Prevalence of sleep disturbances, disorders, and problems following traumatic brain injury: A meta-analysis

Sleep Medicine 13 (2012) 898–905

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Sleep Medicine journal homepage: www.elsevier.com/locate/sleep

Original Article

Prevalence of sleep disturbances, disorders, and problems following traumatic brain injury: A meta-analysis J.L. Mathias ⇑, P.K. Alvaro School of Psychology, University of Adelaide, Adelaide, SA 5005, Australia

a r t i c l e

i n f o

Article history: Received 13 December 2011 Received in revised form 29 March 2012 Accepted 2 April 2012 Available online 15 June 2012 Keywords: Traumatic brain injury Sleep Sleep disorders Sleep problems Prevalence Meta-analysis

a b s t r a c t Background: Sleep is often disrupted following a traumatic brain injury (TBI), which may compromise recovery and quality of life. Prevalence rates vary widely, reflecting differences in the criteria and measures that are used to assess sleep, as well as sample differences. This meta-analysis examined the prevalence of general and specific, and formally and informally diagnosed, sleep disturbances following TBI in order to establish the nature and extent of these sequelae and their potential impact on recovery. Methods: Data from 21 studies, which assessed (1) sleep disturbances, regardless of type or severity, (2) diagnosed sleep disorders, and (3) specific sleep problems following TBI, were analyzed and compared to data for the general population. Results: Overall, 50% of people suffered from some form of sleep disturbance after a TBI and 25–29% had a diagnosed sleep disorder (insomnia, hypersomnia, apnea) – rates that are much higher than those seen in the general population. They were also two to four times more likely to experience problems with sleep maintenance and efficiency, nightmares, excessive sleepiness, early awakenings, and sleep walking. Conclusion: Sleep disturbances are very common after TBI and have the potential to seriously undermine patient rehabilitation, recovery, and outcomes; making it important to routinely screen for such problems in order to assess both treatment needs and their potential impact on recovery and outcome. Crown Copyright Ó 2012 Published by Elsevier B.V. All rights reserved.

1. Introduction Sleep is often disrupted following a traumatic brain injury (TBI) [1–3] and may cause or intensify a variety of co-morbidities, such as depression, anxiety, irritability, fatigue, cognitive deficits, pain, and functional impairments [3,4]. In addition, disrupted sleep may compromise a person’s recovery and return to pre-injury activities, and reduce a person’s quality of life [2–5]. Disrupted sleep may arise from trauma-induced physical and biochemical changes [3] or co-morbid conditions, such as depression [6], and may be impacted by pre-injury sleep problems [7]. Indeed, disrupted sleep is also very common and often overlooked in the general community, and is associated with a wide range of health, social, and economic costs [8]. However, the frequency and type of sleep disturbances experienced following a TBI, and the extent to which they differ from those of the general community, have yet to be clearly established. Estimates of the prevalence of post-TBI sleep disturbances range between 30% and 84% [9–12]. The large variability in these estimates limits their clinical utility and is likely to reflect differences in the definitions (i.e., broad vs specific), criteria (e.g., formal ⇑ Corresponding author. Tel.: +61 8 8303 5266; fax: +61 8 8303 3770.

diagnosis or not), types of measures (e.g., subjective vs objective), and sources of information (e.g., self-report vs observation) that are used to identify sleep disturbances, combined with differences in the samples that are studied (e.g., non-selected vs symptomatic samples; mild vs severe TBI). A more detailed examination of postTBI sleep disturbances, which considers these sources of variability, is therefore needed in order to develop clinically informative estimates of the prevalence and type of sleep disturbances that occur after TBI. Moreover, these prevalence rates need to be considered in the context of community base-rates for sleep disturbances. Research examining changes to sleep following TBI has conceptualized these problems in a number of different ways. Some studies take a broad approach, using either formal or informal criteria; reporting the proportion of people who have any form of disturbance to their sleep, regardless of its type or severity [1,9,10,13,14]. Other studies report the number of people who have sleep disorders (e.g., insomnia, obstructive sleep apnea) that meet recognized diagnostic criteria, such as the International Classification of Sleep Disorders (ICSD-I, ICSD-R, ICSD-II, American Academy of Sleep [AAS]) [15–17] or the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV, American Psychiatric Association [APA]) [18]. Finally, there are studies that report the frequency of specific sleep problems, such as problems with initiating or staying

E-mail address: [email protected] (J.L. Mathias). 1389-9457/$ - see front matter Crown Copyright Ó 2012 Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.sleep.2012.04.006

J.L. Mathias, P.K. Alvaro / Sleep Medicine 13 (2012) 898–905

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asleep, as well as symptoms that may be suggestive of sleep disorders but were not identified using accepted diagnostic criteria (e.g., insomnia, snoring, or excessive daytime sleepiness) [2,19–22]. Not only do the definitions and criteria for identifying sleep disturbances following TBI differ between studies, so too do the measures that are used to assess sleep (subjective vs objective) and the methods by which the data are obtained (self-report, clinical interview, and observation). Indeed, sleep data have been collected using: self-report questionnaires [20,23], such as the Pittsburgh Sleep Quality Index [24] and Epworth Sleepiness Scale [25]; structured diagnostic [26,27] or clinical interviews [28,29]; observational measures obtained while a person is sleeping [14]; or objective measures [9,30], which include recordings of sleep-wake cycles obtained in sleep laboratories (polysomnography). These different methodologies are likely to have a significant impact on estimates of sleep disturbances following TBI. For example, many people who complain of insomnia are found to have normal sleep patterns when objectively assessed [3], possibly due to the subjective nature of these problems [2,3] or the impact of compensation claims on self-reported problems [9]. In contrast, people who are formally diagnosed with obstructive sleep apnea often fail to recognize the problem, instead tending to describe poor daytime vigilance [3]. Similarly, large differences have been found between the frequency of problems identified via self-report and those found via clinical interview [2,29]. Thus, the various methods that are used to collect data can yield different estimates of the frequency of sleep disturbances after TBI and need to be considered separately. Moreover, the fact that a person believes that their sleep is disrupted in the absence of evidence that it is does not necessarily negate the impact of the problem. Rather, different treatments may be required in order to optimize a person’s quality of life and well-being. Finally, there are variations in the samples that are investigated, particularly in relation to where participants are recruited. Participants with a TBI who are seeking a diagnosis or treatment for sleep problems are likely to have more problems than those who are recruited on a prospective/non-selected basis. Similarly, people who are referred for formal sleep laboratory investigations are likely to be a biased sample, as only those people with more severe problems tend to be referred for specialist investigations of this type. In addition, between-study differences in injury severity and the post-injury time interval may also impact on the nature and frequency of sleep disturbances that are reported. The current study was designed to examine the frequency and type of sleep problems that occur following TBI, taking into consideration the breadth of problems that were reported (presence of any sleep disturbance vs diagnosed sleep disorders vs specific sleep problems) and the method by which data was obtained (self-report, clinical interview, observation, laboratory tests). Where possible, sample characteristics (symptomatic vs non-selected TBI sample) and the severity of injury (mild, moderate, severe) were also considered.

which was verified by medical records, and were aged over 16 years (if the sample included any penetrating injuries, 65% had this type of injury); (3) frequency data for sleep disturbances (of any type or severity) or diagnosed sleep disorders or specific sleep problems/symptoms were reported; (4) samples sizes were greater than 10 (excludes very small samples and case studies); and (5) participants were not reported to have had a previous TBI, pre-existing sleep disorder, or other neurological, psychiatric, or medical disorder that could independently affect sleep. The initial search identified 551 and 305 potentially eligible studies from PubMed and PsychINFO, respectively (46 duplicates). Preliminary application of the inclusion criteria to the titles and abstracts of these studies narrowed the focus to 148 studies, for which full-text versions were obtained (refer to Supplementary content: Table B for a summary of the reasons for exclusion). Subsequent re-application of the inclusion criteria reduced the number of eligible studies to 30. Data that are meta-analyzed must be obtained from independent samples [31]: there were 14 studies where independence was in question. Based on information provided by the authors (in the article or by correspondence), one group of four studies [4,23,26,32], two groups of three studies ([9,33,34] and [13,35,36]), and two sets of two studies ([6,27] and [37,38]) were combined and treated as one. Effectively, these 14 papers were collapsed into five studies; yielding a final total of 21 independent studies for which data were analyzed.

2. Method

3. Results

2.1. Literature search and inclusion criteria

3.1. Participant details

A comprehensive search of the PsycINFO and PubMed databases between January 1990 (coinciding with the introduction of the ICSD classification criteria for sleep disorders) and April 2011 was undertaken using a large number of search terms (Supplementary content: Table A). For a study to be included in the current meta-analysis, it had to meet the following criteria: (1) was published in a journal in English and contained original data (excludes reviews); (2) participants had sustained a non-penetrating TBI,

The 21 studies included in this meta-analysis provided data for a total of 1706 participants. The background data for these studies are summarized in Table 1, where it can be seen that the majority of participants were male (71%) and young adults (mean age = 35.3, SD = 13.1). A limited number of studies reported the time-since-injury (Nstudies = 9; Mean = 32.9 months, SD = 43.1) and even fewer reported Glasgow Coma Scale (GCS) Scores and educational levels (Nstudies = 5 and 4, respectively), thereby

2.2. Data collection and effect size calculation Demographic and injury information (e.g., age, gender, years of education, injury severity, time-since-injury), methodological data (e.g., sample characteristics: symptomatic vs general TBI, use of medication; type of data: presence of any sleep disturbance vs diagnosed sleep disorders vs frequency of specific sleep problems/symptoms; and method of data collection: self-report vs clinical interview vs observation vs laboratory tests), and statistical data necessary for the calculation of effect sizes were extracted from each study for analysis. The current study used proportions as the effect size [39] in order to summarize the prevalence of general and specific sleep disturbances that were formally or informally diagnosed using subjective (self-report, clinical interview, observation) or objective (polysomnography) measures following TBI. Weighted mean proportions were calculated for those variables where data were available for more than one study (Nstudies > 1). The inverse variance (inverse of the squared standard error), which provides a measure of the precision of an effect size [40], was used to weight the proportions obtained from individual studies before averaging them (Mean Pw) Ninety-five percent confidence intervals (95% CIs) were also calculated to provide the upper and lower bounds, within which we can be 95% confident that the true population prevalence rate lies.

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J.L. Mathias, P.K. Alvaro / Sleep Medicine 13 (2012) 898–905

Table 1 Demographic and injury characteristics for the meta-analysed studies. Nstudies

Nparticipants

21 13 17 9 5 4

1706 1172 1361 1007 223 586

Injury severity Mild Mod, sev Mild, mod, Sev

4 1 9

214 38 1147

Cause of injury MVA Assault Falls Other Unknown Missing data

12 7 10 8 2 1

787 23 87 38 22 119

Sample size Age Gender (males) Time-since-injury (months) Injury severity (GCS) Education (years)

%

Mean

SD

86.9 35.3

101.2 13.1

32.9 8.9 12.3

43.1 3.4 2.3

71.3

these problems. The data from samples that were known to be symptomatic were not excluded from this analysis due to a lack of reliable information for the other studies but are highlighted in the text and tables. Medication use was reported in 13 studies (62%), three of which excluded sedating or sleep medications, one excluded stimulants, one of which excluded psychotropic medications, one of which excluded all forms of medication, and seven of which had no restrictions. The remaining eight studies did not report medication status. 3.2. Overall prevalence of sleep disturbances

73.1 2.1 8.1 3.5 2.0 11.1

Note: Nstudies and Nparticipants refer to the total number of studies and participants for which data were available. MVA = Motor Vehicle Accidents; GCS = Glasgow Coma Scale.

precluding an analysis of the relationship between the frequency of sleep disturbances/disorders/problems and both time-since-injury and injury severity. Some studies (Nstudies = 14) provided descriptive categorical information relating to injury severity (refer to Table 1), which revealed that the majority of these studies examined mixed samples of mild, moderate, and severe TBIs (Nstudies = 9), with the remainder studying either mild TBI (Nstudies = 4) or moderate to severe TBI (Nstudies = 1). Of the studies that used mixed samples, two had a majority of mild participants [19,28], four had a majority of severe participants [9,27,37,41], two had approximately equal numbers of mild and severe participants [13,42], and one had roughly equal numbers of mild, moderate, and severe TBIs [6]. Thus, while injury severity varied, the available data did not allow a comparison of sleep disturbances following mild versus moderate versus severe TBI. A total of seven (33%) studies recruited participants from rehabilitation settings, seven (33%) from hospitals/trauma centers, three (14%) from TBI support groups, one (5%) from private practice, one (5%) from the general community, and two (10%) did not report their recruitment source. Three studies indicated that participants were selected because they had presented with sleep problems [6,30,42]. Of the remaining 18 studies, two indicated that they neither selected nor excluded participants who presented with sleep disturbances but the other 16 did not indicate whether or not all or some of their participants were selected because of

The data from all 21 studies were combined to estimate the overall prevalence of any form of sleep disturbance following TBI, regardless of its type or severity, the criteria that was used to define the sleep disturbance (formal diagnostic criteria vs informal criteria), the measure (subjective vs objective), or the source of information (clinical interview, observation, self-report). This data is summarized in Table 2, where it can be seen that, when all of the data is combined (regardless of criteria and source of data), an average of 50% of people with TBI experienced some form of sleep disturbance. The data that were used to determine the overall prevalence of sleep disturbances were also partitioned into studies that used formal diagnostic criteria to identify the presence of a sleep disturbance (Nstudies = 5) and those that used only informal criteria (Nstudies = 17), and by method of assessment (e.g., objective test, self-report). This revealed that, on average, approximately 53% of people suffered from a diagnosed sleep disorder, based on objective sleep tests. Those studies that used informal criteria to identify sleep disturbances (i.e., did not use ICSD or DSM criteria) also reported a high average prevalence of 49%, largely on the basis of self-reports (Nstudies = 11), which generally involved either answering a single question about sleep disturbances following TBI (Nstudies = 3) or completing a self-report questionnaire (Nstudies = 8) such as the Epworth Sleepiness Scale [25] or Pittsburgh Sleep Quality Index [24]. Interestingly, the studies that used informal criteria to identify sleep disturbances but used objective tests (Nstudies = 3) or sleep ratings from trained observers (Nstudies = 1) both reported higher prevalence rates: 81% and 68%, respectively. However, it is also important to note that two of the three studies that provided objective assessments of sleep specifically recruited symptomatic samples, which is likely to inflate this estimate. Importantly, the 95% CIs confirm that when the prevalence rates for sleep disturbances in the TBI population were estimated using objective assessments, patient observations, or self-report, they were all very high. Clinical interviews, on the other hand, identified far fewer cases.

Table 2 Overall prevalence of sleep disturbances (regardless of type or severity). Criteria

source of data

Nstudies

Nparticipants

Mean Pw

95% CIs

Study references

Total

21

1706

.50

.49

.51

[1,6a,9,10,13,14,19–21,23,27–29,30a,37,41,42a,51–54]

5 5

201 201

.53 .53

.46 .46

.60 .60

[6a,9,13,41,54] [6a,9,13,41,54]

2 3 1 11 17

209 95 31 1204 1539

.25 .81 .68 .50 .49

.15 .70 .50 .50 .50

.38 .88 .82 .51 .54

[28,29] [30a,42a,53] [14] [1,10,19–21,23,27,29,37,51,52] [1,10,14,19–21,23,27–29,30a,37,42a,51–53]

Overall Formal diagnostic criteria Objective Total Informal criteria Clinical interview Objective Observational Self-report Total

Note: Nstudies and Nparticipants refer to the total number of studies and participants for which data were available; Mean Pw = mean weighted proportion (weighted by inverse variance; weighting not possible for Nstudies = 1); 95% CIs = 95% confidence intervals. a Study specifically recruited participants who were symptomatic for sleep problems.

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J.L. Mathias, P.K. Alvaro / Sleep Medicine 13 (2012) 898–905 Table 3 Proportion of people with a TBI with formally diagnosed sleep disorders. Diagnosis

Source of data

Nstudies

Nparticipants

Mean Pw

95% CIs

Study references

Insomnia

Clinical interview Objective measures Overall

3 1 4

567 14 581

.28 .71 .29

.25 .56 .26

.32 .83 .33

[13,26,27] [6a] [6a,13,26,27]

Hypersomnia

Clinical Interview Objective measures Overall

1 2 3

60 152 212

.50 .16 .28

.38 .11 .22

.62 .23 .36

[42a] [9,13] [9,13,42a]

Obstructive sleep apnoea

Objective measures

6

283

.25

.20

.30

[9,13,20,41,42a,54]

Periodic limb movements

Objective measures

3

212

.19

.13

.25

[9,13,42a]

Narcolepsy

Clinical Interview Objective measures Overall

1 1 2

65 87 152

.03 .06 .04

.01 .03 .02

.11 .13 .10

[13] [9] [9,13]

Note: Nstudies and Nparticipants refer to the total number of studies and participants for which data were available; Mean Pw = mean weighted proportion (weighted by inverse variance; weighting not possible for Nstudies = 1); 95% CIs = 95% confidence intervals. a Study specifically recruited participants who were symptomatic for sleep problems.

3.3. Prevalence of diagnosed sleep disorders The ICSD [15–17] and DSM IV [18] provide diagnostic criteria for a variety of sleep disorders, including dyssomnias, in which the amount, quality, and timing of sleep is affected (e.g., insomnia), and parasomnias, which refer to undesirable events that occur during sleep (e.g., sleep walking, nocturnal bed-wetting). The TBI sleep literature has primarily focused on dyssomnias, with nine studies providing data for formally diagnosed sleep disorders, six of which used ICSD, one of which used DSM IV, and two of which used both criteria. A variety of diagnosed disorders have been examined in the TBI literature; however, only those that were examined by more than one study are reported here. The proportion of people diagnosed with sleep disorders is presented in Table 3. Clinical interviews or objective tests undertaken in sleep laboratories were used to diagnose five sleep disorders: namely, insomnia (inadequate sleep), hypersomnia (excessive sleepiness), obstructive sleep apnea (episodes of upper airway obstruction causing reduced blood oxygenation), periodic limb movement (episodes of limb movements causing sleep disruption), and narcolepsy (excessive urge to sleep at inappropriate times). Overall, insomnia was the most commonly diagnosed sleep disorder (29%), followed by hypersomnia (28%), obstructive sleep apnea (25%), periodic limb movement during sleep (19%), and narcolepsy (4%). Notably, a diagnosis of insomnia was particularly common (71%) in a small sample of symptomatic participants who underwent objective laboratory investigations, probably reflecting a bias in those who underwent these tests (i.e., more severe problems). This pattern was not observed for hypersomnia, where objective assessments detected fewer cases than clinical interviews, although the latter statistic may have been inflated by the fact that the sample was known to be symptomatic. 3.4. Prevalence of specific sleep problems Finally, 15 studies provided data for specific sleep problems (e.g., problems with initiating or staying asleep) that were not identified using formal diagnostic criteria (refer to Table 4). A total of 65 sleep problems were examined by these studies, 56 of which were only investigated by one study, leaving nine in the final analysis (Nstudies > 1). In many cases, these problems were assessed using self-report measures, although objective assessments and clinical interviews were also used. Regardless of the method by which they were assessed, these problems do not represent formally diagnosed sleep disorders. Insomnia (broad term used by researchers to refer to problems with sleep initiation, maintenance, awakenings, non-restorative

sleep), excessive daytime sleepiness, and sleep initiation were the most frequently studied sleep problems (Nstudies = 5–8; Nparticipants = 368–1001), followed by sleep maintenance and early awakenings (Nstudies = 4; Nparticipants = 309–364). In contrast, nightmares, sleep efficiency (defined as No. minutes asleep  No. minutes in bed) [43], sleep walking, and snoring have only been examined by a couple of studies with far fewer participants (Nstudies = 2; Nparticipants = 65–99). Most sleep problems were experienced by between 25% and 60% of people who had sustained a TBI. Overall, snoring (60%) was the most prevalent problem, followed by insomnia (50%) and poor sleep maintenance (50%), reduced sleep efficiency (49%), early awakenings (38%), longer sleep initiation (36%), nightmares (27%), and daytime sleepiness (27%). Sleepwalking was the only low frequency problem (9%). Large discrepancies were observed between the objective assessments and self-reports for a number of sleep problems, with objective tests identifying many more problems than self-reports of problems with sleep maintenance (70% vs 45%), sleep efficiency (62% vs 26%), and early awakening (93% vs 37%), possibly reflecting differences in the samples who are referred for formal tests. For sleep efficiency, both the objective and self-report data were based on small samples of participants, some of whom were known to be selected because they were symptomatic for sleep problems (rather than representing the broader TBI population). In the case of sleep maintenance and early awakening, only the objective data included known symptomatic participants, which would contribute to the higher estimate. 3.5. Data source and differences in prevalence rates There were a small number of studies that used two methods of assessment with the same sample, enabling a direct comparison between the prevalence rates derived from these methods, although none of them provided data relating to extent of overlap in the cases identified by the two methods. Specifically, one study [29] examined sleep disturbances using clinical interviews and self-reports and found that sleep disturbances were present in 21% of their sample using clinical interviews and 51% using self-reports, suggesting that prevalence rates are likely to be considerably higher when self-reports are used. In addition, there were two studies that assessed insomnia (formally diagnosed sleep disorder) (Nstudies = 2, Nparticipants = 502) [26,27,32] and one that assessed nightmares (sleep problem) (Nstudies = 1, Nparticipants = 33) [29] using both clinical interviews and self-report measures. Once again, these studies revealed higher prevalence rates when using self-reports (insomnia: self-report = 50% vs interview = 29%; nightmares: self-

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Table 4 Proportion of people with a TBI who had specific sleep problems. Sleep problem

Source of data

Nstudies

Snoring

Objective Self-report Total

1 1 2

Insomnia

Clinical interview Self-report Total

Sleep maintenance

Nparticipants

Mean Pw

95% CIs

Study reference

26 39 65

.50 .62 .60

.26 .50 .49

.74 .73 .70

[30a] [21] [21,30a]

1 6 7

60 941 1001

.25 .50 .50

.16 .50 .50

.37 .51 .51

[42a] [19,23,27,37,51,52] [19,23,27,37,42a,51,52]

Objective Self-report Total

2 2 4

68 241 309

.70 .45 .50

.58 .39 .44

.80 .51 .55

[6a,42a] [19,21] [6a,19,21,42a]

Sleep efficiency

Objective Self-report Total

2 1 3

69 50 119

.62 .26 .49

.51 .16 .40

.72 .40 .58

[42a,53] [32] [32,42a,53]

Early morning awakening

Objective Self-report Total

1 3 4

60 304 364

.93 .37 .38

.83 .29 .38

.97 .46 .54

[42a] [19,21,37] [19,21,37,42a]

Sleep initiation

Objective Self-report Total

1 4 5

14 354 368

.28 .36 .36

.11 .31 .31

.56 .41 .41

[6a] [19,21,32,37] [6a,19,21,32,37]

Nightmares

Clinical interview Self-report Total

2 2 3

94 73 133

.06 .35 .27

.02 .26 .20

.13 .45 .35

[29,42a] [21,29] [21,29,42a]

Excessive daytime sleepiness

Objective Self-report Total

4 7 8

248 564 651

.28 .27 .27

.22 .23 .24

.35 .30 .29

[9,13,20,42a] [13,19–21,37,42a,52] [9,13,19–21,37,42a,52]

Sleepwalking

Clinical interview Self-report Total

1 1 2

60 39 99

.08 .10 .09

.04 .05 .05

.18 .20 .16

[42a] [21]] [21,42a]

Note: Nstudies and Nparticipants refer to the total number of studies and participants for which data were available; Mean Pw = mean weighted proportion (weighted by inverse variance; weighting not possible for Nstudies = 1); 95% CIs = 95% confidence intervals. a Study specifically recruited participants who were symptomatic for sleep problems.

report = 30% vs interview = 3%). Finally, there were three studies that examined excessive daytime sleepiness using objective and self-report measures (self-report: Nparticipants = 161; objective: Nparticipants = 129) [13,20,42]. On average, these studies found a prevalence rate of 31% using objective measures and 37% using selfreport measures. These findings highlight the fact that prevalence rates are likely to be higher when based on participant reports. 3.6. Frequency of sleep disturbances, disorders, and problems relative to the community Given the high frequency of sleep disturbances in the general population, this study also examined whether the prevalence of sleep disturbances following TBI differs from that of the general community. First, where studies used a control group, this data was compared to that of the TBI group. However, given the limited use of control groups by the 21 studies included in this meta-analysis, comparative base rates were also sourced from large published epidemiological studies (see Table 5 for details) and compared to the current data. In both cases, the significance of the difference between proportions (i.e., proportion of problems in TBI sample vs controls/general community) was tested using Z scores. Four studies provided data for both TBI and control groups in terms of the overall number of sleep disturbances, as well as specific problems with sleep initiation (Nstudies = 2) and excessive day-time sleepiness (Nstudies = 2) (refer to Table 5). When compared, the TBI samples experienced significantly more problems, overall, than Controls (56% vs 32%), as well as significant delays in sleep initiation (41% vs 5%) and excessive daytime sleepiness (24% vs 10%). When the base rates from large-scale community studies were compared with the TBI prevalence of overall sleep disturbances (regardless of type or severity), sleep disorders, and sleep prob-

lems, these analyses revealed that the TBI group experienced significantly more: sleep disturbances (50% vs 41%), diagnosed sleep disorders (insomnia: 29% vs 10%, hypersomnia: 28% vs 10%, obstructive sleep apnea: 25% vs 2%, periodic limb movements: 8% vs 4%; narcolepsy: 4% vs .047%), and sleep problems (snoring: 60% vs 42%, insomnia: 50% vs 31%, poorer sleep maintenance: 50% vs 27% and sleep efficiency: 49% vs 27%, delayed sleep initiation: 36% vs 27%, nightmares: 27% vs 8%, excessive daytime sleepiness: 27% vs 9%, early awakenings: 38% vs18%, sleep walking: 9% vs 2%). These differences are also likely to be clinically meaningful, with people who had sustained a TBI being between approximately two (periodic limb movements), three (insomnia, hypersomnia), twelve (sleep apnea), or more (narcolepsy) times as likely to have diagnosed sleep disorders following their injury, and between two to four times more likely to have problems with sleep maintenance and efficiency, nightmares, excessive sleepiness, early awakenings, and sleep walking. Thus, it appears that, although sleep problems are relatively common in the general community, they are significantly more prevalent following TBI.

4. Discussion Individual estimates of the frequency of sleep disturbances following TBI vary widely, limiting the clinical utility of this research. The present study was designed to consolidate the existing research and determine the prevalence of sleep disturbances (of any type or severity), diagnosed sleep disorders, and specific sleep problems, with an emphasis on how the different research methodologies (e.g., formal diagnostic criteria vs informal diagnosis; subjective vs objective sleep measures, etc.) impact on these estimates.

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J.L. Mathias, P.K. Alvaro / Sleep Medicine 13 (2012) 898–905 Table 5 Frequency of sleep disturbances, disorders, and problems following TBI, compared to control groups or community samples. Source of data

Sleep variable

Sleep category Healthy controls Sleep disturbance Sleep problem Community samples Sleep disturbance Sleep disorders

Sleep problem

Community

TBI

Community

TBI

Nparticipants

Nparticipants

P

P

.32 .05 .10

.56 .41 .24

3.02 5.33 2.65

.003 <.001 .008

[6a,20,30a,37] [6a,37] [20,37]

.41 .10 .10 .02 .04 .00b .42 .31 .27 .27 .27 .08 .09 .18 .02

.50 .29 .28 .25 .08 .04 .60 .50 .50 .49 .36 .27 .27 .38 .09

5.59 9.94 8.38 15.51 2.95 17.11 3.56 11.8 8.96 4.93 3.80 7.43 15.27 9.76 4.85

<.001 <.001 <.001 <.001 .003 <.001 <.001 <.001 <.001 <.001 <.001 <.001 <.001 <.001 <.001

[55] [45] [46] [44] [56] [57] [58] [59] [60] [45] [60] [55] [61] [60] [62]

Overall Sleep initiation Excessive daytime sleepiness

66 77 85

85 77 99

Overall Insomnia Hypersomnia Obstructive sleep apnoea Periodic limb movements Narcolepsy Snoring Insomnia Sleep maintenance Sleep efficiency Sleep initiation Nightmares Excessive daytime sleepiness Early morning awakening Sleep walking

2187 1007 7954 1741 18,980 18,980 2629 6340 24,600 1007 24,600 2187 16,583 24,600 4972

1706 581 212 283 212 152 65 1001 309 119 368 133 651 364 99

Study reference Z

prob

Note: Nstudies and Nparticipants refer to the total number of studies and participants for which data were available. P = proportion. a Study specifically recruited participants who were symptomatic for sleep problems. b Community prevalence of narcolepsy = .00047 (.047%).

Overall, 50% of people experienced some form of sleep disturbance after their TBI, indicating that sleep disturbances are extremely common and have the potential to impact on both the recovery and, ultimately, the outcome of many people [9,23]. Moreover, they occur significantly more often than in healthy controls or the general community. Fifty-three percent of people suffered from sleep disturbances that were assessed using objective tests and met formal diagnostic criteria following a TBI, and 49% experienced some form of sleep disturbances when informal criteria were used, often based on self-reports, with the latter figure increasing to between 68% and 81% when more formal assessments were used (trained observers or sleep laboratory) but as low as 25% when clinical interviews were used. The higher frequency of problems identified in sleep laboratories probably reflects the greater sensitivity and specificity of these tests, combined with the fact that the people who were referred for testing were also more likely to be experiencing more serious problems and, therefore, were less representative of the broader TBI population. Not surprisingly, the prevalence of sleep disturbances (Table 2) exceeded that of formally diagnosed sleep disorders (Table 3), as the former includes both diagnosed disorders, which require multiple criteria to be met (symptoms, frequency, and severity), and single problems, often of unspecified severity. Nine studies examined diagnosed sleep disorders and revealed a significantly higher prevalence of insomnia (29%), hypersomina (28%), and sleep apnea (25%) following TBI than has been found in the general population (10%, 10%, and 2%, respectively) [44– 46]. The magnitude of differences in these prevalence rates for TBI and community groups indicate that these findings are also of clinical significance. Specifically, clinicians need to be aware of how common these problems are and of their potential to impact on physical, psychological, and cognitive recovery and outcome. Left undiagnosed and untreated, sleep disorders may unnecessarily undermine patient rehabilitation and recovery [47]. In contrast, periodic limb movements and narcolepsy occurred less frequently (8% and 4%, respectively), albeit significantly more frequently than the general community (4% and .047%, respectively). Our analyses also revealed that specific sleep problems were significantly more common following TBI, particularly snoring

(60% vs 42%), insomnia (50% vs 31%), poor sleep maintenance and sleep efficiency (49–50% vs 27%), delayed sleep onset (36% vs 27%), nightmares and excessive daytime sleepiness (27% vs 8– 9%), early awakening (38% vs 18%), and sleepwalking (9% vs 2%). Many of these problems were additionally verified by objective measures of sleep quality and timing. Once again, the evidence suggests that specific sleep problems are extremely common after TBI and, as with diagnosable disorders, may impact on patient outcomes and quality of life. Finally, when we compared the findings from a small number of studies that used two methods of assessment (clinical interview or objective assessment and self-report) to measure sleep disturbances and sleep problems in the same samples, we found that the prevalence rates were consistently higher when based on participant reports of problems than were revealed by either clinical interview or objective tests. Unfortunately, none of the studies provided the data needed to assess the degree of overlap between the cases identified by each of these methods of assessment. 4.1. Limitations and methodological recommendations for future research There are a number of limitations that warrant consideration. First, although we only included studies in which participants were not known to have a pre-existing disorder that could independently affect sleep (e.g., sleep disorder or other neurological, psychiatric, or medical disorder), many studies did not report this information. Thus, we cannot be certain that there was not a higher level of pre-injury sleep problems in the samples that suffered a TBI or the people who reported sleep disturbances after their injury. Indeed, sleep disorders, such as insomnia and sleep apnea, increase the risk of motor vehicle accidents and TBIs [48,49]. This, combined with the fact that sleep apnea is under-diagnosed in the general population [50] may mean that at least some of the TBI participants had pre-existing undiagnosed or unreported sleep disorders. Moreover, these pre-existing problems may have predisposed them to having a TBI and, consequently, increased the estimated prevalence of sleep disturbances. Thus, it is essential that researchers explicitly state whether or not participants had any

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type of pre-existing sleep or other condition that could independently affect their findings. Secondly, we had hoped to be able to examine whether the prevalence of sleep problems changed in the months and years after an injury. However, only a limited number of studies (N = 9) provided details about the post-injury interval, and they often examined different aspects of sleep, precluding a reliable analysis of this variable. Similarly, had the data been available, it was our intention to examine the impact of injury severity on the frequency of sleep disturbances following TBI. Most studies examined mixed samples of mild, moderate, and severe TBI, some of which had a preponderance of mild injuries and others severe injuries. Only a few examined mild TBI and none examined only moderate or severe. Consequently, it was not possible to examine this potential moderator variable in any reliable way. This could be addressed if researchers provided more detailed descriptions of their samples, including their injury severity (GCS and/or category) and timesince-injury. Thirdly, we were unable to control for the effects of other variables, such as medication use or pain, on our estimates. A variety of medications are frequently prescribed after a TB that may impact on sleep (e.g., antidepressants, anti-psychotics) [3] in either a detrimental or favorable way. While three studies reported excluding sedating or sleep medications, one study each excluded stimulants, psychotropic medications, or all forms of medication, seven had no restrictions, and eight did not report medication status. Thus, there is the potential for considerable variation in the medication regimes of the study samples. Once again, researchers need to provide more detailed background information for their samples, including medication use and pain levels, due to the potential confounding effects of these variables on sleep. In addition, only four studies used control groups to assess the base-rates of sleep disturbances, disorders, and problems, necessitating the use of data from independent large-scale communitybased studies in order to assess whether the prevalence rates are higher after TBI. While the failure to provide data for matched controls may be considered a limitation, the fact that most of the comparative data came from large, and presumably more representative, samples can also be considered a strength, as the control groups were much smaller and, consequently, are less likely to have captured the full extent of sleep disturbances in the general community. However, a quasi-experimental design with a matched non-TBI control group, which completes the same measures, should be the goal for all future research of this type in order to more accurately estimate differences in the prevalence of sleep disturbances. Lastly, researchers could raise the quality of the literature on sleep disturbances following TBI by providing other important information, including whether participants were recruited because they were known to be symptomatic or whether they were recruited on a prospective basis and the criteria that were used to identify a sleep disturbance. In addition, it would be useful to have separate data for different injury severity categories (where a study is not confined to one severity, e.g., mild) and, where multiple sleep measures are used, the degree of overlap between the cases that are identified by the different measures (i.e., contingency tables) in order to enable an evaluation of the consistency of the methodologies.

5. Conclusions This analysis highlights the high prevalence of a variety of sleep disorders (particularly insomnia, hypersomnia, and obstructive sleep apnea) and problems (particularly snoring, insomnia, poor sleep maintenance and sleep efficiency, early awakening, and

delayed sleep onset), with approximately 50% of all people suffering from one or more sleep disturbances after their TBI. These disturbances occur significantly more frequently than they do in the general population and represent a serious challenge for clinicians. Although it appears that individuals may report more problems with sleep than are confirmed by other methods of assessment, this does not necessarily negate the impact of these problems on an individual’s quality of life. Rather, different treatments, such as teaching good sleep habits (sleep hygiene), may be needed to assist in minimizing any associated distress. If left unrecognized and untreated, problems with sleep have the potential to seriously and insidiously undermine patient rehabilitation, recovery, and outcomes. It is therefore recommended that sleep quality be routinely assessed using readily available screening questionnaires, such as the Pittsburgh Sleep Quality Index [24], in order to determine both the need for more detailed sleep assessments and medical treatment and the potential impact of sleep problems on patient outcomes after TBI.

Conflict of interest The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: http://dx.doi.org/10.1016/j.sleep.2012.04.006.

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