Sleep and Wake Disorders Following Traumatic Brain Injury ... · and sleep. Regardless of injury...

317Volume 21 Numbers 3-4

Critical Reviews™ in Physical and Rehabilitation Medicine, 21(3-4): 317-374 (2009)

0896-2960/09/$35.00© 2009 by Begell House, Inc.

Sleep and Wake Disorders Following Traumatic Brain Injury: A Systematic Review of the Literature

Catherine Wiseman-Hakes,1* Angela Colantonio,2,3 and Judith Gargaro2

1Graduate Department of Rehabilitation Science, University of Toronto; 2Department of Occupational Therapy and Occupational Science, University of Toronto; 3Toronto Rehabilitation Institute, Toronto, Ontario, Canada

* Address all correspondence to Catherine Wiseman-Hakes, Graduate Department of Rehabilitation Science, Faculty of Medicine, University of Toronto, 160-500 University Ave.Toronto, ON, M5G 1V7, Canada; Tel.: 416-946-8575; Fax. 416-946-8570; [email protected]

ABSTRACT: Traumatic brain injury is a leading cause of death and disability in both Canada and the United States. Disorders of sleep and wakefulness are among the most commonly reported sequelae postinjury, across all levels of severity. Despite this, sleep and wakefulness are neither routinely, nor systematically, assessed and are only recently beginning to receive more clinical and scientific attention. Objectives: This review aims to systematically appraise the literature regarding sleep and wake disorders associated with traumatic brain injury according to the following domains: epidemiology, pathophysiology, neuropsychological implications, and inter-vention; to summarize the best evidence with a goal of knowledge translation to clinical practice; and to provide recommendations as to how the field can best be advanced in the most scientifically rigorous manner. Methods: Systematic review and rating of the quality of evidence. Results: Forty-three articles were reviewed for levels and quality of evidence. Fifty-six percent of the literature was classified as Level III, and 24 percent were Level IVA. Overall, 89 percent of the studies were rated as moderate quality. A separate summary was provided for the pediatric literature. Conclusions: A comprehensive review of the emerging literature revealed wide ranges in estimates for incidence and prevalence of sleep disorders following TBI depending on characteristics of patients, measures used, and length of follow-up. Few treatments have been found to be effective, and as such more research is recommended. Our overview of the pediatric literature shows that this is an important issue for survivors of all ages. Overall, further work is needed to fully understand this complex disorder and to identify appropriate and timely interventions.

KEY WORDS: traumatic brain injury, mild traumatic brain injury, sport-related concussion, sleep, sleep disorders, insomnia, hypersomnia, excessive somnolescence, treatment

I. BACKGROUND AND INTRODUCTION

A. Overview and Objectives

Traumatic brain injury (TBI), defined as an ac-quired nondegenerative, noncongenital insult to the brain from an external mechanical force, is a leading cause of death and disability in both Canada and the United States for both adults and children.1 Furthermore, although the literature re-

viewed in this paper is truly international in scope, at this time in the United States, “the nature of modern tactical engagement…in the current Iraq and Afghanistan conflicts has resulted in the largest proportion of identified traumatic brain injuries in any conflict in the nation’s history.” 2(p. 1004) In fact, the US Department of Defense reported an incidence of 10,963 diagnosed conflict-related TBIs in the year 2000. However, this incidence was reported as 27,862 by December 31, 2009,

318 Critical Reviews™ in Physical and Rehabilitation Medicine

which represents an increase of 145%.3 TBI can result in significant impairments in physical, neurocognitive, and psychosocial/emotional func-tion, as well as impairments in communication and sleep. Regardless of injury severity, these impairments may be transient or permanent, re-sulting in profound disruption for survivors and their families.

Disorders of sleep and wakefulness are among the most commonly reported sequelae postinjury, across all levels of severity.4,5 Despite this, sleep and wakefulness are neither routinely, nor system-atically, assessed postinjury, and are only recently beginning to receive more clinical and scientific attention. Previous reviews by Ouellet and col-leagues,6 Orff and colleagues,7 and most recently by Zeitzer and colleagues8 indicate that the field is still in a developmental stage and a body of literature is beginning to emerge. These previous reviews focused primarily on the prevalence and nature of sleep disorders and, to a lesser extent, on implications and effective treatment strategies among adult TBI survivors.

As of yet, there has been no systematic ap-praisal of the literature, nor has there been a review that has included literature pertaining to a pediatric population. The literature on pediatrics is of particular relevance given the fact that ap-proximately 500,000 children aged younger than 17 years are hospitalized each year with TBIs in the United States.9,10 This statistic does not include those children with minor TBIs who were either seen by their family physician/pediatrician or remained undiagnosed. Furthermore, TBI is the leading cause of disability in those under the age of 24 years, and the peak age of occurrence for TBI is 15–24 years.11 Thus, the unique con-tributions of this paper are: 1) to systematically update and extend previous reviews on sleep and brain injury6–8 by conducting a thorough critical appraisal of the methodological quality of the lit-erature that includes both children and adults and then, based on the identified strengths, weaknesses, and inconsistencies in the current literature; 2) to summarize the best evidence that currently exists with a goal of translating knowledge to clinical practice; and 3) to provide specific recommenda-tions as to how the field can best be advanced in the most scientifically rigorous manner, given the unique complexities of this disorder.

In summary, the objectives of this review are to systematically appraise the literature regarding sleep and wake disorders associated with TBI according to the following domains: epidemiol-ogy (including sports-related concussion), patho-physiology, neuropsychological implications, and intervention. Furthermore, we will identify practice points and provide recommendations for a research agenda, based on the current body of literature.

In order to provide readers with a clearer understanding of the importance of sleep (and wakefulness) in the rehabilitation and recovery process, we begin with a brief definition of sleep and an overview of the role and functions of sleep.

B. Definition of Sleep and Its Functions

To fully grasp the significance of the impact of sleep disturbances postinjury, it is important to have a clear understanding of the actual definition of sleep and the critical roles and function it plays in human (and animal) physiology and homeostatic regulation. In 1995, Tobler12 defined sleep as a physiological, complex, and integrated behavior characterized by a significant reduction of the response to external stimuli, by a characteristic posture usually in a special environment, by a characteristic change in the neurophysiological recordings of brain activity, and by a homeostatic increase after its restriction. Sleep is a critical function that serves to reverse and/or restore biochemical and/or physiological processes that are progressively degraded during prior periods of wakefulness.

Sleep is believed to be essential for optimal immune function by influencing cellular (T-cell) immunity. Furthermore, an increase in growth hormone secretion is observed immediately fol-lowing sleep onset, concurrently with a rise in cortisol in the latter half of sleep. This is critical for growth and development and is also important from the perspective of recovery from trauma, because not only does human growth hormone stimulate growth and cell reproduction, it also plays a critical role in cell regeneration. Further-more, cortisol plays a crucial role in facilitating the body’s adaptation to physical and mental stress, in the suppression of inflammation, enhancement


of wound healing, modulation of plasma glucose, and increased production of erythrocytes (red blood cells).13

Sleep is divided into non-REM (rapid eye movement) and REM sleep. Studies of non-REM and REM sleep and the importance of their temporal succession in both animals and humans reveal that these stages have been found to play key roles in certain types of memory and learning, as well as cerebral plasticity.14–16 REM sleep, which occurs at the end of each sleep cycle, and the overall length of the REM cycle peaks prior to wakening also play a key role in aspects of memory consolidation and new learn-ing. Furthermore, REM sleep during the neonatal period plays an important role in brain growth, neuronal maturation, connectivity, and synaptic plasticity in infants.17 Thus, recognition of the critical role that sleep plays in endocrine and immune function, thermoregulation, cognition, and behavior underscores the need to evaluate and optimize sleep during recovery from brain injury.

II. METHODOLOGY

An extensive and iterative literature search was conducted using the Ovid, Medline, PsychInfo, CINAHL, and EMBASE databases to ensure the capture of any relevant studies pertaining to the assessment of sleep after TBI. Medical subject heading terms included: brain injuries or brain concussion or brain hemorrhage, traumatic or brain injury, chronic or diffuse axonal injury/sleep disorders/insomnia, and hypersomnia. The search was limited to articles published in English from 1998–2009. Only peer-reviewed full-text articles were considered for this study.

The search was initially exhaustive to include titles relating to both acquired brain injury and TBI, as the terms are sometimes used synonymously. This allowed us to ensure that we captured all relevant studies. Each article abstract was then reviewed to further ensure relevance. Additional search strategies were also employed and as such, the reference lists of all articles were scanned for additional studies that may be relevant for review. Because the literature on the relationship between sleep disturbances and TBI is still developing,

our inclusion criteria were quite broad and all identified articles were reviewed.

We then subdivided the articles into five different domains of scientific inquiry, including epidemiology, pathophysiology, pediatrics, in-tervention, and neuropsychological implications. Because there are a limited number of articles in the different subcategories of focus, all identified articles from Level II to Level V were included. In all, 68 articles were evaluated and 43 articles were included for the purposes of this review. We excluded only those that we deemed to be opinion papers or consensus papers not based on the results of a specific scientific study.

To critically appraise and stratify the quality of the evidence, the articles were evaluated on their research design and scientific rigor. Although it was not our intention to conduct a meta-analysis such as those undertaken by the Cochrane Collabo-ration Group, the ranking criteria were selected from the literature on evidence-based practice in rehabilitation, with a goal of providing guidance to end users about the studies likely to be most valid. Thus, the articles were categorized ac-cording to the scientifically validated hierarchy developed by Holm and edited by Boschen and colleagues (Table 1).18,19 Other rating systems are available;20–22 however, the Holm hierarchy18,19 was chosen in order to better differentiate among the published studies that exist at this point in the development of the literature on sleep and TBI. Given the early stage of development and the inherent complexities of the field, few randomized control trials (RCTs) have been conducted. It is, therefore, necessary to use a hierarchy that gives weight to non-RCT designs and also has a place for well-designed qualitative studies. Although the Holm hierarchy is an appropriate choice, it still did not fully differentiate the literature for our purposes. Thus, the edited and published version used by Boschen and colleagues19 was used for this systematic review.

Boschen and colleagues added two additional levels to the Holm hierarchy: the first is Level IIA, which was added to evaluate review papers that did not meet the criteria for Level I as they included non-RCT designs, and the second is Level IVA, which was added to separate out the well-designed non-experimental research designs such as cost analyses and the qualitative designs


from the purely opinion and descriptive studies classified as Level V articles.

To fully capture the literature in its current state of evolution, we also considered review articles of multiple well-designed studies (called Level I and Level IIA studies in this hierarchy) in our article inclusion criteria. These review articles were considered separately from the single-study articles because they gave us a better perspective of the historical development of research in the field of sleep and TBI. Single studies were clas-sified into levels based on the extent to which they met the criteria of the individual designated levels within this published hierarchy.

The process of assigning articles to levels was completed independently by two of the authors. Discrepancies were discussed and consensus was reached. Articles categorized as Level I or Level IIA were read and summarized but were not criti-cally reviewed, as they were review articles in and of themselves. Published hierarchies do exist for the evaluation of systematic reviews; however, because none of the review articles identified for this systematic review were systematic in nature, these hierarchies were not applicable.

Each of the articles was evaluated using a template generated for use in this study. The templates addressed the purpose, study design, sample, outcome measures, significant findings, relevant conclusions, and comments made by the authors of the articles, as well as any special notes from the article reviewers. Two of the authors and an undergraduate student completed the templates for the articles.

In order to critically appraise the quality of the articles, information was abstracted from the tem-plates in regard to the following seven questions:

1. Were baseline characteristics described and equivalence of groups evaluated?

2. Was the intervention/methodology de-scribed in detail, that is, sufficient for replication?

3. Was blinding employed?4. What was the sample size per group used

for data analysis?5. What was the attrition rate?6. Were the outcome measures used for the

study standardized?7. Was there a follow-up data collection

point?

TABLE 1Total Number of Articles Retrieved by Level of Evidence

Level of Evidence No. of Articles

Article Type

Level Ia 0 Systematic reviews of randomized controlled trials (RCTs)Level II 2 Properly designed individual RCTs of appropriate size

Level IIAb 2 Systematic reviews of case-controlled, cohort, or other experimental de-signs (including RCTs reviewed together with other experimental designs)

Level III 25Well-designed trials without randomization, single group pre-post, cohort, time series, or matched case-controlled studies (also cross-sectional stud-ies and case series)

Level IV 0 Well-designed non-experimental studies from more than one center or research group

Level IVAb 10 Well-designed individual non-experimental studies, cost analysis studies, and case studies

Level V 6 Reports of expert committees, descriptive studies, clinical observations, opinions of respected authorities, or testimonialsTotal

Total Reviewed 45

aBased on Holm.18

bAdapted from Boschen and colleagues19 to further differentiate the evidence.


This latter question was added specifically for the purposes of this review. The authors attempted to assess whether the intervention/methodology was described in sufficient detail to allow for understanding of the key elements and to allow for replication. These items were identified based on the items used in meta-analytic and other systematic reviews.23 The presence of the above-listed seven quality elements and their description in the articles was further rated on a three-point scale developed by Boschen and colleagues19 (Table 2). The classification of the quality rating - the sum of the scores of each of the six elements - was made using a trichotomous scheme representing “low” (summed score of <3), “moderate” (summed score of ≥3 and <5), and “high” (summed score ≥5) quality determined by the developers, based on the previous work of Boschen and colleagues. The abstraction and rating were performed independently by two of the authors and discrepancies were discussed and consensus was reached.

In addition, the articles on intervention were assigned a rating using the Downs and Black Rating System.20 As the Downs and Black system is widely known and accepted, we attempted to use this for the evaluation of all of the articles included. However, although it is an excellent

tool for the assessment of the quality of evidence specific to intervention studies, we encountered a number of difficulties in applying it to the nonin-tervention studies reviewed in this article. Thus, the Downs and Black System was applied only to the intervention studies. The use of these two quality assessment methodologies for the interven-tion studies allowed for comparison and a more thorough description of the literature.

III. RESULTS

A. Previous Reviews of Sleep Disorders and Insomnia Following TBI: A Historical Overview of the Literature to Date

To date, three reviews of the literature pertain-ing to sleep and/or insomnia following TBI have been published (Ouellet and colleagues,6 Orff and colleagues,7 and Zeitzer and colleagues8). The thorough Ouellet review,6 which we consider to be Level IIA, was the first to be conducted on the topic of sleep disturbance following TBI. This review made a number of important contributions to our understanding of the early adult literature on this complex topic. The authors aimed to re-

TABLE 2Criteria Used to Assess the Quality of the Studies

Rating of Assessed Characteristic

Baseline Characteristics: Described, “Equivalence”

Blinding Sample Size (per group)

Attrition Standardized Outcomes

Description of Intervention

Length of Follow-Up

1 Both elements present in the article

Double >75 <15% All Sufficient to replicate

>3 months

0.5 Either charac-teristics were described or equivalence was noted, but not both

Single 30-75 15-25% Some Some de-scription

0-3 months

0 Neither presented

No blind-ing or not stated

<30 >25% None No sufficient description

None


view the evidence on epidemiology, etiology, and treatment of insomnia in the context of TBI, and to propose areas for future research.

With regard to the early literature on preva-lence, Ouellet and colleagues6 reviewed nine studies and concluded that there were significant methodological issues in many of them, including the lack of an operational definition of insomnia, and heterogenous approaches (lack of consistency) to the assessment measures used to evaluate the presence and clinical significance of the insom-nia. Furthermore, they identified that most of the studies varied in terms of the time of evaluation postinjury and the level of severity of the brain injury, making it difficult to draw any specific conclusions regarding prevalence.

Among the studies reviewed by Ouellet and colleagues, they identified a range of reported symptoms of insomnia from 30–70% in patients with TBI, with symptoms of poor sleep initia-tion and maintenance being the most prevalent.6 They also noted a range of time postinjury that symptoms (of insomnia) were present from 6–12 weeks postinjury up to several years. This was an important conclusion/observation because Ouellet and colleagues identified that “insomnia appears to develop a chronic course in a significant pro-portion of TBI patients.”6(p. 188)

In addition, Ouellet and colleagues also iden-tified a number of potential etiological factors that may be associated with the development of insomnia following TBI, including predisposing, precipitating, and perpetuating factors.6 Finally, they reviewed the literature on potential psycho-logical and behavioral consequences of insomnia, and summarized the few studies on intervention, including pharmacotherapy and psychotherapies. The authors concluded the article with some basic practical recommendations based on the literature to date. They felt comfortable conclud-ing that insomnia is a common problem after TBI, the etiology and maintenance of which is complicated. They further concluded that the presence of insomnia in patients with TBI likely has detrimental consequences; however, more research is needed to identify effective treatments. They suggested that because insomnia can be chronic, combinations of pharmacological and psychological treatment options should possibly be used. Data collected from non-TBI patients

suggest that cognitive behavioral therapy (CBT) has promise.

In 2009, Orff and colleagues7 conducted an in-depth review of the literature, which we also identified as being Level IIA. This review, which builds on the previous work by Ouellet and colleagues,6 included a clearly defined search strategy, key search terms, and methodology. This review aimed to address “the etiology and implications of sleep problems in TBI, particu-larly mild TBI (mTBI), across 4 general domains of current scientific inquiry and observation: subjective impressions of poor sleep; objective changes in sleep-related parameters; alterations in circadian rhythms; and neurophysiologic and/or neuropsychologic abnormalities associated with TBI.”7(p. 155)

In the five years since the Ouellet review, the prevalence of sleep disturbances following TBI (both subjectively reported and objectively measured, although the latter has some contrary findings) has been further established, and the literature has thus evolved to more closely look at this complex disorder. With regard to subjective impressions of poor sleep, Orff and colleagues7 identified that the majority of studies surveyed had reasonably large sample sizes and provided replicable findings of insomnia in TBI patients, particularly those with mild TBI (mTBI). Results of the studies surveyed on the topic of objective changes in sleep parameters were not quite so conclusive. The authors identified several studies with objective evidence of changes in sleep quan-tity and quality, as well as other sleep disorders such as obstructive sleep apnea (OSA), periodic limb movements (PLM), and narcolepsy. How-ever, they also cited a number of studies in which objective changes in sleep parameters were not found, despite subjective complaints of the sub-jects. The authors cited similar methodological concerns as those previously addressed by Ouellet and colleagues, and further cited the lack of, or inconsistent reporting on, other important factors such as prior TBIs and past/current medical and psychiatric status, “making it difficult to evalu-ate the role of these variables in sleep-related outcomes and complicating comparisons between studies.”7(p. 163)

Orff and colleagues7 reviewed the literature on TBI and circadian changes, and reported that


although the literature is relatively sparse and somewhat conflicting at this time, there is a grow-ing body of evidence to suggest that sleep distur-bances following TBI may be due to alteration in the timing and rhythms of sleep (i.e., circadian rhythm sleep disorders) in a subset of patients. In addition, they reviewed the literature on neuro-physiologic and neuropsychological disturbances associated with sleep. They reported endocrine changes that may explain sleep disturbances in this population and also highlighted the limited but important research that suggests that deficits in cognitive performance after TBI may be related, in part, to the degree of sleep disturbance.

Consistent with the Ouellet review, Orff and colleagues also summarized the literature on interventions to date, which remains limited to a few studies addressing pharmacotherapy and CBT. Finally, they discussed limitations of the literature and identified that although the body of work has grown since the Ouellet review in 2004,6 there remain similar methodological limitations such as small sample sizes, considerable variation in age, time since injury, level of severity, and measures used to assess sleep. Orff and colleagues recommend that future research needs to focus on uncovering the specific types, causes, and severity of TBI that most often lead to sleep problems; the consequences of sleep disturbance; and the most effective treatment strategies.

The final review studied for this article is by Zeitzer and colleagues.8 This review, which we identified as being a Level V and lacking the methodological strength of the previous two reviews, was conducted for the US Department of Veterans Affairs (VA). As such, its focus seems to consider insomnia in the context of TBI from the perspective of those assessing and treating veterans diagnosed with mTBI, hampered by a co-morbid sleep disorder. (Note: Sleep apnea may in fact be preexisting because it is, interestingly, present in about half of the Department of VA patient population8[p. 829]). This review lacks a clearly defined objective and systematic review approach; however, the authors state that they will “consider insomnia directly caused by TBI (e.g., secondary to neural damage), indirectly caused by TBI (e.g., secondary to depression), and un-related to TBI but occurring within individuals with TBI.”8(p. 827)

Consistent with previous reviews, Zeitzer and colleagues cited studies of TBI populations of varying severities (mild-moderate) and vary-ing lengths of time postinjury from 6 weeks to greater than 10 years. They reported that insomnia occurs in approximately 40% of individuals with a TBI of any severity, even though it is more com-monly reported among patients with mTBI, and is the most prevalent somatic complaint across all levels of severity. The authors also postulated two components of TBI-related insomnia. First, there is a general predisposition to develop sleep disturbance as a result of alterations or disruptions in neurotransmitters involved in the regulation of sleep (and they state further that the litera-ture on this topic is for the most part limited to those with moderate-severe TBI). Second, acute stressors may trigger insomnia. They highlighted non-sleep comorbidities such as depression, pain and post traumatic stress disorder, all of which are of particular relevance to individuals with TBI in general and to veterans with mTBI. From this discussion, they highlighted two future research questions. First, can mTBI cause disruptions in the regulation of sleep? The authors stated further that the literature on this topic is, for the most part, limited to those with moderate-severe TBI. Second, can acute stressors trigger the insomnia? They highlighted non-sleep comorbidities such as depression, pain, and posttraumatic stress dis-order, all of which are of particular relevance to individuals with TBI in general and to veterans with mTBIs. They also identified two additional research questions: Can mTBI cause disruptions in the neurotransmitters critical for sleep and wakefulness?; and, What is the effect of psychi-atric comorbidities on the occurrence or severity of insomnia in the context of TBI? The latter question aims to assist the physician in treating insomnia as a primary or secondary pathology.

Finally, Zeitzer and colleagues8 briefly sum-marized the literature on pharmacological and non-pharmacological treatments. As per the previous two reviews, the literature on treatment remains limited. As a result, these authors identified some cautionary caveats in the use of pharmacotherapy and described nonpharmacological interventions such as CBT plus various combinations of sleep hygiene, sleep restriction, and relaxation training. The authors highlighted the critical need for further


nonpharmacological studies as viable alternatives to treatment of insomnia in patients with mTBI. The authors concluded that more systematic re-search is required to “provide a foundation for an evidence-based medical approach to treatment of insomnia in the context of mTBI.”8(p. 832)

B. Single Study Papers

As shown in Table 1, the majority of the literature (56%) is classified as Level III (Well-designed tri-als without randomization, single group pre-post, cohort, time series, or matched case-controlled studies [also cross-sectional studies and case se-ries]). The next largest level is Level IVA, with 24% of the categorized articles (well-designed individual non-experimental studies, cost analysis studies, and case studies). The published literature is getting stronger as there are fewer Level V studies than Level III or IVA studies, but is still clearly in development as there are no Level I studies and few Level II or IIA studies.

Single study papers were organized into the following categories: epidemiology (comparison group studies or single group/cohort studies), pathophysiology, pediatrics, neuropsychology, and intervention (see Tables 3, 4, and 5). It is important to note that there are Level III studies in each of the above categories, but as of yet the Level II

studies are only with regard to pharmacological interventions. Only one of the studies reviewed was considered of low quality, the majority were of moderate quality (89%), and only a few were of high quality (10%). Each of the studies is summarized in detail in Table 5, which lists the level, quality, and key details relating to the conduction of the reported study. Each category of studies will be discussed below in the order in which they appear in the table. Following each summary there will be an in-text box summarizing the research agenda and practice points identified with the authors of the reviewed studies, followed by our recommendations.

1. Epidemiology

The evidence relating to the epidemiology of sleep and wake disturbances following TBI has historically been the primary focus of the lit-erature, comprising 23 of the 43 articles across the five subtopics we identified for this review. Epidemiological investigation of a phenomenon is a necessary starting point as it provides a solid foundation for all further investigations to follow. We subdivided the studies on epidemiology, all of which were rated as Level III study designs, to include nine papers with a comparison group, all of moderate quality, and 12 articles that used a

TABLE 3Article Scope and Level of Articles

Article Scope Total No. of Articles Level II/IIA Level III Level IVA Level V

Epidemiology - Comparison group

9 9

Epidemiology - Single group/cohort

14 5 6 3

Pathophysiology 3 2 1

Pediatrics 6 6

Neuropsychology 4 1 2 1

Intervention 6 2 3 1

Review 3 2 1

Total 45 2/2 26 10 5


single group design, 10 of which were moderate quality, and two were of high quality.24,25 Both of these studies were also classified as Level III. Among the single group studies, there were five rated as Level III, five rated as Level IVA, and two rated as Level V. The use of a comparison group is a stronger design; however, our quality rating scheme studies included several elements, weighted equally, to assess overall quality so that a study weak in one area can be strong in other areas.

There are several important elements that should be addressed in a good quality epide-miological study. Recruitment is a key issue and recruitment methods must be carefully con-sidered to make sure that any selection bias is eliminated. Recruitment from the perspective of time postinjury is also a factor for consideration in that it allows us to observe the developmental time course of the disorder. Among the articles we reviewed, 65% of the studies (15/23) used consecutive recruitment; however, only 13% (3/23) used consecutive recruitment directly from the acute setting. Twenty-six percent were consecutively recruited as patients entered reha-bilitation and the remaining 26% were recruited while in rehabilitation or upon discharge from rehabilitation. Parcell and colleagues26 recruited all patients with TBI, with no preference for those

with sleep complaints, thus reducing bias in their sample. The remainder of the studies included retrospective chart review or recruitment by advertising. In contrast to the Parcell study, the study by Ouellet and colleagues,4 with the largest sample size of 452, recruited participants with reported symptoms of insomnia via mailings sent to 1500 prospective participants from archives of Québec City’s largest rehabilitation center, local brain injury associations, and support groups. The authors specifically reported using liberal inclusion criteria to try and capture a “broad portrait of the TBI population.”4(p. 201)

It is also important to consider possible con-founders or variables that influence interpretation of the findings, such as preexisting, concurrent, and secondary comorbidities; age at onset of injury; time since injury; severity of injury; etiol-ogy of injury; and gender. In an “ideal” study, the sample population would be large enough to allow stratification on some or all of these variables, so that the findings would be more generalizable and create a more thorough picture of the phenomenon.

Overall, the objective of the epidemiological studies reviewed for this article was to document the incidence, prevalence, and nature of sleep disturbances following TBI, primarily “insomnia” per se, with the inclusion of the most recent data relating specifically to sports-related concussion.

TABLE 4Article Scope and Quality of Articles

Article Scope Total Moderate Quality High Quality3 3.5 4 4.5 5 6.5

Epidemiology - Comparison group 9 6 3

Epidemiology - Single group/cohort 14 1 3 4 4 2

Pathophysiology 3 1 1 1Pediatrics 6a 2 1 1 1Neuropsychology 4 1 2 1Intervention 6 1 1 2 1 1Review 3Total 45 1 8 15 12 3 1

aOne article was of low quality with a rating of 2.5.


TAB

LE 5

Slee

p an

d W

ake

Dis

orde

rs fo

llow

ing

Trau

mat

ic B

rain

Inju

ry: S

umm

ary

of R

evie

wed

Art

icle

s

Ref

eren

ceSt

udy

Obj

ectiv

eR

esea

rch

Des

ign

Sam

ple

Size

In

clus

ion/

Excl

usio

n

Subj

ects

Dat

a

Col

lect

ion

Met

hods

/M

easu

res

Sign

ifica

nt

Find

ings

Com

men

tsQ

ualit

ya

Epid

emio

logy

/Pre

vlae

nce/

Des

crip

tion:

Com

paris

on G

roup

Fitc

henb

erg

et a

l. 20

02

US

A

Type

:E

pi/P

rev/

Des

cE

stab

lish

frequ

ency

of

inso

mni

a (d

iagn

osis

us-

ing

DS

M-IV

) in

TB

I and

com

-pa

re it

with

in

som

nia

rate

s in

oth

er r

ehab

ou

tpat

ient

s

Leve

l III

Rec

ruitm

ent:

Pro

spec

-tiv

e co

hort

Con

secu

tive

OR

; Cro

ss-

sect

iona

l; C

ompa

rison

gr

oup

(Con

trols

):re

habi

litat

ion

outp

atie

nts

(sam

e #

SC

I an

d M

SK

)

TBIb

= 50

Con

trols

= 5

0M

SK

= 2

5S

CI =

25

Incl

usio

n:•

Gal

vest

on

Orie

ntat

ion

and

Am

nesi

a (G

OAT

) sc

ore

>75

• ≥

Ran

cho

Los

Am

igos

Lev

el V

IE

xclu

sion

:•

not i

n P

TA s

tate

Age

, yrs

: (P

< .0

5)TB

I: 36

.5 ±

14

.5;

SC

I: 38

.2 ±

13

.5;

MS

K: 4

7.3

± 12

.2G

ende

r:

(P<.

05)

TBI:

44%

FS

CI:

24%

FM

SK

80%

FG

CS:

sTB

I 42%

mod

TBI:

18%

mTB

I: 40

%Ti

me

sinc

e: 3

.8

± 7.

4 m

os.

PS

QI

BD

IS

leep

di

arie

s (T

BI

only

)In

som

ina

diag

nosi

s us

ing

DS

M-

IV c

riter

ia

TBI:

↓ sl

eep

qual

ity (

initi

a-tio

n pr

oble

ms

2x d

urin

g pr

oble

ms)

; ↑

slee

p du

ra-

tion

TBI:

30%

in

som

nia

diag

nosi

s (D

SM

-IV)

TBI:

↓ P

SQ

I gl

obal

sco

res

TBI:

< in

som

-ni

a ra

te th

an

cont

rols

Pre

vale

nce

of

inso

mni

a is

1/3

of

TBI p

opul

atio

nFi

rst p

aper

to u

se

form

al d

iagn

osis

of

inso

mni

a Li

mita

tions

:D

id n

ot s

tratif

y re

sults

by

seve

r-ity

, rel

iabi

lty o

f se

lf-re

port

slee

p di

arie

s

Mod

erat

e:4.

5/7

Bas

elin

e: 1

Blin

ding

: 0S

ampl

e si

ze:

0.5

Attr

ition

:1S

tand

ardi

zed

outc

omes

: 1D

escr

iptio

n: 1

Follo

w-u

p: 0

Par

cell

et

al. 2

006

Aus

tralia

Type

:E

pi/P

rev/

Des

cE

xplo

re

subj

ect s

leep

re

ports

from

pe

rson

s w

ith

TBI

Leve

l III

Rec

ruitm

ent:

Con

secu

-tiv

e P

R (

≥ 2

wks

pos

t di

scha

rge)

Lo

ngitu

di-

nal s

urve

y de

sign

Con

trols

: gr

ener

al

com

mun

ity,

TBI =

63

Con

trols

= 6

3In

clus

ion:

• 16

-65

yrs

• Fa

cilit

y in

Eng

lish

• N

o tra

nsm

erid

ian

trave

l > 1

tim

e zo

ne in

pre

viou

s 12

mos

• N

o pr

einj

ury

slee

p di

sord

er•

No

benz

odia

-

Age

, yrs

: TB

I 32

.5 ±

1.7

;C

ontro

ls: 3

0.5

± 1.

2G

ende

r:

Bot

h gr

oups

: 43

% F

GC

S: 9

.6 ±

.57

PTA

: 19.

8 ±

2.7:

use

d fo

r se

verit

ym

TBI =

8

7-da

y se

lf re

port

slee

p-w

ake

diar

y (s

leep

and

w

ake

times

, sl

eep

onse

t la

tenc

y,

frequ

ency

, an

d du

ratio

n of

noc

turn

al

awak

enin

gs

and

dayt

ime

TBI:

> sl

eep

chan

ges;

>

nigh

t-tim

e aw

aken

ings

an

d lo

nger

sl

eep

onse

t la

tenc

y; m

ore

frequ

ently

re

porte

d by

m

TBI;

↑ an

xiet

y an

d de

pres

sion

Stre

ngth

s:Fo

llow

-up

and

used

a 7

-day

di-

ary;

Con

side

red

othe

r po

tent

ial

fact

ors

impa

ctin

g sl

eep;

Li

mita

tions

: D

iffer

ence

in

time

used

to n

ote

chan

ges

(TB

I, 8

mos

; Con

trols

3

mos

)

Mod

erat

e:

4.5/

7B

asel

ine:

1B

lindi

ng: 0

Sam

ple

size

: 0.

5A

ttriti

on: 0

Sta

ndar

dize

d ou

tcom

es: 1

Des

critp

ion:

1Fo

llow

-up:

1


TAB

LE 5

(CO

NTI

NU

ED)

age

and

gend

er

mat

ched

TB

I refl

ect

on c

hang

es

sinc

e in

jury

an

d co

ntro

ls

refle

ct o

n ch

ange

s in

th

e la

st 3

m

osD

ata

colle

c-tio

n:in

itial

and

3

mos

zepi

nes

or o

ther

sl

eepi

ng m

edic

a-tio

ns•

No

prev

ious

B

I, ne

urlo

gica

l di

sord

er, o

r m

ajor

ph

ysch

iatri

c di

sord

erS

cree

ned

by

neur

opsy

chol

o-gi

st to

det

erm

ined

el

igib

ility

mod

TBI =

13

sTB

I = 2

7;vs

TBI =

14

Tim

e si

nce:

m

ean

230

days

naps

)G

ener

al

slee

p qu

es-

tionn

aire

to

eva

lu-

ate

slee

p ch

ange

s an

d qu

ality

ES

SH

AD

S

asso

ciat

ed

with

↑ r

epor

t-in

g of

sle

ep

chan

ges

Wat

son

et

al. 2

007

US

A

Type

:E

pi/P

rev/

Des

cE

valu

ate

the

prev

alen

ce o

f sl

eepi

ness

fol-

low

ing

TBI

Leve

l III

Rec

ruitm

ent:

Pro

spec

tive

coho

rtC

onse

cu-

tive

ALo

ngitu

dina

l2

com

pari-

son

grou

ps;

C1

non-

cra-

nial

trau

ma

adm

issi

ons;

C2

traum

a fre

e se

lect

ed

from

frie

nds

of T

BI

Dat

a co

llec-

tion:

1 m

o an

d 1

yr

post

inju

ry

TBI =

512

(n

= 3

46 a

t 1 m

o; n

=

410

at 1

yr)

C1

= 13

2 (n

= 1

31 a

t 1 m

o; n

=

124

at 1

yr)

C2

= 10

2 (n

= 1

01 a

t 1 m

o; n

=

88 a

t 1 y

r)In

clus

ion:

• A

ny p

erio

d of

LO

C•

PTA

≥ 1

hr

• O

ther

obj

ectiv

e ev

iden

ce o

f hea

d tra

uma

• H

ospi

taliz

atio

n**

Som

e ha

d pr

e-ex

istin

g co

nditi

ons:

pr

ior T

BI,

alco

hol

abus

e, s

igni

fican

t ps

ychi

atric

dis

orde

r

Age

, yrs

:TB

I: 30

± 1

4C

1: 3

1.4

± 13

.5C

2: 2

4.5

± 8.

1G

ende

r:TB

I: 27

% F

;C

1: 2

8% F

,C

2: 5

6% F

GC

S: ≤

10

at

adm

issi

onIn

jury

sev

erity

: tim

e fro

m in

jury

to

a c

onsi

sten

t G

CS

sco

re o

f 6Ti

me

sinc

e: 1

m

os a

nd 1

yea

r at

follo

w-u

p

Sic

knes

s Im

-pa

ct P

rofil

e (S

IP):

slee

p an

d re

st

subs

cale

co

nsis

ting

of

4 qu

estio

ns

TBI:

55%

en

dors

ed ≥

1

slee

pine

ss

item

s 1

mo

post

inju

ry v

s C

1 41

% a

nd

C2

3%TB

I 27%

en

dors

ed ≥

1

slee

pine

ss

item

s 1

yr

post

inju

ry v

s C

1 23

% a

nd

C2

1%TB

I: sl

eepi

er

than

C1

at 1

m

o bu

t not

1

yr T

BI a

re

slee

pier

par

-tic

ular

ly th

ose

with

mor

e se

-ve

re in

jurie

s;

slee

pine

ss

Stre

ngth

s:

Goo

d fo

llow

-up

Lim

itatio

ns:

Wea

k ou

tcom

e m

easu

re; n

ot s

ep-

arat

ely

valid

ated

; ju

st d

escr

iptiv

e da

ta, l

arge

attr

ition

Maj

ority

wer

e m

TBI a

s sT

BI n

ot

able

to c

ompl

ete

the

SIP

; may

lead

to

und

eres

timat

e of

the

true

slee

pi-

ness

pat

tern

in

TBI

Mod

erat

e:

4.5/

7B

asel

ine:

1B

lindi

ng: 0

Sam

ple

size

: 1A

ttriti

on: 0

Sta

ndar

dize

d ou

tcom

es: 0

.5D

escr

itpio

n: 1

Follo

w-u

p: 1


TAB

LE 5

(CO

NTI

NU

ED)

↓ in

TB

I bu

t abo

ut

25%

rem

ain

slee

py a

fter

1 yr

(al

so tr

ue

for

C1)

Bee

tar

et

al. 1

996

US

A

Type

:E

pi/P

rev/

Des

cC

ompa

re th

e in

cide

nce

of

slee

p an

d pa

in

in T

BI a

nd

com

para

tive

neur

olog

ic

popu

latio

ns

Leve

l III

Rec

ruitm

ent:

OR

(neu

rops

y-ch

olog

y se

rvic

e)

Cro

ss-s

ec-

tiona

l C

ase-

cont

rol

stud

y C

onse

cutiv

e ch

art r

evie

wC

ompa

rison

gr

oup:

gene

ral

neur

olog

ic

patie

nts

refe

rred

for

neur

opsy

-ch

olog

ical

as

sess

men

t

mTB

I = 1

27m

od to

sTB

I = 7

5C

ontro

ls =

123

Use

d M

ild T

BI

Com

mitt

ee o

f the

H

ead

Inju

ry In

ter-

disc

iplin

ary

Spe

cial

In

tere

st G

roup

of

the

Am

eric

an C

on-

gres

s of

Reh

abili

ta-

tion

Med

icin

e

Age

, yrs

:TB

I: 36

.1 ±

11

.7;

Con

trols

: 43.

3 ±

13.6

Gen

der:

TBI:

32%

F;

Con

trols

: 42%

FG

CS:

NI

Tim

e Si

nce:

TBI:

23.9

± 2

.2

mos

(in

jury

); C

ontro

ls: 3

5.5

± 23

.3 m

os

(sym

ptom

)

Cha

rt re

view

Pat

ient

re-

port

of s

leep

an

d or

pai

n pr

oble

ms

Sle

ep

mai

nten

ance

m

ost c

om-

mon

sle

ep

prob

lem

; TB

I: 55

%

had

inso

mni

a co

mpl

aint

s vs

Con

trols

<3

3%; T

BI:

> in

som

nia

and

pain

com

-pl

aint

s (2

.5 x

m

ore)

; pre

s-en

ce o

f pai

n ↑

inso

mni

a re

port

2 x;

TB

I with

out

pain

: > s

leep

co

mpl

aint

s th

an C

ontro

ls

and

mTB

I >

mod

/sTB

I; m

TBI >

pai

n th

an m

od/

sTB

I; C

om-

plai

nts

↓ w

ith

> tim

e si

nce

inju

ry

Stre

ngth

s:O

ne o

f ear

liest

st

udie

s to

doc

u-m

ent i

ncid

ence

Lim

itatio

ns:

Ret

rosp

ectiv

e an

d su

bjec

tive

data

co

llect

ion

Mod

erat

e:

4/7

Bas

elin

e: 1

Blin

ding

: 0S

ampl

e si

ze: 1

Attr

ition

: 1S

tand

ardi

zed

outc

omes

: 0D

escr

itpio

n: 1

Follo

w-u

p: 0

Oue

llet &

M

orin

200

6Ty

pe:

Epi

/Pre

v/D

esc:

Leve

l III

Rec

ruit-

TBI =

14

m to

sTB

IC

ontro

ls =

14

Age

, yrs

: TB

I: 30

.4 ±

9.7

Dia

gnos

tic

Inte

rvie

w fo

rTB

I: P

SG

sh

owed

71%

Res

ults

sim

ilar

to

thos

e w

ith p

rimar

yM

oder

ate:

4/

7


TAB

LE 5

(CO

NTI

NU

ED)

Can

ada

Com

pare

su

bjec

tive

and

obje

ctiv

e m

ea-

sure

s of

sle

ep

in T

BI

LC R

eha-

bilit

atio

n ce

nter

s an

d ad

ver-

tisem

ents

se

nt to

TB

I as

soci

atio

ns

and

sup-

port

grou

ps

mai

ling

lists

); C

ross

-se

ctio

nal;

Com

pari-

sion

gro

up:

heal

thy

good

sle

ep-

ers

mat

ched

on

age

and

ge

nder

to

TBI;

recr

uit-

ed th

roug

h ad

verti

se-

men

ts a

nd

acqu

ain-

tanc

es o

f th

e au

thor

s;

2 ni

ghts

of

PS

G

Incl

usio

n:•

18-5

0 yr

s•

TBI ≤

last

5 y

rs•

Sta

ble

phys

ical

he

alth

• N

o lo

nger

an

inpa

tient

• H

ave

an in

som

-ni

a sy

ndro

me

Exc

lusi

on:

• M

ajor

unt

reat

ed

or u

nsta

ble

co-

mor

bid

cond

ition

• S

leep

diff

icul

ties

befo

re T

BI

• E

vide

nce

of

anot

her

slee

p di

sord

er•

Sig

nific

ant p

ain

• U

nabl

e to

com

-pl

ete

the

ques

-tio

nnai

res

Con

trols

: 30.

0 ±

10.0

Gen

der:

56%

F

GC

S: 4

mild

, 1

mild

-mod

, 4

mod

, 3 m

od-

sev,

2 s

ev (

cri-

teria

in a

rticl

e)Ti

me

sinc

e:21

mos

Inso

mia

S

leep

dia

ryP

SG

Sle

ep s

ur-

vey

ISS

MFI

BD

IB

eck

Anx

iety

In

vent

ory

with

inso

mni

a La

rge

effe

ct

size

s fo

r to

tal

slee

p tim

e w

ake

afte

r sl

eep

onse

t, aw

aken

ings

lo

nger

than

5

min

, and

sl

eep

ef-

ficie

ncy

TBI:

> po

rtion

of

sta

ge 1

sl

eep

Whe

n th

ose

usin

g ps

ycho

-tro

pic

med

s ex

clud

ed, T

BI

had

> aw

ak-

enin

gs la

stin

g lo

nger

than

5

min

and

a

shor

t RE

M

slee

p on

set

late

ncy

inso

mia

or

inso

mni

a-re

late

d to

dep

ress

ion

Lim

itatio

ns:

Sm

all s

ampl

e si

ze a

nd a

lot

of v

aria

bilit

y in

TB

I gro

up a

nd

pres

ence

of s

leep

pr

oble

ms

in C

on-

trol g

roup

Mul

tiple

com

pari-

son

and

lack

of

stat

istic

al p

ower

Blin

ding

: 0S

ampl

e si

ze: 0

Attr

ition

: 1

Sta

ndar

dize

d ou

tcom

es: 1

Des

crip

tion:

1Fo

llow

-up:

0

Par

cell

et

al. 2

008

Aus

tralia

Type

:E

pi/P

rev/

Des

cE

valu

ate

chan

ges

in

slee

p qu

ality

an

d ch

ange

s in

obj

ectiv

e re

cord

ed s

leep

pa

ram

eter

s af

ter T

BI a

nd

Leve

l III

Rec

ruitm

ent:

AI (

mod

to

sTB

I);

Cro

ss-

sect

iona

l; S

urve

y an

d la

b-ba

sed

noct

urna

l P

SG

;

TBI =

10

Con

trols

= 1

0In

clus

ion:

• 16

-65

yrs

• E

nglis

h fa

cilit

y•

Nor

mal

bod

y m

ass

inde

x•

No

trans

mer

idia

n tra

vel a

cros

s >

1 tim

e zo

ne in

Age

, yrs

:TB

I: 38

.8 ±

4.3

;C

ontro

ls: 3

7.8

± 44

.4G

ende

r:40

% F

GC

S: 1

0.9

± 1.

040

% m

od T

BI;

40%

sTB

I; 20

%

Dem

o-gr

aphi

c an

d m

edic

atio

n de

tails

at

recr

uitm

ent

and

inju

ry

deta

ils fr

om

med

ical

re

cord

s;

Sle

ep-w

ake

TBI:

poor

er

slee

p qu

ality

an

d hi

gher

le

vels

of

anxi

ety

and

depr

essi

on;

TBI:

↑ in

de

ep (

slow

w

ave)

sle

ep,

↓ in

RE

M, >

Doc

umen

ts o

f im

porta

nce

of

subj

ectiv

e re

port

as c

entra

l to

diag

-no

sis

and

treat

-m

ent b

ut n

eed

to

cons

ider

obj

ectiv

e da

ta a

s w

ell

Pro

vide

s m

any

impo

rtant

pra

ctic

e

Mod

erat

e:

4/7

Bas

elin

e: 1

Blin

ding

: 0S

ampl

e si

ze: 0

Attr

ition

: 1S

tand

ardi

zed

outc

omes

: 1D

escr

itpio

n: 1

Follo

w-u

p: 0


TAB

LE 5

(CO

NTI

NU

ED)

inve

stig

ate

the

rela

tions

hip

betw

een

moo

d st

ate

and

inju

ry c

hara

c-te

ristic

s

Com

paris

on

grou

p ag

e-

and

gend

er-

mat

ched

co

ntro

ls

in g

ener

al

com

mun

ity;

PS

G o

ver

2 ni

ghts

with

in

1 w

k; e

valu

-at

ed in

TB

I an

d co

ntro

l pa

irs

prev

ious

12

mos

• N

o pr

einj

ury

slee

p di

sord

er•

No

benz

odia

z-ep

ines

or

othe

r sl

eepi

ng m

edic

a-tio

ns•

No

prev

ious

B

I, ne

urol

ogi-

cal d

isor

der,

or

maj

or p

sych

iatri

c di

sord

er

vsTB

I; P

TA

16.4

4 ±

4.3

days

Tim

e si

nce:

51

6 ±

124

days

diar

y fo

r 7

days

; ES

S

Sle

ep q

ualit

y qu

estio

n-na

ire (

TBI

chan

ges

sinc

e in

jury

an

d C

ontro

ls

chan

ges

in

last

3 m

os);

PS

QI;

Noc

-tu

rnal

PS

G;

HA

DS

> ni

ght-t

ime

awak

en-

ings

; TB

I: >

anxi

ety

and

depr

es-

sion

, whi

ch

co-v

arie

d w

ith th

e ob

-se

rved

sle

ep

chan

ges

poin

ts; i

s a

stro

ng

cont

ribut

or to

clin

i-ca

l and

res

earc

h lit

erat

ure

Sch

reib

er

et a

l. 20

08

Isra

el

Type

:E

pi/P

rev/

Des

c:Id

entif

y th

e ch

arac

teris

-tic

s of

sle

ep

dist

urba

nce

in a

dults

afte

r m

TBI

Leve

l III

Rec

ruitm

ent:

Ret

ro-

spec

tive;

C

onse

cutiv

e O

R (

whe

re

slee

p la

b da

ta a

vail-

able

); C

ross

-se

ctio

nal

Com

pari-

son

grou

p:

mat

ched

an

d re

ferr

ed

for

slee

p ev

alua

tion

as p

art o

f th

e ro

u-tin

e pr

e-em

ploy

men

t as

sess

men

tTB

I 2 n

ight

s P

SG

(no

t on

a w

eeke

nd);

Con

trols

mTB

I = 2

6C

ontro

ls =

20

(app

aren

tly h

ealth

y)In

clus

ion:

• 21

-50

yrs

• D

ocum

ente

d (≥

1

yr s

ince

mTB

I)•

Nor

mal

bra

in C

T,

MR

I•

Neg

ativ

e E

EG

• N

o pa

st h

isto

ry o

f C

NS

pat

holo

gy•

No

pre-

mor

bid

or p

rese

nt m

ajor

ps

ychi

atric

dia

g-no

sis

• N

o sl

eep

apne

a or

res

tless

leg

synd

rom

e

Age

, yrs

:TB

I: 31

.6 ±

8.8

Con

trols

: 33.

8 ±

7.8

Gen

der:

NI

GC

S: N

ITi

me

sinc

e: 1

2 m

os to

21

yrs

PS

GM

SLT

TBI:

slee

p pa

ttern

s di

s-tu

rbed

; sle

ep

arch

itect

ure

alte

red;

<

RE

M s

leep

sc

ores

and

>

NR

EM

sco

res

TBI:

MS

LTdo

cum

ente

d si

gnifi

cant

E

DS

Impo

rtant

to

iden

tify

thos

e w

ho

need

trea

tmen

t for

sl

eep

prob

lem

sLi

mita

tions

:C

ontro

ls w

ere

not a

ll w

ithin

the

norm

al v

alue

sP

ossi

ble

issu

es o

f re

call

bias

Wid

e ra

nge

of

time

post

inju

ryD

iffer

ence

in d

ata

colle

ctio

n st

rate

gy

betw

een

the

2 gr

oups

Mod

erat

e:

4/7

Bas

elin

e: 1

Blin

ding

: 0S

ampl

e si

ze: 0

Attr

ition

: 1S

tand

ardi

zed

outc

omes

: 1D

escr

itpio

n: 1

Follo

w-u

p: 0


TAB

LE 5

(CO

NTI

NU

ED)

only

1 n

ight

M

SLT

on

day

betw

een

the

2 ni

ghts

Will

iam

s et

al.

2008

C

anad

a

Type

:E

pi/P

rev/

Des

cC

hara

cter

ize

the

exte

nt a

nd

natu

re o

f dis

-ru

pted

sle

ep

in in

divi

dual

s w

ith lo

ng-

term

sle

ep

com

plai

nts

subs

eque

nt

to m

TBI (

i.e.,

spor

t-rel

ated

co

ncus

sion

) To

det

erm

ine

whe

ther

sle

ep

dist

urba

nces

in

mTB

I are

m

ore

char

-ac

teris

tic o

f ps

ycho

logi

cal,

psyc

hiat

ric,

or id

iopa

thic

in

som

nia

Leve

l III

Rec

ruitm

ent:

LC (

univ

er-

sity

set

ting)

Cro

ss-s

ec-

tiona

l C

ompa

risio

n gr

oup

Face

-to-fa

ce

inte

rvie

w

and

labo

ra-

tory

PS

G

TBI =

9C

ontro

ls =

9In

clus

ion:

• 18

-26

yrs

TBI:

• B

etw

een

6 m

os

and

6 yr

s po

st-

inju

ry

• S

ympt

oms

of

Pos

t Con

cuss

ion

Syn

drom

e (P

CS

) at

the

time

of

inju

ry•

Cle

arly

dis

tin-

guis

h be

twee

n sl

eep

patte

rns

befo

re a

nd a

fter

inju

ry•

Sle

ep d

iffic

ultie

s w

ithin

1 m

o of

in

jury

• S

leep

com

plai

nts

char

acte

rized

by

slee

p on

set o

f >

30 m

in o

n ≥

4 or

da

ys in

a w

eek

Con

trols

:•

No

prev

ious

BI

• N

o sl

eep

diffi

cul-

ties

Age

, yrs

:TB

I: 21

.4 ±

2.4

Con

trols

: 20.

7 ±

2.1

Gen

der:

TBI:

33%

F;

Con

trols

: 56%

FG

CS:

mild

ra

nge;

LO

C fo

r ≤

5 m

inTi

me

sinc

e:

TBI

27.8

± 1

5.5

mos

Per

sona

lity

Ass

essm

ent

Inve

ntor

y (P

AI):

de-

pres

sion

and

an

xiet

y B

rock

A

dapt

ive

Func

tion-

ing

Que

s-tio

nnai

re

(BA

FQ)

PS

QI

Sle

ep D

isor

-de

rsQ

uest

ion-

naire

(S

DQ

)B

rock

sle

ep

and

inso

m-

nia

ques

tion-

naire

Sle

ep lo

g fo

r 2

wks

PS

G fo

r 3

cons

ecut

ive

nigh

tsP

ower

spe

c-tra

l (FF

T)

anal

ysis

of

the

slee

p on

set p

erio

d

TBI:

long

-te

rm tr

oubl

e w

ith in

itiat

ing/

mai

ntai

ning

sl

eep

with

at

tent

ion

and

mem

ory

and

affe

ctiv

e (d

epre

ssio

n an

d an

xiet

y)

abno

rmal

ities

; si

gnifi

cant

di

ffere

nce

show

n in

PA

I, B

AFQ

, PS

QI

TBI:

4%

less

effi

cien

t sl

eep,

sho

rter

RE

M o

nset

la

tenc

ies,

lo

nger

sle

ep

onse

t lat

en-

cies

(va

ri-ab

ility

with

in

sam

ple)

; FFT

re

veal

ed

grea

ter

intra

-sub

ject

va

riabi

lity

in

sigm

a, th

eta,

an

d de

lta

pow

er d

urin

g sl

eep

onse

t TB

I diff

eren

t

Sle

ep d

istu

rban

c-es

can

per

sist

w

ell a

fter

inju

ry;

Stre

ngth

s: V

ery

thor

ough

stu

dyLi

mita

tions

:S

mal

l sam

ple,

sa

mpl

e of

con

-ve

nien

ce (

stu-

dent

vol

unte

ers)

; C

onfir

mat

ion

of

subj

ectiv

e se

lf-re

ports

with

PS

G;

Hig

hlig

hts

need

to

look

at s

port-

rela

ted

conc

ussi

on

Mod

erat

e:

4/7

Bas

elin

e: 1

Blin

ding

: 0S

ampl

e si

ze: 0

Attr

ition

:1S

tand

ardi

zed

outc

omes

: 1D

escr

itpio

n: 1

Follo

w-u

p: 0


TAB

LE 5

(CO

NTI

NU

ED)

from

Con

trols

bu

t not

eas

l-ity

cla

ssifi

ed

into

exi

stin

g in

som

nia

subt

ypes

Gos

selin

et

al.

2009

C

anad

a

Type

:E

pi/P

rev/

Des

cIn

vest

igat

e th

e ef

fect

s of

sp

ort-r

elat

ed

conc

ussi

on o

n su

bjec

tive

and

obje

ctiv

e sl

eep

qual

ity

Leve

l III

Rec

ruitm

ent:

LC (

inde

-pe

nden

t of

the

natu

re

of r

epor

ted

sym

ptom

s)C

ross

-sec

-tio

nal

Use

d co

ncus

sion

di

agno

stic

cr

iteria

Com

paris

on

grou

p:N

o hi

stor

y of

co

ncus

sion

; m

atch

ed o

n ag

e, g

ende

r, ed

ucat

ion,

an

d ag

e st

arte

d pl

ay-

ing

the

spor

tP

SG

on

2 co

nsec

utiv

e ni

ghts

in th

e la

b

AB

I = 1

0C

ontro

ls =

11

Incl

usio

n:•

AB

I: hi

stor

y of

at

leas

t 2 c

oncu

s-si

ons

Exc

lusi

on:

• P

rese

nce

of

neur

olog

ical

or

psyc

hiat

ric d

is-

ease

s•

Ext

rem

ely

early

or

late

hab

itual

be

d tim

es•

Use

of d

rugs

kn

own

to a

ffect

sl

eep

or d

aytim

e sl

eepi

ness

• W

ork

the

nigh

t sh

ift•

Trav

el to

ano

ther

tim

e zo

ne in

last

2

mos

Age

, yrs

:A

BI:

24.3

± 6

.1

yrs;

Con

trols

: 22.

6 ±

2.4

Gen

der:

AB

I: 30

% F

Con

trols

: 34%

FG

CS:

AB

I all

13-1

5#

conc

ussi

ons:

4.

6 ±

2.1

with

at

leas

t 1 in

last

yr

Tim

e si

nce:

NI

PS

GQ

EE

Q: a

s-se

ssm

ent

of 1

0-m

in

perio

d of

w

akef

ul-

ness

30-

min

af

ter

slee

p of

fset

; Pos

t C

oncu

ssio

n S

ymp-

tom

Sca

le

(PC

SS

); P

SQ

I; E

SS

; B

DI;

Loca

lly

deve

lope

d qu

estio

n-na

ire o

n sl

eep

qual

-ity

; Cog

S

port

com

-pu

ter

bat-

tery

: sho

rt ne

urpy

scho

l-og

y ev

alua

-tio

n ad

apte

d fro

m N

FL

batte

ry

AB

I: >

sym

ptom

s,

wor

se s

leep

qu

ality

; >

delta

act

ivity

an

d <

alph

a ac

tivity

dur

ing

wak

eful

ness

; C

oncu

ssio

n se

ems

to b

e as

soci

ated

w

ith a

wak

e-fu

lnes

s pr

ob-

lem

, rat

her

than

sle

ep

dist

urba

nce;

A

thle

tes

with

wor

se

slee

p qu

ality

(P

SQ

I) an

d sy

mpt

oms

(PC

SS

) >

rela

tive

delta

po

wer

dur

ing

dayt

ime;

AB

I lo

wer

PS

QI

asso

ci-

ated

with

↓ in

R

EM

sle

ep

effic

ienc

y P

SQ

I and

P

CS

S c

or-

Dis

crep

ancy

be

twee

n su

bjec

-tiv

e an

d ob

jec-

tive

findi

ngs;

not

ex

plai

ned

by

depr

essi

on n

or

hype

raro

usal

Lim

itatio

ns:

Sm

all s

ampl

e w

ith

excl

usio

ns th

e sa

mpl

e be

cam

e ev

en s

mal

ler,

how

ever

, hig

h-lig

hts

need

to

asse

ss s

leep

an

d w

akef

ulne

ss

follo

win

g sp

ort-

rela

ted

conc

ussi

onO

nly

a pi

lot s

tudy

Mod

erat

e:

4/7

Bas

elin

e: 1

Blin

ding

: 0S

ampl

e si

ze: 0

Attr

ition

: 1S

tand

ardi

zed

outc

omes

: 1D

escr

itpio

n: 1

Follo

w-u

p: 0


TAB

LE 5

(CO

NTI

NU

ED)

rela

ted;

Abs

o-lu

te s

pec-

tral p

ower

sh

owed

hig

h in

ter-

subj

ect

varia

tion

in

AB

I; th

eref

ore

anal

yze

on

the

rela

-tiv

e sp

ectra

l po

wer

Epid

emio

logy

/Pre

vale

nce/

Des

crip

tion:

Coh

ort/S

ingl

e G

roup

Bau

man

n et

al.

2007

S

witz

erla

nd

Type

: E

pi/P

rev/

Des

cD

eter

min

e th

e fre

quen

cy

and

clin

ical

ch

arac

teris

tics

of p

osttr

au-

mat

ic S

WD

; as

sess

CS

F hy

pocr

etin

le

vels

6 m

os

afte

r TB

I and

ris

k fa

ctor

s fo

r po

sttra

umat

ic

SW

D

Leve

ll III

Rec

ruitm

ent:

Pro

spec

-tiv

e st

udy;

C

onse

cutiv

e A

; (w

ithin

4

days

of

inju

ry);

Long

itudi

nal;

Sin

gle

grou

p B

asel

ine:

labo

ra-

tory

test

s; 6

m

os: o

ther

ou

tcom

es,

subs

ampl

e re

peat

ed

labo

rato

ry

test

s

TBI =

65

(96

en-

rolle

d; 7

6 av

aila

ble

for

follo

w-u

p)In

clus

ion:

• A

cute

, firs

t eve

r TB

IE

xclu

sion

:•

Sle

ep-w

ake

or

psyc

hiat

ric d

isor

-de

rs d

iagn

osed

pr

ior

to T

BI

Age

, yrs

: 16-

72, m

ean

38 ±

16

yrs

Gen

der:

14%

FG

CS:

mea

n 10

.2,

mTB

I: 40

%m

odTB

I: 23

%sT

BI:

37%

Tim

e si

nce:

6

mos

afte

r TB

I

CT

scan

; C

SF

hypo

-cr

etin

-1 le

v-el

s; H

uman

le

ukoc

yte

antig

en

(HLA

) ty

ping

In

terv

iew

: so

cial

sta

tus

and

resi

dual

sy

mpt

oms

post

inju

ry,

incl

udin

g sl

eep

habi

ts;

Neu

rolo

gica

l ex

amin

ia-

tion

usin

g a

stan

dard

pr

otoc

ol,

with

the

Fol-

stei

n M

MS

EB

DI;

Med

ical

O

utco

mes

S

tudy

For

m

- 36

; ES

S;

SW

D a

re

com

mon

afte

r TB

I, E

DS

/fa-

tigue

= 5

5%;

Pos

ttrau

mat

ic

hype

rsom

nia

= 22

%; L

ow

hypo

cret

in

leve

ls fo

und

in 1

9% 6

m

os a

fter

inju

ry v

s 93

%

in fi

rst d

ays

afte

r in

jury

; 6

mo

hypo

-cr

etin

leve

ls

wer

e lo

wer

in

thos

e w

ith

post

trau-

mat

ic S

WD

; N

o ot

her

sign

ifica

nt

rela

tions

hips

w

ere

foun

d;

Hyp

ocre

tin

Stre

ngth

s:Ve

ry th

orou

ghLi

mita

tions

:A

ttriti

on w

as la

rge

and

not a

ll av

ail-

able

for

labo

rato

ry

follo

w-u

p

Hig

h:

5/7

Bas

elin

e: 0

.5B

lindi

ng: 0

Sam

ple

size

: 1A

ttriti

on: 0

.5S

tand

ardi

zed

outc

omes

: 1D

escr

itpio

n: 1

Follo

w-u

p: 1


TAB

LE 5

(CO

NTI

NU

ED)

Sle

ep A

pnea

S

cale

of t

he

Sle

ep D

isor

-de

rs Q

ues-

tionn

aire

; U

llanl

inna

N

arco

leps

y S

cale

; PS

G;

MS

LT; A

c-tig

rapy

syst

em p

os-

sibl

e co

ntrib

-ut

or to

pat

ho-

phys

iolo

gy o

f po

sttra

umat

ic

SW

D

Cas

triot

ta

et a

l. 20

07

US

A

Type

:E

pi/P

rev/

Des

cD

eter

min

e th

e pr

eval

ence

an

d co

nse-

quen

ces

of

slee

pine

ss a

nd

slee

p di

sor-

ders

afte

r TB

IE

xplo

re th

e re

latio

nshi

p be

twee

n pr

esen

ce o

f sl

eep

diso

r-de

rs, i

njur

y ch

arac

teris

cs

and

subj

ect

varia

bles

Leve

l IV

AR

ecru

itmen

t: P

rosp

ectiv

e st

udy

AI (

3 ce

nter

s);

Sin

gle

grou

p;

Cro

ss-s

ec-

tiona

l

TBI =

87

Incl

usio

n:•

>18

yrs

old

• ≥

3 m

os p

ost-

inju

ryE

xclu

sion

:•

Pre

senc

e of

ci

rcad

ian

rhyt

hm

diso

rder

• U

se o

f sed

atin

g m

edic

atio

ns•

Una

ble

to g

ive

info

rmed

con

sent

Age

, yrs

: 38.

3 ±

15.1

Gen

der:

28%

FG

CS:

NI

Sev

erity

: mild

8%

, mod

erat

e 17

5, m

oder

ate-

seve

re 6

%,

seve

re 3

3%,

unkn

own

36%

Tim

e si

nce:

64

.3 ±

117

.7

mos

PS

G; M

SLT

; E

SS

; PV

T;

PO

MS

; FO

SQ

23%

OSA

; 46

% a

bnor

-m

al s

leep

st

udie

s; 1

1%

post

traum

atic

hy

pers

omni

a;

6% n

arco

-le

psy;

7%

pe

riodi

c lim

b m

ovem

ents

; 25

% w

ith o

b-je

ctiv

e ED

S;

No

corre

latio

n be

twee

n ES

S

and

MSL

T (r

= 0.

10)

; No

diffe

renc

es in

de

mog

raph

-ic

s an

d in

jury

ch

arac

teris

-tic

s be

twee

n sl

eepy

(SI

) an

d no

n-sl

eep

(NSI

) Su

bjec

ts:

BMI:

SI>N

SI;

PVT:

SI<

NSI

; FO

SQ: S

I

Stre

ngth

s:Fi

rst s

tudy

to

show

that

a s

leep

di

sord

er a

dds

an

addi

tiona

l cog

ni-

tive

burd

enLi

mita

tions

:N

o ob

ject

ive

mea

sure

of d

aily

fu

nctio

ning

Hig

h:

5/7

Bas

elin

e: 1

Blin

ding

: 0S

ampl

e si

ze: 1

Attr

ition

: 1S

tand

ardi

zed

outc

omes

: 1D

escr

itpio

n: 1

Follo

w-u

p: 0


TAB

LE 5

(CO

NTI

NU

ED)

bette

r N

SI

PO

MS

: no

diffe

renc

es

Fitc

henb

erg

et a

l. 20

00

US

A

Type

: E

pi/P

rev/

Des

cR

elat

ion-

ship

bet

wee

n in

som

nia

and

dem

ogra

phci

s,

inju

ry, a

nd

psyc

holo

gica

l va

riabl

es in

po

st-a

cute

TB

I

Leve

l IV

AR

ecru

itmen

t:P

ospe

c-tiv

e st

udy;

C

onse

cutiv

e O

R; C

ross

-se

ctio

nal;

Sin

gle

grou

p

TBI =

91

Incl

usio

n:•

Dia

gnos

is o

f TB

I on

basi

s of

ex

amin

iatio

n•

Rec

over

y to

pos

t-ac

ute

phas

e•

Med

ical

det

erm

i-na

tion

of n

eed

for

outp

atie

nt n

euro

-re

habi

litat

ion

Exc

lusi

on•

In s

tate

of P

TA•

Rat

ed b

elow

Le

vel V

I on

Leve

ls o

f Cog

ni-

tive

Func

tioni

ng

Sca

le (

LCS

F)•

Usi

ng s

leep

m

edic

atio

n

Age

, yrs

:33

.8 ±

14.

5G

ende

r:41

% F

GC

S:13

-15:

33%

9-12

: 21%

3-8:

46%

Tim

e si

nce:

m

ean

3.3

mos

PS

QI;

BD

I; G

OAT

; LC

FS

Stro

ng

rela

tions

hip

betw

een

inso

mni

a an

d de

pres

-si

on; P

ain

dist

urba

nce

of s

leep

was

si

gnifi

cant

ly

asso

ciat

ed

with

inso

m-

nia;

BD

I: 68

%

depr

esse

d w

ere

suf-

fere

ing

from

in

som

nia

Stre

ngth

s:In

dent

ifies

a

deve

lopm

enta

l pa

ttern

that

may

pr

ogre

ss fr

om a

ph

ysio

logi

cal b

asis

to

a s

econ

dary

di

sord

er a

ssoc

i-at

ed w

ith d

epre

s-si

on

Mod

erat

e:4.

5/7

Bas

elin

e: 0

.5B

lindi

ng: 0

Sam

ple

size

: 1A

ttriti

on: 1

Sta

ndar

dize

d ou

tcom

es: 1

Des

critp

ion:

1Fo

llow

-up:

0

Oue

llet,

Bea

ulie

u-B

onne

au &

M

orin

200

6 C

anad

a

Type

:E

pi/P

rev/

Des

c;

To d

eter

min

e th

e fre

quen

cy

of in

som

nia

acco

rdin

g to

D

SM

-IV a

nd

Inte

rnat

iona

l C

lass

ifica

tion

of S

leep

Dis

-or

ders

(IC

SD

) cr

iteria

. To

de-

scrib

e cl

inic

al

and

soci

ode-

Leve

l IV

AR

ecru

itmen

t:LC

(Fr

ench

-sp

eaki

ng

from

re

habi

lita-

tion

cent

er

arch

ives

and

on

mai

ling

lists

of T

BI

asso

ciat

ions

in

Que

bec)

; M

aile

d qu

es-

tionn

aire

TBI =

452

Incl

usio

n:•

≥ 16

yrs

• TB

I: m

inor

, mild

, m

oder

ate

or

seve

re

Age

, yrs

:40

.2 ±

13.

1G

ende

r: 3

5% F

GC

S: N

IS

ever

ity:

59.9

% s

TBI

23.3

% m

odTB

I13

.7%

mTB

I(c

riter

ia in

clud

es

GC

S)

Tim

e si

nce:

mea

n 7.

8 yr

s

Que

stio

n-na

ire b

ookl

et

entit

led

“Qua

lity

of s

leep

an

d le

vel

of fa

tigue

fo

llow

ing

a TB

I”: L

ocal

ly

deve

lope

d qu

estio

nsIS

SM

ulti-

dim

en-

sion

al

Inso

mni

a pr

eval

ent

afte

r TB

I, 64

.3%

with

sl

eep

onse

t in

som

nia,

76

.6%

w

ith s

leep

m

aint

enan

ce

inso

mni

a;

Pre

dict

ors

of in

som

nia:

le

sser

sev

er-

ity o

f BI,

Lim

tatio

ns:

Onl

y su

bjec

tive

data

U

nder

resp

rese

nta-

tion

of m

TBI

Thos

e w

ith in

-so

mni

a pr

oble

ms

may

hav

e be

en

mor

e m

otiv

ated

to

resp

ond

Not

abl

e to

de-

term

ine

inso

mni

a su

btyp

es

Mod

erat

e:4.

5/7

Bas

elin

e: 1

Blin

ding

: 0S

ampl

e si

ze: 1

Attr

ition

: 1S

tand

ardi

zed

outc

omes

: 0.5

Des

critp

ion:

1Fo

llow

-up:

0


TAB

LE 5

(CO

NTI

NU

ED)

mog

raph

ic

char

acte

ristic

s of

inso

mni

a in

TB

I

Cro

ss-s

ec-

tiona

l; S

in-

gle

grou

p;

Sig

nific

ant

othe

rs

com

plet

ed a

br

ief p

aral

lel

eval

uatio

n

fatig

ue

inve

ntor

y In

-di

ce d

e dé

-tre

sse

psy-

chol

ogiq

ue

de

L’E

nquê

te

San

té Q

ué-

bec

(Fre

nch

adap

tatio

n of

Psy

chia

t-ric

Sym

p-to

m In

dex)

S

igni

fican

t O

ther

’s

Eva

luat

ion

Que

stio

n-na

ire (

si-

gific

ant o

ther

ve

rsio

ns

of IS

S a

nd

othe

r ab

ove

ques

tions

)

Rao

et a

l. 20

08 U

SA

Type

:E

pi/P

rev/

Des

cTo

ass

ess

the

prev

alen

ce o

f an

d ris

k fa

c-to

rs fo

r sl

eep

dist

urba

nces

in

acut

e po

sttra

u-m

atic

TB

I

Leve

l III

Rec

ruitm

ent:

PAC

(w

ithin

3

mos

of

traum

a);

Long

itudi

nal

obse

rva-

tiona

l stu

dy;

Sin

gle

grou

p; D

ata

colle

ctio

n:

1) w

ithin

2

wks

of i

njur

y to

ass

ess

hist

ory

of

TBI =

54

Incl

usio

n:•

≥ 18

yrs

• A

ble

to p

rovi

de

info

rmed

con

sent

• A

dmitt

ed to

hos

-pi

tal w

ith e

xper

i-en

ce o

f LO

C•

GC

S ≤

15

• P

ositi

ve C

T fin

d-in

gsE

xclu

sion

:•

Prio

r TB

I•

Ope

n he

ad in

jury

• H

isto

ry o

f oth

er

Age

, yrs

:43

.2 ±

17.

7G

ende

r:41

% F

GC

S:m

ean

12.5

±

3.6;

65%

mild

, 11%

m

oder

ate,

and

19

% s

ever

eTi

me

sinc

e:≥

3 m

os

Stru

ctur

ed

Clin

ical

In

terv

iew

for

DS

M-IV

Axi

s 1

diso

rder

s (S

CID

-IV

); G

en-

eral

Med

i-ca

l Hea

lth

Rat

ing

Sca

le

(GM

HR

); M

OS

; Sel

f-re

port

for

anxi

ety

and

de

pres

sion

Wor

se o

n m

ost s

leep

m

easu

res

afte

r TB

I co

mpa

red

to b

efor

e TB

I; A

nxi-

ety

diso

rder

se

cond

ary

to

TBI w

as m

ost

cons

iste

nt

sign

ifica

nt

risk

fact

or to

be

ass

ocia

ted

with

wor

sen-

Stre

ngth

s:A

sses

s sl

eep

prob

lem

s in

the

acut

e pe

riod;

P

artic

ipan

ts h

ad a

ra

nge

of s

ever

ities

Lim

itatio

ns:

Sub

ject

ive

data

an

d re

call

bias

m

ight

be

an is

sue

Lack

of i

nfo

on

othe

r po

tent

ial

influ

enci

ng fa

ctor

s (p

ain,

med

ical

pr

oble

ms

and

Mod

erat

e:4.

5/7

Bas

elin

e: 0

.5B

lindi

ng: 0

Sam

ple

size

: 0.

5A

ttriti

on: 1

Sta

ndar

dize

d ou

tcom

es: 1

Des

critp

ion:

1Fo

llow

-up:

0.5


TAB

LE 5

(CO

NTI

NU

ED)

psyc

hiat

ric

and

slee

p pr

oble

ms

2) w

ithin

1-

3 m

os o

f in

jury

; for

so

me

both

at

the

sam

e tim

e

type

of i

llnes

sin

g sl

eep

stat

usm

edic

atio

ns

Clin

chot

et

al. 1

998

US

A

Type

:E

pi/P

rev/

Des

cD

efine

and

co

rrel

ate

the

inci

denc

e an

d ty

pe o

f sle

ep

dist

urba

nces

th

at o

ccur

afte

r B

I

Leve

l VR

ecru

itmen

t:P

rosp

ectiv

e st

udy

Con

secu

tive

AI

Sin

gle

grou

pLo

ngitu

dina

lB

asel

ine

and

1 yr

fo

llow

-up

post

dis

-ch

arge

via

te

leph

one

inte

rvie

w

TBI =

145

Incl

usio

n:•

≥ 14

yrs

with

su

stai

ned

BI

Exc

lusi

on:

• N

ot a

cute

inju

ry•

Prim

arily

the

re-

sult

of a

nore

xia

Age

, yrs

:31 G

ende

r:23

% F

GC

S:

Med

ian

= 4

Tim

e si

nce:

m

ean

20 d

ays

Dire

ct o

bser

-va

tion;

Med

i-ca

l rec

ord

extra

ctio

ns;

Agi

tate

d B

ehav

iour

S

cale

; FIM

; W

echs

ler

Mem

ory

Sca

le;

Hal

stea

d R

eita

n

Neu

rops

y-ch

olog

ical

B

atte

ry;

Follo

w-u

p in

terv

iew

: C

omm

unity

In

tegr

atio

n Q

uest

ion-

naire

; Sle

ep

diffi

culti

es,

med

ical

pr

oble

ms,

m

edic

atio

ns,

serv

ices

us

ed

50%

diff

icul

ty

with

sle

ep,

25%

sle

ep-

ing

mor

e an

d 45

% d

iffic

ulty

fa

lling

sle

epG

CS

≤ 7

less

lik

ely

to h

ave

prob

lem

s w

ith s

leep

th

an G

CS

>

7; 6

4%

with

sle

ep

diffi

culty

wak

-in

g up

too

early

; Sle

ep

com

plai

nts

corr

elat

ed

with

pre

senc

e of

fatig

ue, >

G

CS

, bet

ter

imm

edia

te

mem

ory,

po

sitiv

e su

bsta

nce

abus

e hi

stor

y,

> ag

e, a

nd

bein

g fe

mal

e

Lim

itatio

n:La

rge

num

ber

lost

to

follo

w-u

p; th

ose

lost

mor

e lik

ely

to

have

a h

isto

ry o

f su

bsta

nce

abus

eS

elf-r

epor

t of

slee

p di

fficu

lties

Mod

erat

e:4/

7B

asel

ine:

0.5

Blin

ding

: 0S

ampl

e si

ze: 1

Attr

ition

: 0S

tand

ardi

zed

outc

omes

: 1D

escr

itpio

n:

0.5

Follo

w-u

p: 1

Web

ster

Type

:Le

vel I

V A

TBI =

28

Age

, yrs

:O

vern

ight

S

leep

-rel

ated

Stre

ngth

s:M

oder

ate:


TAB

LE 5

(CO

NTI

NU

ED)

et a

l. 20

01U

SA

Epi

/Pre

v/D

esc

Det

erm

ine

the

occu

renc

e an

d na

ture

of

slee

p-re

late

d br

eath

ing

diso

rder

s in

ad

ults

with

TB

I

Rec

ruitm

ent:

Pro

spec

tive

obse

rvat

ion-

al s

tudy

Con

secu

tive

AI;

Sin

gle

Gro

up

Incl

usio

n:•

18-6

5 yr

s•

<3 m

os p

ostin

jury

• R

anch

o ≥

3E

xclu

sion

:•

Pre

viou

sly

docu

-m

ente

d sl

eep

apne

a, n

arco

-le

psy

or h

abitu

al

snor

ing

• Tr

ache

osto

my

• H

isto

ry o

f oth

er

prem

orbi

d ne

uro-

logi

c or

pul

mo-

nary

con

ditio

ns

34.5

Gen

der:

25%

FG

CS:

low

est

durin

g th

e fir

st

24 h

rs; 7

1%

GC

S ≤

8, 2

5%

GC

S 9

-12,

4%

G

CS

> 1

2 P

TA >

1 d

ayR

anch

o 95

%Le

vel V

I or

VII

Tim

e si

nce:

<3

mos

slee

p st

udy

usin

g po

rta-

ble

6-ch

an-

nel m

onito

r-in

g sy

stem

; ca

lcul

ated

a

resp

irato

ry

dist

urba

nce

inde

x

brea

thin

g di

sord

ers

defin

ed b

y a

resp

irato

ry

inde

x of

5

or g

reat

er

seem

to b

e co

mm

on in

ad

ult s

ubje

cts

with

TB

I; E

vide

nce

of

slee

p ap

nea

was

foun

d in

36%

of

subj

ects

Pro

spec

tive

and

cons

ecut

ive

desi

gn; N

ew in

fo

rega

rdin

g th

e oc

-cu

rren

ce o

f sle

ep

apne

a in

ear

ly

reco

very

pha

se;

Atte

mpt

to e

limi-

nate

con

foun

ding

fa

ctor

sLi

mita

tions

:Low

po

wer

; Hom

oge-

neou

s sa

mpl

e;

Not

abl

e to

col

lect

E

EG

dat

a

4/7

Bas

elin

e: 0

.5B

lindi

ng: 0

.5

Sam

ple

size

: 0A

ttriti

on: 1

Sta

ndar

dize

d ou

tcom

es: 1

Des

critp

ion:

1Fo

llow

-up:

0

Mas

el e

t al.

2001

US

ATy

pe:

Epi

/Pre

v/D

esc

Det

erm

ine

prev

alen

ce,

dem

ogra

phic

s,

and

caus

es o

f E

DS

in a

dults

w

ith B

I and

in

vest

igat

e re

latio

nshi

p be

twee

n su

bjec

tive

and

obje

ctiv

e da

ta

Leve

l III

Rec

ruitm

ent:

Con

secu

tive

AI

Cas

e se

ries

Cro

ss-s

ec-

tiona

lS

ingl

e gr

oup

2 ov

erni

ght

slee

p ev

alu-

atio

ns 1

wk

apar

t; ac

-tig

raph

y fo

r 2

wks

afte

r 2n

d P

SG

TBI =

71

Com

plet

e m

edic

al

hist

ory

and

phys

i-ca

l exa

min

atio

n;

Incl

usio

n: N

one

Exc

lusi

on: N

one

Age

, yrs

:32

± 1

1G

ende

r:38

% F

GC

S: o

nly

for

56%

: Non

hy

pers

omni

a (N

H):

6 ±

4;P

ost t

raum

atic

hy

pers

omni

a (P

TH):

7 ±

5;

Hyp

erso

mni

a w

ith a

bnor

mal

in

dice

s (H

AI):

8

± 5

Ran

cho

≥ Le

vel

IV Tim

e Si

nce:

38

± 6

0 m

os

Act

igra

phy

PS

G; M

SLT

; E

SS

; PS

QI;

Mill

on C

lini-

cal M

ultia

xial

In

vent

ory-

II (M

CM

-II);

Neu

rops

y-ch

olog

ic

batte

ry;

Dia

gnos

is o

f na

rcol

epsy

an

d po

st-

traum

atic

hy

pers

omni

a us

ing

the

ICS

D

Hyp

erso

mni

a w

as c

omm

on

with

hig

h pr

esen

ce o

f sl

eep

apne

a hy

popn

ea

synd

rom

e,

perio

dic

limb

mov

emen

ts,

and

PTH

; N

H: n

= 3

8;

PTH

: n =

21;

H

AI:

n =

12;

No

rela

tion-

ship

bet

wee

n hy

pers

omni

a gr

oups

and

G

CS

, psy

-ch

opat

holo

gy,

time

post

in-

jury

and

de

mog

raph

ic

Sug

gest

may

be

that

pat

ient

s w

ith

TBI h

ave

an in

-ab

ility

to p

erce

ive

thei

r hy

pers

omno

-le

nce

Lim

itatio

n: W

ide

rang

e of

tim

e po

stin

jury

; Sel

f-se

lect

ion

bias

Mod

erat

e:4/

7B

asel

ine:

0.5

Blin

ding

: 0S

ampl

e si

ze:

0.5

Attr

ition

: 1S

tand

ardi

zed

outc

omes

: 1D

escr

itpio

n: 1

Follo

w-u

p: 0


TAB

LE 5

(CO

NTI

NU

ED)

varia

bles

; no

sign

ifica

nt

diffe

renc

es o

f no

te o

n th

e ne

urol

ogic

te

sts;

No

sign

ifica

nt

corr

elat

ion

betw

een

ES

S

or P

SQ

I and

M

SLT

Verm

a et

al

. 200

7 U

SA

Type

:E

pi/P

rev/

Des

cD

eter

min

e th

e sp

ec-

trum

of s

leep

di

sord

ers

in

patie

nts

with

ch

roni

c TB

I an

d de

term

ine

if th

e se

verit

y of

sle

ep d

isor

-de

r is

rel

ated

to

sev

erity

of

chro

nic

TBI

Leve

l VR

ecru

itmen

t:R

etro

spec

-tiv

e LC

(r

efer

red

for

eval

uatio

n fo

r sl

eep

diso

rder

); C

ross

-sec

-tio

nal;

Sin

gle

grou

p; O

ne

over

nigh

t P

SG

TBI =

60

Incl

usio

n: N

IE

xclu

sion

: NI

Age

, yrs

: 20

-69,

mea

n 41

Gen

der:

37%

FG

CS:

NI

Sev

erity

as-

sess

ed b

y G

AF:

mild

40%

mod

erat

e 20

%se

vere

40%

Tim

e si

nce:

3 m

os to

2 y

rs

Det

aile

d m

edic

al

hist

ory,

ne

urol

ogic

al

exam

, nec

k si

ze, c

hin

size

and

po

sitio

n, ja

w

alig

nmen

t, an

d or

pha-

ryng

eal

exam

inat

ion;

P

SG

; MS

LT;

ES

S; B

DI;

Ham

ilton

A

nxie

ty

Sca

le

A fu

ll sp

ec-

trum

of s

leep

di

sord

ers

occu

r in

pa

tient

s w

ith

chro

nic

TBI

Com

plic

ated

re

latio

nshi

p w

ith s

ever

ity

of in

jury

ED

S w

as

mos

t com

-m

on p

rese

nt-

ing

sym

ptom

, w

hich

may

le

ad to

oth

er

prob

lem

s lik

e in

som

nia,

an

xiet

y an

d de

pres

sion

Stre

ngth

s:Id

entifi

es a

nd

desc

ribes

the

spec

trum

of s

leep

di

sord

ers;

Sle

ep

dist

urba

nces

can

co

mpr

omis

e re

hab

proc

ess

and

retu

rn to

wor

k;

Lim

itatio

ns:

Ret

rosp

ectiv

e;

1 ni

ght o

f PS

G;

Lack

of e

xclu

sion

of

pos

sibl

e ef

fect

s of

med

s an

d pa

in;

HA

S a

nd B

DI

not c

olle

cted

on

all p

artic

ipan

ts;

GA

F m

ay n

ot b

e be

st e

valu

atio

n of

se

verit

y

Mod

erat

e:4/

7B

asel

ine:

0.5

Blin

ding

: 0S

ampl

e si

ze:

0.5

Attr

ition

: 1S

tand

ardi

zed

outc

omes

: 1D

escr

itpio

n: 1

Follo

w-u

p: 0

Cas

triot

ta

& L

ai 2

001

US

A

Type

:E

pi/P

rev/

Des

cD

eter

min

eth

e fre

quen

cy

of s

leep

dis

or-

Leve

l III

Rec

ruitm

ent:

Pro

spec

tive

coho

rt st

udy;

Con

secu

tive

TBI =

10

Incl

usio

n:•

Sub

ject

ive

exce

s-si

ve s

leep

• ≥

18 y

rs o

r ol

der

Age

, yrs

:56

.3 ±

5.3

Gen

der:

60%

F;

GC

S: s

TBI 6

0%

Clin

ical

in

terv

iew

; E

SS

; PS

G;

MS

LT

Sle

ep

diso

rder

ed

brea

thin

g w

as fo

und

in

7 su

bjec

ts;

Stre

ngth

s:P

rosp

ectiv

eLi

mita

tions

:S

mal

l sam

ple

Mod

erat

e:3.

5/7

Bas

elin

e: 0

.5B

lindi

ng 0

Sam

ple

size

: 0


TAB

LE 5

(CO

NTI

NU

ED)

orde

rs a

ssoc

i-at

ed w

ith T

BI;

inve

stig

ate

rela

tions

hip

betw

een

post

traum

atic

sl

eep

dis-

orde

rs a

nd

pret

raum

atic

sl

eep

diso

r-de

rs

yet t

imin

g po

stin

-ju

ry u

ncle

ar-

Cro

ss-s

ec-

tiona

l; S

ingl

e gr

oup;

Use

cr

iterio

n

stan

dard

to

diag

nose

sl

eep

diso

r-de

rs; T

hose

w

ith o

vert

slee

p ap

nea

had

a 2n

d P

SG

with

tit

ratio

n of

na

sal C

PAP

• A

lert

and

ori-

ente

dE

xclu

sion

:•

Med

icat

ions

to

caus

e hy

pers

om-

nole

nce

• P

regn

ancy

• P

atie

nts

with

ca

rdio

pulm

o-na

ry a

nd r

ecen

t ab

dom

inal

and

th

orac

ic in

jurie

s

mTB

I: 40

%Ti

me

Sin

ce:

≥ 72

hrs

; 110

19

1 m

os

Ove

rt O

SA

in

5 su

bjec

tsN

acro

leps

y in

2

subj

ects

Trea

tabl

e sl

eep

diso

r-de

rs s

eem

to

be c

omm

on

in s

leep

y TB

I po

pula

tion

All

10 h

ad

treat

able

sl

eep

diso

r-de

rs; 3

had

sy

mpt

oms

of

hype

rsom

nia

befo

re in

jury

Attr

ition

: 1D

escr

itpio

n: 1

Follo

w-u

p: 0

Cha

put

2009

C

anad

a

Type

:E

pi/P

rev/

Des

cA

sses

s th

e re

latio

nshi

ps

amon

g sl

eep

com

plai

nts,

he

adac

hes,

an

d m

ood

alte

ratio

n in

m

TBI

Leve

l III

Rec

ruitm

ent:

Ret

rosp

ec-

tive

char

t re

view

; C

onse

cutiv

e E

R; S

ingl

e gr

oup;

Lo

ngitu

di-

nal;

Dat

a re

vtrie

val

at 1

0 da

ys

and

6 w

ks;

Sel

f-rep

ort:

in o

rder

to

pre

vent

se

lect

ion

bias

, tho

se

patie

nts

asse

ssed

by

self-

repo

rt

TBI =

443

At 1

0 da

ys: 8

7.8%

At 6

wee

ks: 6

4.1%

Incl

usio

n•

See

n fo

r ≥

1 vi

sit w

here

pos

t-in

jury

sym

ptom

s w

ere

not d

ue to

al

coho

l or

othe

r ill

egal

sub

stan

ce,

or m

edic

atio

n, o

r ot

her

inju

ries,

or

2° to

trea

tmen

t of

othe

r in

jury

• m

TBI d

iagn

osis

by

neu

rosu

rgeo

n ba

sed

on ta

sk

forc

e cr

iteria

Exc

lusi

on:

• ≤

16 y

rs•

Lang

uage

bar

rier

Age

, yrs

:m

ean

46.9

Gen

der:

31.8

% F

Sev

erity

: m

TBI

GC

S: s

cene

: m

ean

13.2

(10

-da

y gr

oup)

and

15

(6-

wk

grou

p)E

mer

genc

y de

partm

ent:

13.9

(10

day

gr

oup)

and

15

(6-w

k gr

oup)

, 42

% a

bnor

mal

C

T-sc

anTi

me

sinc

e:

<10

days

pos

t-tra

uma

and

<6

wks

Rev

iew

of

past

med

i-ca

l his

tory

in

clud

ing

curr

ent

med

icat

ions

, kn

own

alle

r-gi

es, a

s w

ell

as s

mok

ing,

al

coho

l and

dr

ug in

take

ha

bits

; CT

scan

s w

ere

revi

ewed

if

pres

ent;

Riv

erm

ead

post

-co

ncus

sion

sy

mpt

om

asse

ssm

ent

ques

tionn

aire

Sle

ep c

om-

plai

nt p

reva

-le

nce:

13.

3%

and

33.5

%

(sig

nific

antly

m

ore

likel

y at

6

wks

); P

res-

ence

of s

leep

co

mpl

aint

s is

si

gnifi

cant

ly

asso

ciat

ed

with

hea

d-ac

hes,

de

pres

sive

sy

mpt

oms,

an

d fe

elin

g irr

itabl

e at

10

day

s an

d 6

wks

; Ear

ly

deve

lopm

ent

of s

ympt

oms

Lim

itatio

ns:

Did

not

ass

ess

cure

nt s

tress

ors;

S

ubje

ctiv

e na

ture

of

dat

a co

llect

ed

Mod

erat

e:3.

5B

asel

ine:

0.5

Blin

ding

: 0S

ampl

e si

ze: 1

Attr

ition

: 0S

tand

ardi

zed

outc

omes

: 0.5

Des

critp

ion:

0.

5Fo

llow

-up:

1


TAB

LE 5

(CO

NTI

NU

ED)

and

hist

ory

wer

e no

t ex

clud

ed

but r

ated

for

pres

ence

or

abse

nce

of

6 ty

pes

of

slee

p co

m-

plai

nts

Kno

wn

hist

ory

of

men

tal r

etar

da-

tion,

dia

gnos

is

dem

entia

or

lear

ning

dis

-ab

ility

impa

iring

th

e co

gniti

ve

and

reas

onin

g pr

oces

s, o

r co

-ex

istin

g ps

ychi

at-

ric il

lnes

s

may

in-

crea

se r

isk

of

chro

nici

ty o

f sy

mpt

oms

See

m to

in

dica

te a

n al

tera

tion

in s

leep

ho

meo

stat

-si

s fo

llow

ing

mTB

I des

pite

ab

senc

e of

ph

ysic

al p

ain

as p

rese

nted

at

10

days

Mak

ley

2009

US

ATy

pe:

Epi

/Pre

v/D

esc

Inve

stig

ate

whe

ther

im-

prov

emen

ts in

sl

eep

effic

ien-

cy c

orre

late

w

ith d

urat

ion

of P

TA a

fter

clos

ed h

ead

inju

ry

Leve

l IV

AR

ecru

itmen

t: P

rosp

ectiv

e;

Con

secu

tive

AI;

Sin

gle

grou

p;

Long

itudi

nal;

Act

igra

phy

with

in 7

2 hr

s of

adm

is-

sion

and

for

dura

tion

of

stay

(m

in

of 7

day

s);

Dai

ly m

ea-

sure

men

t of

PTA

; cle

ared

w

hen

O-

LOG

sco

re

of ≥

25

on

2 co

ns-

cutiv

e da

ys;

Follo

w-u

p

CH

I = 1

4E

xclu

sion

:•

Kno

wn

hist

ory

of

a sl

eep

diso

rder

, an

oxic

inju

ry,

activ

e ps

ychi

atric

ill

ness

, obe

sity

, un

treat

ed th

yroi

d di

seas

e, d

egen

-er

ativ

e ne

urol

ogic

co

nditi

on, s

igni

fi-ca

nt te

trapa

resi

s or

imm

obili

ty

Age

:24

-45

yrs

Gen

der:

NI

GC

S: N

ITi

me

sinc

e: 1

5 da

ys (

9-23

)

Com

plet

e ne

urol

ogic

an

d ph

ysic

al

exam

inat

ion

on a

dmis

-si

on; F

IM

at a

dmis

-si

on a

nd

disc

harg

e;

Act

igra

phy;

O

-LO

G to

m

easu

re

PTA

by

SLP

s bl

ind-

ed to

sle

ep

scor

es; B

ed-

side

sle

ep

logs

kep

t by

nurs

ing

staf

f; Fo

llow

-up:

DR

S; S

uper

-vi

sion

Rat

ing

Sca

le

78%

had

m

ean

Wee

k-1

slee

p ef

ficie

ncy

in

the

seve

rely

im

paire

d ra

nge;

Tho

se

adm

itted

hav

-in

g al

read

y cl

eare

d P

TA

had

sign

ifi-

cant

ly b

ette

r W

eek-

1 sl

eep

effic

ienc

y th

at

thos

e w

ith

ongo

ing

am-

nesi

a; T

hose

w

ith o

ngoi

ng

amne

sia:

ea

ch 1

0-un

it

incr

ease

in

slee

p ef

fi-ci

ency

cor

re-

Act

igra

phy

a go

od

met

hod

to m

ea-

sure

sle

ep p

at-

tern

s in

imm

edia

te

post

-acu

teS

treng

ths:

Effo

rt m

ade

to

mea

sure

/elim

inat

e po

tent

ial c

on-

foun

ding

var

iabl

esLi

mita

tions

:S

mal

l sam

ple

with

la

rge

attri

tion

(onl

y 9

avai

labl

e fo

r an

alys

is)

Mod

erat

e:3.

5B

asel

ine:

0.5

Blin

ding

: 0.5

Sam

ple

size

: 0A

ttriti

on: 0

Sta

ndar

dize

d ou

tcom

es: 0

.5D

escr

itpio

n: 1

Follo

w-u

p: 1


TAB

LE 5

(CO

NTI

NU

ED)

3 m

osS

WLS

;P

SQ

Ila

ted

with

1

unit

↑ in

O-

LOG

sco

reA

ssoc

iatio

n be

twee

n im

prov

e-m

ent i

n sl

eep

effic

ienc

y an

d re

turn

of

awar

enes

s >

for

thos

e ad

mitt

ed w

ith

PTA

Wor

thin

g-to

n &

Mel

ia

2006

UK

Type

:E

pi/P

rev/

Des

cIn

vest

igat

e th

e im

pact

of

diso

rder

s of

ar

ousa

l and

sl

eep

dis-

turb

ance

on

ever

yday

livi

ng

and

parti

cipa

-tio

n in

reh

abili

-ta

tion

Leve

l VR

ecru

itmen

t:R

etro

-sp

ectiv

e na

tura

listic

ob

serv

atio

n;

Rec

ruitm

ent

AI (

7 ce

n-te

rs);

Cro

ss-

sect

iona

l; S

ingl

e gr

oup

AB

I = 1

35In

clus

ion:

• A

dmis

sion

to s

er-

vice

on

grou

nds

of s

igni

fican

t co

gniti

ve a

nd/o

r be

havi

or d

isor

der

• S

ever

e B

I•

All

able

to p

artic

i-pa

te in

reh

abE

xclu

sion

: NI

Age

, yrs

:38

± 1

1.4

Gen

der:

25%

FG

CS:

rang

e, 3

-7Ti

me

sinc

e:11

9.3

± 10

8.8

mos

Stru

ctur

ed

ratin

g fo

rm:

5 ke

y fe

a-tu

res

incl

ud-

ing

dela

yed

slee

p on

set,

frequ

ent

wak

ing

at

nigh

t, ea

rly

mor

ning

w

akin

g, d

e-la

yed

mor

n-in

g w

akin

g,

and

ED

S

47%

dis

-tu

rban

ce o

f ar

ousa

l and

sl

eep

pat-

tern

s; S

igni

fi-ca

nt a

dver

se

effe

ct o

n ac

tivity

in

66%

of 4

7%;

Dis

orde

red

arou

sal c

ould

pe

rsis

t up

to 1

0 yr

s po

st-in

jury

; C

oncu

rren

t ps

ychi

atric

ill-

ness

, but

not

ep

ileps

y, w

as

asso

ciat

ed

with

aro

usal

an

d sl

eep

diso

rder

; N

onph

ar-

mac

olog

ical

in

terv

entio

ns

Stre

ngth

s:

Firs

t siz

eabl

e st

udy

to a

ddre

ss

the

impa

ct a

nd

man

agem

ent o

f ar

ousa

l dis

orde

rs

afte

r B

I

Mod

erat

e:3/

7B

asel

ine:

0.5

Blin

ding

: 0S

ampl

e si

ze: 1

Attr

ition

: 1S

tand

ardi

zed

outc

omes

: 0D

escr

itpio

n:

0.5

Follo

w-u

p: 0


TAB

LE 5

(CO

NTI

NU

ED)

used

in 3

4%

of c

ases

ben

-zo

dias

epin

e/hy

pnot

ic

drug

s 20

%Lo

ng-te

rm

outc

ome

from

sB

I affe

cted

by

end

urin

g di

stur

banc

e of

aro

usal

, m

ost c

om-

mon

ly n

oted

as

sle

ep

diso

rder

Path

ophy

siol

ogy

Ayal

on e

t al

. 200

7 U

SA

Type

:P

atho

phys

iol-

ogy

D

escr

ibe

the

phys

iolo

gic

and

beha

vior

al

char

acte

ristic

s of

CR

SD

s fo

llow

ing

mTB

I in

pat

ient

s co

mpl

aini

ng o

f in

som

nia

Leve

l III

Rec

ruitm

ent:

LC; D

escr

ip-

tive;

Coh

ort;

Cro

ss-s

ec-

tiona

l; D

ata

colle

ctio

n ev

ery

2 hr

s fo

r 24

hrs

TBI =

42

Age

, yrs

:m

ean

26(r

ange

, 17-

45)

Gen

der:

20%

FG

CS:

mTB

ITi

me

sinc

e: N

I

Act

igra

phy;

S

aliv

a m

ela-

toni

n; O

ral

tem

pera

ture

; P

SG

; Sel

f-re

port

ques

-tio

nnai

re to

de

term

ine

circ

adia

n pr

efer

ence

: m

orni

ng-

ness

-eve

-ni

ngne

ss

ques

tion-

naire

36%

had

C

RS

D; 1

9%

had

DS

PS

: sh

owed

↑

tem

p, r

hyth

m,

ampl

itude

; 17

% h

ad ir

-re

gula

r sl

eep-

wak

e pa

ttern

: ha

d w

eake

r ci

rcad

ian

rhyt

hmic

-ity

- a

ccou

nt

for

beha

vior

di

ffere

nces

in

slee

p-w

ake

patte

rn?

Dis

tinct

pro

-fil

es o

f 24-

hr

perio

dici

ty

of m

elat

onin

rh

ythm

and

mTB

I mig

ht c

on-

tribu

te to

em

er-

genc

y of

CR

SD

s;

Impo

rtant

to h

ave

corr

ect d

iagn

osis

or

can

inap

pro-

pria

tely

trea

t for

in

som

nia

Mod

erat

e:4.

5/7

Bas

elin

e: 0

.5B

lindi

ng: 0

Sam

ple

size

: 1A

ttriti

on: 1

Sta

ndar

dize

d ou

tcom

es: 1

Des

critp

ion:

1Fo

llow

-up:

0


TAB

LE 5

(CO

NTI

NU

ED)

24-h

r pe

riod-

icity

of o

ral

tem

pera

ture

Bau

man

n et

al.

2005

S

witz

erla

nd

Type

:P

atho

phys

iol-

ogy

A

sses

s th

e C

SF

hypo

cre-

tin-1

leve

ls in

pa

tient

s w

ith

TBI

Leve

l III

Rec

ruitm

ent:

Con

secu

tive

A; C

ohor

t; C

ross

-sec

-tio

nal;

Dat

a co

llect

ion

1-4

days

po

st-T

BI

TBI =

44

Con

trols

= 2

0 (n

o ne

urol

ogic

pro

b-le

ms)

Incl

usio

n:•

Acu

te T

BI,

1-4

days

pos

t-inj

ury

Exc

lusi

on: N

I

Age

, yrs

:m

ean

36

(ran

ge, 1

7-69

)G

ende

r:73

% F

GC

S: 3

1 sT

BI;

8 m

od T

BI;

5 m

TBI

Tim

e si

nce:

1-4

days

TBI:

Hyp

o-cr

etin

-1

leve

ls a

s-se

ssed

ven

-tri

cula

r C

SF

(n =

37)

and

sp

inal

CS

F (n

= 8

) by

ra

dioi

mm

u-no

assa

yC

ontro

ls:

leve

ls a

s-se

ssed

vi

a sp

inal

an

aest

hesi

a an

d so

me

vent

ricul

arU

sed

Mar

shal

l to

cate

goriz

e th

e C

T

Hyp

ocre

tin-1

le

vels

abn

or-

mal

ly lo

w in

95

% o

f mod

-s

TBI a

nd in

97

% o

f tho

se

with

pos

ttrau

-m

atic

bra

in

CT

chan

ges;

S

ite o

f CS

F sa

mpl

e di

d no

t mat

ter;

Mar

shal

l I: 8

, II-

IV: 3

6n

= 9

con-

com

itant

di

seas

es

Cha

nge

in le

vels

m

ay r

eflec

t hyp

o-th

alm

ic d

amag

e an

d m

ay b

e lin

ked

to S

WD

May

als

o re

flect

lo

ss o

f con

scio

us-

ness

Lim

itatio

n:S

mal

l sam

ple

Mod

erat

e:4/

7B

asel

ine:

0.5

Blin

ding

: 0S

ampl

e si

ze:

0.5

Attr

ition

: 1S

tand

ardi

zed

outc

omes

: 1D

escr

itpio

n: 1

Follo

w-u

p: 0

Qui

nto

et

al. 2

000

US

A

Type

:P

atho

phys

iol-

ogy

D

escr

ibe

the

expe

rienc

e of

D

SP

S in

AB

I

Leve

l IVA

Rec

ruitm

ent:

LC; S

ingl

e su

bjec

t cas

e st

udy

TBI =

1S

leep

ons

et in

som

-ni

a: n

ot r

espo

nsiv

e to

pha

rmac

olog

ical

tre

atm

ent

Age

, yrs

: 48 G

ende

r:M

ale

GC

S: N

ITi

me

sinc

e: N

I

Sle

ep lo

gsA

ctig

raph

yS

leep

ons

et

inso

mni

a w

ith fr

eque

nt

awak

en-

ings

; Chr

o-no

ther

apy

unsu

cces

sful

de

clin

ed;

Pho

toth

erap

y de

clin

ed

Aut

hors

hyp

oth-

esiz

e le

sion

to

supr

achi

asm

atic

nu

cleu

s, w

hich

is

the

site

of h

uman

ci

rcad

ian

cloc

kE

mph

asiz

ed n

eed

to b

e aw

are

of

DS

PS

as p

oten

tial

cons

eque

nce

of

AB

I whe

n di

-ag

nosi

ng s

leep

pr

oble

ms

Mod

erat

e:3.

5/7

Bas

elin

e: 0

.5B

lindi

ng: 0

Sam

ple

size

: 0A

ttriti

on: 1

Sta

ndar

dize

d ou

tcom

es: 1

Des

critp

ion:

1Fo

llow

-up:

0


TAB

LE 5

(CO

NTI

NU

ED)

Pedi

atric

Bee

be e

t al

. 200

7 U

SA

Type

:P

edia

tric

Det

erm

ine

the

effe

ct o

f mod

an

d se

vere

TB

I on

slee

p of

sch

ool-a

ged

child

ren

Leve

l III

Rec

ruitm

ent:

Con

curr

ent

pros

pec-

tive

coho

rt A

(chi

l-dr

en a

ged

6-12

yrs

); Lo

ngitu

dina

l 3

grou

ps:

mod

TBI,

sTB

I, or

tho-

paed

ic in

ju-

ry; B

asel

ine

(ret

rosp

ec-

tive

pare

ntal

re

port

of

prei

njur

y sl

eep

at 3

w

ks p

ost),

an

d 6,

12,

an

d 48

mos

po

st-in

jury

mod

TB

I = 5

6sT

BI =

35

Con

trols

= 8

0In

clus

ion:

• 1

nigh

t in

hosp

tial

for

all 3

gro

ups

• N

o ev

iden

ce o

f ab

use

or p

revi

-ou

s ne

urol

ogic

al

diso

rder

• E

nglis

h-sp

eaki

ng

Age

at i

njur

y,

yrs:

9.5

± 2.

0G

ende

r:33

% F

GC

S: u

sed

low

est p

ost-

resu

scita

tion/

inju

ry s

core

Tim

e si

nce:

3

wks

pos

tO

ther

:68

% C

auca

sian

Chi

ld

Beh

avio

ur

Che

cklis

t: 7

item

s on

ly

(ass

esse

d st

abili

ty in

co

mpa

risio

n to

full

scal

e)

mod

TBI

wor

se p

re-

inju

ry s

leep

m

odTB

I and

C

ontro

ls:

smal

l ↓ in

sl

eep

from

pr

e to

pos

t; sT

BI:

↑ in

po

stin

jury

pr

oble

ms:

da

ytim

e sl

eepi

ness

an

d no

ctur

nal

slee

p du

ra-

tion

Lim

itatio

ns:

Tim

ing

of fo

llow

-up

s va

ried;

R

etro

spec

tive

data

co

llect

ion;

Wea

k in

stru

men

t (on

ly 7

ite

ms

and

part

of

larg

er s

cale

)

Mod

erat

e:4.

5/7

Bas

elin

e: 1

Blin

ding

: 0S

ampl

e si

ze: 1

Attr

ition

: 0S

tand

ardi

zed

outc

omes

: 0.5

Des

critp

ion:

1Fo

llow

-up:

1

Kau

fman

et

al.

2001

Is

rael

Type

:P

edia

tric

Sub

ject

ive

and

obje

ctiv

e ch

arac

teriz

a-tio

n th

e lo

ng

term

effe

cts

of

mH

I on

slee

p in

ado

lesc

ents

Leve

l III

Rec

ruitm

ent:

Pro

spec

tive

coho

rt A

(arc

hive

s);

Cro

ss-s

ec-

tiona

l; m

HI:

subj

ectiv

e an

d ob

jec-

tive

mea

-su

res

C1,

C

2: o

bjec

-

mH

I = 1

9C

1 (h

ealth

y) =

16

C2

(hea

lthy)

= 1

5In

clus

ion

• 10

-18

yrs

• H

ospi

tal a

dmis

-si

on w

ith m

HI

(ICD

-10

code

s)•

GC

S ≥

13

• 3

yrs

post

inju

ry•

Com

plai

ned

of

slee

p di

stur

banc

e

Age

, yrs

:13

.5 ±

1.7

Gen

der:

mH

I21

% F

;C

1 19

% F

C2

20%

FG

CS

: ≥ 1

3Ti

me

sinc

e: 3

yr

s po

st-in

jury

Loca

lly

deve

lope

d qu

estio

n-na

ire: m

edi-

cal h

isto

ry,

deta

ils o

f th

e in

jury

, sl

eep

habi

ts,

and

slee

p di

stur

banc

-es

: pre

and

po

st s

leep

mH

I: si

g-ni

fican

t ↓ in

sl

eep

perio

d tim

e, to

tal

slee

p tim

e an

d sl

eep

ef-

ficie

ncy;

mH

I: si

gnifi

cant

↑

min

aw

ake

and

num

ber

of a

wak

en-

ings

>3

min

Stre

ngth

s:Th

roro

ugh

eval

uatio

n; U

se o

f he

alth

y co

ntro

ls;

Sub

ject

ive

cor-

robo

rate

d ob

jec-

tive

for

the

mos

t pa

rt; P

artic

ipan

ts

3 yr

s po

st-in

jury

so

idei

ntifi

es/c

on-

firm

s lo

ng-te

rm

slee

p pr

oble

ms

Mod

erat

e:3.

5/7

Bas

elin

e: 1

Blin

ding

: 0S

ampl

e si

ze: 0

Attr

ition

: 1S

tand

ardi

zed

outc

omes

: 0.5

Des

critp

ion:

1Fo

llow

-up:

0


TAB

LE 5

(CO

NTI

NU

ED)

tiv

e on

ly;

C1,

C2

mat

ched

for

age,

gen

der;

recr

uite

d by

ad

verti

se-

men

t, w

ord

of m

outh

; O

ne d

ata

colle

ctio

n,

incl

udin

g 5

days

of

actig

raph

y

Exc

lusi

on: N

IP

SG

(m

HI

and

C1)

: 1

nigh

t; A

ctig

-ra

phy

(mH

I an

d C

2): 5

da

ys w

ithin

3

mos

of

PS

G

mH

I: su

bjec

-tiv

e re

port

diffi

culty

fa

lling

asl

eep,

di

fficu

lty

wak

ing

in th

e m

orni

ng, d

ay-

time

slee

pi-

ness

, res

tless

sl

eep,

fear

ful

awak

enin

gs

from

sle

ep,

para

som

nias

Lim

itatio

ns:

Sm

all s

ampl

e bu

t re

flect

ive

of th

e re

aliti

es o

f thi

s ty

pe o

f res

earc

h

Milr

oy e

t al.

2007

UK

Type

:P

edia

tric

Obt

ain

ob-

ject

ive

and

subj

ectiv

e re

-po

rts o

f sle

ep

dist

urba

nces

in

sch

ool-a

ged

child

ren

with

m

TBI

Leve

l III

Rec

ruitm

ent:

A (fr

om

data

base

); C

ross

-se

ctio

nal;

2 gr

oups

: m

TBI a

nd

orth

opae

dic

cont

rols

with

in

jury

to

wris

t or

arm

mTB

I = 1

8 (4

3% o

f ad

mis

sion

s)C

ontro

ls =

30

(61%

of

adm

issi

ons)

Incl

usio

n:•

7-12

yrs

• ≥

6 m

os s

ince

la

st h

ospi

tal a

t-te

ndan

ce•

Adm

issi

on <

48

hrs

Exc

lusi

on:

• D

evel

opm

enta

l de

lay,

epi

leps

y,

psyc

hiat

ric, o

r sl

eep

diso

rder

s•

Atte

nds

a sp

ecia

l sc

hool

• O

ther

rec

ent

hosp

italiz

atio

n•

His

tory

of n

onac

-ci

dent

al in

jury

Age

, yrs

: m

ean

TBI:

9.7

± 1.

5C

ontro

ls:

9.7

± 1.

5G

ende

r:TB

I 56%

F,

Con

trols

40%

FG

CS:

GC

S o

f 15

= 16

GC

S o

f 13

= 1

GC

S o

f 14

= 1

2% r

ecor

ded

PTA Tim

e si

nce:

23

.9 m

os; C

on-

trols

25

mos

Act

igra

phy

for

5 ni

ghts

; P

aren

tal a

nd

self-

repo

rt qu

estio

n-na

ires:

Chi

l-dr

en’s

Sle

ep

Hab

its; S

elf-

repo

rt S

leep

S

cale

S

treng

ths

and

diffi

cul-

ties;

Dem

o-gr

aphi

c an

d in

jury

-rel

ated

qu

estio

ns

mTB

I: P

ar-

ents

rep

ort >

sl

eep

dist

ur-

banc

es w

hen

com

pare

d to

C

ontro

ls (

me-

dium

effe

ct

size

); m

TBI

and

Con

trols

: di

d no

t diff

er

on m

easu

res

of s

leep

ef-

ficie

ncy

Hig

her

porti

on in

bo

th g

roup

s w

ith

slee

p di

fficu

lties

th

an e

xpec

ted

Diff

eren

ces

betw

een

pare

ntal

re

port

and

obje

c-tiv

e m

easu

res

of

inte

rest

as

thes

e m

easu

res

serv

e di

ffere

nt p

urpo

ses

and

may

iden

tify

diffe

rent

type

s of

sl

eep

diffi

culti

es;

Sel

f sel

ectio

n bi

as

poss

ible

Mod

erat

e:4/

7B

asel

ine:

1B

lindi

ng: 0

Sam

ple

size

: 0A

ttriti

on: 1

Sta

ndar

dize

d ou

tcom

es: 1

Des

critp

ion:

1Fo

llow

-up:

0

Nec

ajau

s-ka

ite e

t al.

Type

:P

edia

tric

Leve

l III

Rec

ruitm

ent:

TBI =

102

Con

trols

= 1

02A

ge, y

rs:

4-16

Loca

lly d

e-ve

lope

d16

.7%

of p

ar-

ents

rep

orte

d Li

mita

tions

:C

riter

ia m

easu

red

Mod

erat

e:3.

5/7


TAB

LE 5

(CO

NTI

NU

ED)

2005

Li

thua

nia

Inve

stig

ate

the

clin

ical

fe

atur

es a

nd

prev

alen

ce

of s

ympt

oms

of P

CS

in

child

ren

with

m

TBI a

nd

eval

uate

ch

ange

s ov

er

time

A; C

ross

-se

ctio

nal;

Two

grou

ps:

TBI:

sing

le

mTB

I; C

on-

trols

: mild

bo

dy in

jury

; 2

ques

tion-

naire

s m

aile

d se

para

tely

: fir

st, f

or

perio

d du

r-in

g th

e la

st

year

and

du

ring

the

last

mon

th

with

no

ref

to tr

aum

a (to

red

uce

bias

); se

c-on

d (ju

st

TBI g

roup

) fo

r pe

riod

shor

tly a

fter

the

traum

aC

ompa

red

thos

e <2

yrs

po

st-in

jury

to

thos

e 2-

5 yr

s po

st-

inju

ry

Gro

ups

mat

ched

on

gen

der,

age,

da

te o

f adm

issi

on

Gen

der:

28%

FG

CS:

NI

Tim

e si

nce:

1-5

yr

s po

st a

dmis

-si

on

stan

dard

ized

qu

estio

n-na

ire a

d-dr

essi

ng:

heal

th a

nd

sym

ptom

s (ir

ritab

ility

, fe

ars,

sle

ep

diso

rder

s,

lear

ning

pr

oble

ms,

co

ncen

-tra

tion

prob

lem

s,

mem

ory

diso

rder

s,

head

ache

s,

and

con-

com

itant

sy

mpt

oms

prio

r to

tra

uma)

slee

p pr

ob-

lem

s sh

ortly

af

ter

head

tra

uma

wer

e no

t rel

i-ab

le e

stim

ates

of

long

-last

ing

PC

S;

Wea

k m

easu

res;

O

nly

1 da

ta

colle

ctio

n fro

m

Con

trols

; Ret

ro-

spec

tive;

pos

sibl

e is

sues

of r

ecal

l bi

as

Bas

elin

e: 1

Blin

ding

: 0S

ampl

e si

ze: 1

Attr

ition

: 1S

tand

ardi

zed

outc

omes

: 0D

escr

iptio

n:

0.5

Follo

w-u

p: 0

Kor

inth

en-

berg

et

al. 2

004

Ger

man

y

Type

:P

edia

tric

Inve

stig

ate

pred

ictiv

e fa

c-to

rs o

f pos

t-

Leve

l III

Rec

ruitm

ent

Pro

spec

tive

coho

rt C

on-

secu

tive

A

mH

I = 9

8In

clus

ion:

• LO

C <

10 o

r no

ne•

Abl

e to

ans

wer

qu

estio

ns a

t

Age

, yrs

:3-

5 (n

= 2

6),

6-9

(n =

42)

,10

-13

(n =

30)

Gen

der:

EE

GP

roto

col o

f “e

xam

inat

ion

of c

hild

with

m

inor

neu

ro-

At f

ollo

w-u

p:

23%

pre

-se

nted

with

so

mat

ic a

nd

psyc

hiat

ric

Stre

ngth

s:La

rge

sam

ple

size

Thor

ough

in-

vest

igat

ion

with

fo

llow

-up

Mod

erat

e:5/

7B

asel

ine:

0.5

Blin

ding

: 0S

ampl

e si

ze: 1


TAB

LE 5

(CO

NTI

NU

ED)

traum

atic

sy

ndro

me

in

child

ren

with

m

HI

(use

d sp

e-ci

fic c

riter

ia);

Long

itudi

nal;

Obj

ectiv

e an

d su

bjec

-tiv

e m

ea-

sure

sD

ata

col-

lect

ion:

ba

selin

e an

d fo

llow

-up

at

4-6

wks

adm

issi

on•

No

com

plic

a-tio

ns, c

onfu

sion

or

intra

cran

ial

hem

orrh

age

• A

ge 3

-13

yrs

• C

hild

and

par

ents

sp

eak

Ger

man

, pa

rent

ava

ilabl

e fo

r in

terv

iew

Exc

lusi

on: N

I

40%

GC

S: N

ITi

me

sinc

e:

<24

hrs

sinc

e ad

mis

sion

logi

cal

dysf

unct

ion”

; S

truct

ured

va

lidat

ed

inte

rvie

w

com

plai

nts

in-

clud

ing

slee

p di

stru

banc

e an

d fa

tigue

, w

hich

did

no

t cor

rela

te

with

som

atic

, ne

urol

ogic

, or

EE

G fi

ndin

gs

imm

edia

tely

po

stin

jury

Lim

itatio

ns:

Bet

ter

with

a fu

r-th

er fo

llow

-up

Attr

ition

:1

Sta

ndar

dize

d ou

tcom

es: 1

Des

crip

tion:

1Fo

llow

-up:

0.5

Pill

ar e

t al.

2003

Isra

elTy

pe:

Ped

iatri

cA

sses

s th

e pr

eval

ence

an

d ris

k fa

c-to

rs o

f lon

g-te

rm s

leep

di

stur

banc

es

in a

dole

scen

ts

afte

r m

HI

Leve

l III

Rec

ruitm

ent:

Ret

rosp

ec-

tive

coho

rt A

(“ra

ndom

” se

lec-

tion

from

ar

chiv

es);

Cro

ss-

sect

iona

l; M

atch

ed

cont

rolle

d co

mpa

ri-si

on g

roup

(h

ealth

y)

mH

I = 9

8C

ontro

ls =

80

Incl

usio

n:•

7-15

yrs

at i

njur

y•

Adm

itted

to h

osp-

tial w

ith m

HI

• IC

D-1

0 co

des

506.

0•

GC

S ≥

13

on

adm

issi

on to

ER

Exc

lusi

on: N

I

Age

, yrs

: 13

.5 ±

2.3

(ran

ge, 8

-18)

Gen

der:

32%

FG

CS:

14.

7 ±

0.6

on a

dmis

-si

onTi

me

sinc

e:0.

5-6

yrs

Det

aile

d 60

-ite

m q

ues-

tionn

aire

mH

I: 28

%

had

slee

p pr

oble

ms

(vs

Con

trols

11

%; P

<

.05)

; mH

I >

Con

trols

: av-

erag

e sc

ore

of s

leep

co

mpl

aint

s (P

<

.05)

; mH

I w

ith s

leep

co

mpl

aint

s (n

=

27)

had

> bo

dy w

eigh

t, >

BM

I, pa

rent

s le

ss

educ

ated

, ↑

brux

ism

, sh

orte

d w

eeke

nd

slee

p tim

e

Stre

ngth

s:La

rge

sam

ple

Com

preh

ensi

ve

ques

tionn

aire

; La

rge

rang

e po

st-

inju

ry; C

ompa

ri-si

on g

roup

Lim

itatio

ns:

2/3

resp

onse

rat

eN

o in

form

atio

n on

BM

I at t

ime

of

inju

ry

Low

:2.

5/7

Bas

elin

e: 1

Blin

ding

: 0S

ampl

e si

ze: 1

Attr

ition

: 0S

tand

ardi

zed

outc

omes

: 0D

escr

itpio

n:

0.5

Follo

w-u

p: 0

Neu

rops

ycho

logy

Mah

moo

d et

al.

2004

.Ty

pe:

Neu

rops

y-Le

vel I

VAR

ecru

itmen

t:TB

I = 8

7In

clus

ion:

Age

, yrs

:N

IP

SQ

I, B

DI;

Glo

bal s

cale

37%

had

sl

eep

dist

ur-

PS

QI b

ette

r at

id

entif

ying

inso

m-

Mod

erat

e:4.

5/7


TAB

LE 5

(CO

NTI

NU

ED)

US

Ach

olog

y

Exa

min

e th

e re

latio

nshi

p be

twee

n sl

eep

dist

urba

nces

an

d ne

uroc

og-

nitiv

e ab

ility

po

st-T

BI

Con

secu

tive

AI (

arch

ival

re

cord

s)

Cor

rela

tiona

l C

ross

-sec

-tio

nal

• TB

I bas

ed o

n m

edic

al e

xam

, re

cove

ry to

pos

t-ac

ute

phas

e,

med

ical

ly d

eter

-m

ined

nee

d fo

r re

hab,

cog

nitiv

e fu

nctio

n at

Lev

el

VI (

Leve

ls o

f C

ogni

tive

Func

-tio

n S

cale

)•

Indi

catio

n of

at

leas

t a c

oncu

s-si

on (

LOC

or

conf

usio

n or

po

sitiv

e ne

uroi

m-

agin

g)E

xclu

sion

: NI

Gen

der:

43

.7%

FG

CS:

mild

: 24;

m

od 1

9; s

ev 4

4Ti

me

sinc

e:

97%

with

in a

ye

ar o

f inj

ury;

89

.7%

with

in

6 m

os; 7

0.1%

w

ithin

3 m

os

form

; M

emor

y A

sses

smen

t; S

cale

s; N

eu-

rops

ycho

l-og

y te

sts:

W

ide

rang

e;

Ach

ieve

men

t te

st; (

WR

AT-

3) -

est

imat

e of

pre

mor

bid

IQ; D

igit

Spa

n; D

igit

Sym

bol;

Gro

oved

P

eg B

oard

; B

lock

De-

sign

; Tra

il m

akin

g-B

; C

ontro

lled

Ora

l Wor

d A

sso-

ciat

ion

Test

(C

OW

AT)

banc

es m

TBI

mor

e sl

eep

dist

urbe

d th

an s

ever

eP

erfo

rman

ce

on s

elec

ted

mea

sure

s of

cog

nitiv

e fu

nctio

n ↑

pred

ictio

n of

sle

ep

dist

urba

nce

acco

unt-

ing

for

14%

of

var

ianc

e be

yond

that

ac

coun

ted

by

inju

ry s

ever

ity

and

gend

er

(17%

); E

xecu

tive

func

tioni

ng

and

spee

d of

in

form

atio

n pr

oces

sing

di

fficu

lties

m

ay b

e as

-so

ciat

ed w

ith

slee

p di

stur

-ba

nces

nia

but m

ay h

ave

not h

ave

capt

ured

hy

pers

omni

aN

eed

a re

liabl

e in

dica

tor

bette

r ab

le to

det

ect

and

repo

rt sl

eep

dist

urba

nces

Nee

d to

furth

er

asse

ss th

e in

flu-

ence

of g

ende

r; ex

plor

e th

e th

resh

old

leve

l an

d ch

ange

s ov

er

time

Bas

elin

e: 0

.5B

lindi

ng: 0

Sam

ple

size

: 1A

ttriti

on: 1

Sta

ndar

dize

d ou

tcom

es: 1

Des

crip

tion:

1Fo

llow

-up:

0

Wild

e et

al.

2007

US

ATy

pe:

Neu

rops

ycho

l-og

yE

xam

ine

the

impa

ct o

f co

mor

bid

OS

A on

cog

nitiv

e

Leve

l III

Rec

ruitm

ent:

PA (

3 ce

n-te

rs, s

leep

di

sord

er

cent

ers,

and

a

reha

b

TBI =

35

OS

A =

19N

o O

SA

= 16

Incl

usio

n:•

> 18

yrs

• ≥

3 m

os p

ost-

inju

ry

Age

, yrs

:>1

8G

ende

r:O

SA

: 11%

FN

o O

SA

: 25%

FG

CS:

OS

A 53

%

unkn

own,

16%

Neu

rops

y-ch

olog

ical

pe

rfor-

man

ce:

Psy

chom

o-to

r Vi

gila

nce

test

OS

A ↓

on v

erba

l an

d vi

sual

de

laye

d-re

call

mea

sure

s an

d >

atte

n-tio

n la

pses

Stre

ngth

s:Fi

rst s

tudy

to a

d-dr

ess

this

issu

eO

SA

asso

ciat

ed

with

mor

e im

pair-

men

t of s

usta

ined

at

tent

ion

and

Mod

erat

e:

4/7

Bas

elin

e: 1

B

lindi

ng: 0

Sam

ple

size

: 0A

ttriti

on: 1

Sta

ndar

dize

d


TAB

LE 5

(CO

NTI

NU

ED)

func

tion

of p

er-

sons

with

TB

Ipr

ogra

m)

Cas

e co

ntro

lled;

C

ross

-se

ctio

nal;

2 TB

I gro

ups:

O

SA

and

No

OS

A; C

on-

trolle

d us

ing

age,

edu

ca-

tion,

tim

e po

stin

jury

, an

d se

verit

y of

inju

ry a

nd

GC

S (

whe

n av

ail);

OS

A di

agno

sed

by n

octu

rnal

P

SG

Exc

lusi

on: N

Im

od, 5

% m

od-

sev,

26%

sev

; N

o O

SA

: 50%

; un

know

n, 1

2%

mod

, 19%

mod

-se

v, 1

9% s

evTi

me

sinc

e: ≥

3

mos

pos

t-inj

ury

Rey

Com

-pl

ex F

igur

e R

ey A

udi-

tory

-Ver

bal

Lear

ning

; D

igit

Spa

n fro

m W

MS

-R

; Fin

ger

tapp

ing;

E

SS

on

nigh

t of P

SG

an

d M

SLT

Effe

ct

size

s us

ing

Coh

en’s

d

med

ium

and

la

rge

mem

ory;

Tre

at-

men

t of O

SA

did

not i

mpr

ove

outc

omes

Lim

itatio

ns:

Lack

ed d

ata

on

leve

ls o

f sev

erity

, di

fficu

lt to

gen

eral

-iz

e fin

ding

s; S

mal

l sa

mpl

e bu

t effe

ct

size

s go

od

outc

omes

:1D

escr

iptio

n: 1

Follo

w-u

p: 0

Wis

eman

-H

akes

et

al. 2

010

Can

ada

Type

:N

euro

psyc

hol-

ogy

A

sses

s as

pect

s of

co

gniti

on a

nd

com

mun

icat

ion

over

a c

ours

e of

trea

tmen

t fo

r P

TH

Leve

l IVA

Rec

ruitm

ent:

LC Sin

gle

case

st

udy

Trea

tmen

t: 17

wks

1)

Bas

elin

e:

12 m

os

post

inju

ry,

lora

zepa

m

1 m

g an

d ci

talo

pram

20

mg

for

1 m

o 2)

At

1 yr

1 m

o,

cita

lopr

am ↑

40

mg

3) A

t 1

yr 2

mos

:

TBI =

1A

ge, y

rs:

late

teen

sG

ende

r: m

ale

GC

S: in

itial

3,

hosp

ital 5

PTA

> 1

mo

Tim

e si

nce:

11

mos

Dai

ly C

ogni

-tiv

e-C

omm

u-ni

catio

n an

d S

leep

Pro

file

(D-C

CA

SP

)E

SS

Sta

nfor

d S

leep

ines

s S

cale

PS

GM

aint

enan

ce

of W

akef

ul-

ness

Tes

ting

(MW

T) (

at

follo

w-u

p)

Rel

atio

nshi

p be

twee

n qu

ality

of

slee

p an

d la

ngua

ge p

ro-

cess

ing

Pro

long

ed

RE

M la

tenc

yP

ositi

ve r

ela-

tions

hip

be-

twee

n sl

eep

and

lang

uage

pr

oces

sing

, su

stai

ned

atte

ntio

n/vi

gila

nce,

m

emor

y an

d ch

ange

s in

m

edic

atio

n

Lim

itatio

ns:

Sin

gle

case

stu

dy

and

expl

orat

ory

in

natu

re

Mod

erat

e:

4/7

Bas

elin

e: 0

.5

Blin

ding

: 0S

ampl

e si

ze: 0

Attr

ition

: 1S

tand

ardi

zed

outc

omes

: 0.5

Des

crip

tion:

1Fo

llow

-up:

0


TAB

LE 5

(CO

NTI

NU

ED)

add

met

h-yl

phen

idat

e 20

mg;

4)

1 w

eek

late

r m

ethy

lphe

-ni

date

↑ 4

0 m

g da

ily 5

) S

leep

Stu

dy

2: m

odafi

nil

repl

aced

m

ethy

lphe

-ni

date

and

m

irtaz

epin

e w

as a

dded

Bas

elin

e, 1

7 w

ks d

aily

da

ta c

olle

c-tio

n, fo

llow

-up

at 3

yrs

8

mos

Able

to

impr

ove

daily

fu

nctio

ning

an

d re

sum

e at

tend

ance

at

scho

ol

Hen

ry e

t al.

2000

US

ATy

pe:

Neu

rops

ycho

l-og

yTo

inve

stig

ate

neur

opsy

-ch

olog

ical

, ps

ycho

logi

cal

and

beha

vior

al

func

tioni

ng

follo

win

g no

n-im

pact

BI

Leve

l VR

ecru

itmen

t:R

etro

spec

-tiv

e O

R

Cro

ss-s

ec-

tiona

lIn

terv

iew

ed

at o

ne p

oint

in

tim

eC

ompa

red

with

pub

-lis

hed

norm

s

Non

impa

ct T

BI

= 32

Incl

usio

n:•

His

tory

of w

hip-

lash

with

brie

f or

no

LOC

and

no

evi

denc

e of

cr

ania

l tra

uma

• N

o ph

ysic

al e

vi-

denc

e th

at h

ead

stru

ck w

ind-

shie

ld/h

eadr

est

• S

ubje

ctiv

e re

port

of a

n al

tera

tion

in m

enta

l sta

tus

at a

ccid

ent w

ith

no o

bjec

tive

evid

ence

Exc

lusi

on:

Age

, yrs

: m

ean

41.8

(ran

ge, 8

-64)

Gen

der:

53%

FG

CS:

NI

Tim

e si

nce:

1

wk

to 5

yrs

Clin

ical

in

terv

iew

s co

rrob

orat

ed

via

inte

r-vi

ews

with

si

gnifi

cant

ot

hers

/co-

wor

kers

Neu

ro-

psyc

hol-

ogy

batte

ry:

Wec

hsle

r A

dult

Inte

lli-

genc

e S

cale

-

revi

sed

(WA

IS-R

), W

MS

-R,

Rey

figu

res,

H

oope

r,

Cog

nitiv

e de

f-ic

its o

bser

ved

parti

cula

rly

with

exe

cu-

tive

func

tion-

ing

(atte

ntio

n an

d co

n-ce

ntra

tion)

; PA

SAT

mos

t se

nsiti

ve te

st;

Som

e ex

peri-

ence

of m

ild

depr

essi

on;

Pro

blem

s ob

serv

ed w

ith

beha

vior

al

cont

rol,

slee

p an

d se

xual

ity;

EE

Q s

how

ed

Whi

plas

h ca

n pr

o-du

ce w

ide-

rang

ing

circ

uitry

dys

func

-tio

n (s

imila

r to

m

TBI)

Mod

erat

e:

3.5/

7B

asel

ine:

0.5

B

lindi

ng: 0

Sam

ple

size

: 0.

5A

ttriti

on: 1

Sta

ndar

dize

d ou

tcom

es: 1

Des

crip

tion:

0.

5Fo

llow

-up:

0


TAB

LE 5

(CO

NTI

NU

ED)

P

revi

ous

whi

plas

h or

clo

sed

BI,

neu-

rolo

gica

l dis

orde

r se

izur

e, p

sych

iatri

c pr

oble

m s

ubst

ance

ab

use

or m

edic

al

cond

ition

or

med

i-ca

tion

that

com

-pr

omis

e ne

rvou

s sy

stem

inte

grity

Bos

ton

nam

-in

g an

d ve

r-ba

l flue

ncy,

Tr

ails

A a

nd

B W

isco

nsin

C

ard

Sor

t, S

troop

, au

dito

ry,

cons

onan

t tri

gram

s,

PAS

AT

front

-cen

tral

slow

ing

and

↑ in

spi

ke

activ

ity

Inte

rven

tion

Jha

et a

l. 20

08 U

SA

Type

:In

terv

entio

nTe

st th

e ef

ficac

y of

m

odafi

nil i

n tre

atin

g fa

tigue

an

d E

DS

Leve

l II

Dow

ns a

nd

Bla

ck:

23/2

8 R

ecru

it-m

ent:;

PA

; D

oubl

e-bl

ind,

pl

aceb

o-co

ntro

lled

cors

sove

r tri

al: 4

wk,

w

asho

ut

perio

d, 4

wk

open

labe

l tri

al a

t end

of

mod

afini

l: 2

x 10

0 m

g tw

ice

a da

y fo

r 8

wks

w

ith 2

wks

gr

adua

ted

in

(man

ufac

tur-

er p

rovi

ded)

Dat

a co

llec-

tion:

bas

e-

E1

= 24

(dr

ug fi

rst)

E2

= 22

(pl

aceb

o fir

st)

Incl

usio

n:•

1 yr

pos

t-TB

I (s

ever

e en

ough

to

req

uire

inpa

-tie

nt r

ehab

)•

18-6

5 yr

s•

Rep

ort f

atig

ue

and/

or E

DS

co

mpr

omis

ing

func

tioni

ngE

xlcu

sion

:•

neur

olog

ic/n

eu-

ron

psyc

hiat

ric

diag

nosi

s•

Oth

er d

iagn

osis

fo

r E

DS

• C

oncu

rren

t sig

-ni

fican

t sys

tem

ic

dise

ase

• E

pile

psy

• C

ardi

ovas

cula

r di

seas

e•

Sig

nific

ant

Age

, yrs

: 38.

25±

12.2

0G

ende

r:31

.4%

FG

CS:

sev

ere:

3-

8 (5

1%);

mod

erat

e 9-

12

(23.

5%; m

ild

13-2

5 (2

5.5%

); Ti

me

sinc

e:

5.77

± 4

.97

yrs

Mod

ified

Fa

tigue

Im-

pact

Sca

le;

Fatig

ue S

e-ve

rity

Sca

le;

ES

S; M

OS

-12

item

; S

F-12

; Pos

t C

oncu

ssio

n;

Ass

essm

ent

Cog

nitiv

e Te

stin

g (Im

pact

) C

onno

r’s

cont

inuo

us

perfo

rman

ce

test

IIB

DI I

I

ES

S: E

1>E

2 at

wee

k 4

but

not a

t wee

k 10

: onl

y sh

ort-t

erm

be

nefit

In

som

nia

repo

rted

mor

e of

ten

with

dru

g th

an p

lace

bo;

Saf

e an

d w

ell

tole

rate

d;

Ther

e w

ere

no s

igni

fican

t di

ffere

nces

be

twee

n m

odaf

inil

and

plac

ebo

and

no c

onsi

sten

t an

d pe

rsis

-te

nt c

linic

ally

si

gnifi

cant

di

ffere

nces

Stre

ngth

s:Th

orou

gh c

om-

plet

e in

form

atio

n w

ith d

emog

raph

-ic

s, m

etho

dolo

gy;

Ack

now

ledg

ed

com

plex

ity o

f fa-

tigue

and

rel

atio

n-sh

ip w

ith s

leep

i-ne

ssLi

mita

tions

: A

ll sl

eep

mea

-su

res

self-

repo

rt;

Sta

ndar

d do

s-ag

e, th

eref

ore

not

able

to ta

ilor

to

indi

vidu

al (

mod

ify

to m

eet i

ndiv

idua

l re

spon

ses

(ex.

ta

per)

); S

ingl

e ce

nter

; Mul

tiple

st

at te

sts,

Clin

ical

si

gnifi

canc

e co

m-

plic

ated

as

mos

t di

d op

en la

bel

Hig

h:

6.5/

7B

asel

ine:

1

Blin

ding

: 1S

ampl

e si

ze:

0.5

Attr

ition

: 1S

tand

ardi

zed

outc

omes

: 1D

escr

iptio

n: 1

Follo

w-u

p: 1


TAB

LE 5

(CO

NTI

NU

ED)

line,

wee

k 4,

wee

k 10

, w

eeks

4

and

10 a

fter

cros

sove

r

psyc

hiat

ric o

r be

-ha

vior

sym

ptom

s •

Non

-Eng

lish

• P

regn

ant f

emal

es

or p

oten

tial c

hild

-be

arin

g un

less

us

ing

cont

race

p-tiv

es

Cas

triot

ta

2008

US

ATy

pe:

Inte

rven

tion

Det

erm

ine

whe

ther

trea

t-m

ent o

f sle

ep

diso

rder

s id

entifi

ed in

BI

adul

ts r

esul

ts

in r

esol

u-tio

n of

thos

e di

sord

ers

and

impr

ovem

ent

of s

ympt

oms

and

dayt

ime

func

tion

Leve

l III

Dow

ns

and

Bla

ck:

17/2

8R

ecru

itmen

t: P

rosp

ectiv

e un

sele

cted

pa

tient

s A

I (3

cen

ters

); Lo

ngitu

dina

l; B

asel

ine

and

3 m

os;

neur

opsy

-ch

olog

ical

te

stin

g pe

rform

ed

at 1

0:30

to

con

trol

for

diur

nal

varia

tion;

on

ly th

ose

with

sle

ep

diso

rder

did

th

e sl

eep

asse

ssm

ent

agai

n at

3

mos

TBI =

57

Incl

usio

n:•

> 18

yrs

• ≥

3 m

o po

st-

inju

ryE

xclu

sion

:•

Pre

senc

e of

ci

rcad

ian

rhyt

hm

diso

rder

• U

nabl

e to

giv

e in

form

ed c

onse

nt•

Use

of s

edat

ing

med

icat

ions

Age

, yrs

:38

.6 ±

14.

8G

ende

r:25

% F

GC

S: u

sed

with

C

T fin

ding

s ac

-co

rdin

g to

crit

e-ria

to e

stab

lish

seve

rity

30%

sT

BI;

5% m

od-

sTB

I; 18

% m

od

TBI;

9% m

TBI;

38%

mis

sing

Tim

e si

nce:

67

.8 ±

126

.3

mos

Sle

ep:

NP

SG

; M

SLT

; ES

S;

Neu

rops

y-ch

olog

ical

: P

VT;

PO

MS

; FO

SQ

; U

rine

sam

-pl

e to

test

fo

r dr

ugs/

med

icat

ions

; Tr

eatm

ent:

CPA

P fo

r O

SA

; M

odafi

nil f

or

narc

olep

sy

and

PTH

P

ram

ipex

ole

for

Per

i-od

ic L

imb

Mov

emen

t S

yndr

ome

(PLM

S)

39%

had

ab

norm

al

slee

p st

udie

s:

23%

OSA

, 3%

PTH

, 5%

na

crol

epsy

, 7%

PLM

S;

21%

ED

S;

GC

S ↓

for

slee

p di

sor-

dere

d; S

leep

di

sord

ered

>

redu

ctio

ns

in te

nsio

n an

d an

ger

and

ESS

th

an n

on-

diso

rder

ed;

Apne

a/hy

-po

pnea

Inde

x im

prov

ed w

ith

treat

men

t ↑

Amou

nt o

f R

EM T

reat

-m

ent m

ay

resu

lt in

N

PG r

esol

u-tio

n w

ithou

t ch

ange

in

slee

pine

ss o

f

Stre

ngth

s:R

igor

ous

met

h-od

s; u

sed

esta

b-lis

hed

crite

ria a

s m

uch

as p

ossi

ble

Lim

itatio

ns:

Med

icat

ions

not

tit

rate

d; L

arge

m

issi

ng s

ever

ity

data

; Sub

sam

ples

sm

all;

MS

LT n

ot

the

right

m

ea-

sure

as

it se

ems

that

sle

ep a

nd

wak

eful

ness

are

2

sepa

rate

act

ive

proc

esse

s

Mod

erat

e:

5/7

Bas

elin

e: 1

B

lindi

ng: 0

Sam

ple

size

: 0A

ttriti

on: 1

Sta

ndar

dize

d ou

tcom

es: 1

Des

crip

tion:

1Fo

llow

-up:

1


TAB

LE 5

(CO

NTI

NU

ED)

neur

opsy

-ch

olog

ical

fu

nctio

n

Fran

cisc

o &

Ivan

hoe

1996

US

A

Type

: Int

erve

n-tio

n

Effe

cts

of

met

hylp

he-

nida

te o

n po

sttra

umat

ic

narc

olep

sy

Leve

l IVA

D

owns

and

B

lack

:11/

28R

ecru

itmen

t:LC

; Sin

gle

case

stu

dy;

Met

hylp

heni

-da

te: 1

0 m

g 2x

/day

then

↑

to 3

0 m

g 2x

/day

ove

r 4

mos

TBI =

1

Cla

ssic

tetra

d of

na

rcol

epsy

(ca

ta-

plex

y, E

DS

, sle

ep

para

lysi

s hy

pnag

o-gi

c ha

lluci

natio

ns);

diag

nosi

s co

n-fir

med

by

PS

G a

nd

MS

LT; N

o st

ruc-

tura

l, m

etab

olic

, or

card

iac

abno

rmal

i-tie

s th

at e

xpla

in th

e sy

mpt

oms

Age

, yrs

: 27

Gen

der:

Mal

eG

CS:

3 a

t in-

jury

site

but

7 a

t E

D; m

od T

BI

Tim

e si

nce:

22

mos

PS

G; M

SLT

1 m

o af

ter

initi

atio

n ca

tapl

exy

and

ED

S s

tarte

d to

impr

ove

6 m

os a

fter

the

star

t of

treat

men

t the

pa

tient

is a

s-ym

ptom

atic

At 1

2 m

os

med

icat

ion

was

invo

lun-

taril

y w

ith-

draw

n an

d sy

mpt

oms

retu

rned

Dru

gs le

adin

g to

no

repi

neph

rine

rele

ase

may

be

help

ful i

n re

vers

-in

g th

e sy

mpt

oms

of n

arco

leps

y

Mod

erat

e:

4.5/

7B

asel

ine:

0.5

Blin

ding

: 0S

ampl

e si

ze: 0

Attr

ition

: 1S

tand

ardi

zed

outc

omes

: 1D

escr

iptio

n: 1

Follo

w-u

p: 1

Oue

llet a

nd

Mor

in 2

007

Can

ada

Type

:In

terv

entio

nD

eter

min

e th

e ef

ficac

y of

co

gniti

ve b

e-ha

vior

ther

apy

(CB

T) in

TB

I

Leve

l III

Dow

ns a

nd

Bla

ck:1

6/28

Rec

ruitm

ent

OR

; Sin

gle

case

des

ign

with

mul

tiple

ba

selin

es

acro

ss

subj

ects

8

wk

CB

T ad

dres

sing

st

imul

us

cont

rol,

slee

p re

stric

tion

cogn

itive

TBI =

11

Incl

usio

n:•

18-5

0 yr

s•

TBI i

n la

st 5

yrs

• N

ot a

n in

patie

nt•

Inso

mni

a sy

n-dr

ome

(ope

ra-

tiona

l def

initi

on)

• If

taki

ng m

eds

for

6 m

os a

nd

stab

leE

xclu

sion

:•

Maj

or u

ntre

ated

or

uns

tabl

e m

ed-

ical

or

psyc

hiat

-ric

com

orbi

dity

• M

eds

know

n to

Age

, yrs

: 27.

3G

ende

r: 4

6% F

GC

S: 3

-14;

2

no d

ata;

mTB

I to

sTB

I as

eval

uate

d by

m

ultid

isci

plin

ary

team

usi

ng

stan

dard

crit

eria

Tim

e si

nce:

25

.64

mos

Sle

ep d

iary

(T

otal

wak

e tim

e, S

leep

ef

ficie

ncy)

; D

iagn

ostic

In

terv

iew

for

Inso

mni

a;

ISI;

MFI

; D

ysfu

nc-

tiona

l B

elie

fs a

nd

Atti

tude

s A

bout

Sle

ep

Sca

le; B

DI;

BA

I; 2-

nigh

t P

SG

; Sho

rt te

leph

one

Bas

elin

e re

-su

lts s

how

ed

varia

bilit

y as

ex

pect

ed;

clin

ical

and

si

gnfic

ant

redu

ctio

ns

in to

tal w

ake

time

and

slee

p ef

-fic

ienc

y fo

r 8/

11 (

74%

); P

rogr

ess

gene

rally

wel

l m

aint

aine

d at

follo

w-u

p;

Sle

ep e

ffici

-

Stre

ngth

s:G

ood

base

line

tabl

e; C

BT

seem

s pr

omis

ing

Li

mita

tions

: N

eede

d to

incl

ude

desc

riptio

n of

C

BT;

Did

not

as

sess

cog

ni-

tive

func

tioni

ng;

Wom

en w

ere

over

repr

esen

ted;

S

elf-s

elec

ted

so

may

be

mor

e m

o-tiv

ated

to c

hang

e

Mod

erat

e:

4.5/

7B

asel

ine:

0.5

B

lindi

ng: 0

.5S

ampl

e si

ze: 0

Attr

ition

: 1S

tand

ardi

zed

outc

omes

: 1D

escr

iptio

n:

0.5

Follo

w-u

p: 1


TAB

LE 5

(CO

NTI

NU

ED)

rest

ruct

ur-

ing,

sle

ep

hygi

ene,

ed

ucat

ion

and

fatig

ue

man

age-

men

t; S

leep

di

ary

for

2 w

ks a

t fo

llow

-up

and

3,5,

or

7 w

ks

rand

omly

de

term

ined

ac

ross

su

bgro

ups

of 3

; 1-m

o an

d 3-

mos

fo

llow

-up

prod

uce

inso

mni

a•

Sle

ep d

istu

rban

c-es

bef

ore

TBI

• A

noth

er s

leep

di

sord

er

• U

nabl

e to

com

-pl

ete

ques

tion-

naire

• E

xper

ienc

e si

g-ni

fican

t pai

n

inte

rvie

w a

t fo

llow

-up

by

inde

pend

ent

inte

rvie

wer

cien

cy

augm

ente

d;

↓ fa

tigue

sy

mpt

oms

Oue

llet &

M

orin

200

4 C

anad

a

Type

:In

terv

entio

nTo

test

the

ef-

ficac

y of

CB

T fo

r in

som

nia

with

TB

I in

a pe

rson

with

di

fficu

lty fa

lling

al

seep

and

st

ayin

g as

leep

si

nce

inju

ry

Leve

l III

Dow

ns a

nd

Bla

ck:1

0/28

Rec

ruitm

ent

OR

; Sin

gle

case

stu

dy;

8 w

kly

indi

vidu

al

man

ual-

ized

CB

T se

ssio

ns

(ada

pted

fo

r TB

I) ad

dres

sing

st

imul

us

cont

rol,

slee

p re

-st

rictio

n, c

og

rest

ruct

urin

g,

N =

1D

iagn

ostic

clin

ical

in

terv

iew

det

er-

min

ed h

ad m

ixed

in

som

nia

(ICS

D

and

DS

M)

Age

, yrs

: lat

e 30

sG

ende

r: m

ale

GC

S: 1

3/15

, no

com

a, P

TA 5

-7

days

, mod

erat

e TB

ITi

me

sinc

e: N

I

Sle

ep d

iary

fo

r 5

wks

of

base

line,

8

wks

CB

T,

2 w

ks p

ost

treat

men

t an

d fo

llow

-up

at 1

and

3

mos

PS

G

(5 n

ight

s: 3

pr

e an

d 2

post

) In

som

-ni

a S

ever

ity

Inde

x (IS

I) D

ysfu

nc-

tiona

l Bel

iefs

an

d A

tti-

tude

s ab

out

Sle

ep S

cale

Sle

ep o

nset

↓

from

47

min

to 1

8 an

d no

ctur

nal

awak

enin

gs

↓ fro

m 8

5 to

28

min

; bot

h be

low

clin

ical

cr

iteria

Sle

ep e

ffi-

cien

cy ↑

from

58

% to

83%

P

SG

cor

robo

-ra

ted

data

M

ajor

ity o

f ga

ins

wer

e m

aint

aine

d at

follo

w-u

p (ta

perin

g of

Stre

ngth

s:W

as a

dapt

ed fo

r TB

I Th

e be

havi

oral

re

com

men

datio

ns

in th

e in

terv

entio

n w

ere

sim

ple

and

stra

ight

fow

ard

Pro

mis

e fo

r no

npha

rmac

olog

i-ca

l int

erve

ntio

ns,

parti

cula

rly C

BT

Mod

erat

e:

4/7

Bas

elin

e: 0

.5

Blin

ding

: 0S

ampl

e si

ze: 0

Attr

ition

: 1S

tand

ardi

zed

outc

omes

: 0.5

Des

crip

tion:

1Fo

llow

-up:

1


TAB

LE 5

(CO

NTI

NU

ED)

and

slee

p hy

gien

e ed

ucat

ion

give

n by

a

clin

ical

ps

ycho

logi

st

5 w

ks o

f ba

selin

e, 8

w

ks C

BT,

2

wks

pos

t-tre

atm

ent

and

follo

w-

up a

t 1 a

nd

3 m

os

MFI

BA

Im

edic

atio

n w

as o

ccur

ing)

IS

I dro

pped

fro

m c

linic

al

to s

ubcl

inic

al

scor

e

Sha

n &

A

shw

orth

20

04

Can

ada

Type

:In

terv

entio

nA

sses

s th

e ef

-fe

cts

of lo

raz-

epam

ver

sus

zopi

clon

e on

co

gniti

on

Leve

l II

Dow

ns a

nd

Bla

ck:

23/2

8R

ecru

itmen

t: C

onse

cutiv

e A

I; D

oubl

e-bl

ind,

cro

ss-

over

tria

l S

elf-r

egul

ate

(0, 0

.5 o

r fu

ll ta

blet

) of

lo

raze

pam

(0

.5-1

.0 m

g)

or z

opic

lone

(3

.75-

7.5

mg)

at

bedt

ime

for

7 da

ysS

tart-

ing

dose

ra

ndom

ly

gene

rate

d A

t 2 w

ks

AB

I and

stro

ke =

18

(A

BI:

6)E

1 =

9E

2 =

9In

clus

ion:

• >1

8 yr

s•

Sec

onda

ry

caus

es o

f ins

om-

nia

okay

: dep

res-

sion

, apn

ea,

rest

less

legs

Exc

lusi

on:

• A

cute

ly il

l•

Non

-Eng

lish/

Fren

ch s

peak

ing

• U

nabl

e to

rea

d qu

estio

ns•

Sev

ere

cogn

itive

im

pairm

ent

Age

, yrs

: 56.

6G

ende

r:44

% F

GC

S: N

ITi

me

sinc

e: N

I

Fols

tein

M

MS

E:

base

line,

du

ring

wee

k 1

and

wee

k 2;

Rat

e qu

ality

of

slee

p fro

m

nigh

t bef

ore

(2 o

f 7 d

ays

but n

ot th

e fir

st 3

day

s)

- lo

cally

de

velo

ped

Tota

l sle

ep

time

re-

cord

ed b

y nu

rsin

g st

aff

ques

tion-

naire

eve

ry

30 m

in o

r 1

hrN

urse

s ra

ted

rest

fuln

ess

The

med

ica-

tions

see

m

to b

e eq

ually

ef

fect

ive

Lim

itatio

ns:

Non

phar

mac

olog

i-ca

l int

erve

ntio

ns

used

Crit

eria

par

-tic

ipan

ts u

sed

for

self-

dosi

ng n

ot

clea

rW

eak

mea

sure

s:lo

cally

dev

elop

ed

as c

onve

nien

ce,

thou

ght m

ore

sens

itive

than

M

orni

ng S

leep

Q

uest

ionn

aire

and

no

gol

d st

anda

rdE

xclu

ded

seve

re

impa

irmen

t

Mod

erat

e:

3.5/

7B

asel

ine:

0.5

B

lindi

ng: 1

Sam

ple

size

: 0A

ttriti

on: 1

Sta

ndar

dize

d ou

tcom

es: 0

Des

crip

tion:

1Fo

llow

-up:

0


TAB

LE 5

(CO

NTI

NU

ED)

stat

e w

hich

in

terv

entio

n pr

efer

and

drow

si-

ness

on

a 1-

4 sc

ale

test

ing

for

atax

ia

a Ove

rall

qual

ity (

sum

acr

oss

all t

he e

lem

ents

abo

ve; 0

.5 r

ound

ed d

own)

: 5, 6

, or

7 in

dica

te h

igh

qual

ity; 3

or

4 in

dica

te m

oder

ate

qual

ity; a

nd 1

or

2 in

dica

te

low

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It has been consistently reported in the literature that individuals with TBI experience symptoms of insomnia and other sleep disturbances across the spectrum of recovery from the acute stage and beyond, across all levels of severity, with some patients continuing to report sleep disturbances for many years postinjury.4,6,29–37

Thus, in order to try and present the litera-ture in a manner that might further elucidate our understanding of the developmental course of posttraumatic sleep disturbances over time, we attempted to discuss the studies from the perspec-tives of sleep in the acute stage, early recovery/rehabilitation (to 1 year), and 1–3 years and beyond. However, consistent with the reports of Ouellet and colleagues6 and Orff and colleagues7 in their previous reviews, we experienced diffi-culties in doing so, particularly for those studies (the majority of which we identified) that were cross sectional, that is, evaluating sleep at only one time period.

Most studies clearly identified the average time postinjury of their participants and the range/standard deviation, but the ranges were, in fact, quite wide. Among the studies that utilized a com-parison group (these studies were methodologi-cally stronger than studies that did not involve a comparison group), the ranges of time postinjury were the following (in chronological order from publication date): from 2.7 months to 5 years, average 2 years post;35 2 weeks to 53 months, average 3.8 months post;32 7 to 41 months, average 20.96 months post;4 20 to 1194 days, average 230 days;29 12 months to 21 years, mean not given;36 74 to 1194 days, average 516 days;26 12.3 to 43.3 months, average 27.8 mos;37 and up to 1 year post, specifics not given.27 Thus, among these studies, we identified an overall 21-year range in time postinjury of subjects. The results, however, were not stratified in any of the studies by time postinjury, thus making it extremely difficult to draw any definitive conclusions regarding the developmental time course of the sleep disorders.

Furthermore, sleep disorders may well be con-founded over time by the subsequent development of depression, anxiety, reduced activity and weight gain, again making it difficult to draw specific conclusions about the etiology of these disorders. It is necessary to acknowledge and mitigate potential factors that may confound the results,

whether these are factors that were preexisting to the brain injury or have developed secondary to the brain injury. However, from the perspective of recruitment at various times postinjury, there were studies that reported on sleep findings, including both prevalence and nature, at specific time points across different levels of severity. Thus, we have attempted to summarize the literature regarding the prevalence and nature of sleep disorders following TBI based on the source of patient recruitment: acute/postacute, rehabilitation, and community. Only those studies that delineated recruitment by time postinjury and level of severity, as well as stratified results according to the source of patients (e.g., acute care, rehabilitation settings) and level of severity, are included below. Thus, those studies that did not stratify their findings by level of severity are not included in our analysis. In addition, we only included studies that had substantial measures of sleep versus a single item documenting sleep problems.

a. Patients Recruited From Acute and Post-acute Care

We identified five studies that recruited participants from acute care settings.26,28,30,32,39

Acute mild. Chaput and colleagues38 con-ducted a retrospective chart review to determine the prevalence of sleep complaints in a sample of 443 patients diagnosed with mTBI. The authors used two time points: 10 days postinjury and again at 6 weeks postinjury. Of this sample, 13.3% reported sleep changes at 10 days postinjury, and this increased to 33.5% at 6 weeks postinjury with a smaller sample. Furthermore, the prevalence of sleep complaints at 6 weeks was 2.9 times more likely if such a symptom was present at 10 days (P = .004) and was associated with concomitant headaches, depressive symptoms, and irritability. Given the large sample size and the fact that they recruited all of those patients within the diag-nostic category rather than just those with sleep complaints, the sample bias is minimized and the results are more generalizeable to the whole mTBI population. The nature of the sleep complaints, however, was not delineated.

Acute and postacute moderate-severe. Makley and colleagues28 followed a sample of 14 patients


with moderate-severe injuries recruited at 9 to 23 days postinjury from acute care, and reported that 78% had severely impaired mean sleep effi-ciency (<63%), as measured by actigraphy. These patients were subdivided into two groups, those with ongoing posttraumatic amnesia (PTA) and those whose PTA had resolved. Of significance, they reported that sleep efficiency improved once patients were no longer in a state of PTA (P = .032). Baumann and colleagues24 consecutively recruited 96 patients within the first 4 days after TBI; at 6 months following TBI, 65 patients were evaluated using a combination of polysomnography (PSG), Multiple Sleep Latency Test (MSLT), actigraphy and clinical interview. The authors determined that at 6 months postinjury, among patients across all levels of severity (60% moderate-severe), 72% had sleep problems, 28% had subjective daytime sleepiness, 25% had objectively measured day-time sleepiness, 17% reported fatigue, and 22% reported “sensu strictu” (an increased sleep need over 24 hours). An additional 5% had insomnia. The authors further noted that in 43% of patients, the only possible cause of these problems was directly attributed to the TBI.

Rao and colleagues30 recruited a sample of 54 patients within 3 months of trauma across all levels of severity; however, all had experienced a loss of consciousness. Results of the Medical Outcome Scales for sleep indicated significantly increased sleep disturbance (P = .018), decreased sleep adequacy (P = .023), and increased daytime sleepiness (P = .0002) in comparison to self-reports of preinjury sleep. Watson and colleagues39 looked specifically at the prevalence of hypersomnia in a consecutive sample of 346 patients with TBI recruited from admissions to a Level 1 trauma hos-pital, in comparison with trauma controls (without TBI) and trauma-free controls. Data on sleepiness were collected at 1 month postinjury, with follow-up at 1 year. The level of severity was determined by the time taken to follow commands according to the motor component of the Glasgow Coma Scale (GCS). Although 78% of subjects took less than 24 hours to follow commands, they presented with serious enough symptoms in the emergency room that they were admitted to hospital and as such we have included them in our discussion of patients with moderate-severe TBI. At 1 month postinjury, 55% of all TBI subjects endorsed one

or more sleepiness items on the Sickness Impact Profile, in comparison with 41% of trauma controls and 3% of trauma-free controls (P < .001).

b. Patients Recruited From Rehabilitation Populations

Mild. We identified only four recent studies in which mild subjects from a rehabilitation outpa-tient population were recruited. Beetar and col-leagues35 conducted a retrospective chart review to determine the prevalence of sleep complaints in a consecutive series of 202 patients with TBI referred for neuropsychological assessment. The sample included 127 mTBI patients, 75 moderate-severe TBI patients, and 123 non-TBI controls. The authors found that, overall, 56.4% of the TBI patients had significantly more complaints of in-somnia in comparison with controls (30.9%; P < .001), and the mTBI group reported approximately 50% more insomnia complaints than those with moderate-severe injuries (P < .001). This study was an important early contribution to the litera-ture on sleep and TBI. Even though the authors did not use an operational definition of insomnia, their large sample size, use of a control group, and delineation of results by severity provided a strong foundation for future research. With regard to prevalence, Clinchot and colleagues40 also reported on a sample of patients recruited from consecutive admissions to rehabilitation and contacted at 1 year postinjury. The authors found that approximately 75% of subjects (GCS score of 13–15) subjectively reported sleep disturbance.

Schreiber and colleagues36 studied the nature of sleep disturbance, conducting a retrospec-tive study of 26 patients with mTBI and sleep disturbance who were consecutively admitted to ambulatory rehabilitation. In comparison with healthy age- and sex-matched controls (who had routine sleep evaluations as part of a preemploy-ment assessment procedure), the mTBI group had objective changes in sleep architecture, including increased light sleep (nREM) in 54.5% of subjects in comparison with controls (46.6%), and signifi-cantly lower total sleep time (P < .05). They also reported increased excessive daytime sleepiness objectively measured by MSLT in comparison with controls (higher number of falling asleep


episodes (P ≤ .05) and shorter time to fall asleep (P < .0005). Baumann and colleagues24 (also dis-cussed in the section above on acute and postacute moderate-severe TBI) reported objectively mea-sured sleep efficiency of 92% among their mild subjects; however, they identified 2 subjects (13%) with sleep efficiency well below the age-adjusted 25% percentile values. It is important to consider that the findings of these three studies may not be generalized to the population of mTBI as a whole. Despite the fact that the subjects were classified as mild, they all required rehabilitation and/or were referred for neuropsychological evaluation, thus placing them in a more “involved or severe/complicated” category of “mild” injury.

Moderate-severe. Although we identified seven studies that examined the prevalence and/or nature of sleep disturbances in samples recruited from a moderate-severe rehabilitation population,25,31,32,40–43 only the most recent (and higher quality) study stratified or reported results according to severity,25 with the exception of the earlier work by Clinchot.40 Clinchot and col-leagues40 (recruitment described above) found that approximately 57% of patients with a GCS score of 8–12, 24% of patients with a GCS score of 5–7, and 40% of patients with a GCS score of 3–4, reported subjective sleep complaints. Castriotta and colleagues25 conducted an objective evalua-tion of sleep in 87 patients who were at least 3 months postinjury and were recruited from the rehabilitation services at three academic medical centers. Abnormal sleep studies were found in 46% of subjects. With regard to the nature of the sleep disturbances, 20% had OSA, 11% had posttrau-matic hypersomnia, 6% had narcolepsy, and 7% had PLM. Among all subjects, 22% had objective excessive daytime sleepiness as measured by the MSLT. Interestingly, they identified no differences in injury severity and/or time postinjury between sleepy and non-sleepy subjects with TBI.

Finally, we identified two studies that recruited patients from rehabilitation, and although they identified objectively measured sleep and wake disturbances among participants, neither study identified any significant differences in injury severity or time postinjury between sleepy and non-sleepy subjects.25,31 Castriotta and colleagues25 examined the prevalence of sleep disorders in a prospective sample of 87 patients with TBI who

were recruited from the rehabilitation services at three academic medical centers. Abnormal sleep studies (PSGs) were found in 46% of participants, including 23% with OSA, 11% with posttraumatic hypersomnia, and 7% with PLMs. Objective excessive daytime sleepiness was found in 25% of participants. Consistent with the findings of Verma,31 OSA was more common in obese partici-pants (body mass index [BMI] > 30). Furthermore, these investigators did not find any differences in severity of injury or time postinjury between sleepy and nonsleepy participants (P < .05).

c. Patients Recruited From the Community

We identified eight articles in which samples of individuals with TBI who had returned to the community were recruited.4,26,27,29,31,37,39,44

Mild. Williams and colleagues37 studied the extent and nature of sleep complaints in a sample of nine university students with previous mTBIs (range, 1.4–3.6 years postinjury) in comparison with age- and gender-matched controls. They identified 4% less efficient sleep, shorter REM onset latencies, and longer sleep onset latencies in comparison with controls, objectively measured by PSG. Although this study is quite thorough and rigorous in design, the small sample size and “sample of convenience” (i.e., student volunteers), weakens the generalizability of the findings. Sch-reiber and colleagues36 characterized the nature of sleep disturbances in a sample of 26 chronic mTBI patients with sleep complaints who were at least 1 year postinjury. They reported changes in sleep architecture (as measured by PSG), includ-ing increased light non-REM sleep, in 54.5% of patients (±13.4%) in comparison with controls (46.6% ± 10.4%).

Moderate-severe. Parcell and colleagues29 reported on a sample of 63 participants with TBI consecutively recruited after discharge from rehabilitation, in comparison with 63 age- and sex-matched controls. Eighty percent of patients reported subjective changes in sleep relative to controls (23%), including more nighttime awakenings, and longer sleep-onset latency. In another study,26 Parcell and colleagues recruited 10 community-based participants with TBI and 10 age- and sex-matched controls. The authors


reported objectively measured increases in slow-wave sleep, reductions in REM sleep, and reduced sleep efficiency in comparison with controls, as well as subjective reports of poorer sleep quality.

Ouellet and colleagues4 recruited a sample of 452 participants from mailings distributed to 1500 people with TBIs identified through the archives of the rehabilitation center, as well as TBI associa-tions and support groups. Their sample included 59.9% with severe injuries, 23.3% with moderate injuries, 13.7% with mild injuries, and 3.1% with “minor” TBIs. Participants completed a detailed questionnaire that was then mailed back to the authors, who identified that 50.2% of their sample reported insomnia symptoms and 29.4% fulfilled the diagnostic criteria for an insomnia syndrome. This study continues to have the largest sample size of all of the literature to date pertaining to the prevalence of insomnia following TBI. In ad-dition, it is one of the few that actually delineated between those who presented with symptoms of insomnia and those who met the diagnostic criteria for insomnia, thus providing a more reli-able and valid estimate of the true prevalence. It is not possible, however, to completely eliminate sample bias without having information regard-ing the 1000 others who chose not to participate.

In another study, Ouellet and Morin44 ex-amined the nature of insomnia in the context of TBI by recruiting a sample of 14 adults with TBI who presented with an insomnia syndrome (nine of whom were moderate-severe), and 14 healthy, age- and sex-matched controls. It was not clear from the article how or where the participants were recruited. The authors reported that 71% of subjects had objective findings of insomnia, including more awakenings and shorter REM onset latencies. Furthermore, in comparison with controls, those with TBI had significantly more awakenings lasting longer than 5 minutes (P = .059), as well as significantly shorter REM latency (for those with TBI taking no medications) (P = .050). In the 1-year follow-up to their study of the prevalence of hypersomnia in the acute stage following TBI, Watson and colleagues39 found that 27% of participants continued to endorse subjec-tive symptoms of sleepiness, in comparison with 23% of trauma controls and 1% of nontrauma controls (P < .001). However sleepiness did im-

prove in 84–100% of participants with TBI, with the smallest improvement being 84% in the mild-est group (≤24 hours to respond to commands). Verma and colleagues31 objectively examined the nature and spectrum of sleep disorders in chronic TBI by recruiting a sample of 60 patients who presented with postinjury sleep complaints. It is not clear where or how the participants were recruited. Sixty percent of patients in the sample had moderate-severe injuries. Hypersomnia was the presenting complaint in 50% of all partici-pants, which the authors reported was “mostly due to” underlying sleep apnea, narcolepsy, and PLMs. Of interest, 45% of the sample exceeded a BMI of 30, which is considered to be obese. Insomnia was the presenting complaint in 25% of participants, and half of those had difficulties with sleep onset.

Sport-related concussion. New to the literature is a 2009 study that evaluates sleep following sport-related concussions. Gosselin and col-leagues27 examined both subjective and objective sleep quality in 10 subjects/athletes with a sport-related concussion, and compared their findings to those of 11 nonconcussed control athletes from noncontact sports. The concussed group had a history of 4.6 (±2.1) concussions on average, sustaining at least one in the previous year. Ob-jective measures of sleep included two consecu-tive nights of PSG, and electroencephalography (EEG) spectral power; subjective measures of sleep included the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Post Concussion Symptom Scale, as well as a subjec-tive questionnaire that was developed specifically for the study. The authors reported that although the concussed athletes identified more symptoms and worse sleep quality than controls, this was not corroborated by any polysomnographic vari-ables, or REM and nREM sleep quantitative EEG variables. However, concussed athletes showed considerably more relative delta activity, and reduced alpha activity and relative alpha power, during wakefulness than controls. Based on these findings, the authors concluded that sport-related concussions are thus associated with wakefulness problems, rather than sleep disturbances per se. Although this study has a small sample size and as such the Gosselin and colleagues’ findings are preliminary, their strong methodological design is


such that this is an important first step in exam-ining this population. Their findings are relevant and timely, given that sport-related concussions occur at a predictable rate in “high-risk” sports (i.e., football, hockey, etc.), ranging from 7–12% of the participant population in any given year, and that the sequelae of sport-related concussion is currently receiving much attention.45–47

d. Prevalence

As the literature has continued to evolve, we have attempted (as have others before us) to identify ranges of the prevalence of sleep disturbances identified among the studies based on time postin-jury of recruitment. The results of these studies confirm that disorders of sleep and wakefulness are prevalent across all stages of recovery from TBI, from the early acute stage until many years postinjury, and across all levels of severity. However, defining conclusive “ranges” contin-ues to be problematic due to the heterogeneity within and between samples, inconsistencies in the measures used, different study objectives, and variations in reporting. Some studies utilized percentages for reporting findings; alternatively, others reported on regression analysis of sleep, along with various associated phenomenon (i.e., depression, anxiety); identified changes in sleep architecture; looked specifically at insomnia as a global phenomenon; reported on the symptoms of insomnia; or, looked at other types of sleep disorders such as hypersomnia in and of itself, or secondary to apnea. As such, a valid synthesis of prevalence rates among studies remains elusive, and larger epidemiological studies across levels of severity and varying time points are warranted.

e. Methodological Limitations

Although the studies continue to become more scientifically rigorous as the literature evolves, the results to date are representative of methodological limitations in study design, as most of the literature is based on a clinical subset of TBI survivors who: a) present with sleep complaints, therefore intro-ducing bias into the sample; and b) have received rehabilitation and therefore represent a subset of

this patient population with likely more severe injuries, even those who are classified as “mild”. Thus it is likely that the data are skewed and are not fully representative of the TBI population as a whole. However, Parcell and colleagues26 specifically identified that their sample of 10 in-cluded “the first ten willing participants, with no preference for patients with sleep complaints,” and Fichtenberg and colleagues32 recruited a prospec-tive sample of 50 consecutive admissions to an outpatient rehabilitation program. The advantage of recruiting consecutively upon admission to the acute setting or from the emergency room is that all patients diagnosed with TBI are included in the study sample and followed regardless of whether they require postacute care. By following patients from the acute stage the issue of time since injury becomes negated, as all of the sample will be entered into the study at time of injury. As soon as recruitment takes place after the acute stage, researchers are already introducing forms of selec-tion bias into the sample that should be addressed when discussing the generalizability of the find-ings. Given that such a small percentage of the studies were able to recruit consecutively from the acute setting the epidemiological understanding of this phenomenon is going to be fraught with issues of generalizability and difficulty in making clear conclusions.

An ideal study would follow a large sample consecutive series of patients from acute care for at least three years to understand how sleep prob-lems manifest themselves, or not, and how these change over time, considering natural recovery by levels of severity.

Confounds. Some of the researchers made sure to exclude concurrent potential confounders, whereas others collected data on potential con-founders (usage of caffeine, alcohol, medications, or drugs, BMI, and emotional state). However, with the exception of emotional state, which is also identified as a concurrent risk factor, the re-sults were not stratified according to any of these confounds, nor were they addressed in discussion. Thus, we are only able to comment that these confounders exist, but are not able to make any definitive comments regarding their influence.

Risk factors. Ten studies identified risk factors specifically associated with insomnia following TBI, and two studies identified risk factors for


other types of posttraumatic sleep and wake disorders. Beetar and colleagues35 identified pain and mTBI as being risk factors for insomnia complaints in a case-controlled sample of 200 TBI patients of mixed severity. Among a sample of 91 consecutive patients admitted to an out-patient rehabilitation program, Fichtenberg and colleagues41 identified three risk factors associ-ated with insomnia including milder injuries, the presence of pain, and depression. Of the three factors, depression had the strongest association with insomnia. Consistent with Fichtenberg’s findings, Ouellet and colleagues4 reported that among a sample of 460 survivors recruited from the community (averaging 7.85 years postinjury, 83.2% of whom with moderate-severe injuries), risk factors for insomnia included milder injuries, depression, and pain. They also identified high levels of fatigue as a further risk factor.

Among a sample of 60 patients with varying levels of severity, ranging from 3 months to 2 years postinjury, Verma and colleagues31 noted that those with complaints of insomnia had elevated Beck Depression Inventory (BDI) scores and Hamilton Anxiety scores, thus further confirming that de-pression and anxiety are risk factors for insomnia following TBI across all levels of severity. They also identified 45% of their sample as having a significantly high BMI. Chaput and colleagues38 identified headaches, depressive symptoms, and irritability as co-occurring with sleep complaints in a sample of 443 patients with mTBI, at both 10 days and 6 weeks. Rao and colleagues30 also identified depression and anxiety as coexisting risk factors for symptoms of insomnia. Clinchot and colleagues40 was the only study to identify gender (female) as a risk factor for symptoms of insomnia (P = .033), in addition to older age (P = .035), milder injuries, and a GCS score greater than 7 (P = .034). Baumann and colleagues24 identified that severe TBI (sTBI) was associated with the development of posttraumatic hypersomnia (P = .02), but not with the presence, characteristics, and severity of other posttraumatic sleep disorders. The association between more severe TBI and the development of hypersomnia was also confirmed by Watson and colleagues.39 Castriotta and col-leagues25 identified that among the 46% of their sample with abnormal sleep studies (with five different types of sleep and/or wake disorders),

the sample participants were significantly older than the nonsleep-disordered subjects (P < .01) and had a significantly higher BMI (P < .05).

Sample size. TBI is very heterogeneous and as a result it is complicated to conduct research that is generalizable. Ideally, studies would be able to recruit a large number of patients so that stratification on a number of variables would be possible: age at injury, gender, etiology of injury, severity of injury, and time since injury. Only 39% (9/23) of the studies reviewed used sample sizes of greater than 75. Thirty-five percent (8/23) of the studies involved studies with sample sizes of less than 30 and thus were compromised in their statistical analysis and their ability to generalize to the different subgroups of brain injury.

Definition of insomnia. Another method-ological limitation, also identified by Ouellet and Morin,44 is the lack of an operational definition of insomnia. Among the five comparison group stud-ies that evaluated subjective reports of insomnia, sleep, and hypersomnia postinjury,29,32,35,39,44 only two utilized an operational definition of insomnia, the International Classification of Sleep Disorders and the DSM-IV.32,44 Related to this is the lack of consistency in or development of an operational framework for assessing severity of brain injury. Many studies use the GCS score to assess severity but the GCS score is not always available and other factors are included: length of PTA, period of loss of consciousness, cerebral computed tomography (CT) findings, and neuropsychological findings. One study39 determined injury severity based on time taken to follow commands. Baumann and colleagues,24 one of the two methodologically strongest studies reviewed, specifically cited us-ing GCS scores and CT findings based on the Marshall48 criteria (I = no visible intracranial pathology, II–IV = midline shift, and V = mass lesion). It is necessary that there be consistency as to how to combine all of these factors together so that severity distinctions can be enabled when only some of the above features are present.

Measures. As per the comments of Orff and colleagues,7 there is also a significant discrepancy among the measures utilized. Of the 23 studies we evaluated under the epidemiology category, investigators used 19 different methods to evaluate sleep, of which four are objective (PSG, actigraphy, MSLT, Multiple Wake Test [MWT]). There is no


gold standard of standardized instruments that is accepted. Although locally developed measures and those that are clinically developed may be very useful, it is impossible to compare from one study to the next when different types of measures are being used to assess the outcomes. The issue is that sleep itself is very difficult to assess, as it is composed of many components. It would seem that among the validated instruments, the most commonly used and accepted are the Diagnostic Interview for Insomnia (DII), Insomnia Sever-ity Index (ISI), PSQI, and the ESS. It has been proposed that the MWT may be more suitable for this population than the MSLT, as daytime sleepiness seems to be a hallmark of this condi-tion. One study30 utilized the 12-item Medical Outcome Scale for Sleep,49 which has been found to have good psychometric properties and has been found to be useful for assessing sleep problems in adults. Each of these instruments contributes a unique component to the assessment of insomnia and sleep difficulties and as such should be used in combination, rather than in isolation.

The subjective or self-report measures ranged from the early work of Beetar, which relied on a

chart review, and concluded that “a sleep problem was judged as present if it was mentioned in the chart as reported by the patient,”35(p. 1299) to the more robust PSQI used by Fichtenberg32 (and validated for use with TBI patients), the battery used by Ouellet and colleagues44 that included the DII, ISI, Multidimensional Fatigue Inventory, in addition to other measures and nocturnal PSG, sleep diaries, and ESS used by Parcell and col-leagues.26,29 The most commonly used measures included the PSQI, PSG, and some form of a sleep diary. It is positive to note that as the literature evolves, overall, the use of measures to evaluate sleep and wake disorders have become increas-ingly comprehensive, sensitive, and “robust” over time. This in and of itself, however, further emphasizes the weakness of recent studies that rely on limited and/or weak measures, such as the study by Watson and colleagues.39 Although we recognize that this study was part of a larger study and had the strength of a follow-up in its design, the sole reliance on data obtained via four questions about sleep from the Sickness Impact Profile weakens the validity/generalizability of the overall findings.

TABLE 6

Practice Points Research Agenda1. Sleep and wake disorders are

present across all levels of severity at all stages across the continuum of recovery following TBI.

1. A large scale multi-center collaborative trial involving all those with TBI (i.e., not limited to those who present with sleep prob-lems) recruited in the acute stage, followed longitudinally into the community and evaluated at regular time points is warranted.

2. Sleep and wakefulness should be routinely and systematically as-sessed for the duration of medical and neuropsychological follow-up after TBI.

2. Functional measures should be used in addition to formal mea-sures of cognition.

3. Risk factors for insomnia include mTBI, pain, anxiety, depression, fatigue, and older age.

4. Risk factors for hypersomnia in-clude more severe TBI.

5. Increased BMI (>30) is a risk fac-tor for OSA.

6. The PSQI, followed by the ISI, are appropriate measures for initial screening and corroboration of the impact of the problem.


2. Pathophysiology

We identified three papers, all of moderate quality, which look at varying aspects of pathophysiol-ogy of sleep/wake disturbances following TBI, including two Level III studies50,51 and one Level IVA study.52 In 2005, Baumann and colleagues50 sought to test the hypothesis that deficiencies in hypocretin-orexin-1 (Orexin A) neurotransmission in acute TBI may play a role in the emergence of subsequent sleep/wake disorders. Orexin A is an excitatory hypothalamic neuropeptide involved in the regulation of the sleep/wake cycle, and its levels are typically reduced in persons with narcolepsy. Hypocretin-1 levels were measured in 44 patients by radioimmunoassay at 1–4 days following TBI (males, n = 32; 31 patients with sTBI, 8 with moderate TBI [modTBI], and 5 with mTBI), and compared with hypocretin-1 levels in healthy controls (n = 20). Their results indicated that in comparison with controls, hypocretin-1 levels were abnormally lower in 95% of patients with moderate-severe TBI, and in 95% of patients with posttraumatic brain CT findings. The authors postulated that hypocretin-1 deficiency following TBI may be reflective of hypothalamic damage (specifically to the posterolateral hypothalamus) and may be linked with the frequent development of posttraumatic sleep wake disorders. These findings are an important contribution to the determination of risk factors.

Ayalon and colleagues51 conducted a study to diagnose and describe the physical and behavioral characteristics of circadian rhythm sleep disorders (CRSDs) in patients with mTBI. Forty-two pa-tients with mTBI and complaints of insomnia were screened, and those who were suspected of having CRSDs underwent further diagnostic evaluation. In total, 15 of the 42 patients (36%) were formally diagnosed with CRSDs, eight patients displayed a delayed sleep phase syndrome (DSPS), and seven patients displayed an irregular sleep-wake pattern (ISWP). All patients exhibited a 24-hour period of melatonin rhythm, and those with DSPS exhibited a 24-hour periodicity oral-temperature rhythm. However, three of the seven patients with ISWP lacked such a daily rhythm. Furthermore, the pa-tients with ISWP exhibited smaller amplitudes of temperature rhythm. Given that the authors found that as many as 36% of their particular sample had

been diagnosed with insomnia when in fact they had a CRSD, they concluded that CRSDs may be a relatively frequent sleep disorder among these patients, and that misdiagnosis of patients with CRSDs as insomniacs may lead to inappropriate prescription of hypnotic medications.

Quinto and colleagues52 described the case of posttraumatic DSPS in a 48-year-old male, 4 years following TBI. (Note: the authors use the term cerebral concussion; however, as the patient was in coma for “several days,” we will consider this to be a severe TBI [sTBI]). Although the pa-tient was 4 years postinjury, the emergence of his sleep onset insomnia was during the acute phase of recovery. Since his injury, it took him 1 to 2 hours to fall asleep. He reported through a sleep diary that he would go to bed between 3:00 and 5:00 a.m., awaken after 1 to 1-and-a-half hours, return to sleep, and awaken between 11:00 a.m. and 12:00 p.m. These findings were confirmed by actigraphy. The patient did not have any other medical or psychiatric disorders. Circadian rhythms are quite strict and are in fact slightly less than 24 hours in humans. The “circadian clock” located in the suprachiasmatic nucleus (SCN) of the hypothalamus serves to keep physiologic functions in synchrony with each other and with the environmental light/dark cycle, thus making a small daily phase advance to entrain to the 24-hour day. A decreased ability to make this phase advance in response to environmental cues is thought to be the underlying pathophysiology behind DSPS, and the authors of this study postulate that damage to the SCN sustained during trauma may result in circadian cycle disorder.

3. Pediatrics

We identified six studies, five of which were of moderate quality, which reported sleep complaints in children and adolescents. Five of these studies focused specifically on mTBI. In a 2001 study of 19 adolescents 3 years following minor head injury (mHI), Kaufman and colleagues53 reported that in comparison with healthy controls, head-injured teens had significantly reduced periods of sleep time, total sleep time, and sleep efficiency, as well as an increased number and length of awakenings, objectively measured by PSG and


actigraphy over 5 days. Subjectively, those with mHI reported significantly more difficulties falling asleep, difficulty waking in the morning, restless sleep and parasomnias, fearful awakenings from sleep, and increased daytime sleepiness than did healthy controls. Further investigations by this group of authors54 found that in comparison with healthy controls, nearly one third (27/98) of the subjects aged 8–18 years, with 0.5–6 years fol-lowing mHI, had subjective complaints of sleep disturbance and shorter weekend sleep time than did healthy controls. The authors identified that those with mHI and complaints of sleep distur-bance were also more likely to complain of brux-ism and manifested a significantly greater BMI. Furthermore, these subjects came from families with a lower level of parental education. Although no information was available regarding preinjury BMI or any patterns of weight gain postinjury, the authors concluded that risk factors for sleep disturbance in mHI include heavier body mass and lower levels of parental education.

In 2004, Korinthenberg and colleagues55 examined predictive factors of posttraumatic syn-drome in children (range, 3–13 years) with mHI.

The authors used data from EEG, in addition to a published neurological examination protocol and a structured validated interview at two time points (T1: within 24 hours of the injury, and T2: 4–6 weeks postinjury) to identify that at follow-up, 23 of 98 patients continued to present with psychiatric complaints, including sleep disturbance and fatigue. These findings did not correlate with the severity of the injury, or somatic, neurologic, or EEG findings immediately postinjury. In their discussion, the authors stated that the “lack of a correlation with the acute concussional symptoms, acute neurological findings and the acute EEG abnormalities suggests that post traumatic com-plaints in our patients are not primarily caused by organic structural or functional changes.“55(p.116) They noted that parental and patient anxiety is a frequent problem even after mHI, and it correlates with persistent symptoms.

In contrast, however, Necajauskaite and col-leagues56 studied 102 matched pairs of children aged 4–16 years, including a case group with mTBI and comparison group with mild bodily injury but no mTBI. They found that although 16.7% of the parents in the case group reported

TABLE 7

Practice Points Research Questions1. It may be of benefit to measure hypocretin-1 in

patients with moderate-severe TBI (who are being monitored for Intracranial Pressure [ICP]) during the acute stage as a potential marker/risk factor for the emergence of sleep and wake disorders.

1. “Future research specifically designed to explore the role of neurophysiologic and psychological factors in the emergence of CRSDs following mTBI may improve our understanding of the nature of this association.” 51(p.1139)

2. Lesions/damage to the hypothalmus are a risk factor for sleep/wake disorders following TBI.

3. Awareness of DSPS as a possible consequence of TBI is important as its symptoms may be over-looked and attributed to the “typical” postconcus-sion syndrome complex.

4. Proper diagnosis of CRSDs is important as a misdiagnosis of insomnia may lead to inappropri-ate prescription of hypnotic medication, which “may help patients fall asleep, but would not be efficacious in normalization of the sleep-wake cycle.” 51(p. 1139)

5. Treatments with melatonin or bright light may be more appropriate with CRSDs.


sleep disturbances in their children shortly after the trauma (exact time not defined), they did not find any significant differences in subjective reports of sleep disturbance between the two groups in the month prior to follow-up (1–5 years postinjury; mean, 27 months).

In the most recent study to examine sleep in children with mTBI, Milroy and colleagues57 compared 18 children aged 7–12 years with mTBI with 30 children with orthopaedic injuries (aver-age time postinjury, 24 months). These authors used both subjective and objective measures (parental and self-report sleep questionnaires and actigraphy), and while parents reported greater sleep disturbances in the mTBI group, there were no significant differences between the groups with respect to daytime sleepiness, children’s self-report of sleep disturbance, and actigraphy results.

We found only one study that examined sleep in children with moderate-severe TBI. Beebe and colleagues58 compared parental reports of sleep be-haviors in approximately 100 children (aged 6–12 years), 50 with modTBI and 50 with sTBI, with a comparison group of 80 children with orthopaedic

injuries. The children were followed longitudinally over three time points at approximately 6, 12, and 48 months postinjury. The authors reported that for both groups, daytime sleepiness and nocturnal sleep duration were increased following TBI. The modTBI group reported higher baseline sleep problems than the sTBI group and the orthopaedic group; however, this declined over the follow-up period (the specific time course was not specified) to a level consistent with the general population (6–9%). However, the authors reported that the sTBI group displayed an injury-associated increase in sleep problems, with the prevalence nearly doubling from 16% at baseline to 31% postinjury (again, specific timelines were not specified). The authors cautioned that these results should be con-sidered as preliminary given the limitations of the outcome measure; however, they concluded that sleep problems emerge after severe pediatric TBI (and are present in the postacute stage in modTBI).

In conclusion, there is emerging conclusive evidence to support the incidence and prevalence of sleep disturbances in children and adolescents following TBI, across all levels of severity. There

TABLE 8

Practice Points Research Questions1. Children and adolescents with

mTBI/mHI need to be systematically and routinely assessed for subjec-tive complaints of sleep disturbanc-es and followed-up over time.

1. Sleep (and wake) problems in children and adolescents with both mild and moderate-severe TBIs should be evaluated longitudinally by both objective and subjective measures begin-ning at the onset of injury, to determine any patterns in the developmental course of sleep distrubance.

2. Children with moderate-severe TBIs should be followed and assessed for emergence of sleep problems, with provisions of appropriate sleep interventions.

3. Adolescents with mHI, higher BMI, and lower levels of parental educa-tion are at increased risk for sleep disturbances. Educating adoles-cents and parents about healthy eating and regular activity may be of benefit.

4. Providing parents with education and information during the acute stage post mHI may help to allevi-ate anxiety and improve outcome.


is both subjective and objective evidence docu-menting the prevalence of sleep disturbance in adolescents with mTBI several years postinjury. There is emerging subjective evidence to suggest that sleep disturbances become more prevalent over time in children with sTBI, yet decline over time postinjury in children with modTBI. There is evidence to suggest that sleep problems in children with mTBI do not correlate with initial neuro-logical findings. Clearly, the research on sleep disturbances in children with TBI is in the early stage and warrants further scientific investigation to more clearly identify the nature and patterns of the disturbance, any functional implications, and appropriate interventions.

4. Neuropsychological Implications

Sleep disturbances following TBI have been reported to exacerbate cognitive and behavioral sequelae. We identified four studies of moder-ate quality: three evaluated neuropsychological (and cognitive-communication) function in rela-tion to sleep disorders following TBI, and one documented both sleep and neuropsychological sequelae following nonimpact brain injury. In 2000, Henry and colleagues59 retrospectively investigated the neuropsychological and behav-ioral functioning of 32 adults (aged 18–66 years) with “non-impact brain injury” (i.e., whiplash) up to 65 months postinjury. The authors used a comprehensive battery of standardized neuro-psychological and psychological tests to assess cognition, motor skills, and mood functioning. As the study was retrospective, some subjects had had structural neuroimaging, and three had undergone overnight sleep studies, in addition to neurological examination and interview. Re-sults indicated that patients with whiplash injury demonstrated persistent cognitive, behavioral, and emotional dysfunction years postinjury. Fifty-three percent had problems with sleep (not defined) in addition to difficulties with attention, concentration, executive functions, reduced information processing, word finding, sexuality, anxiety, and depression. Of the three subjects who underwent a nocturnal sleep study, sleep maintenance insomnia was identified with altered sleep stage percentages and altered REM

rhythms. Although the authors cite methodologi-cal limitations as precluding any conclusions regarding causation, finding sleep disturbance following whiplash is not surprising given the shearing injury and potential involvement of the hypothalamus.

In 2004, Mahmood and colleagues60 conducted an investigation of the relationship between sleep disturbance and neurocognitive ability in 87 adults with TBI across all levels of severity who had been admitted to a comprehensive outpatient rehabilitation program. The authors conducted a cross-sectional examination of scores on patients’ neuropsychological examinations, the BDI-II and the PSQI. They reported that: “as would be expected, PSQI scores and BDI-II scores were sig-nificantly correlated because of the partial overlap of depression symptoms and insomnia.”60(p.382) The authors also reported that measures sensitive to higher-order executive functioning and speed of information processing showed a positive relation-ship with PSQI scores. Their findings supported a hypothesis of a predictive relationship between performance on neuropsychological tests and reports of sleep disturbance in adults with TBI.

In 2007, Wilde and colleagues61 examined the impact of comorbid OSA (diagnosed after the TBI) on the cognitive functioning of 19 pa-tients with TBI, in comparison with 16 patients with TBI but without OSA. The subjects were otherwise comparable in terms of age, education, injury severity, time postinjury, and GCS score (where available). The patients with TBI and OSA performed significantly worse on verbal and visual delayed recall measures, and had more at-tention lapses than the patients with TBI without OSA. Interestingly, they did not differ on other measures of visual construction and motor and attention tests. The authors concluded that patients with TBI and OSA had greater impairments in sustained attention and memory than did those patients with TBI without OSA.

In 2010, Wiseman-Hakes and colleagues62 assessed daily self- and clinician (rehabilitation worker) reports of changes in cognitive and communication functioning, including sustained auditory attention/vigilance, speed of language processing, verbal memory, and communica-tion, in response to a course of pharmacological intervention phased in over 17 weeks for post-


traumatic hypersomnia. The self-report measure used in this study is the newly developed Daily Cognitive-Communication and Sleep Profile (D-CCASP), which is currently undergoing reliability and validity testing (Wiseman-Hakes, 2005, un-published measure). This case-study participant was a young man in his late teens 11 months after sTBI when the study began. As treatment progressed, the authors found a clear positive relationship between improved quality of sleep and language processing (defined as the ability to follow and participate in conversation), sus-tained attention/vigilance (defined as the ability to pay attention and concentrate over time), and memory (defined as the ability to remember things that one has heard, done, or seen). This was seen across the different phases of the medi-cation regime (P < .01). A follow-up conducted at 3 years and 8 months indicated that the gains in sleep, daytime wakefulness, and cognitive-communication function had been maintained. Although the data were limited to one subject, the findings suggest that appropriate, timely, and effective diagnosis, and management of sleep/wake disturbances following TBI, may facilitate improved cognitive-communication function. The authors concluded that their results need to be corroborated with a larger sample size and the addition of standardized neuropsychological and cognitive-communication assessment measures to clinically evaluate reported functional changes.62

5. Intervention

The literature on the treatment of sleep distur-bances following TBI is relatively limited at this time. This may be a reflection of the complexity of this disorder from a number of perspectives; that is, the lack of a clear etiology in many patients, mixed diagnoses, lack of consistency regarding the developmental course of the disorder, and in-teractions with secondary issues such as pain and depression. We identified six papers for review in total: four were of moderate quality and two of high quality. Four of the six articles focused upon pharmaceutical management; of these four, one was for the treatment of fatigue and excessive daytime sleepiness following TBI, one was for the treatment of narcolepsy, another was for the

treatment of insomnia following TBI and stroke, and only one addressed treatments for a number of different types of sleep disorders commonly associated with TBI. The remaining two articles focused on behavioral intervention specifically for insomnia.

These latter two moderate-quality articles by Ouellet and Morin63,64 assessed the efficacy of a protocol of CBT administered by a registered clinical psychologist over a period of 8 weeks. The first paper reports an individual case study and the second reports a single case series. The authors state that cognitive therapy for insomnia consists of “identifying, challenging and altering a set of dysfunctional beliefs and attitudes about sleep,” with the objective of “breaking the cycle of insomnia; dysfunctional thoughts and emotional distress that lead to further sleep disturbances.”63(p.

1299) The authors do a thorough job of delineating the treatment protocol, which was adapted to take into account the deficits in memory, attention, and processing that can occur following TBI.

The results of the case study are promising; the participant experienced reduced sleep onset latencies and nocturnal awakenings, and an in-crease in sleep efficiency. These results were well maintained at follow-up at both 1 and 3 months. The authors built upon these initial results by ex-panding their assessment measures and number of subjects in a single-case series of 11 individuals (six males, five females) with mild to severe TBI. There are a number of relative strengths of this article, despite the small sample size. Subjects were recruited from a variety of locations using a variety of methods, including major rehabilita-tion centers across Quebec, Canada, as well as through advertisements to TBI associations and local support groups. Furthermore, all levels of injury severity were represented, indicating that although the sample size is small, their sample is likely fairly representative of the post-TBI popu-lation. Their results indicated a decline in total overnight wake time relative to baseline, as well as a reduction in overnight sleep variability in 8 of 11 participants. Treatment effects were seen 1–2 weeks after the beginning of therapy. All participants increased their sleep efficiency, and 5 of 11 achieved a sleep efficiency of greater than 90% at the 3-month follow-up. At posttreatment, 7 of 11 no longer fulfilled the diagnostic criteria


for insomnia. Based on their results, the authors suggest that insomnia associated with TBI can be successfully improved in a large proportion of cases with short-term cognitive behavioral intervention.

The remaining four papers for review ad-dressed pharmacological intervention. Jha and colleagues65 examined the efficacy of modafinil in treating fatigue and excessive daytime sleepiness in individuals with TBI. This high quality, com-prehensive, and well-conceived study consisted of a double-blind placebo cross-over trial in which 53 patients with TBI were randomly assigned to receive up to 400 mg of modafinil, or an equal number of inactive placebo tablets. The partici-pants were a minimum of 1 year postinjury, with a severity level such that they required inpatient rehabilitation (no other information regarding lev-els of severity was provided). For the modafinil regime, patients took 100 mg (one tablet) once per day at noon for 3 days, and then increased to 100 mg 2 times per day for the next 11 days, followed by the maintenance dose of 200 mg twice daily in the morning and at noon. Following the end of the randomized study, both groups were offered a 4-week open label period in which they could receive modafinil using individually clinically monitored titration and a maintenance dosage. However, results indicated that after adjusting for baseline scores and period effects, there were no statistically significant differences between improvements with modafinil versus placebo on any of the outcome measures (Fatigue Severity Scale, the Modified Fatigue Impact Scale, and the ESS). Thus, despite the scientific rigor of this study, there were no consistent and/or persistent clinical improvements.

The next study by Li Pi Shan and Ashworth66 focused specifically on insomnia post-TBI and stroke, and aimed to compare the efficacy of lorazepam and zoplicone as treatment options. This study also followed a double-blind cross-over trial involving 18 patients with TBI or stroke (six patients with TBI, six with a right hemisphere stroke, and six with a left hemisphere stroke; no information about severity or time postinjury). Participants were prescribed 0.5–1.0 mg loraz-epam at bedtime as needed for 7 days, followed by 3.75–7.5 mg zoplicone at bedtime also as needed. Participants were able to regulate their own dosage from 0 to 0.5 to 1 tablet per night,

to “empower them and to simulate what normally happens on our ward.”66(p. 422) Results indicated no significant differences in total sleep time or in subjective measures of sleep. Furthermore, the authors evaluated cognition using the Mini-Mental State Exam (which in our view is an extremely weak and insensitive measure for this purpose, particularly for the TBI population), and found no changes with either medication. The authors concluded that zoplicone and lorazepam are equally effective in the treatment of insomnia for both populations. However, because the authors do not report any baseline information on sleep, the reader is not able to determine any actual level of improvement and any clinical application of their findings is thus negated, which is another weakness of this study.

The most recent study by Castriotta and col-leagues67 aimed to determine whether treatment of specific sleep disorders (which they diagnosed by means of PSG) would result in resolution of those disorders and improvement of symptoms and daytime function. The investigators conducted a thorough, high-quality prospective evaluation of 57 unselected patients with TBI, >3 months postinjury using PSG, MSLT, ESS, and neuro-psychological testing, including the Psychomotor Vigilance Test (PVT), Profile of Mood States, (POMS), and the Functional Outcome of Sleep Questionnaire (FOSQ), prior to and after treat-ment for OSA (23% of 22/57), posttraumatic hypersomnia (PTH) (3%), narcolepsy (5%), PLM (7%), and objective excessive daytime sleepiness (22%). In total, 22 of 57 subjects had abnormal polysomnograms (39%). Treatments included continuous positive airway pressure (CPAP) for OSA, modafinil (200 mg) for narcolepsy and PTH, or pramipexole (0.375 mg) for PLM. In terms of response to treatment, the investigators found that the apneas (and hypopneas, as well as snoring) were eliminated by CPAP; however, there was no significant change in MSLT scores. In addi-tion, they found that PLMs were eliminated with pramipexole. One of three narcolepsy subjects and one of two subjects with PTH had resolutions of hypersomnia with modafinil. However, there were no significant changes in FOSQ, POMS, or PVT results after treatment. The authors concluded that treatment of various sleep disorders after TBI may result in polysomnographic resolution,


without change in sleepiness or neuropsychologi-cal function.

Overall, the results of these four studies on pharmacotherapy leave us with somewhat of a clinical conundrum. The results of Castriotta and colleagues67 may provide guidance to those treat-ing posttraumatic apnea (and hypopneas), PLMs, and hypersomnia, which makes intuitive sense from a clinical perspective because these disorders are relatively more “clear cut” in their etiology. However, insomnias can be more complex and multi-faceted in their etiology, potentially includ-ing a combination of underlying physiological and psychiatric issues, and thus are often harder to manage pharmacologically without a combina-tion of medications. Furthermore, results of the Shan and Ashworth study66 lead us to conclude that standardized dosages may not be effective, and that any medication regime needs to be fine tuned to the individual needs of the patient, an important protocol built into the final 4 weeks of the study by Jha and colleagues.65 Thus, an ideal treatment regimen may include a trial of cognitive behavior therapy with the addition of pharmacotherapy as needed, specifically tailored to the individuals’ symptoms, body weight, and tolerance. In addition, Castriotta and colleagues67 reported resolution of polysomnographic findings without associated improvements in daytime func-tion, which suggests that a follow-up study may be of benefit, with an individual case-series design in which additional treatments and/or medications could be added that are specific to each participant. Based on the current findings to date, it is clear that intervention for sleep and wake disorders following TBI is an area of significant need with respect to future research directions.

IV. DISCUSSION

This systematic review was conducted to sum-marize the current literature on the topic of sleep and wake disorders following TBI and to critically appraise the research directions. In summary, our findings concur with previous re-views: sleep and wake disorders are a prevalent and complex sequelae of TBI, occurring at all stages across the continuum of recovery from acute, to postacute, to rehabilitation, in both

children and adults, and for a number of patients, continuing for many years postinjury, long into the community. These disorders are complex and multi-factorial, and have an impact on neu-ropsychological functioning and participation in rehabilitation and quality of life. They may evolve from a neurophysiological disruption in brain function to a secondary disorder associ-ated with depression, anxiety, weight gain, and other factors. As such, intervention is equally complex and much more work needs to be done to fully understand the underlying etiologies and to find appropriate treatments. With regard to methodological quality and scientific rigor of the literature, there is a readily observable trend toward higher-quality, more methodologi-cally sound studies as the literature evolves over time. To date, however, most studies have been limited by small sample sizes, large ranges in time postinjury of participants, loss to, or lack of, follow-up, and sample bias due to timing and methods of recruitment. Thus, it is still unclear exactly which members of the TBI population are affected and how the disorder evolves over time. Furthermore, it is unclear why those with mTBI are more likely to present with insomnia or symptoms of insomnia, and whether this is a true manifestation of the disorder or a reflection of other issues such as self-awareness or the challenges of returning to work, school, and/or the community. We recognize, however, that the current state of the literature also reflects the inherent complexities of conducting clinical research with this highly diverse, heterogeneous population.

A. Limitations

Although the current review utilized a systematic approach for the critical appraisal and determina-tion of methodological quality of the literature, we recognize a number of limitations in this methodology. All of the articles included have been peer-reviewed and, as such, there is publica-tion bias. Furthermore, while we have attempted to fully capture all of the recent relevant articles with our search criteria, it is possible that we may have missed articles; thus, this review may not be fully representative of the current literature.


Given constraints of time, we did not contact any of the study authors directly to clarify any points of confusion; our quality rating system is based upon our understanding of the reporting of the methodology and results, and thus may not be truly representative of the actual study design and quality.

B. What This Review Adds

Despite its limitations, this review adds to the body of knowledge regarding sleep and wake disorders following TBI. To date, it is the most comprehen-sive review, with the inclusion of literature specific to the pediatric population, and is also the first to attempt to delineate the prevalence and nature of sleep disorders by timing of recruitment and levels of severity across the continuum of recovery. It is also the first review to systematically appraise the methodological quality of the current literature.

C. Conclusions and Future Research Directions

Sleep and wake disorders following TBI have received increasingly considerable attention among the clinical and scientific community. Researchers have attempted to quantify the incidence and prevalence of these disorders, as well as to define and describe the nature of the disorder with both subjective and objective measures. Furthermore, attempts have been made to understand the underlying pathophysiological mechanisms and other contributing factors, as well the functional implications and treatment options. However, additional research is needed to fully understand this complex disorder and to identify appropriate and timely interventions. A large, multi-center study is needed that follows all of those with TBI from the acute stage with regular follow-up into the community, such that results can be reliable, valid, and stratified by nature and severity of injury, age, sex, imaging results, and development of the disorder over time. In addition, we recommend that outcomes for either epidemiological or intervention studies should also capture functional outcomes in addition to sleep measures and cognitive measures to fully assess

the impact of the intervention. Finally, we concur with statements by Dr. Richard Castriotta in his recent editorial that “careful study will require much effort and many resources,” which can best be brought to fruition “through collaborative efforts across multiple centers,” with an aim to “elucidate the causes, foster early diagnosis, and develop optimal treatment for these problems.”68(p.

177) These continuing efforts will further inform clinical practice and ultimately contribute to the development of practice guidelines for the systematic evaluation and treatment of sleep and wake disorders following TBI.

ACKNOWLEDGMENTS

This work was supported by the Canadian Insti-tutes of Health Research (CIHR) through a Fel-lowship in Clinical Research and by the Toronto Rehabilitation Institute, which receives funding under the Provincial Rehabilitation Research Pro-gram from the Ministry of Health and Long-Term Care in Ontario, Canada. The views expressed do not necessarily reflect those of the Ministry. None of the authors have any conflicts of interest.

We gratefully acknowledge the assistance of Ms. Reema Farhat and Ms. Sandra Sokoloff, and Ms. Marcia Winterbottom, librarian at the Toronto Rehabilitation Institute, for her assistance with the literature search.

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Sleep and Wake Disorders Following Traumatic Brain Injury ... · and sleep. Regardless of injury...

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