chin

2

20

manual scoring

SINBAR (Frauscher

2012)*

Any EMG activity

Phasic EMG activity

SINBAR EMG activity

Tonic EMG activity

Any EMG activity

Phasic EMG activity

SINBAR EMG activity

18 %

16 %

32 %

10 %

15 %

11 %

27 %

chin

chin

chin + FDS

chin

chin

chin

chin + FDS

3

3

3

30

30

30

30

manual scoring

Frauscher and Högl In: Disorders of Sleep and Circadian

Rhythms in Parkinson’s Disease. Videnovic A, Högl B (eds.), in press

RBD - Differential Diagnosis

• NREM parasomnias

• Nocturnal seizures

• Disorders of arousal

• Nocturnal psychogenic dissociative disorder

• Obstructive sleep apnea

• Malingering

29 iRBD > 50yo after 12.7±7.3 years parkinsonsim 38% (1996)

Neurology 1996

46:388-93.

44 RBD after 11.5 years: 45% PD/DLB/MSA/MCI (2006)

R.B. Postuma, MD: J.F. Gagnon, PhD;M. Vendette, BSc; M.L. Fantini, MD; J. Massicotte-Marquez, PhD; J. Montplaisir, MD,PhD

93 RBD

5-Year Risk 17.7%

10-Year Risk 40.6%

12-Year Risk 52.4% for parkinsonism or MCI

•16 year Update on previous series: 81% after median 14 years

RBD - harbinger of parkinsonism

- Imaging -

• Reduced pre-synaptic dopamine transporters in idiopathic RBD

using IPT-SPECT; Eisensehr, 2000.

RBD - harbinger of parkinsonism

- Imaging -

2

2.5

3

3.5

4

4.5

Controls

Subcl RBD

RBD

PD

RBD - harbinger of parkinsonism

– EEG

– NEUROPSYCHOLOGICAL TESTING

– COLOUR DISCRIMINATION

– CARDIAC AUTONOMIC ACTIVITY

– OLFACTORY FUNCTION

Parkinsonism – RBD

An Anatomic Hypothesis?

• Lai T, Siegel J. Molecular neurobiology 2003:137-151

Neuronal degeneration can

begin in either part of the

ventral brainstem and extend

either rostrally or caudally

VMPJ as initial site:

RBD as initial symptom

RVMD as initial site: parkinsonism as initial symptom

MCI AD

MCI AD

RBD SYNUCLEINOPATHY

Postuma, 2008

• 53 PD patients with RBD

• Improvement of at least one component of motor control during RBD – 100%

• Improved movements - 87%

• faster 87%

• stronger 87%

• smoother 51%

• Improved speech - 77%

• more intelligible 77%

• louder 38%

• better articulated 57%

• Normalized facial expression - 47%

RBD in PD

- Treatment -

• Protective measures

• Clonazepam

• Donepezil

• Melatonin

• Pramipexole

Future directions

PPMI

P-PPMI - enrolling patients with RBD