962 501

research-article2020 NNRXXX10.1177/1545968320962501Neurorehabilitation and Neural RepairFulk et al

Neurorehabilitation and
Neural Repair
2020, Vol. 34(11) 1050 –1061 ©
The Author(s) 2020 Article
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DOI:
10.1177/1545968320962501https://d

The Impact of Sleep Disorders on

oi.org/10.1177/1545968320962501
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Functional Recovery and Participation

Following Stroke: A Systematic
Review and Meta-Analysis
Introduction with stroke have sleep disordered breathing (SDB). 18 In
Sleep is vital for overall health and quality of life. 1,2 Abnormal addition, other sleep disorders such as insomnia 23 and periodic
sleep is associated with obesity, diabetes, cardiovascular limb movements24 may also occur after stroke.
disease, hypertension, poor mental health, and dementia. 3-9 Sleep disorders may be more relevant than previously
Sleep disorders are also associated with mood disorders 10,11 and recognized in the context of stroke recovery and rehabilitation.
cognitive disability.12-14 Sleep appears to have an important moderating influence on
motor learning, which is a central mechanism of rehabilitation
Disordered sleep is both a risk factor and consequence of
interventions after stroke. This impact is likely a result of
George D. Fulk, PhD1 , Pierce Boyne, PhD2, Makenzie Hauger1, Raktim Ghosh1,
Samantha Romano1, Jonathan Thomas1, Amy Slutzky, PhD1, and
Karen Klingman, PhD1

Abstract
Background. Adequate sleep is vital for health and quality of life. People with stroke and a concomitant sleep
disorder may have poorer outcomes than those without a sleep disorder. Objective. To systematically evaluate the
published literature to determine the impact of sleep disorders on physical, functional recovery at the activity and
participation level after stroke. Methods. A systematic review was conducted using PubMed, CINAHL, Scopus, and
PsycINFO. Studies were selected that reported outcomes on physical, functional recovery at the activity and
participation levels in participants with stroke and a diagnosed sleep disorder. A meta-analysis was performed on
included studies that reported Barthel Index (BI) and modified Rankin Scale (mRS) scores. Results: A total of 33
studies were included in the systematic review with 9 of them in the meta-analysis. The mean mRS score was 0.51
points higher in participants with stroke and sleep disorders versus participants with stroke without sleep disorder
[95% CI: 0.23-0.78]. The mean BI score was 10.2 points lower in participants with stroke and sleep disorders
versus participants with stroke without sleep disorder [95% CI: −17.9 to −2.6]. Conclusions. People with stroke and
a sleep disorder have greater functional limitations and disability than those without a sleep disorder.
Rehabilitation professionals should screen their patients with stroke for potential sleep disorders and further
research is needed to develop sleep and rehabilitation interventions that can be delivered in combination.
PROSPERO registration number: CRD42019125562.

Keywords
stroke, sleep disorders, limitation of activity, community participation, systematic review
stroke.15-21 For example, in a recent meta-analysis, Li and consolidation during sleep after motor skill practice. 25-28 In
colleagues15 reported that obstructive sleep apnea (OSA) is people with chronic stroke, Siengsukon and Boyd29 found that
associated with an increased risk of stroke (relative risk of sleep enhanced off-line motor learning of both implicit and
2.10). Sleep apnea also appears to be the most common sleep explicit motor tasks. Other research has found that after a
22
disorder after stroke. An estimated 40% to 92% of people night’s sleep, people with stroke perform
2 Neurorehabilitation and Neural Repair 34(11)
1
Upstate Medical University, Syracuse, NY, USA
2
University of Cincinnati, Cincinnati, OH, USA
Supplementary material for this article is available on the
Neurorehabilitation & Neural Repair website at
https://journals.sagepub. com/home/nnr.
Corresponding Author:
George D. Fulk, Department of Physical Therapy Education, Upstate
Medical University, 750 East Adams Street, 3321 Academic Building,
Syracuse, NY 13210, USA.
Email: fulkg@upstate.edu
newly learned motor tasks with less error. 30 Sleep also
appears to be important for motor learning of functional
tasks in older adults.31 It is thought that consolidation of
procedural memory occurs during rapid eye movement
(REM) sleep by enhancing long term potentiation (LTP)
and neuroplasticity.27 In stroke this is supported by the
findings of Siengsukon and colleagues 30 who found that
time in REM sleep was related to the magnitude of off-line
motor learning. Additionally, other factors that are
negatively affected by disordered sleep in people with
stroke such as cognition,32 attention,32,33 anxiety,34 and
depression34 make active participation in stroke
rehabilitation challenging and are associated with worse
rehabilitation outcomes after stroke.
There is evidence to suggest that individuals with sleep
disorders across the stages of recovery after stroke appear
to have worse outcomes than those who do not have sleep
disorders.35-37 Individuals with stroke and SDB are more
dependent both early and late after stroke compared to
those without SDB,35,36,38 have longer lengths of stay in the
hospital,36 and poorer quality of life. 37,39 Insomnia and
periodic limb movements with sleep may also negatively
impact recovery after stroke.40,41 Balance and quality of life
have been found to be different in patients with stroke with
insomnia versus those without insomnia. 23,40 People with
stroke and restless leg syndrome are more dependent and
have poorer quality of life early and later after stroke 24,42
More recently, Fleming and colleagues43 found that sleep
quality was associated with poor functional and motor
outcomes during in-patient rehabilitation after stroke. In
this study, the authors did not identify any specific sleep
disorder in the participants. These findings indicate that
sleep likely plays an important role during rehabilitation
after stroke and abnormal sleep may negatively impact
outcomes during rehabilitation as well.
Sleep has a profound impact on many aspects of health
and life. It also appears that sleep may impact recovery
after stroke. However, there are conflicting findings as
some studies have reported no differences in functional
outcomes between those with and without a sleep disorder
after stroke rehabilitation.44-46 The growing body of
literature in this area has not been previously synthesized.
Therefore, the purpose of this systematic review was to
evaluate the published literature to determine the impact of
sleep disorders on physical, functional recovery at the
activity and participation level after stroke.
Methods
A systematic review was conducted in accordance with the
Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) Statement.47 The protocol of this
systematic review was registered with PROSPERO, an
international database of prospectively registered
systematic reviews (PROSPERO registration number:
CRD42019125562).
Information Sources and Search Strategy
Four databases—PubMed, CINAHL, Scopus, and
PsycINFO—were searched for potentially relevant articles.
Search strategies for each database were developed, tested, and
refined in collaboration with a medical librarian (ARS). Key
concepts (sleep disorders and stroke) were broadly defined,
using combinations of controlled vocabulary (where available)
and keywords, to maximize the probability of finding all
relevant articles. All searches were run on November 30, 2018,
with no restriction on publication date. Search results were
limited to English-language articles. Complete search strategies
are presented in Supplemental Appendix 1. In addition to these
database searches, 2 other data sources were included: (1)
contents of the journal Sleep Medicine Research were searched
separately, as its contents are not fully indexed in any of the
included databases and (2) articles listed in the reference lists
of included articles were reviewed for eligibility in this study.
Study Eligibility
Studies were included if the participants had a diagnosis of a
stroke, at least some of the participants had a diagnosis of a
sleep disorder as defined by the American Academy of Sleep
Medicine (AASM), and reported outcomes that included
measures of physical function at the activity level or
participation level of the International Classification of
Functioning, Disability, and Health (ICF). Specifically, we
included outcome measures that assessed physical aspects of
mobility, self-care, domestic life, major life areas, and
community, social and civic life aspects of activity and
participation. Examples of outcome measures include the
Barthel Index (BI), gait speed, and the Stroke Impact Scale
(SIS). Any type of study design was acceptable except if the
study was a randomized controlled trial where one group
received an intervention to treat the sleep disorder and another
group did not. In this case the study was included only if data
Fulk et al
prior to the intervention comparing the groups was available.
This was done because the intervention (e.g. continuous
positive airway pressure) may have had an impact on
functional recovery. Other inclusion criteria were published in
English and in a peer reviewed journal.
Exclusion criteria were (1) the study included health
conditions other than stroke and data on stroke not separated
out; (2) description of sleep disturbance but no AASM-
recognized diagnosed sleep disorder; (3) the outcome solely
measured the impact on cognition, memory, or attention; (4)
the study solely examined how having a sleep disorder prior to
stroke might predict having a stroke; and (5) conference
proceeding.
Study Selection
References identified through the above information sources
and search strategies were downloaded to Covidence. Each title
and abstract were screened independently by 2 researchers
working in pairs (RG/MH and SR/ JT) for possible inclusion. If
there was a difference of opinion regarding including or
excluding a study, the title and abstract were reviewed by a
third researcher (GF) who made the final decision to include or
exclude the study after discussion with the group. Next, the full
text of the remaining articles was read independently by 2
researchers working in pairs (RG/MH and SR/JT). If there was
a difference of opinion between the 2 researchers regarding
including or excluding the study, a third researcher (GF)
reviewed the article and discussed the differences with the
group to reach consensus. Finally, reference lists of the
remaining studies were screened for possibly relevant articles;
full text of these articles were the read and assessed for
inclusion or exclusion by one researcher (GF).
Data Extraction
Each included article was read independently by two
researchers working in pairs (RG/MH and SR/JT) and the
following data were extracted: purpose, sample size, time since
stroke, stroke severity, setting, type of sleep disorder and how
it was diagnosed, and outcome measures at the activity and
participation level used. If there was a difference in the data
extracted between the two researchers, then a third researcher
(GF) reviewed the article and its data and discussed the
differences with the group to reach consensus.
Risk of Bias of Individual Studies
One researcher (GF) reviewed all included studies and rated
them for potential bias using a modified version of the
Newcastle Ottawa Quality Assessment Scale for Cohort
Studies (NOQASCS). The NOQASCS assesses potential bias
across 3 main areas: selection, comparability, and outcome.
Selection consists of representativeness of the cohort (were the
3
participants with stroke and a sleep disorder truly
representative of the average person with stroke for the setting
in which the study was conducted), selection of the nonexposed
cohort (were the participants with stroke without a sleep
disorder drawn from the same community as the participants
with stroke with a sleep disorder), ascertainment of the
exposure (was the sleep disorder diagnosed using a valid
method recommended by the AASM), and demonstration that
the outcome of interest was not present at the start of the study.
We did not include this last aspect of selection from the
NOQASCS in our rating of potential bias as our purpose was to
explore the impact of sleep disorders on activity and
participation at inception, not to determine if a sleep disorder
developed after stroke.
Comparability of the cohorts was assessed by
ascertaining if the participants with stroke and a sleep
disorder were similar to the participants with a stroke and
without a sleep disorder in important characteristics such as
age, gender, and stroke severity at the start of the study.
Outcome consists of assessment of outcome (was the
assessor independent and blind to sleep disorder diagnosis),
follow-up (was follow-up long enough for change to have
happened since initial assessment), and adequacy of follow-
up (was followup complete, all subjects accounted for or
follow-up rate greater than 80% or description of those lost
to follow-up suggest no difference from those who follow
up).
Data Synthesis
Initially, due to an expected heterogeneity of sleep
disorders, methods of diagnosing sleep disorders,
methodologies, and outcome measures used we did not
anticipate being able to synthesize the data using a meta-
analysis. We planned on only using a narrative approach to
summarize the evidence for the impact of each type of sleep
disorder on recovery after stroke on the outcomes of
interest: mobility, self-care, domestic life, major life areas,
and community, social and civic life aspects of activity and
participation. However, on completion of the search and
data extraction we determined that performing a meta-
analysis was also possible, as many studies reported scores
on either the BI and/or modified Rankin Scale (mRS).
Because of this we were able to also perform a meta-
analysis examining the effect of sleep disorder on recovery
as assessed by the BI and mRS.
To be included in the meta-analysis, studies had to report
means, standard deviations and sample sizes for either the
mRS or BI in both a stroke + sleep disorder group and a
control group (people with stroke without a sleep disorder).
Effect sizes were extracted for each dependent variable
(mRS and BI) at each study timepoint when sleep disorder
4 Neurorehabilitation and Neural Repair 34(11)
and control groups were compared. Because the purpose of
the study was to determine the impact of sleep disorders on
poststroke function (ie, cross-sectional impact) we included
data from every available time point to maximize the
precision of the pooled effect size estimate and to minimize
risk of bias from selective data inclusion. These effect sizes
were calculated as the mean score in the sleep disorder
group minus the mean score in the control group. Variances
for each effect size were calculated using the following
formulae48,49:
2 2
( )
Var Xa −Xb = +σ σ
na nb
σ2 = (na −1n n)aσ+ −a2 + −b(nb2
1)σb2
where σa and σb are the standard deviations in the sleep
disorder and control groups, respectively, and na and nb are
the group sample sizes.
The overall meta-analysis for each dependent variable
calculated a pooled effect size estimate across all available
studies and time points. Meta-regression models were then
conducted to assess the association between study effect
size and each independent variable of interest, including
sleep disorder type (SDB vs restless leg syndrome [RLS]),
stroke chronicity (<3 months poststroke vs ≥3 months) and
mean level of the dependent variable. One study of
insomnia was excluded from the sleep disorder type
metaregression because there was only a single BI
comparison for this sleep disorder type.
All models included a random effect for study to model
between-study variance. In cases where multiple effect
sizes were included from different measurement time
points within the same study, a second random effect was
added for time point to account for within-study
correlation. For the BI, this strategy had to be modified
because the available dataset was insufficient to model the
required number of covariance parameters. Instead of being
nested withinstudy, the second random effect had to pool
information across studies to estimate the covariance
between time points. To determine the extent to which this
might have influenced the BI results, we also performed a
sensitivity analysis that only included a single time point
from each study (thus eliminating the need for a second
random effect). For this sensitivity analysis, the 3-month
poststroke time points were selected because they were
nearest the middle time point for these studies.
Results
Article Selection
All database searches were conducted on November 30,
2018. Together, these searches identified 2773 articles.
Through the title and abstract screening and full text
review, this was narrowed to 29 articles. A review of the
reference lists of these 29 articles identified 4 additional
articles that met the inclusion criteria, resulting in a total of
33 articles that were included in this review. The primary
reasons studies were excluded were not reporting an
outcome measure at the activity or participation level,
wrong population (no diagnosed sleep disorder), and study
focus on sleep disorder as a predictor of stroke. See Figure
1 for the article selection process.
Twenty-three studies35,36,38,39,44-46,50-65 examined the impact
of SDB on recovery after stroke. In these studies, there
were a total of 1,998 participants, with a prevalence of
SDB of 57.4%. One study by Brooks and colleagues 52 only
had participants with SDB (45 participants). Ten
studies23,24,40-42,66-70 examined the impact of other sleep
disorders. These included RLS24,41,42,66,67 with a prevalence
of 18.0% in 5 studies and insomnia23,40,68-70 with a
prevalence of 44.5% in 5 studies. The majority of
participants across all of the studies exhibited mild to
moderate stroke severity as measured by the National
Institutes of Health Stroke Scale (NIHSS) or other similar
scale.
The most commonly used outcome measures at the physical
functioning level of activity was the BI, which was used in 19
studies, and the mRS, which was used in 15 studies. Other
measures of physical functioning at the level of activity that
were used were the Functional Independence Measure (FIM),
Utrecht Scale for Evaluation of Rehabilitation (USER),
Functional Ambulation Categories (FAC), Berg Balance Scale
(BBS), 9-hole peg test, and Purdue Peg test. Measures of
participation included the 36-Item Short Form Survey (SF-36),
EuroQol-5, 8-Item Short Form Survey (SF-8), and the Stroke
Specific Quality of Life (SSQoL).
Sleep Disordered Breathing
Activity. The impact of SDB, which in these studies included
OSA, central sleep apnea (CSA), and Cheyne Stokes
respirations, on recovery of physical function at the activity
level was mixed. Seven studies35,36,38,39,51,61,63 found that
participants with SDB had worse outcomes at the activity level
during the acute/subacute stage of recovery (<3 months
poststroke) compared with participants without SDB. However,
8 studies35,44,45,55,56,58-60 found no difference in outcomes of
physical function at the activity level in the acute/ subacute
stages of recovery. The BI and the FIM were the most
Fulk et al 5

commonly used outcomes to measure physical functioning at
the activity level. A variety of methods were used to diagnose
SDB, including polysomnography (PSG), nocturnal oximetry,
and home sleep apnea testing system (HSATS). There were
also differences across studies in the criteria used to diagnose
SDB (eg, Apnea Hypopnea Index [AHI] > 15 vs AHI > 30).
See online Table 1 with specific information on each study.
During the chronic stage of recovery (≥3 months
poststroke), the findings were also mixed. Five studies 35,50,54,57,61
found that participants with SDB had worse outcomes at the
activity level compared to participants without SDB, while 5
studies44,51,56,64 found no difference in activity levels. The BI
was also commonly used and there were variety of methods
used to diagnose SDB including (HSATS, PSG, and nocturnal
oximetry). There were also differences across studies in the
criteria used to diagnose SDB. See online Table 1 with specific
information on each study.
Participation. The impact of SDB on participation during the
acute/subacute stage of recovery poststroke was also mixed.
One study39 found that participants with SDB had significantly
worse outcomes on measures of participation Figure 1. Article
selection. and 2 studies39,44 found no difference in participation
outcomes between participants with and without SDB. A
HSATS was used to diagnose SDB in most of the studies.
There were also differences across studies in the criteria used to
diagnose SDB. See online Table 1 with specific information on
each study.
No studies were found that examined the impact of SDB on
participation in the chronic stage of recovery.
There were four studies52,53,62,65 that had participants with
stroke both with and without SDB in which the authors did not
directly compare activity or participation outcomes between the
groups. Brooks and colleagues52 found no relationship between
AHI and FIM and a little to moderate relationship (r = 0.30)
with the BI during inpatient rehabilitation. Yan-fang and
colleagues65 reported that AHI at admission to the hospital was
an independent predictor of independence measured by the BI
at 3-month poststroke. Pace and colleagues62 reported that there
was a significant difference in admission AHI between
participants with a good outcome (mRS ≤2) and a poor
outcome (mRS >2) at discharge. Cadilhac and colleagues53

PubMed CINAHL Scopus PsycINFO

(n = 1339) (n = 57) (n = 1293) (n = 84)

Records idenfied through

Idenficaon

database searching
(n = 2773)

Records aer duplicates removed

(n = 2290)
Screening

Records screened Records excluded

(n = 2,290) (n = 2,201)

Full-text arcles assessed

Full-text arcles excluded,
for eligibility
Eligibility

(n=42):
(n = 71)
• Wrong outcome
measure, n = 13
• Wrong populaon, n=14
• Wrong study design
Studies included in qualitave synthesis (examined if having a
and who’s reference lists were reviewed for sleep disorder predicted
other possible arcles having a stroke), n=12
(n = 29) • Conference proceeding,
Included

n=2

Arcles idenfied and

• Not in English, n=1
eligible through review • See Appendix 2 for a list
of full text arcles
of references of assessed but not
included arcles Total studies included in included.
(n = 4) qualitave synthesis
(n = 33)
6 Neurorehabilitation and Neural Repair 34(11)
reported that dependency (mRS ≥2) at 1 month, 6 months, and
3 years poststroke showed no significant effect on AHI ≥15.
They also reported that dependency (mRS ≥2) at 1 month
poststroke was found to be significantly associated with having
an AHI ≥15 at 3 years poststroke. See online Table 1 with
specific information on each study. studies. The median score
on the NOQASCS in studies that examined the impact of SDB
on recovery was 4/7 with a range of 2/7 to 7/7, see online Table
2.
Other Sleep Disorders: Restless Leg
Syndrome, Insomnia, and Excessive Daytime
Sleepiness
Restless Leg Syndrome. Five studies24,41,42,66,67 examined the
impact of restless leg syndrome (RLS) on recovery after
stroke. Two studies24,41 found that participants with RLS
had significantly worse outcomes at the activity level
compared to participants without RLS during the
acute/subacute stage of recovery after stroke. While 1
study67 found that there was no significant difference in
activity levels between participants with and without RLS,
another study24 found that participants with RLS had
significantly worse outcomes at the activity level compared
to participants without RLS during the chronic stage of
recovery after stroke. During the acute/subacute stage of
recovery, 1 study42 found that participants with RLS had
significantly worse outcomes at the participation level
compared to participants without RLS. During the chronic
stage of recovery, 1 study42 found that participants with
RLS had significantly worse outcomes at the participation
level compared to those without RLS. One study did not
report on differences between groups but reported finding
no significant correlations between RLS measures and the
BI.66 An interview using the RLS criteria established by the
International RLS Study Group was commonly used to
diagnose RLS. See online Table 3 for specific information
on each study. The median score on the NOQASCS in
studies that examined the impact of RLS on recovery was
4/7 with a range of 3/7 to 5/7, see online Table 2.
Insomnia. Five studies23,40,68-70 examined the impact of
insomnia on recovery after stroke. The findings were also
mixed. During the acute/subacute stage of recovery after
stroke, 3 studies40,68,69 found no significant difference in
activity between participants with stroke with and without
insomnia, while 1 study40 found that participants with
insomnia had significantly worse outcomes on measures of
activity compared to participants without insomnia. During
the chronic stage of recovery after stroke, 1 study 23 found
no significant difference in activity between those with and
without insomnia. Measures of activity in these studies
include the BI, BBS, 9-hole peg test, and Purdue peg board
test. For participation, 1 study69 during the acute/subacute
stage of recovery after stroke and 1 study 23 during the
chronic stage of recovery after stroke found that
participants with stroke and insomnia had significantly
worse outcomes in participation compared to participants
with stroke and without insomnia. Measures of
participation in these studies included the SF-8, and
SSQoL. Another study70 that did not directly compare
differences between participants with and without insomnia
reported a small relationship between the mRS and scores
on the Insomnia Severity Index (ISI). Insomnia was
diagnosed by using a researcher developed questionnaire or
the ISI. See online Table 3 for specific details on each
study. The median score on the NOQASCS in studies that
examined the impact of insomnia on recovery was 2/7 with
a range of 1/7 to 3/7, see online Table 2.
Meta-Analysis Results for Impact of Sleep
Disorder on Activity and Participation
For the mRS meta-analysis, there were 18 total time point
comparisons among 9 studies with available data from 957
total participants (Table 1; Figure 2a). The overall metaanalysis
estimated that the mean mRS score was 0.51 points higher in
sleep disorders versus control groups [95% CI: 0.23, 0.78].
From the meta-regression analyses, this effect size did not
significantly differ based on sleep disorder type, stroke
chronicity or mean mRS score (Table 1; right column). Within
subgroups, the sleep disorder versus control difference was
statistically significant for sleep apnea studies but not RLS
studies (2 studies with 5 total time point comparisons). This
difference was also statistically significant for both early time
points (<3 months poststroke) and later time points (Table 1).
For the BI meta-analysis, there were 12 total time point
comparisons among 7 studies with available data from 756
total participants (Table 1; Figure 2b). The overall meta-
analysis estimated that the mean BI score was 10.2 points
lower in sleep disorders versus control groups [95% CI: −17.9,
−2.6]. From the meta-regression analyses, this effect size did
not significantly differ based on sleep disorder type or stroke
chronicity but did vary based on mean BI score (online Table
4; right column). Studies and time points with a higher mean BI
showed greater between-group differences. Within subgroups,
the sleep disorder versus control difference was statistically
significant for sleep apnea studies but not the RLS study (1
study with 3 total time point comparisons). The sleep disorder
versus control difference was also statistically significant for
early time points (<3 months poststroke) but not quite for later
time points (P = .0594), despite a slightly larger point estimate
(online Table 4). In the sensitivity analysis that only included
Fulk et al 7

one–time point comparison from each study, none of the above likely to score approximately 10 points lower on the BI and 0.5
findings were meaningfully altered (Table 1; bottom rows). points higher on the mRS (higher score indicates greater
disability) than people with stroke without a sleep disorder.
This is true even when controlled for baseline severity.
Discussion Although the meta-analysis found that when all sleep
Based solely on a descriptive analysis of the findings of the disorder types were pooled there was a negative effect on
systematic review there appeared to be mixed evidence to recovery, these findings are more applicable to people with
support the notion that sleep disorders negatively affect stroke with SDB compared to RLS and insomnia. The meta-
recovery at the physical function level of activity and analysis
Table 1. Summary of Random Effects Meta-Analysis Results.a results
showed
Reference Comparison
Comparison –
that
Sleep disorder – Control Sleep disorder – Control Reference Estimate people
Subgroup/condition estimate [95% CI] Subgroup/condition estimate [95% CI] [95% CI] with
Modified Rankin Scale (mRS): All time points (9 studies, 18 comparisons, 957 stroke
participants) and
All studies and time points 0.51 [0.23, 0.78] SDB
had
Sleep disordered breathing 0.59 [0.28, 0.89] Restless leg syndrome 0.24 [−0.33, 0.81] −0.34 [−0.99,
worse
0.30]
<3 months poststroke 0.43 [0.16, 0.70] ≥3 months poststroke 0.74 [0.33, 1.15] 0.31 [−0.10, 0.72]
Mean mRS 0.51 [0.19, 0.84] Every 1 unit ↑ −0.17 [−0.45,
Barthel Index (BI): All time pointsb (7 studies, 12 comparisons, 756 participants) 0.11]
All studies and time points −10.2 [−17.9, −2.6]

Sleep disordered breathing −12.4 [−21.6, −3.2] Restless leg syndrome −12.1 [−32.2, 8.0] 0.3 [−21.4, 22.0]
<3 months poststroke −9.9 [−19.5, −0.3] ≥3 months poststroke −10.5 [−21.6, 0.5] −0.7 [−13.1,
11.7]
Mean BI −12.3 [−16.3, −8.4] Every 10 unit ↑ −2.4 [−3.4, −1.4]
Barthel Index (BI): One time point per study (7 studies, 7 comparisons, 756
participants)
All studies −11.6 [−20.0, −3.2]

Sleep disordered breathing −14.3 [−24.3, −4.2] Restless leg syndrome −10.8 [−41.5, 19.9] 3.4 [−28.8, 35.7]
<3 months poststroke −13.2 [−24.6, −1.8] ≥3 months poststroke −8.8 [−23.7, 6.0] 4.3 [−14.4, 23.1]
Mean BI −13.2 [−18.4, −8.0] Every 10 unit ↑ −2.4 [−4.0, −0.7]

a
The reference columns (left) show the effect size estimates for the overall meta-analysis (All studies) and the reference levels of the independent
variables for the meta-regression models. The comparison columns show the effect size estimates for the comparison subgroups for dichotomous
independent variables. The comparison – reference columns show the associations between the independent variables and the effect sizes. For
dichotomous independent variables, this is the effect size estimate for the difference between the comparison and reference levels of the
independent variable. For continuous independent variables, this is the effect size estimate for every unit increase in the independent variable.
CI, confidence interval.
b
Accounting for within-study repeated-measures correlations was approximate for the BI due to an insufficient number of studies to estimate
the full
set of covariance parameters (see Methods section for details). outcomes on the BI and mRS compared to people with stroke
without a sleep disorder. There was not enough power to detect
a difference between those with RLS and those without a sleep
participation after stroke. With approximately 50% of the
disorder or a difference between those with SDB and RLS.
studies showing a significant difference in outcomes between
People with a sleep disorder had worse outcomes on the BI
those with and without a sleep disorder and the other ~50%
before 3 months poststroke than those without a sleep disorder
showing no difference. However, the metaanalysis
and there was a trend toward worse outcomes on the BI at ≥3
demonstrated that people with stroke and a sleep disorder are
months poststroke. Disability as measured by the mRS was
likely to have worse outcomes at the activity level as measured
by the BI and mRS. People with stroke and a sleep disorder are worse both prior to and ≥3 months poststroke. We are also
more confident in the findings as they relate to SDB as the risk
8 Neurorehabilitation and Neural Repair 34(11)
of bias in these studies was lower than in those with RLS or
insomnia.
Our findings provide further evidence of the wide-
ranging negative effects of disturbed sleep on recovery after
stroke. Birkbak and colleagues71 reported an increased risk
of recurrent stroke and mortality in people with stroke or
transient ischemic attack with SDB. People with stroke with
disturbed sleep but no diagnosed sleep disorder demonstrate
poorer functional mobility and greater limitations in ability
to complete activities of daily living.72,73
Our results are consistent with those found in the other
populations with sleep disorders. Sleep apnea and insomnia
in the general population is associated with greater
incidence of work related disability.74-77 People with
multiple sclerosis with sleep apnea or RLS have greater
disability,78,79 higher levels of fatigue, 80 and lower quality of
life81 than people with multiple sclerosis without these sleep
disorders. In people with traumatic brain injury, insomnia is
associated with poorer quality of life as well.82 Older adults
with RLS have greater functional disability than those
without RLS.83,84 In addition, the AASM and Sleep
Research Society (SRS) concluded that poor or insufficient
sleep is associated with deficits in performance, increased
occurrence of errors, and higher likelihood of accidents (as
well as worse physical and psychiatric health) and thus
jointly recommended amounts of sleep for healthy
adults.85,86
Fulk et al 9
10
Figure 2. (a) Forest plot of modified Rankin Scale mean differences by sleep disorder type. (b) Forest plot of Barthel Index mean
differences by sleep disorder type. SD, standard deviation; CI, confidence interval; (T), time point; RE, random effects.
The prevalence of sleep disorders among people with stroke
found in this review indicate that some sleep disorders are more
highly prevalent in people with stroke when compared with the
general population. For example, in the general population,
SDB is reported to be 9% to 38%,87 chronic insomnia disorder
at 10%88 to 20%,89 RLS at 5% to 10% (increasing with age), 88
EDS at 12.7%89 and insufficient sleep disorder at 30%.90 The
higher prevalence of SDB in people with stroke is likely related
to risk factors: high BMI, sedentary lifestyle, and hypertension
are all known to increase risk for both stroke and obstructive
sleep apnea.88
The many causes of sleep disorders and the fact that they
may coexist91 make it challenging to determine exact
mechanisms of how disordered sleep negatively affects
recovery poststroke. In stroke, sleep disordered breathing may
be due to loss of or limited pharyngeal muscle activity due to
paresis or to damage to pontomedullary structures resulting in
impaired neural output.92,93 Obesity, which is common in
people with stroke, is also a risk factor for SDB 94 that further
complicates the understanding of how SDB affects recovery
after stroke. Insomnia is considered a stressrelated event 95 and
this coupled with factors such as anxiety and depression that
are common after stroke can lead to chronic insomnia.
Although we cannot determine the exact mechanisms by which
sleep disorders impact functional recovery from this systematic
review, we believe it is multifactorial. Disordered sleep during
the early stages of recovery likely has a negative influence on
motor learning, attention, and executive function all of which
are important components of rehabilitation. During the chronic
stage of recovery, the general negative health consequences of
sleep disorders likely contributes. The bidirectional relationship
between sleep and activity96,97 is an especially important
consideration in the context of stroke recovery. Inactivity,
which is common after stroke, may promote disturbed sleep
while disturbed sleep may lead to inactivity.
These findings provide important opportunities for
rehabilitation professionals. Tools such as the Sleep Disorders
Symptom Checklist-25,98 Berlin Questionnaire,99 Epworth
Sleepiness Scale,100 STOP-Bang,101,102 Insomnia Severity
Index,103 and Cambridge Hopkins Restless Leg Syndrome
questionnaire104 should be used to screen clients with stroke to
identify possible sleep disorders and assist with referral to an
appropriate health care professional. Research is needed that
pairs sleep interventions such as continuous positive airway
pressure,105 cognitive behavioral therapy for insomnia, 106,107 or
sleep hygiene education108 with rehabilitation interventions.
Concomitant delivery of these interventions may have
increased benefit compared with delivery in isolation.
There are some important limitations in this systematic
review and meta-analysis that should be kept in mind when
Neurorehabilitation and Neural Repair 34(11)
interpreting and applying the findings. There was not a
consistent method for diagnosing the different sleep disorders.
For example, studies used different AHI cutoff points and
different devices to diagnose SDB. Most of the studies included
participants with mild to moderate stroke. Perhaps a sleep
disorder in people with severe stroke has an even greater
negative impact on recovery compared with what we report.
There was limited to no follow-up in many of the included
studies, approximately 50% of the studies had no follow-up. It
is not clear if the negative impact of the sleep disorder was
compounded over time or stayed the same. We also cannot
completely rule out the possibility that the observed
associations could be confounded by other factors causing
increased risk of both sleep disorders and worse outcomes (eg,
obesity, diabetes, cardiovascular disease, poor mental health,
dementia). The results of the meta-analysis should be
interpreted with caution as there is potential for bias in some of
the included studies based on the NOQASCS scale. Many of
the studies included were not designed to specifically answer
the specific purpose of this study and there is no single
validated tool specifically designed to measure risk of bias
across the wide variety of modified study designs that are
included here. We believe the risk of bias in these studies is not
sufficient to explain the entirety of the observed effect. This
meta-analysis provides a preliminary estimate of the effect of
sleep disorders on recovery after stroke that should be
confirmed with future studies.
This is the first systematic review and meta-analysis that
that has examined the impact of sleep disorders on physical
functioning and participation in people with stroke. People
with stroke and a sleep disorder have greater functional
limitations and disability than those without a sleep
disorder. Rehabilitation professionals should screen their
patients with stroke for potential sleep disorders and further
research is needed to develop sleep and rehabilitation
interventions that can be delivered in combination.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
ORCID iD
George D. Fulk https://orcid.org/0000-0001-9139-2238
Fulk et al
References
1. Lee M, Choh AC, Demerath EW, et al. Sleep disturbance in
relation to health-related quality of life in adults: the Fels
Longitudinal Study. J Nutr Health Aging. 2009;13:576-583.
2. Magnavita N, Garbarino S. Sleep, health and wellness at work:
a scoping review. Int J Environ Res Public Health.
2017;14:1347.
3. Aziz M, Ali SS, Das S, et al. Association of subjective and
objective sleep duration as well as sleep quality with non-
invasive markers of sub-clinical cardiovascular disease (CVD):
a systematic review. J Atheroscler Thromb. 2017;24:208-226.
4. Buxton OM, Marcelli E. Short and long sleep are positively
associated with obesity, diabetes, hypertension, and
cardiovascular disease among adults in the United States. Soc
Sci Med. 2010;71:1027-1036.
5. Cappuccio FP, Cooper D, D’Elia L, Strazzullo P, Miller MA.
Sleep duration predicts cardiovascular outcomes: a systematic
review and meta-analysis of prospective studies. Eur Heart J.
2011;32:1484-1492.
6. Itani O, Jike M, Watanabe N, Kaneita Y. Short sleep duration
and health outcomes: a systematic review, meta-analysis, and
meta-regression. Sleep Med. 2017;32:246-256.
7. Liu Y, Wheaton AG, Chapman DP, Croft JB. Sleep duration
and chronic diseases among US adults age 45 years and older:
evidence from the 2010 Behavioral Risk Factor Surveillance
System. Sleep. 2013;36:1421-1427.
8. Shi L, Chen SJ, Ma MY, et al. Sleep disturbances increase the
risk of dementia: a systematic review and meta-analysis. Sleep
Med Rev. 2018;40:4-16.
9. Sofi F, Cesari F, Casini A, Macchi C, Abbate R, Gensini GF.
Insomnia and risk of cardiovascular disease: a metaanalysis.
Eur J Prev Cardiol. 2014;21:57-64.
10. Alvaro PK, Roberts RM, Harris JK. A systematic review
assessing bidirectionality between sleep disturbances, anxiety,
and depression. Sleep. 2013;36:1059-1068.
11. Malik S, Kanwar A, Sim LA, et al. The association between
sleep disturbances and suicidal behaviors in patients with
psychiatric diagnoses: a systematic review and meta-analysis.
Syst Rev. 2014;3:18.
12. Williamson AM, Feyer AM. Moderate sleep deprivation
produces impairments in cognitive and motor performance
equivalent to legally prescribed levels of alcohol intoxication.
Occup Environ Med. 2000;57:649-655.
13. Leng Y, Blackwell T, Stone KL, Hoang TD, Redline S, Yaffe
K. Periodic limb movements in sleep are associated with greater
cognitive decline in older men without dementia. Sleep.
2016;39:1807-1810.
14. Chen JC, Espeland MA, Brunner RL, et al. Sleep duration,
cognitive decline, and dementia risk in older women.
Alzheimers Dement. 2016;12:21-33.
15. Li M, Hou WS, Zhang XW, Tang ZY. Obstructive sleep apnea
and risk of stroke: a meta-analysis of prospective studies. Int J
Cardiol. 2014;172:466-469.
16. Lin TC, Zeng BY, Chen YW, et al. Cerebrovascular accident
risk in a population with periodic limb movements of sleep:
a preliminary meta-analysis. Cerebrovasc Dis. 2018;46:1-9.
11
17. Leppavuori A, Pohjasvaara T, Vataja R, Kaste M, Erkinjuntti T.
Insomnia in ischemic stroke patients. Cerebrovasc Dis.
2002;14:90-97.
18. Johnson KG, Johnson DC. Frequency of sleep apnea in stroke
and TIA patients: a meta-analysis. J Clin Sleep Med.
2010;6:131-137.
19. Johnson KG, Johnson DC. Obstructive sleep apnea is a risk
factor for stroke and atrial fibrillation. Chest. 2010;138:239.
20. Loke YK, Brown JW, Kwok CS, Niruban A, Myint PK.
Association of obstructive sleep apnea with risk of serious
cardiovascular events: a systematic review and meta- analysis.
Circ Cardiovasc Qual Outcomes. 2012;5:720-728.
21. Xiaolin Gu MM. Risk factors of sleep disorder after stroke: a
meta-analysis. Top Stroke Rehabil. 2017;24: 34-40.
22. Laver KE, Spargo C, Saggese A, et al. Sleep disturbance and
disorders within adult inpatient rehabilitation settings: a
systematic review to identify both the prevalence of disorders
and the efficacy of existing interventions. J Am Med Dir Assoc.
Published online April 17, 2020. doi: 10.1016/
j.jamda.2020.03.002
23. Tang WK, Grace Lau C, Mok V, Ungvari GS, Wong KS.
Insomnia and health-related quality of life in stroke. Top Stroke
Rehabil. 2015;22:201-207.
24. Medeiros CA, de Bruin PF, Paiva TR, Coutinho WM, Ponte
RP, de Bruin VM. Clinical outcome after acute ischaemic
stroke: the influence of restless legs syndrome. Eur J Neurol.
2011;18:144-149.
25. Christova M, Aftenberger H, Nardone R, Gallasch E. Adult
gross motor learning and sleep: is there a mutual benefit?
Neural Plast. 2018;2018:3076986.
26. Gudberg C, Johansen-Berg H. Sleep and motor learning:
implications for physical rehabilitation after stroke. Front
Neurol. 2015;6:241.
27. Diekelmann S, Born J. The memory function of sleep. Nat Rev
Neurosci. 2010;11:114-126.
28. Rasch B, Born J. About sleep’s role in memory. Physiol Rev.
2013;93:681-766.
29. Siengsukon CF, Boyd LA. Sleep to learn after stroke: implicit
and explicit off-line motor learning. Neurosci Lett. 2009;451:1-
5.
30. Siengsukon C, Al-Dughmi M, Al-Sharman A, Stevens S. Sleep
parameters, functional status, and time post-stroke are
associated with offline motor skill learning in people with
chronic stroke. Front Neurol. 2015;6:225.
31. Al-Sharman A, Siengsukon CF. Performance on a functional
motor task is enhanced by sleep in middle-aged and older
adults. J Neurol Phys Ther. 2014;38:161-169.
32. Li J, You SJ, Xu YN, et al. Cognitive impairment and sleep
disturbances after minor ischemic stroke. Sleep Breath.
2019;23:455-462.
33. Pearce SC, Stolwyk RJ, New PW, Anderson C. Sleep
disturbance and deficits of sustained attention following stroke.
J Clin Exp Neuropsychol. 2016;38:1-11.
34. Glozier N, Moullaali TJ, Sivertsen B, et al. The course and
impact of poststroke insomnia in stroke survivors aged 18 to 65
years: results from the Psychosocial Outcomes In StrokE
(POISE) Study. Cerebrovasc Dis Extra. 2017;7:9-20.
12
35. Good DC, Henkle JQ, Gelber D, Welsh J, Verhulst S. Sleep-
disordered breathing and poor functional outcome after stroke.
Stroke. 1996;27:252-259.
36. Kaneko Y, Hajek VE, Zivanovic V, Raboud J, Bradley TD.
Relationship of sleep apnea to functional capacity and length of
hospitalization following stroke. Sleep. 2003;26:293-297.
37. Fulk G, Duncan P, Klingman KJ. Sleep problems worsen
health-related quality of life and participation during the first 12
months of stroke rehabilitation. Clin Rehabil. Published online
June 30, 2020. doi:10.1177/0269215520935940
38. Kumar R, Suri JC, Manocha R. Study of association of severity
of sleep disordered breathing and functional outcome in stroke
patients. Sleep Med. 2017;34:50-56.
39. Jeon H, Sohn MK, Jeon M, Jee S. Clinical characteristics of
sleep-disordered breathing in subacute phase of stroke. Ann
Rehabil Med. 2017;41:556-563.
40. Joa KL, Kim WH, Choi HY, et al. The effect of sleep
disturbances on the functional recovery of rehabilitation
inpatients following mild and moderate stroke. Am J Phys Med
Rehabil. 2017;96:734-740.
41. Chen CY, Yu CC, Chen CL. Nocturnal periodic limb
movements decrease antioxidant capacity in post-stroke
women. Acta Neurol Scand. 2016;133:245-252.
42. Boulos MI, Wan A, Black SE, Lim AS, Swartz RH, Murray BJ.
Restless legs syndrome after high-risk TIA and minor stroke:
association with reduced quality of life. Sleep Med.
2017;37:135-140.
43. Fleming MK, Smejka T, Henderson Slater D, et al. Sleep
disruption after brain injury is associated with worse motor
outcomes and slower functional recovery. Neurorehabil Neural
Repair. 2020;37:661-671.
44. Bassetti CL, Milanova M, Gugger M. Sleep-disordered
breathing and acute ischemic stroke: diagnosis, risk factors,
treatment, evolution, and long-term clinical outcome. Stroke.
2006;37:967-972.
45. Bonnin-Vilaplana M, Arboix A, Parra O, Garcia-Eroles L,
Montserrat JM, Massons J. Cheyne-stokes respiration in
patients with first-ever lacunar stroke. Sleep Disord.
2012;2012:257890.
46. Boulos MI, Wan A, Im J, et al. Identifying obstructive sleep
apnea after stroke/TIA: evaluating four simple screening tools.
Sleep Med. 2016;21:133-139.
47. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P.
Preferred reporting items for systematic reviews and meta-
analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.
48. Deeks JJ, Higgins JPT, Altman DG. Analysing data and
undertaking meta-analyses. In: Higgins JPT, Thomas J,
Chandler J, et al eds. Cochrane Handbook for Systematic
Reivews of Interventions version 6.0: Cochrane Collaboration;
2019.
49. Cohen J. Statistical Power Analysis for the Behavioral
Sciences. 2 ed. Lawrence Erlbaum; 1988.
50. Aaronson JA, van Bennekom CA, Hofman WF, et al.
Obstructive sleep apnea is related to impaired cognitive and
functional status after stroke. Sleep. 2015;38:1431-1437.
51. Ahn SH, Kim JH, Kim DU, Choo IS, Lee HJ, Kim HW.
Interaction between sleep-disordered breathing and acute
ischemic stroke. J Clin Neurol. 2013;9:9-13.
Neurorehabilitation and Neural Repair 34(11)
52. Brooks D, Davis L, Vujovic-Zotovic N, et al. Sleepdisordered
breathing in patients enrolled in an inpatient stroke
rehabilitation program. Arch Phys Med Rehabil.
2010;91(4):659-662.
53. Cadilhac DA, Thorpe RD, Pearce DC, et al. Sleep disordered
breathing in chronic stroke survivors. A study of the long term
follow-up of the SCOPES cohort using home based
polysomnography. J Clin Neurosci. 2005;12:632-637.
54. Camilo MR, Schnitman SV, Sander HH, et al. Sleepdisordered
breathing among acute ischemic stroke patients in Brazil. Sleep
Med. 2016;19:8-12.
55. Cherkassky T, Oksenberg A, Froom P, Ring H. Sleeprelated
breathing disorders and rehabilitation outcome of stroke
patients: a prospective study. Am J Phys Med Rehabil.
2003;82:452-455.
56. Iranzo A, Santamaria J, Berenguer J, Sanchez M, Chamorro
A. Prevalence and clinical importance of sleep apnea in the
first night after cerebral infarction. Neurology. 2002;58: 911-
916.
57. Kotzian ST, Stanek JK, Pinter MM, Grossmann W, Saletu MT.
Subjective evaluation of sleep apnea is not sufficient in stroke
rehabilitation. Top Stroke Rehabil. 2012;19:45-53.
58. Lawrence E, Dundas R, Higgens S, et al. The natural history
and associations of sleep disordered breathing in first ever
stroke. Int J Clin Pract. 2001;55:584-588.
59. Lefevre-Dognin C, Stana L, Jousse M, et al. Lack of
repercussions of sleep apnea syndrome on recovery and
attention disorders at the subacute stage after stroke: a study of
45 patients. Ann Phys Rehabil Med. 2014;57:618-628.
60. Mansukhani MP, Bellolio MF, Kolla BP, Enduri S, Somers VK,
Stead LG. Worse outcome after stroke in patients with
obstructive sleep apnea: an observational cohort study. J Stroke
Cerebrovasc Dis. 2011;20:401-405.
61. Menon D, Sukumaran S, Varma R, Radhakrishnan A. Impact of
obstructive sleep apnea on neurological recovery after ischemic
stroke: a prospective study. Acta Neurol Scand. 2017;136:419-
426.
62. Pace M, Camilo MR, Seiler A, et al. Rapid eye movements
sleep as a predictor of functional outcome after stroke: a
translational study. Sleep. 2018;41.
63. Sandberg O, Franklin KA, Bucht G, Gustafson Y. Sleep apnea,
delirium, depressed mood, cognition, and ADL ability after
stroke. J Amer Geriatr Soc. 2001;49:391-397.
64. Turkington PM, Allgar V, Bamford J, Wanklyn P, Elliott MW.
Effect of upper airway obstruction in acute stroke on functional
outcome at 6 months. Thorax. 2004;59: 367-371.
65. Yan-Fang S, Yu-Ping W. Sleep-disordered breathing: impact on
functional outcome of ischemic stroke patients. Sleep Med.
2009;10:717-719.
66. Benbir G, Karadeniz D. Influence of periodic leg movements in
sleep on stroke outcome. Sleep Biol Rhythms. 2013;11: 194-
199.
67. Shiina T, Suzuki K, Okamura M, Matsubara T, Hirata K.
Restless legs syndrome and its variants in acute ischemic
stroke. Acta Neurol Scand. 2019;139:260-268.
68. Kim J, Kim Y, Yang KI, Kim DE, Kim SA. The relationship
between sleep disturbance and functional status in mild stroke
patients. Ann Rehabil Med. 2015;39:545-552.
Fulk et al
69. Kim WH, Jung HY, Choi HY, et al. The associations between
insomnia and health-related quality of life in rehabilitation units
at 1 month after stroke. J Psychosom Res. 2017;96:10-14.
70. Kim KT, Moon HJ, Yang JG, Sohn SI, Hong JH, Cho YW. The
prevalence and clinical significance of sleep disorders in acute
ischemic stroke patients—a questionnaire study. Sleep Breath.
2017;21:759-765.
71. Birkbak J, Clark AJ, Rod NH. The effect of sleep disordered
breathing on the outcome of stroke and transient ischemic
attack: a systematic review. J Clin Sleep Med. 2014;10: 103-
108.
72. Bakken LN, Kim HS, Finset A, Lerdal A. Stroke patients’
functions in personal activities of daily living in relation to
sleep and socio-demographic and clinical variables in the acute
phase after first-time stroke and at six months of follow-up. J
Clin Nurs. 2012;21:1886-1895.
73. Moon HI, Yoon SY, Jeong YJ, Cho TH. Sleep disturbances
negatively affect balance and gait function in post-stroke
patients. NeuroRehabiltation. 2018;43:211-218.
74. Rod NH, Kjeldgard L, Akerstedt T, et al. Sleep apnea, disability
pensions, and cause-specific mortality: a Swedish Nation wide
Register Linkage Study. Am J Epidemiol. 2017;186: 709-718.
75. Overland S, Glozier N, Sivertsen B, et al. A comparison of
insomnia and depression as predictors of disability pension: the
HUNT Study. Sleep. 2008;31:875-880.
76. Sivertsen B, Overland S, Pallesen S, et al. Insomnia and long
sleep duration are risk factors for later work disability. The
Hordaland Health Study. J Sleep Res. 2009;18:122-128.
77. Jansson C, Alexanderson K, Kecklund G, Akerstedt T.
Clinically diagnosed insomnia and risk of all-cause and
diagnosis-specific disability pension: a nationwide cohort study.
Sleep Disord. 2013;2013:209832.
78. Abdel Salam OA, Ghonimi NAM, Ismail MH. Risk of
obstructive sleep apnea in multiple sclerosis: frequency, clinical
and radiological correlates. Mult Scler Relat Disord.
2019;28:184-188.
79. Sieminski M, Losy J, Partinen M. Restless legs syndrome in
multiple sclerosis. Sleep Med Rev. 2015;22:15-22.
80. Braley TJ, Segal BM, Chervin RD. Obstructive sleep apnea and
fatigue in patients with multiple sclerosis. J Clin Sleep Med.
2014;10:155-162.
81. Lebrato Hernandez L, Prieto Leon M, Cerda Fuentes NA, Ucles
Sanchez AJ, Casado Chocan JL, Diaz Sanchez M. Restless legs
syndrome in patients with multiple sclerosis: evaluation of risk
factors and clinical impact. Neurologia. Published online April
5, 2019. doi:10.1016/j.nrl.2018.12.010
82. Cantor JB, Bushnik T, Cicerone K, et al. Insomnia, fatigue, and
sleepiness in the first 2 years after traumatic brain injury: an
NIDRR TBI model system module study. J Head Trauma
Rehabil. 2012;27:E1-E14.
83. Cirillo DJ, Wallace RB. Restless legs syndrome and functional
limitations among American elders in the Health and
Retirement Study. BMC Geriatr. 2012;12:39.
84. Zhang C, Li Y, Malhotra A, Ning Y, Gao X. Restless legs
syndrome status as a predictor for lower physical function.
Neurology. 2014;82:1212-1218.
85. Watson NF, Badr MS, Belenky G, et al. Joint consensus
statement of the American Academy of Sleep Medicine and
13
Sleep Research Society on the recommended amount of sleep
for a healthy adult: methodology and discussion. Sleep.
2015;38:1161-1183.
86. Consensus Conference Panel; Watson NF, Badr MS, et al.
Recommended amount of sleep for a healthy adult: a joint
consensus statement of the American Academy of Sleep
Medicine and Sleep Research Society. J Clin Sleep Med.
2015;11:591-592.
87. Senaratna CV, Perret JL, Lodge CJ, et al. Prevalence of
obstructive sleep apnea in the general population: a systematic
review. Sleep Med Rev. 2017;34:70-81.
88. American Academy of Sleep Medicine. International
Classification of Sleep Disorders. American Academy of Sleep
Medicine; 2014.
89. Ford ES, Cunningham TJ, Giles WH, Croft JB. Trends in
insomnia and excessive daytime sleepiness among US adults
from 2002 to 2012. Sleep Med. 2015;16:372-378.
90. Office of Disease Prevention and Health Promotion. SH-4:
Adults getting sufficient sleep per night (percent, 18+ years) by
sex. Accessed March 8, 2020.
https://www.healthypeople.gov/2020/ topics-
objectives/topic/sleep-health/national-snapshot
91. Janssen H, Venekamp LN, Peeters GAM, Pijpers A, Pevernagie
DAA. Management of insomnia in sleep disordered breathing.
Eur Respir Rev. 2019;28:190080.
92. Arnaud C, Bochaton T, Pepin JL, Belaidi E. Obstructive sleep
apnoea and cardiovascular consequences: Pathophysiological
mechanisms. Arch Cardiovasc Dis. 2020;113:350-358.
93. Javaheri S, Barbe F, Campos-Rodriguez F, et al. Sleep apnea:
types, mechanisms, and clinical cardiovascular consequences. J
Am Coll Cardiol. 2017;69:841-858.
94. Garvey JF, Pengo MF, Drakatos P, Kent BD. Epidemiological
aspects of obstructive sleep apnea. J Thorac Dis. 2015;7: 920-
929.
95. Vargas I, Perlis ML. Insomnia and depression: clinical
associations and possible mechanistic links. Curr Opin Psychol.
2020;34:95-99.
96. Rayward AT, Burton NW, Brown WJ, Holliday EG, Plotnikoff
RC, Duncan MJ. Associations between changes in activity and
sleep quality and duration over two years. Med Sci Sports
Exerc. 2018;50:2425-2432.
97. Chennaoui M, Arnal PJ, Sauvet F, Leger D. Sleep and exercise:
a reciprocal issue? Sleep Med Rev. 2015;20:59-72.
98. Klingman K, Jungquist CR, Perlis ML. Introducing the sleep
disorders symptom checklist-25: a primary care friendly and
comprehensive screener for sleep disorders. Sleep Med Res.
2017;8:17-25.
99. Netzer NC, Stoohs RA, Netzer CM, Clark K, Strohl KP. Using
the Berlin Questionnaire to identify patients at risk for the sleep
apnea syndrome. Ann Intern Med. 1999;131:
485-491.
100. Johns MW. A new method for measuring daytime sleepiness:
the Epworth Sleepiness Scale. Sleep. 1991;14:540-545.
101. Chung F, Subramanyam R, Liao P, Sasaki E, Shapiro C, Sun Y.
High STOP-Bang score indicates a high probability of
obstructive sleep apnoea. Br J Anaesth. 2012;108:768-775.
14 Neurorehabilitation and Neural Repair 34(11)

102. Chung F, Yegneswaran B, Liao P, Sasaki E, Shapiro C, Sun Y.

STOP questionnaire: a tool to screen patients for obstructive
sleep apnea. Anesthesiology. 2008;108:812-821.
103. Morin CM, Belleville G, Belanger L, Ivers H. The Insomnia
Severity Index: psychometric indicators to detect insomnia
cases and evaluate treatment response. Sleep. 2011;34:601-608.
104. Allen RP, Burchell BJ, MacDonald B, Hening WA, Earley CJ.
Validation of the self-completed Cambridge-Hopkins
questionnaire (CH-RLSq) for ascertainment of restless legs
syndrome (RLS) in a population survey. Sleep Med.
2009;10:1097-1100.
105. Ryan CM, Bayley M, Green R, Murray BJ, Bradley TD.
Influence of continuous positive airway pressure on outcomes
of rehabilitation in stroke patients with obstructive sleep apnea.
Stroke. 2011;42:1062-1067.
106. Geiger-Brown JM, Rogers VE, Liu W, Ludeman EM, Downton
KD, Diaz-Abad M. Cognitive behavioral therapy in persons
with comorbid insomnia: a meta-analysis. Sleep Med Rev.
2015;23:54-67.
107. Siengsukon CF, Alshehri M, Williams C, Drerup M, Lynch S.
Feasibility and treatment effect of cognitive behavioral therapy
for insomnia in individuals with multiple sclerosis: a pilot
randomized controlled trial. Mult Scler Relat Disord.
2020;40:101958.
108. Chung KF, Lee CT, Yeung WF, Chan MS, Chung EW, Lin
WL. Sleep hygiene education as a treatment of insomnia: a
systematic review and meta-analysis. Fam Pract. 2018;35:365-
375.