Curr Treat Options Neurol (2019) 21: 1

DOI 10.1007/s11940-019-0543-8

Sleep Disorders (A Iranzo, Section Editor)

Diagnostic Criteria,
Differential Diagnosis,
and Treatment of Minor Motor
Activity and Less Well-Known
Movement Disorders of Sleep
Ambra Stefani, MD*
Birgit Högl, MD
Address
*
Department of Neurology, Medical University of Innsbruck, Anichstrasse 35,
6020, Innsbruck, Austria
Email: [email protected]

Published online: 19 January 2019

* The Author(s) 2019

This article is part of the Topical Collection on Sleep Disorders

Keywords EFM I Neck myoclonus I Isolated RBD I Idiopathic RBD I Prodromal RBD

Abstract
Purpose of review Sleep-related movement disorders (SRMD) include several different
motor activities during sleep. Few of them are well known and well classified, whereas
others are minor motor disorders of sleep which are neither thoroughly characterized and
classified nor have been extensively investigated to clarify their pathogenesis and clinical
relevance. This review will focus on those minor sleep-related movement disorders.
Recent findings Before diagnosing periodic limb movement (PLM) disorder in patients with
PLM during polysomnography, other disorders associated with PLM need to be excluded,
namely restless legs syndrome (RLS), narcolepsy, REM sleep behavior disorder (RBD), and
sleep-related breathing disorder. For the diagnosis of propriospinal myoclonus at sleep-
onset, multi-channel surface electromyography recording during polysomnography is
required and a possible psychogenic origin of the movement disorder has to be considered.
Excessive fragmentary myoclonus (EFM) does not require symptomatic treatment, but
further evaluation is suggested as electrophysiological abnormalities are present in 50%
of cases. Nine percent of healthy sleepers meet the criteria for EFM, raising the question if
current, arbitrarily defined, cutoffs are valid. Hypnagogic foot tremor, rhythmic feet
movements, alternating leg muscle activation, and high-frequency leg movements are
somewhat overlapping minor motor activities during sleep which may exist on their own or
represent stereotyped movements to relieve RLS-like symptoms. Neck myoclonus is prob-
ably a physiological phenomenon related to REM twitching. RBD is formally a parasomnia
1 Page 2 of 14 Curr Treat Options Neurol (2019) 21: 1

but a relevant differential diagnosis when evaluating sleep-related movement disorders.

In particular, prodromal RBD is characterized by electromyographic and behavioral find-
ings on video-polysomnography which needs to be differentiated by minor sleep-related
movement disorders.
Summary Minor SRMD beyond the well-known main motor disorders of sleep should be
correctly diagnosed, distinguished from differential diagnosis, and understood in their
potential clinical relevance, in order also to start an appropriate treatment if needed.

Introduction
Most physicians associate sleep-related movement dis- excessive fragmentary myoclonus (EFM), hypnagogic
orders (SRMD) with restless legs syndrome (RLS), peri- foot tremor (HFT), and alternating leg muscle activation
odic leg movements during sleep (PLMS), and (ALMA), and sleep starts [1] (Table 1). Rhythmic feet
parasomnias with abnormal movements and behaviors movements (RFM) and high-frequency leg movements
during sleep, such as REM sleep behavior disorder (HFLM) are not included in this category. Another fre-
(RBD). According to the ICSD-3 [1], SRMD include quent SRMD, neck myoclonus during (REM) sleep or
RLS, periodic limb movement disorder (PLMD), sleep- head jerks, is also yet not classified in the ICSD-3. RBD is
related leg cramps, sleep-related bruxism, sleep-related listed among the REM sleep parasomnias, but as its
rhythmic movement disorder, benign sleep myoclonus main feature are increased EMG activity, jerks, and
of infancy, and newly in the current edition movements during REM sleep, it represents an impor-
propriospinal myoclonus at sleep onset. Moreover, tant differential diagnosis for some SRMD.
within the ICSD-3 category of SRMD, the subcategory While the most well-known sleep disorders with ab-
of “isolated symptoms and normal variants” includes normal motor activity during the night, such as RLS and

Table 1. ICSD-3 definite sleep-related movement disorders [1]

ICSD-3 definite sleep-related movement disorders

• Restless legs syndrome (RLS)
• Periodic limb movement disorder
• Propriospinal myoclonus at sleep onset
• Sleep related leg cramps
• Sleep related bruxism
• Sleep related rhythmic movement disorder
• Benign sleep myoclonus of infancy
• Propriospinal myoclonus at sleep onset
• Sleep related movement disorder due to a medical disorder
• Sleep related movement disorder due to a medication or substance
• Sleep related movement disorder, unspecified
• Isolated symptoms and normal variants:
- Excessive fragmentary myoclonus
- Hypnagogic foot tremor and alternating leg muscle activation
- Sleep starts
Curr Treat Options Neurol (2019) 21: 1 Page 3 of 14 1

RBD, are the focus of multiple reviews [2•, 3•, 4•, 5•, 6, The aim of this review is to address those minor
7, 8•, 9, 10], the other motor disorders of sleep are often sleep-related movement disorders which are often
considered less frequent, less important, or not clinically misdiagnosed or misinterpreted, focusing on their diag-
relevant. This leads to the fact that some of them are nostic criteria, differential diagnosis, prevalence (as far as
frequently missed or misinterpreted in their meaning data are available), clinical implications, meaning, and,
and implications or confounded in differential diagnosis. as far as it is known, treatment.

Periodic limb movement disorder

Overview
Periodic limb movement disorder (PLMD) is a frequently given diag-
nosis based on PSG only, but in many cases it could be misattributed,
specifically in patients where PLMS are seen in PSG and no further
evaluations regarding other sleep pathologies which frequently go along
with PLM is undertaken.

Diagnostic criteria
According to the ICSD-3[1], diagnosis of PLMD requires documentation in the
PSG of PLMS with an index of 9 5/h in children and 9 15/h in adults. Addi-
tionally, PLMS must cause clinically significant sleep disturbance or impair-
ment in various relevant areas of functioning and cannot be better explained by
another current sleep, medical, or neurological disorder such as RLS, narcolep-
sy, or RBD. Accordingly, if PLMS are seen in PSG, all these abovementioned
other conditions need to be actively excluded before making a diagnosis of
PLMD.

Differential diagnosis
The first step in a patient with PLMS should be an accurate clinical
interview aiming to RLS symptoms, as RLS is a frequent condition and
PLMS are present in more than 80% of patients with RLS [1, 11].
Interestingly, the presence of PLMS even in the absence of RLS has been
associated with RLS risk genes [12, 13••], suggesting common underly-
ing pathogenetic mechanisms in both conditions. If PLMS are found in
PSG in a patient complaining about excessive daytime sleepiness (EDS),
EDS may not be attributed to the PLMD, but narcolepsy has to be
excluded, as PLMS are frequent (up to 75%) in patients with narcolepsy
[1, 14]. In patients with PLMS and dream enactment, the clinical inter-
view should also focus on clinical history of RBD. PLMS are common in
RBD (about 70%), particularly during REM sleep, which is unusual in
other conditions. Moreover, an accurate video-PSG review evaluating
visible movements and the presence of REM sleep without atonia (RWA)
is needed in these cases, in order not to misdiagnose patients with RBD
as this condition has important implications representing an early stage
alpha-synucleinopathy [5•]. Additionally, PLMS are an important differ-
ential diagnosis in case of suspected RBD, as arousals with abnormal
behaviors may follow PLMS, thus mimicking RBD symptoms [15]. PLMS
may also be associated with sleep-related breathing disorder (SRBD)
1 Page 4 of 14 Curr Treat Options Neurol (2019) 21: 1

[16–18]. In case of coexistence of PLMS and SRBD, the latter should be

treated first and the presence of PLMS should be reassessed after ade-
quate treatment of the SRBD.

Prevalence
In 100 healthy sleepers who underwent video-PSG, in which the presence of
any sleep disorder including RLS was excluded by an expert interview, mean
PLMS index was 9.2/h, with a range of 0–62 [19]. In another general population
study, a PLMS index 9 15/h was reported in 28.6% of subjects. However, 25.3%
of these subjects reported RLS symptoms as evaluated by questionnaires [20].
Still, PLMS can be present during sleep as a simple polysomnographic finding
without RLS and without indicating PLMD.
As for a correct diagnosis of PLMD many other conditions need to be
excluded, and diagnosis requires that PLMS cause clinically significant sleep
disturbance or impairment in various relevant areas of functioning, its real
prevalence is not known and it has even been questioned if PLMD really exists.

Clinical implications/meaning
True PLMD (as opposed to PLMS alone) is characterized by definition by
significant sleep disturbances, mainly sleep onset or maintenance problems.
However, EDS is usually absent in patients with PLMD [1]. Apart from causing
sleep disturbances in the context of PLMD, PLMS have been associated with the
risk of cardiovascular events [21–25]. One possible explanation for this asso-
ciation could be the PLMS-related activation of the sympathetic nervous system
[22]. However, the relationship between PLMS and cardiovascular events and
the potential underlying pathogenetic mechanisms still need to be systemati-
cally evaluated [26••].

Treatment
Studies evaluating treatment of PLMD are scarce and medications that are
useful for idiopathic RLS have not been sufficiently investigated in the setting of
PLMD. Dopaminergic treatment is not indicated in PLM alone and it has been
reported that dopaminergic treatment of PLM alone may over time induce RLS
[27]. Few studies in PLMD reported clonazepam and valproate to be effective
on sleep quality but not on PLMS index, whereas melatonin reduced PLMS
index [28]. However, randomized controlled trials on PLMD are lacking.

Propriospinal myoclonus at sleep onset

Overview
Propriospinal myoclonus (PSM) with mainly axial jerks at the sleep-wake
transition was described in 2001 by the Bologna group [29]. They observed and
described myoclonic activity arising during the relaxed wakefulness
(predormitum) preceding sleep in patients referred for insomnia or
complaining of muscular jerks also during wakefulness. While in a regular 30-s
PSG epoch the myoclonus-like activity in these muscle channels might appear
simultaneous, in a more widespread temporal window (e.g., 5-s epoch) it
became visible that the onset of the EMG activity was in the mid-thoracic or
mid-abdominal muscles and subsequently spread rostrally and caudally.
Curr Treat Options Neurol (2019) 21: 1 Page 5 of 14 1

Neurophysiologically, Vetrugno and co-workers were able to demonstrate that

in patients afflicted with involuntary jerks when falling asleep, the spread of this
jerking activity was of the propriospinal type, with a spinal propagation velocity
ranging from 2 to 16 m/s [29]. The authors also showed that it was necessary to
perform PSG with multichannel surface EMG recording in these patients, which
includes cranial nerve innervated muscles (which are usually not affected),
intercostal and paraspinal muscles, as well as upper and lower extremity mus-
cles. They showed that this activity was mostly present during pre-sleep wake-
fulness and in the transition to light sleep [29].
In addition, in daytime movement disorder clinics, it has been found that in
many cases the propriospinal myoclonus represents a voluntary phenomenon,
based on the fact that it is preceded by a Bereitschaftspotential [30]. It might be
speculated that also in patients with suspected propriospinal myoclonus at
sleep onset some cases might have a psychogenic origin. However, this can only
be definitely ruled out with back averaging and clear documentation of the
absence of a Bereitschaftspotential.

Diagnostic criteria
In the ICSD-3, PSM at sleep onset is now listed among the category of
SRMD and is thus recognized as having a definite pathology (as op-
posed to e.g. EFM and ALMA, which are listed as isolated symptoms).
The ICSD-3 criteria for PMS are listed in Table 2. The criteria represent
clearly a clinical definition and no minimum amount of jerks or no
minimum requirement of EMG channels has been defined. Therefore, it
seems plausible that, even following ICSD-3, functional cases may be
misdiagnosed as true PSM [30, 31•, 32•].

Differential diagnosis
PSM at sleep onset should be distinguished from intensified hypnic jerks
and PLM. Hypnic jerks are very common and represent a physiological
condition, but rarely they may be so frequent and severe to cause
insomnia, a condition known as intensified hypnic jerks (IHJ) [33]. They
present different types of motor pattern [34] and can originate in the
cranial muscles spreading without any particular propagation pattern
[35]. These features allow differential diagnosis between IHJ and PSM at
sleep onset. PLM may be considered as a mimic of PSM, however, they
appear with a periodic or pseudo-periodic pattern and involve mainly
the distal limbs, without a propriospinal propagation pattern.

Table 2. ICSD-3 criteria for propriospinal myoclonus [1]

ICSD 3 criteria for propriospinal myoclonus

• The patient complains of sudden jerks, mainly of the abdomen, trunk, and neck
• The jerks appear during relaxed wakefulness and drowsiness, as the patient attempts to fall asleep
• The jerks disappear upon mental activation and with onset of a stable sleep stage
• The jerks result in difficulty initiating sleep
• The disorder is not better explained by another sleep disorder, medical or neurological disorder, mental disorder, medication
use, or substance use disorder.
1 Page 6 of 14 Curr Treat Options Neurol (2019) 21: 1

Prevalence
True PSM at sleep onset is considered to be a rare condition. However, epide-
miological data are lacking [1].

Clinical relevance/meaning
In propriospinal myoclonus in general, which is often also intensified when
laying down, it has been demonstrated that few cases are due to a structural
lesion in the myelon, but the majority are considered functional movement
disorders [30, 32]. In functional propriospinal myoclonus, with back averaging
a Bereitschaftspotential preceding the jerk can be found and the jerks cease with
sleep [30, 32].

Treatment
No guidelines are available regarding treatment of true PSM at sleep onset.
Single reports or case series reported amelioration of symptoms on treatment
with clonazepam [36–38]. Valproate, zonisamide, levetiracetam, and opioids
may improve symptoms in single cases [31•, 32•, 36].
Improvement of secondary propriospinal myoclonus has been described
after the treatment of the underlying condition in few cases [39–43]. Patients
with functional propriospinal myoclonus can benefit from unconventional
therapy, such as autogenic training and biofeedback [44, 45].
Isolated symptoms and normal variants within SRMD
In the ICSD-3 [1], this subcategory comprises hypnic jerks, EFM, HFT, and
ALMA. While these were a separate category named “isolated symptoms, ap-
parently normal variants, and unresolved issues” in the ICSD-2 [46], the ICSD-3
has included them in the SRMD category, as “isolated symptoms and normal
variants” [1]. This might perhaps be subject to change or update in the next
versions due to the evidence given below.

Excessive fragmentary myoclonus of sleep

Overview
Fragmentary myoclonus in NREM sleep was first described by Broughton and
Tolentino in 1984 in a single patient [47]. The next year, Broughton and co-workers
published a series of 38 cases, which they determined to have EFM, defined ad hoc
as “presence of EMG activity consisting of brief, usually less than 150 ms,
hypersynchronous, potentials exceeding 50 μV in amplitude” recorded during at
least 20 consecutive minutes of stage 2, 3, or 4 sleep, with a rate of at least 5/min
[48]. Montagna and co-workers in 1988 described a similar phenomenon, which
they defined as physiological hypnic myoclonus and observed that these findings
were present also in wakefulness and often resembled fasciculation potentials [49].

Diagnostic criteria
According to the AASM scoring manual [50], the following define EFM: a. The
usual maximum EMG burst duration seen in fragmentary myoclonus is
Curr Treat Options Neurol (2019) 21: 1 Page 7 of 14 1

150 msec; b. At least 20 min of NREM sleep with EFM must be recorded; c. At
least five EMG potentials per minute must be recorded. Here, a caveat needs to
be mentioned that the current criteria of EFM are based exclusively on an ad hoc
definition by Broughton and colleagues, who had reviewed 20-min segments of
NREM sleep PSG in a series of 38 patients [48] and defined EFM as described
above.
EFM is usually an incidental finding in the PSG and typically not associated
with visible movements, although the ICSD-3 reports that there may be minor
movements of the corners of the mouth, fingers, or toes [1]. In the AASM
scoring manual [50], wording is slightly different: “in many cases no visible
movements are present. Gross, jerk-like movements across the joint spaces are
not observed. When minor movement across a joint space is present, the
movement resembles the small twitch-like movements of the fingers, toes, and
the corner of the mouth intermittently seen in REM sleep in normal
individuals”.

Differential diagnosis
Differential diagnosis of EFM includes: i. phasic EMG activity in RBD. This is by
definition present in REM sleep; however, the differential diagnosis is not
always easy as EFM may be more intense during REM sleep as compared to
NREM sleep; ii. propriospinal myoclonus, which is characterized by longer
potentials as compared to EFM, and by a typical propagation pattern, as
described before; iii. Head jerks/neck myoclonus (described below), which can
be usually identified by the presence of short “stripe-shaped” movement-
induced artifacts [51].

Prevalence
Our own group has published in 2011 a study on fragmentary myoclonus in
sleep in 62 patients and found that the phenomenon was ubiquitous. It was not
primary sleep related, but present both in sleep and wakefulness instead [52], in
line with a previous finding by Montagna and co-workers [49]. In our cohort,
most patients had low fragmentary myoclonus index and few patients had very
high rates [52]. In 100 healthy sleepers, EFM was scored according to AASM
criteria [50]. Every subject had FM during sleep. The median FM index during
sleep was 25.5/h [19].

Clinical relevance/meaning
Based on the presence of EFM in both sleep and wakefulness, as previously
shown by the Bologna group [49], we hypothesized that EFM during PSG was
just an epiphenomenon of another different underlying pathology. We, there-
fore, performed EMG/NCV analysis in 98 out of 100 patients with EFM and
found that 50% of them had electrophysiological abnormalities (namely
polyneuropathy, nerve root lesions, and benign fasciculations) [53•]. Therefore,
we suggested that EMG/NCV analysis should be performed in subjects with
incidental finding of EFM during PSG to investigate the presence of peripheral
nerve pathology [53•].
Furthermore, we would like to suggest that our finding that 9% of healthy
normal sleepers meet the criteria for EFM [19] probably implicates that these
1 Page 8 of 14 Curr Treat Options Neurol (2019) 21: 1

criteria need to be reconsidered as they might turn out to be too liberal to

distinguish physiological from truly excessive cases.

Treatment
The phenomenon represents an incidental EMG finding on PSG. Patients are
usually not aware of fragmentary myoclonus and do not complain, therefore no
treatment is needed. It has been described that in most cases, the cause appears
to be benign [1]; however, the recent report of an association with electro-
physiological abnormalities in 50% of subjects with EFM [53•] suggests that
further studies are needed before classifying definitely this condition as a
normal variant without clinical implications.

Other minor motor activity during sleep

Overview and diagnostic criteria

HFT, RFM, ALMA, and HFLM represent minor motor activity during sleep with
unclear significance and have somewhat overlapping features.
The term HFT has originally been created by Broughton in 1988 [33]. The
authors described in two patients with severe head injury grouped phasic
tremor potentials at varying frequencies between 0.5 and 1.5/s, recorded inde-
pendently from both anterior tibialis muscles, occurring during pre-sleep
wakefulness and sleep stages 1 and 2 [33]. In 2001, Wichniak and co-workers
described this phenomenon as RFM while falling asleep [54]. RFM was found in
28/375 subjects (7.5%) and was described as rhythmic, oscillating movements
of the whole foot or toes. In the EMG recordings, RFM was characterized by a
series of repetitive phasic bursts of 300–700 msec with a frequency of 1–2 Hz,
mostly occurring as single series with a duration of 10–15 s. RFM was present
mainly during pre-sleep wakefulness and persisted in sleep stages 1 and 2 [54].
In 2003, Chervin and co-workers described a very similar phenomenon as
ALMA. They reported a brief activation of the anterior tibialis in one leg
alternated with similar activation contralaterally, with a movement duration of
0.1–0.5 s and a frequency of 1–2 Hz, with sequences lasting between several
and 20 s. The phenomenon was particularly frequent during arousals [55].
HFLM have been defined by Yang and Winkelman [56] in 2010 as at least
four consecutive discrete EMG bursts of leg muscle activity (unilateral, bilateral,
or alternating) with a duration between 0.1 and 0.5 s and a frequency of 0.3–
4 Hz. HFLM sequences were found in 33% of healthy sleepers [19]. In this
cohort, the median number of HFLM sequences was 2 (range 1–24), with a
mean HFLM sequence duration of 3.4 s (range 1.4–17.5 s) and a frequency of
0.9–4 Hz. There was no influence of age or sex on HFLM, but a moderate
correlation with PLMS index 9 5/h [19]. These data, taken together with the
association between HFLM and RLS complaints reported by Yang and
Winkelman [56], and with the EMG similarities between PLMS and HFLM,
might suggest that HFLM are part of the broad PLMS spectrum [19].

Differential diagnosis
HFT, RFM, ALMA, and HFLM should be distinguished from other SRMD
including PLM and PSM at sleep onset. Moreover, they should be
Curr Treat Options Neurol (2019) 21: 1 Page 9 of 14 1

distinguished from other movement disorders including painful legs and

moving toe, tremor (e.g., in the context of Parkinson disease), and
akathisia [1].

Prevalence
In a cohort of healthy sleepers, HFLM sequences were found in 33%. No
influence of age or sex on HFLM was reported [19]. Epidemiological data on
HFT, RFM, and ALMA are lacking.

Clinical relevance/meaning
It can be speculated that these overlapping minor motor activity during
sleep may represent voluntary or unconscious stereotyped movements
when falling asleep or during arousals, performed to relieve unpleasant
sensations similar to the ones associated with RLS. If patients experience
an urge to move, for instance due to a recognized or untreated RLS, it is
considerable that the semiologic presentation might be similar. There-
fore, RLS symptoms should always be specifically investigated in case of
PSG findings of HFT, RFT, AMLA, or HFLM, as potential underlying
condition causing these phenomena [57].

Treatment
As clinical relevance of HFT, RFT, ALMA, and HFLM is uncertain, and these
SRMD are usually an incidental PSG finding and do not cause sleep distur-
bances, no treatment is indicated.
Neck myoclonus/head jerks
Overview and diagnostic criteria
Neck myoclonus during REM sleep has been defined and systematically
investigated by the Innsbruck group in 2010. It is characterized by
typical “stripe-shaped” movement-induced artifacts visible vertically over
the EEG leads in the PSG, with a duration up to 2 s. Using surface neck
muscle EMG, neck myoclonus can be detected as an increase in EMG
activity over the background, ending in the case of return to background
EMG activity for 9 0.5 s [51].

Differential diagnosis
As neck myoclonus is mainly present during REM sleep, it has to be
distinguished from other EMG activity and movements during REM
sleep, mainly RBD, and REM sleep without atonia (RWA). RBD behav-
iors typically involve the limbs [5], although some patients are reported
who had predominantly head jerks as an expression of RBD behavior
during the video-PSG recording.
Interestingly, recently a periodic presentation of neck myoclonus during
sleep (periodic neck myoclonus during sleep, PNMS) has been reported in
three subjects, fulfilling periodicity criteria used for PLMS. In these subjects,
PNMS was mainly present during NREM sleep, whereas neck myoclonus not
presenting in periodic series was present during REM sleep in the same subjects.
1 Page 10 of 14 Curr Treat Options Neurol (2019) 21: 1

The authors suggest the PNMS may be linked to PLMS and share common
pathogenetic mechanism [58], thus representing a distinct entity from neck
myoclonus without a characteristic of periodicity.

Prevalence
In the original work [51], in a cohort of 205 mixed sleep disorder patient REM
sleep was screened for the characteristic “stripe-shaped” movement-induced
artifacts. If such an artifact was present, the video was inspected for the presence
of neck myoclonus. Neck myoclonus was found in 112/205 patients
representing 54.6%. The index was 1 ± 2.8/h of REM sleep. Younger patients
had a higher index, and neck myoclonus during REM sleep was considered a
physiological phenomenon [51]. In a cohort of 100 healthy sleepers, 35%
presented neck myoclonus, with a median index of 2/h of REM sleep (range
0.7–41.2/h of REM sleep). No age differences in the distribution of neck
myoclonus were found in this study. Neck myoclonus indices were higher in
men than in women [19].

Clinical relevance/meaning
Neck myoclonus is considered a physiological phenomenon, part of the spec-
trum of physiological twitching during REM sleep. However, it might be hy-
pothesized that it represents a prodromal phase of RBD, as no study by now
investigated its potential evolution to full-blown RBD over time. Nevertheless,
the inverse age-relation speaks against this hypothesis. On the other side, the
frequency of neck myoclonus is higher in patients with RBD or RWA than in
patients without RBD or RWA [51]. Evolution of neck myoclonus over time
needs to be investigated in further studies, to clarify whether neck myoclonus
definitely represents a physiological phenomenon and if or when its excessive
appearance should rather be considered prodromal RBD.

Treatment
Generally, no treatment is needed. Notably, in the original work, none of the 13
patients on clonazepam had neck myoclonus [51]. However, if clonazepam
could be a potential treatment, e.g., in case of neck myoclonus causing clinical
complaints, is not known.

Important differential diagnosis: prodromal RBD and isolated

RBD
Although RBD is a parasomnia and not formally classified as a SRMD, it
represents an important differential diagnosis for most of the aforemen-
tioned SRMD. RBD is characterized by vocalizations, jerks, and/or motor
behaviors during REM sleep, often associated with REM-related dream
content, and is accompanied by the absence of the physiological muscle
atonia during REM sleep [1]. Idiopathic RBD (iRBD), in most recent
terminology clinically isolated RBD (iRBD), has been thoroughly reviewed
in a recent update paper [5••]. In this context, the new terminology is
important. The term (clinically) isolated RBD seems to be more appropri-
ate, in light of the increasing evidence that iRBD is not only a harbinger of
Curr Treat Options Neurol (2019) 21: 1 Page 11 of 14 1

neurodegeneration [59, 60] but also that multiple biomarkers of neurode-

generation are present even in those patients with long-standing clinically
isolated (previously named idiopathic) RBD [61••].
Another important new concept is prodromal RBD, based on increasing
evidence coming from EMG and video studies. Prodromal RBD refers to an
intermediate phase in the evolution from normality to iRBD, in which neuro-
physiological and behavioral findings on video-PSG and EMG are present but
do not yet meet established diagnostic criteria for RBD [5••]. The concept of
prodromal RBD [5••, 62] allows for the first time not only to exactly define
when iRBD ends and converts into overt alpha-synucleinopathy but also to start
delineating the transition from prodromal RBD to begin of iRBD.
While treatment recommendations exist for clinically isolated RBD [5••], at
present there is no recommendation if prodromal RBD should also be treated.
While by definition prodromal RBD is often milder than clinically isolated
RBD, no studies have been performed, if prodromal RBD is also at risk for
injuries, which would implicate a need for symptomatic treatment. Further-
more, future disease-modifying therapeutic strategies may not only target iso-
lated RBD as high-risk population to develop future PD but also prodromal
RBD, because intervening at an earlier stage of progress may potentially im-
prove chances to halt or reverse pathologic processes.
Conclusions
For clinicians dealing with neurologic disorders, it is important to be aware of
other minor SRMD beyond the well-known main motor disorders of sleep (e.g.,
RLS, bruxism, rhythmic movement disorders, etc.). Minor motor disorders of
sleep comprise PLMD, propriospinal myoclonus at sleep onset, EFM, HFT,
RFM, ALMA, HFLM, and neck myoclonus/head jerks. They should be correctly
diagnosed, distinguished from differential diagnosis, and understood in their
potential clinical relevance, in order also to start an appropriate treatment if
needed.

Funding Information
Open access funding provided by University of Innsbruck and Medical University of Innsbruck.

Compliance with Ethical Standards

Conflict of Interest
Ambra Stefani reports other from Habel Medizintechnik, Inspire Medical System, OSG, UCB, personal fees from
Axovant, outside the submitted work. Birgit Högl reports other from Otsuka, Mundipharma, UCB, Janssen Cilag,
Lündbeck, AbbVie, Lilly, Axovant, Benevolent AI, outside the submitted work.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.
1 Page 12 of 14 Curr Treat Options Neurol (2019) 21: 1

Open Access

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License
(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduc-
tion in any medium, provided you give appropriate credit to the original author(s) and the source, provide a
link to the Creative Commons license, and indicate if changes were made.

Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References and Recommended Reading

Papers of particular interest, published recently, have been
highlighted as:
• Of importance
•• Of major importance
1. American Academy of Sleep Medicine. International 7. Dauvilliers Y, Schenck CH, Postuma RB, Iranzo A,
classification of sleep disorders. 3rd ed. Darien, IL: Luppi PH, Plazzi G, et al. REM sleep behaviour disor-
American Academy of Sleep Medicine; 2014. der. Nat Rev Dis Primers. 2018;4:19.
2.• Högl B, Stefani A. Restless legs syndrome and pe- 8.• Iranzo A. The REM sleep circuit and how its impair-
riodic leg movements in patients with movement ment leads to REM sleep behavior disorder. Cell Tissue
disorders: Specific considerations. Mov Disord. Res. 2018;373:245–6.
2017;32:669–8. Current knowledge about mechanisms underlying RBD is
This review goes through specific aspects of restless legs syn- clearly summarized in this review.
drome and periodic leg movements in patients with move- 9. St Louis EK, Boeve BF. REM sleep behavior disorder:
ment disorders. diagnosis, clinical implications, and future directions.
3.• Trenkwalder C, Allen R, Högl B, Clemens S, Patton S, Mayo Clin Proc. 2017;92:1723–36.
Schormair B, et al. Comorbidities, treatment, and 10. Heller J, Brcina N, Dogan I, Holtbernd F, Romanzetti S,
pathophysiology in restless legs syndrome. Lancet Schulz JB, et al. Brain imaging findings in idiopathic
Neurol. 2018;S1474–4422(18):30311–. REM sleep behavior disorder (RBD) - a systematic
This recent review provides a complete overview of restless legs review on potential biomarkers for neurodegeneration.
syndrome. Sleep Med Rev. 2017;34:23–33.
4.• Winkelmann J, Allen RP, Högl B, Inoue Y, Oertel W, 11. Montplaisir J, Boucher S, Poirier G, Lavigne G, Lapierre
Salminen AV, et al. Treatment of restless legs syn- O, Lespérance P. Clinical, polysomnographic, and ge-
drome: evidence-based review and implications for netic characteristics of restless legs syndrome: a study of
clinical practice (Revised 2017). Mov Disord. 133 patients diagnosed with new standard criteria.
2018;33:1077–9. Mov Disord. 1997;12:61–5.
Current updated treatment guidelines for restless legs syn- 12. Moore H 4th, Winkelmann J, Lin L, Finn L, Peppard P,
drome are provided and discussed. Mignot E. Periodic leg movements during sleep are
5.•• Högl B, Stefani A, Videnovic A. Idiopathic REM sleep associated with polymorphisms in BTBD9,
behaviour disorder and neurodegeneration - an up- TOX3/BC034767, MEIS1, MAP2K5/SKOR1, and
date. Nat Rev Neurol. 2018;14:40–5. PTPRD. Sleep. 2014;37:1535–42.
This review gives an update on current knowledge about neu- 13.•• Schormair B, Zhao C, Bell S, et al. Identification of
rodegeneration in isolated REM sleep behavior disorder and novel risk loci for restless legs syndrome in genome-
brings up the concept of prodromal RBD. wide association studies in individuals of European
6. Iranzo A, Santamaria J, Tolosa E. Idiopathic rapid eye ancestry: a meta-analysis. Lancet Neurol. 2017;16:898–
movement sleep behaviour disorder: diagnosis, man- 907
agement, and the need for neuroprotective interven- Recent findings on restless legs syndrome risk loci from
tions. Lancet Neurol. 2016;15:405–19. genome-wide association studies are presented.
Curr Treat Options Neurol (2019) 21: 1 Page 13 of 14 1

14. Frauscher B, Ehrmann L, Mitterling T, Gabelia D, a patient with periodic leg movements in sleep. Sleep
Gschliesser V, Brandauer E, et al. Delayed diagnosis, Med. 2003;4:153–5.
range of severity, and multiple sleep comorbidities: a 28. Aurora RN, Kristo DA, Bista SR, et al. The treatment of
clinical and polysomnographic analysis of 100 patients restless legs syndrome and periodic limb movement
of the innsbruck narcolepsy cohort. J Clin Sleep Med. disorder in adults—an update for 2012: practice pa-
2013;9:805–12. rameters with an evidence-based systematic review and
15. Gaig C, Iranzo A, Pujol M, Perez H, Santamaria J. meta-analyses An American Academy of Sleep Medicine
Periodic limb movements during sleep mimicking Clinical Practice Guideline. Sleep. 2012;35:1039–62.
REM sleep behavior disorder: a new form of periodic 29. Vetrugno R, Provini F, Meletti S, et al. Propriospinal
limb movement disorder. Sleep. 2017;40. myoclonus at the sleep-wake transition: a new type of
16. Manconi M, Zavalko I, Fanfulla F, Winkelman JW, parasomnia. Sleep. 2001;24:835–43.
Fulda S. Evidence-based recommendation for a new 30. Erro R, Bhatia KP, Edwards MJ, Farmer SF, Cordivari C.
definition of respiratory-related leg movements. Sleep. Clinical diagnosis of propriospinal myoclonus is un-
2015;38:295–304. reliable: an electrophysiologic study. Mov Disord.
17. Aritake S, Blackwell T, Peters KW, et al. Prevalence and 2013;28:1868–73.
associations of respiratory-related leg movements: the 31.• Antelmi E, Provini F. Propriospinal myoclonus: The
MrOS sleep study. Sleep Med. 2015;16:1236–44. spectrum of clinical and neurophysiological pheno-
18. Fulda S, Heinzer R, Haba-Rubio J. Characteristics and types. Sleep Med Rev. 2015;22:54–6.
determinants of respiratory event associated leg move- Clinical and neurophysiological correlates of propriospinal
ments. Sleep. 2017. https://doi.org/10.1093/sleep/ myoclonus are summarized in this review.
zsx206. 32. Van der Salm SM, Erro R, Cordivari C, et al.
19. Frauscher B, Gabelia D, Mitterling T, Biermayr M, Propriospinal myoclonus: clinical reappraisal and re-
Bregler D, Ehrmann L, et al. Motor events during view of literature. Neurology. 2014;83:1862–70.
healthy sleep: a quantitative polysomnographic study. 33. Broughton R. Pathological fragmentary myoclonus,
Sleep. 2014;37:763–73. intensified hypnic jerks and hypnagogic foot tremor:
20. Haba-Rubio J, Marti-Soler H, Marques-Vidal P, three unusual sleep related movement disorders. In:
Tobback N, Andries D, Preisig M, et al. Prevalence and Koella WP, Obal F, Shulz H, Visser P, editors. Sleep ‘86.
determinants of periodic limb movements in the gen- Stuttgart: G. Fischer Verlag; 1988. p. 240e3.
eral population. Ann Neurol. 2016;79:464–74. 34. Chokroverty S, Bhat S, Gupta D. Intensified hypnic
21. Mirza M, Shen WK, Sofi A, et al. Frequent periodic leg jerks: a polysomnographic and polymyographic anal-
movement during sleep is associated with left ventric- ysis. J Clin Neurophysiol. 2013;30:403e10.
ular hypertrophy and adverse cardiovascular out- 35. Calandra-Buonaura G, Alessandria M, Liguori R,
comes. J Am Soc Echocardiogr. 2013;26:783–90. Lugaresi E, Provini F. Hypnic jerks: neurophysiological
22. Pennestri MHm Mantplaisir J, Fradette L, Laigne G, characterization of a new motor pattern. Sleep Med.
Colombo R, Lanfranchi PA. Blood pressure changes 2014;15:725e7.
associated with periodic leg movements during sleep in 36. Byun JI, Lee D, Rhee HY, Shin WC. Treatment of
healthy subjects. Sleep Med. 2013;14:555–61. propriospinal myoclonus at sleep onset. J Clin Neurol.
23. Mirza M, Shen WK, Sofi A, et al. Frequent periodic leg 2017;13:293–5.
movement during sleep is an unrecognized risk factor
37. Montagna P, Provini F, Plazzi G, Liguori R, Lugaresi E.
for progression of atrial fibrillation. PLoS One.
Propriospinal myoclonus upon relaxation and drows-
2013;8:e78359.
iness: a cause of severe insomnia. Mov Disord.
24. Koo BB, Mehra R, Blackwell T, et al. Periodic limb 1997;12:66–72.
movements during sleep and cardiac arrhythmia in
38. Khoo SM, Tan JH, Shi DX, Jamil HK, Rajendran N, Lim
older men (MrOS sleep). J Clin Sleep Med. 2014;10:7–
TK. Propriospinal myoclonus at sleep onset causing
11.
severe insomnia: a polysomnographic and electro-
25. Winkelman JW, Blackwell T, Stone K, Ancoli-Israel S, myographic analysis. Sleep Med. 2009;10:686–8.
Redline S. Associations of incident cardiovascular
39. Shprecher D, Silberstein H, Kurlan R. Propriospinal
events with restless legs syndrome and periodic leg
myoclonus due to cord compression in the absence of
movements of sleep in older men, for the outcomes of
myelopathy. Mov Disord. 2010;25:1100–1.
sleep disorders in older men study (MrOS Sleep
Study). Sleep. 2017;40. 40. Capelle HH, Wohrle JC, Weigel R, Grips E, Bazner HJ,
Krauss JK. Propriospinal myoclonus due to cervical disc
26.•• Gottlieb DJ, Somers VK, Punjabi NM, Winkelman JW.
herniation: case report. J Neurosurg Spine.
Restless legs syndrome and cardiovascular disease: a
2005;2:608–11.
research roadmap. Sleep Med. 2017;31:10–.
Important aspects regarding the relationship between restless 41. Jang W, Kim JS, Ahn JY, Kim HT. Reversible
legs syndrome and cardiovascular disease are discussed, in- propriospinal myoclonus due to thoracic disc hernia-
cluding research implications. tion: long-term follow-up. J Neurol Sci. 2012;313:32–4.
27. Santamaria J, Iranzo A, Tolosa E. Development of 42. Vetrugno R, Liguori R, D’Alessandro R, D’Angelo R,
restless legs syndrome after dopaminergic treatment in Alessandria M, Montagna P. Axial myoclonus in
1 Page 14 of 14 Curr Treat Options Neurol (2019) 21: 1

paraproteinemic polyneuropathy. Muscle Nerve. function in patients with excessive fragmentary myoc-
2008;38:1330–5. lonus during sleep. Sleep Med. 2016;22:61–.
43. Zhang Y, Menkes DL, Silvers DS. Propriospinal myoc- This study reports a high prevalence of abnormal neurophysi-
lonus associated with gluten sensitivity in a young ological findings in patients with EFM, suggesting that further
woman. J Neurol Sci. 2012;315:141–2. evaluation is required when diagnosing EFM.
44. Sugimoto K, Theoharides TC, Kempuraj D, Conti P. 54. Wichniak A, Tracik F, Geisler P, Ebersbach G, Morrissey
Response of spinal myoclonus to a combination ther- SP, Zulley J. Rhythmic feet movements while falling
apy of autogenic training and biofeedback. asleep. Mov Disord. 2001;16:1164–70.
Biopsychosoc Med. 2007;1:18. 55. Chervin RD, Consens FB, Kutluay E. Alternating leg
45. Slawek J, Wichowicz HM, Cubala WJ, et al. Psycho- muscle activation during sleep and arousals: a new
genic axial myoclonus: report on two cases. Neurol Sci. sleep- related motor phenomenon? Mov Disord.
2010;31:219–22. 2003;18:551–9.
46. American Academy of Sleep Medicine. International 56. Yang CH, Winkelmann JW. Clinical and polysomno-
classification of sleep disorders. In: Diagnostic and graphic characteristics of high frequency leg move-
coding manual. 2nd ed. Westchester, Illinois: American ments. J Clin Sleep Med. 2010;6:431–8.
Academy of Sleep Medicine; 2005. 57. Bergmann M, Stefani A, Brandauer E, Holzknecht E,
Hackner H, Högl B. Alternating leg muscle activation
47. Broughton R, Tolentino MA. Fragmentary pathological
and hypnagogic foot tremor in two cousins: clinical
myoclonus in NREM sleep. Electroencephalogr Clin
and phenomenological considerations. Sleep Med.
Neurophysiol. 1984;57:303–9.
2018; in press.
48. Broughton R, Tolentino MA, Krelina M. Excessive frag- 58. Pérez-Carbonell L, Silva C, Gaig C, Carreño M,
mentary myoclonus in NREM sleep: a report of 38
Santamaria J, Iranzo A. Periodic neck myoclonus dur-
cases. Electroencephalogr Clin Neurophysiol.
ing sleep. Sleep Med. 2017;38:71–2.
1985;61:123–33.
59. Schenck CH, Mahowald MW. REM sleep behavior dis-
49. Montagna P, Liguori R, et al. Physiological hypnic order: clinical, developmental, and neuroscience per-
myoclonus. Electroencephalogr Clin Neurophysiol. spectives 16 years after its formal identification in
1988;70:172–6. sleep. Sleep. 2002;25:120–38.
50. Berry RB, Albertario CL, Harding SM, for the American 60. Iranzo A, et al. Neurodegenerative disease status and
Academy of Sleep Medicine, et al. The AASM manual post-mortem pathology in idiopathic rapid-eye move-
for the scoring of sleep and associated events: rules, ment sleep behaviour disorder: an observational co-
terminology and technical specifications. Version 2.5. hort study. Lancet Neurol. 2013;12:443–53.
Darien, IL: American Academy of Sleep Medicine; 61.•• Iranzo A, Stefani A, Serradell M, Martí MJ, Lomeña F,
2018. Mahlknecht P, et al. Characterization of patients with
51. Frauscher B, Brandauer E, Gschliesser V, Falkenstetter T, longstanding idiopathic REM sleep behavior disorder.
Furtner MT, Ulmer H, et al. A descriptive analysis of Neurology. 2017;89:242–.
neck myoclonus during routine polysomnography. This original manuscript reports that even patients with
Sleep. 2010;33:1091–6. longstanding idiopathic REM sleep behavior disorder present
52. Frauscher B, Kunz A, Brandauer E, Ulmer H, Poewe W, markers of neurodegeneration, with important clinical and
Högl B. Fragmentary myoclonus in sleep revisited: a research implications.
polysomnographic study in 62 patients. Sleep Med. 62. Sixel-Doring F, Zimmermann J, Wegener A,
2011;12:410–5. Mollenhauer B, Trenkwalder C. The evolution of REM
53.• Raccagni C, Löscher WN, Stefani A, Wanschitz J, sleep behavior disorder in early Parkinson disease.
Kraemer L, Heidbreder A, et al. Peripheral nerve Sleep. 2016;39:1737–42.