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J Head Trauma RehabilVol. 24, No. 3, pp. 155165
Copyright c 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Traumatic Brain Injury and SleepDisturbance: A Review ofCurrent Research
Henry J. Orff, MS; Liat Ayalon, PhD; Sean P. A. Drummond, PhD
Objective: To summarize the current literature regarding the significant prevalence and potential consequencesof sleep disturbance following traumatic brain injury (TBI), particularly mild TBI. Design: PubMed andOvid/MEDLINE databases were searched by using key words sleep disturbance, insomnia, TBI, brain injury,and circadian rhythms. Additional sources (eg, abstracts from the annual Associated Professional Sleep Societiesmeeting) were also reviewed. Results: Sequelae of TBI include both medical and psychiatric symptoms and frequentcomplaints of sleep disturbance. Sleep disturbance likely result from and contribute to multiple factors associatedwith the injury, all of which complicate recovery and resolution of symptoms. Interestingly, research now seems toindicate that mild TBI may be more correlated with increased likelihood of sleep disturbance than are severe formsof TBI. Conclusions: Sleep disturbance is a common consequence of TBI, but much more research is required toelucidate the nature and extent of this relation. Research needs to focus on (1) uncovering the specific types, causes,and severity of TBI that most often lead to sleep problems; (2) the specific consequences of sleep disturbance in thispopulation (eg, impaired physical or cognitive recovery); and (3) the most effective strategies for the treatment ofsleep-wake abnormalities in this population. Keywords: delayed sleep phase, insomnia, sleep disturbance, traumatic braininjury
TRAUMATIC BRAIN INJURY (TBI) is a leadingcause of death and permanent disability in theUnited States. The primary causes of TBIs are falls(28%), motor vehicle accidents (20%), being hit by ob-jects (19%), and assaults (11%).1 TBI can be classifiedas mild, moderate, or severe, most often by GlasgowComa Scale score (mild = 1315; moderate = 912; se-vere = 8 out of 15). Symptoms of mild TBI (mTBI) in-clude headache, confusion, lightheadedness, dizziness,blurred vision, tinnitus, bad taste in the mouth, fatigueor lethargy, change in sleep patterns, behavioral or moodchanges, and trouble with memory, concentration, at-tention, or thinking.2 In addition to these symptoms,individuals with moderate or severe TBI may also expe-rience headaches that intensify or do not go away, re-peated vomiting or nausea, convulsions or seizures, aninability to awaken from sleep, dilation of one or both
Author Affiliations: Joint Doctoral Program in Clinical Psychology, SanDiego State University/University of California, San Diego (Mr Orff);Research Service, VA San Diego Healthcare System & Department ofPsychiatry, University of California, San Diego (Dr Ayalon); andPsychology Service, VA San Diego Healthcare System & Department ofPsychiatry, University of California, San Diego (Dr Drummond).
This study was supported by F31 MH077411-01A1 (H.J.O.) and NationalSleep Foundation Pickwick Fellowship (L.A.).
Corresponding Author:Sean P. A. Drummond, PhD, Department of Psychia-try, 9151B University of California, San Diego/VA San Diego Healthcare Sys-tem, 3350 La Jolla Village Dr, San Diego, CA 92161 ([email protected]).
pupils of the eyes, slurred speech, weakness or numbnessin the extremities, loss of coordination, and confusion,restlessness, or agitation.
Sleep disturbance is one of the most common yetleast studied of the post-TBI sequelae. Recent researchsuggests that 30% to 70% of patients experience sleepproblems following TBI and that these sleep disturbanceoften exacerbate other symptoms and impede the reha-bilitation process and the ability to return to work.3 In-terestingly, it has been shown that it is mTBI that is mostfrequently associated with sleep disturbance as opposedto severe TBI.4,5 While the importance of sleep prob-lems in the general population of TBI patients has beenknown for some time, recent events such as the wars inthe Middle East have brought renewed attention to thisissue. Many veterans have sustained a TBI, and the treat-ment of sequelae associated with this type of injury hasbecome a major health policy concern.
PURPOSE OF REVIEW
This review addresses the etiology and implicationsof sleep problems in TBI across 4 general domains ofcurrent scientific inquiry and observation: subjectiveimpression of poor sleep; objective changes in sleep-related parameters; alterations in circadian rhythms; andneurophysiologic and/or neuropsychologic abnormali-ties associated with TBI. Both nonpharmacologic and
155
156 JOURNAL OF HEAD TRAUMA REHABILITATION/MAYJUNE 2009
pharmacologic treatment options for sleep problems inthis population are then presented, as well as limitationsand areas for future research.
For this review, PubMed and Ovid/MEDLINEdatabases were searched by using the following keywords: sleep disturbance, insomnia, TBI, braininjury, and circadian rhythms. Each key word wascrossed with the others and the abstracts of manuscriptsresulting from this search were reviewed by the first au-thor. The review was limited to those studies that focusedspecifically on sleep and TBI. Note that many of thestudies reviewed included patients with TBI of varyingseverities, and they typically did not report results sep-arately for each severity type. Intervention studies wereincluded provided that the primary aim of the study wasnot limited to comparing effectiveness of pharmaceu-tical agents. Additional studies were sourced from ab-stracts from the Associated Professional Sleep Societiesmeetings and published in the journal Sleep over the pastdecade. Also, only articles published in English languagejournals over the past decade (since 1997) and those thatcould be searched electronically were included in the re-view. In all, 33 articles met these criteria and were selectedfor this review (Table 1). Articles were later groupedby domain of inquiry for easier synthesis and readabil-ity. While it is possible that some studies were missedwith this search method, this review provides a broadoverview of the current state of knowledge regardingsleep disturbance and its relation to TBI and recovery.
TBI AND SUBJECTIVELY REPORTEDSLEEP DISTURBANCE
One of the most common and well-documented syn-dromes seen in patients with TBI is insomnia, a disor-der inherently defined by patient self-report. The diag-nostic criteria for insomnia are a problem of initiatingand/or maintaining sleep for at least 1 month accompa-nied by subjective impairment in daytime functioning.37
Evidence showing that insomnia is a problem for TBIpatients has come from several studies. For example, ina questionnaire study of 452 TBI patients, up to 50% ofindividuals reported insomnia symptoms and 29.4% ful-filled the diagnostic criteria for an insomnia syndrome.6
For those who met criteria for insomnia, sleep prob-lems were a severe, chronic, and untreated condition inalmost 60% of cases. Risk factors associated with insom-nia were mTBI, higher levels of fatigue, depression, andpain. In another study of 50 postacute TBI admissionsand a comparison group of 50 rehabilitation outpatients,30% of all patients were found to suffer from insomnia,while an additional 12% experienced a degradation ofsleep quality as measured by the Pittsburgh Sleep Qual-ity Index.7 In this sample, sleep initiation was a problemalmost twice as often as sleep duration.
In a longitudinal study of admissions to a rehabili-tation unit, Clinchot et al8 found that 50% of patientsreported difficulty sleeping, 64% reported waking up tooearly, 25% described sleeping more than usual, and 45%complained of problems falling asleep. Overall, 80% ofsubjects reporting sleep problems also reported prob-lems with fatigue. Furthermore, in a study by Parcelland colleagues,9 63 patients with TBI recruited after dis-charge from rehabilitation and 63 age- and sex-matchedcontrols from the general community were comparedon sleep variables. Patients were shown to have a signif-icantly higher frequency of reported sleep disturbancefollowing their TBI (80%), and they reported more night-time awakenings and longer sleep-onset latency. In com-parison, sleep problems were only reported by 23% ofindividuals in the control group. In keeping with otherstudies, participants with a more mild form of TBI re-ported sleep changes more frequently.
Insomnia not only represents a problem immediatelyfollowing injury but also appears to persist for monthsand years after a TBI. For example, in a review of medicalrecords from 175 patients diagnosed with mTBI taken at2 time intervals (interval 1 = mean 10.7 days vs interval2 = mean 6.3 weeks postinjury), Chaput et al13 foundthat complaints of sleep disturbance were reported by11.1% and 34.7% of patients. Overall, there was a 2-to 3-fold increase in the prevalence of sleep disturbancefrom 11 days to 6 weeks postinjury. In a study of sleepcomplaints in 39 patients with chronic postconcussionsyndrome and a control group of 27 patients with or-thopedic injuries, the former reported more difficultyinitiating and maintaining sleep at night and greater dif-ficulty with sleepiness during the day over a mean 2-yearpostinjury period.10
Among 19 adolescent patients who were 3 years post-mTBI without any discernible clinical sequelae, com-plaints of sleep disturbance could be confirmed by bothpolysomnographic (PSG) and actigraphic (ie, daily ac-tivity) monitoring.11 In addition, in a study of 22 hos-pitalized patients with TBI of recent onset (median3.5 months postinjury) and 77 discharged patients whohad sustained brain injury about 2 to 3 years earlier (me-dian 29.5 months), Cohen et al12 found high rates ofsleep complaints in both groups (72.7% and 51.9%, re-spectively). Difficulty initiating and maintaining sleepwere the most common complaints among hospital-ized patients (81.2%), whereas excessive daytime somno-lence was most common in discharged patients (72.5%).Notably, those discharged patients who reported sleepcomplaints also reported greater neurobehavioral im-pairments and poorer occupational outcomes.
Among the typical consequences of poor nighttimesleep in any population are complaints of daytime fa-tigue or excessive sleepiness. Not surprisingly then, thereis also a relationship between sleep disturbance and
Traumatic Brain Injury and Sleep Disturbance 157
TAB
LE1
Trau
mat
icbr
ain
inju
ryan
dsl
eep
dist
urba
nce
sum
mar
yof
revi
ewed
artic
les
Au
tho
rS
amp
le/a
ge
Sev
erit
yTi
me
sin
cein
jury
Mea
sure
sR
esu
lts
TBIa
ndsu
bjec
tive
slee
pdi
stur
banc
eO
uelle
tet
al6
n=
452
/16+
yTB
I(m
ixed
)m
ean
=7.
85y
ISI,
MFI
,sle
ep,p
sych
olog
ican
dpa
rtne
rqu
estio
nnai
res
Inso
mni
ais
apr
eval
ent
cond
ition
follo
win
gTB
IFi
chte
nber
get
al7
n=
50TB
Ipat
ient
s/36
.5y
n=
50pa
tient
sw
ithsp
inal
cord
inju
ry/3
8.2
yn
=25
patie
nts
with
mus
culo
skel
etal
inju
ries/
47.3
y
TBI(
mix
ed)
2w
k53
mo
PS
QI,
slee
pdi
ary
30%
ofpa
tient
ssu
ffer
edfr
omin
som
nia
Clin
chot
etal
886
patie
nts/
14+
yTB
I(m
ixed
)1
yP
hone
inte
rvie
wne
urop
sych
olog
icm
easu
res
Hig
hpr
eval
ence
ofsl
eep
prob
lem
saf
ter
brai
nin
jury
Par
cell
etal
9n
=63
patie
nts/
32.5
y(
1.7)
TBI(
mix
ed)
301
194
dS
leep
diar
y,E
pwor
thS
leep
ines
sS
cale
TBIg
roup
repo
rted
long
ersl
eep
late
ncie
san
dm
ore
awak
enin
gsn
=63
cont
rols
/30.
5y
(1.
2)P
erlis
etal
10n
=39
patie
nts/
41y
(14
.1)
mTB
I2
ypo
st-in
jury
Que
stio
nnai
reP
atie
nts
had
mor
esl
eep
prob
lem
san
dda
ytim
esl
eepi
ness
n=
27co
ntro
ls/3
7y
(15
)K
aufm
anet
al11
n=
19pa
tient
s/10
16.
5y
mTB
I3
ypr
ior
tost
udy
PS
G,a
ctig
raph
yin
take
ques
tionn
aire
Pat
ient
ssh
owed
low
ersl
eep
effic
ienc
ies
and
mor
ew
ake
time
n=
13P
SG
cont
rols
/sam
eag
esn
=15
actig
raph
yco
ntro
ls/s
ame
ages
Coh
enet
al12
n=
22re
cent
/med
ian
=29
yTB
I(m
ixed
)M
edia
n=
3.5
mo
Que
stio
nnai
reIn
som
nia
asso
ciat
edw
ithre
cent
inju
ryex
cess
ive
slee
pine
ssw
ithpa
stin
jury
n=
77di
scha
rged
/med
ian
=26
ym
edia
n=
29.5
mo
Cha
put
etal
13n
=17
5pa
tient
s/48
.9y
mTB
I10
dan
d6
wk
Riv
erm
ead
Pos
tC
oncu
ssio
nQ
uest
ionn
aire
Sle
epco
mpl
aint
ssh
ow2-
to3-
fold
incr
ease
betw
een
time
1-2
Bel
mon
tet
al14
Rev
iew
artic
leTB
I(m
ixed
)N
otsp
ecifi
edM
ultip
lem
easu
res
Fatig
ueis
pres
ent
in43
%7
3%of
patie
nts
Mas
elet
al15
n=
71/3
2y
(11
)TB
I(m
ixed
)3
mo
27y
PS
G,M
SLT
,act
igra
phy
PS
QI,
Epw
orth
Sle
epin
ess
Sca
leM
SLT
confi
rms
dayt
ime
hype
rsom
nia
inTB
Ipat
ient
sde
spite
nose
lf-re
port
edco
mpl
aint
sLu
ndin
etal
16n
=12
2pa
tient
s/37
.3y
n=
35co
ntro
ls/3
9y
mTB
1,7,
14d,
and
3m
opo
stin
jury
Riv
erm
ead
Pos
tC
oncu
ssio
nQ
uest
ionn
aire
poor
mem
ory,
slee
ppr
oble
ms,
fatig
uem
ost
com
mon
sym
ptom
sin
mTB
IB
aum
ann
etal
17n
=53
patie
nts/
37y
TBI(
mix
ed)
6m
opo
stin
jury
Com
pute
dto
mog
raph
y,la
bora
tory
test
s,M
SLT
,E
pwor
thS
leep
ines
sS
cale
62%
ofpa
tient
sha
da
slee
p-w
ake
com
plai
nt,d
aytim
esl
eepi
ness
mos
tco
mm
on(c
ontin
ues
)
www.headtraumarehab.com
158 JOURNAL OF HEAD TRAUMA REHABILITATION/MAYJUNE 2009
TAB
LE1
Trau
mat
icbr
ain
inju
ryan
dsl
eep
dist
urba
nce
sum
mar
yof
revi
ewed
artic
les
(Con
tinue
d)
Au
tho
rS
amp
le/a
ge
Sev
erit
yTi
me
sin
cein
jury
Mea
sure
sR
esu
lts
TBIa
ndob
ject
ive
slee
pdi
stur
banc
eK
aufm
anet
al11
n=
19pa
tient
s/10
16.
5y
n=
13P
SG
cont
rols
/sam
eag
esn
=15
actig
raph
yco
ntro
ls/s
ame
ages
mTB
I3
ypr
ior
tost
udy
PS
G,a
ctig
raph
yin
take
ques
tionn
aire
Pat
ient
ssh
owed
low
ersl
eep
effic
ienc
ies
and
mor
ew
ake
time
than
did
cont
rols
Sch
reib
eret
al18
n=
26pa
tient
s/31
.6y
(8.
8)n
=26
cont
rols
/33.
8y
(7.
8)m
TBI
12m
o21
yP
SG
,MS
LTS
ubje
ctiv
ean
dob
ject
ive
slee
pdi
stur
banc
ein
patie
nts
Gos
selin
etal
19n
=10
patie
nts/
not
repo
rted
n=
11co
ntro
lsm
TBI
Pas
tye
ar
2ni
ghts
PS
Gan
d10
min
day
PS
G,E
pwor
thS
leep
ines
sS
cale
,PS
QI
Abn
orm
alw
akin
gE
EG
(mor
ede
lta,
less
alph
a)
Laia
ndC
astr
iott
a20
n=
7/50
y(
19.9
)TB
I(m
ixed
)1
29y
Med
ical
revi
ewP
SG
/MS
LTP
atie
nts
with
hype
rsom
nia
atgr
eate
rris
kfo
rap
nea
Cas
trio
tta
etal
21n
=87
/18
yTB
I(m
ixed
)>
3m
oP
SG
/MS
LTE
pwor
thS
leep
ines
sS
cale
,PO
MS
,Fu
nctio
nalO
utco
mes
ofS
leep
Que
stio
nnai
re,
psyc
hom
otor
vigi
lanc
eta
sk
Pat
ient
sat
grea
ter
risk
ofsl
eep
diso
rder
spo
stin
jury
Verm
aet
al22
n=
60/2
069
yTB
I(m
ixed
)3
mo
2y
PS
G,M
SLT
,Epw
orth
Sle
epin
ess
Sca
le,B
DI,
Glo
bal
Ass
essm
ent
ofFu
nctio
ning
,H
amilt
onA
nxie
tyS
cale
Sle
epdi
sord
ers
corr
elat
edw
/TB
Ibu
tno
tw
ithou
tse
verit
y
Bra
dsha
wet
al23
n=
182
patie
nts/
21y
(3.
9)n
=14
5co
ntro
ls/2
3y
(4.
4)m
TBI
Rec
ent
Epw
orth
Sle
epin
ess
Sca
le,
PS
QI
Mor
epr
eexi
stin
gsl
eep
com
plai
nts
and
dayt
ime
slee
pine
ssin
patie
nts
Oue
llet
and
Mor
in24
n=
14pa
tient
s/30
.4y
(9.
7)n
=14
cont
rols
/30
y(
10.1
)TB
I(m
ixed
)7
41m
oP
SG
,sle
epdi
ary,
ISI,
MFI
,BD
I,B
eck
Anx
iety
Inve
ntor
yS
igni
fican
tdi
ffer
ence
sin
subj
ectiv
ebu
tno
tob
ject
ive
slee
pdi
stur
banc
ebe
twee
ngr
oups
Aur
ora
etal
25n
=9/
245
3y
TBI(
mix
ed)
Med
ian
=7
yP
SG
,PS
QI,
dayt
ime
MS
LT,
Epw
orth
Sle
epin
ess
Sca
le,
Glo
balF
atig
ueIn
dex
Poo
rsu
bjec
tive
but
norm
alob
ject
ive
slee
pdi
stur
banc
ein
patie
nts
Kor
inth
enbe
rget
al26
n=
98/3
13
ym
TBI
24h
and
46
wk
late
rE
xam
inat
ion,
inte
rvie
ww
akin
gE
EG
23of
98pa
tient
sha
dsl
eep
prob
lem
sat
follo
w-u
pC
hung
etal
27n
=7/
336
8y
Hea
din
jury
P
ast
hist
ory
Epw
orth
Sle
epin
ess
Sca
le,
Sta
nfor
dS
leep
ines
sS
cale
,P
OM
S,T
oron
toA
lexi
thym
iaS
cale
,Fat
igue
Sev
erity
Sca
le
No
asso
ciat
ion
betw
een
subj
ectiv
ere
port
san
dP
SG
mea
sure
men
ts
(con
tinue
s)
Traumatic Brain Injury and Sleep Disturbance 159
TAB
LE1
Trau
mat
icbr
ain
inju
ryan
dsl
eep
dist
urba
nce
sum
mar
yof
revi
ewed
artic
les
(Con
tinue
d)
Au
tho
rS
amp
le/a
ge
Sev
erit
yTi
me
sin
cein
jury
Mea
sure
sR
esu
lts
TBIa
ndci
rcad
ian
dist
urba
nce
Qui
nto
etal
2848
-yol
dm
an(c
ase
repo
rt)
TBI(
seve
re)
4y
prio
rN
euro
logi
cex
amin
atio
nse
lf-re
port
Pat
ient
exhi
bite
dsi
gnifi
cant
dela
yed
slee
pph
ase
post
inju
ryN
agte
gaal
etal
2915
-yol
dgi
rl(c
ase
repo
rt)
TBI(
mix
ed)
Pos
tinju
ryP
SG
,act
igra
phy
mel
aton
in,
tem
pera
ture
Pro
min
ent
dela
yed
slee
pph
ase
post
-TB
IA
yalo
net
al30
n=
42/2
6y
mTB
I1+
mo
PS
G,a
ctig
raph
yte
mpe
ratu
rean
dm
elat
onin
,ME
Qm
TBIl
eads
toin
crea
sed
chan
ceof
circ
adia
nde
lay
Ste
ele
etal
31n
=10
patie
nts/
38.8
y(
4.3)
n=
10co
ntro
ls/3
7.8
y(
4.4)
TBI(
mix
ed)
741
194
dS
aliv
a,m
elat
onin
,ME
QN
oev
iden
cefo
rci
rcad
ian
chan
gefo
llow
ing
TBI
TBIa
ndne
urop
hysi
olog
ic/n
euro
psyc
holo
gic
dist
urba
nce
Bau
man
net
al32
44pa
tient
s/m
ean
=36
y29
cont
rols
/mea
n=
44y
TBI(
mix
ed)
14
dC
ereb
rals
pina
lflui
dhy
pocr
etin
Hyp
ocre
tinle
vels
low
erin
95%
ofpa
tient
sw
ithm
oder
ate
tose
vere
TBI
Bau
man
net
al33
n=
96/3
8y
(16
)n
=65
(at
6-m
ofo
llow
-up)
TBI(
mix
ed)
4d
and
6m
oP
SG
,Mai
nten
ance
ofW
akef
ulne
ssTe
st,M
SLT
,E
pwor
thS
leep
ines
sS
cale
,la
bora
tory
test
s,qu
estio
nnai
res
TBIc
orre
late
dw
ithsl
eep-
wak
epr
oble
ms,
poss
ible
role
for
hypo
cret
in
Frie
boes
etal
34n
=13
/27.
3y
(6.
2)TB
I(m
ixed
)2.
54.
6m
oP
SG
,hor
mon
ete
sts,
Ham
ilton
Dep
ress
ion
Sca
leS
leep
-end
ocrin
ech
ange
sob
serv
edm
onth
saf
ter
TBI
Bre
edet
al35
n=
258
patie
nts/
237
3y
n=
65co
ntro
lsTB
I(m
ixed
)M
ean
=18
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160 JOURNAL OF HEAD TRAUMA REHABILITATION/MAYJUNE 2009
these daytime symptoms in TBI patients. Fatigue maybe present in as many a 43% to 73% of patients andis one of the primary symptoms in 7% of patients re-gardless of injury severity, time since injury, gender,or medications.14,15 Lundin et al16 found that poormemory, sleep disturbance, and fatigue were the mostcommonly reported symptoms following TBI. Whilethese complaints declined postinjury, correlations be-tween symptoms and disability were still evident at3 months postinjury. Furthermore, patients with earlyhigh symptom load were found to be at risk for develop-ing persisting complaints. In a study by Baumann andcolleagues,17 33 of 53 patients (62%) were found to havea sleep disorder following TBI, of whom 29 (55%) re-ported increased fatigue or excessive daytime sleepinesscompared with pre-TBI. In this study, Epworth Sleepi-ness Scale scores (a measure of trait sleepiness) were ab-normally elevated (>10) in 14 patients (26%), suggest-ing that many patients exhibited high levels of daytimesleepiness (especially those with mTBI as compared withthose with moderate/severe TBI).
Overall, subjectively reported sleep disturbance is oneof the most commonly described problems in TBI pa-tients. The literature reviewed in this section is particu-larly convincing because numerous studies seem to beproviding replicable findings of insomnia in TBI pa-tients. Most of the studies surveyed (especially the studyof Ouellet and Morin)24 had reasonably large samplesizes and utilized a variety of measures to assess sleepdisturbance. In addition, daytime fatigue and sleepinesswere also common findings in these studies. Interest-ingly, it is the research on subjectively defined sleep prob-lems that has brought attention to the observation thatmTBI is more clearly associated with insomnia than se-vere forms of TBI. While the exact cause of subjectivelyreported sleep difficulties and daytime sleepiness is notknown, these problems obviously affect patients bothcognitively and psychologically as they recover fromtheir injuries and impede attempts to return to normalactivities.
TBI AND OBJECTIVELY MEASUREDSLEEP DISTURBANCE
Despite the wealth of information supporting the pres-ence of subjective sleep complaints in TBI patients, ev-idence for measurable objective deficits in sleep hasbeen harder to identify. Some evidence of objectivechanges in sleep quantity and quality has been found byKaufman and colleagues11 in a study of 19 adolescents(3 years post-mTBI) who complained of sleep distur-bance and a group of control participants. Question-naire results revealed that patients subjectively reportedmore severe sleep complaints, a result that was corrob-orated by PSG measurements. In fact, PSG recordings
revealed that in comparison with controls, mTBI wasassociated with lower sleep efficiency, more nocturnalwake time, and more awakenings lasting longer than3 minutes. In a study by Schreiber and colleagues,18
26 mTBI patients with normal brain computed tomo-graphic and negative encephalographic (EEG) studieswere compared with a matched group of healthy con-trols. Patients in this study also showed altered sleeparchitecture, with significantly higher percentage of non-rapid eye movement (NREM) stage 2 than did controlsand significantly lower percentage of rapid eye move-ment (REM) sleep. In addition, Gosselin et al19 foundevidence of objective changes in the EEG during wake-fulness in athletes with concussion relative to controlathletes. In particular, athletes with concussion wereshown to have significantly more delta activity and lessalpha activity during wakefulness. This pattern has beenseen in sleep-deprived and sleep-disordered populationsand suggests that abnormal waking EEG may play a sig-nificant and/or unique role in the symptoms associatedwith TBI, especially daytime dysfunctions and sleepinessexperienced in this population.
Of note, some patients with sleep disturbance afterTBI may experience sleep problems other than insom-nia. Lai et al20 found an increased risk of sleep disorders,including sleep apnea. In addition, several patients inthis study also had a prior history of sleep disorders,which the authors suggest might have contributed tothe TBI. Castriotta et al21 and Verma et al22 have sim-ilarly reported high numbers of sleep disorders such asobstructive sleep apnea, periodic limb movements, andnarcolepsy in patients with TBI. Such findings have ledsome to propose that preexisting sleep disorders and sub-jective daytime sleepiness may be more common in pop-ulations with brain injury and may actually represent arisk factor for accidents or behaviors that predispose tohead injury.23
Contrary to these findings, several studies have failedto find clear evidence of objective sleep impairments inpatients with mTBI. For example, Ouellet and Morin24
found that TBI patients with insomnia, relative tohealthy controls, showed a tendency to overestimatethe subjective impression of their sleep disturbance ascompared with PSG measurements. Despite reports ofsignificant sleep disturbance on subjective measures, pa-tients showed no differences from controls in percentageof stage 2, slow-wave (stages 3 and 4), or REM sleep onPSG measurements. Patients did, however, have a higherproportion of stage 1 sleep, more awakenings lastinglonger than 5 minutes, and shorter REM sleep latencies.Such a pattern of mild sleep disturbance that is overesti-mated on subjective measures is consistent with the over-all insomnia literature, suggesting that the experience ofinsomnia may be similar in persons with and withoutTBI. In a study by Aurora and colleagues,25 5 men and
Traumatic Brain Injury and Sleep Disturbance 161
4 women (aged 2453 years) with a median time frominjury of 7 years were studied with PSG measurements.Results indicated that subjects had normal sleep efficien-cies (median of 90.7%); the median amounts of stage 1,stage 2, slow-wave, and REM sleep were 1.9%, 32.5%,43.8%, and 18.0%, respectively. The authors concludedthat while TBI patients may suffer from subjective com-plaints of fatigue and poor nocturnal sleep, they never-theless manifest relatively normal sleep architecture.
Several other investigations also seem to support thisobservation of a disparity between subjective and objec-tive measures of sleep disturbance following TBI. For ex-ample, Korinthenberg and colleagues26 studied 98 chil-dren (aged 313 years) within 24 hours after a minor headinjury and 4 to 6 weeks later. At follow-up, 23 of 98 stillexhibited posttraumatic complaints with headache, fa-tigue, sleep disturbance, anxiety, and affect instability.These posttraumatic symptoms, however, did not corre-late with somatic, neurologic, or EEG findings observedimmediately after the injury or at the follow-up inves-tigation. Chung et al27 found that subjective reports ofdaytime sleepiness and fatigue in patients with head in-jury were not well substantiated when compared withovernight PSG sleep measures and physiologic tests ofdaytime sleepiness.
Despite containing nearly an equal number ofmanuscripts as the section on subjective sleep distur-bance, the evidence for objective sleep problems inmTBI is the most equivocal of any of the outcome mea-sures reviewed here. Inconsistencies in the literature maybe due to multiple factors such as (1) small sample sizesin most studies (with a few notable exceptions), (2) morevariability in the age ranges across studies (including alarger number of children and adolescents), and (3) useof samples with mixed severity of injury. On the otherhand, the variability in TBI severity and the time sinceinjury are about the same in this set of articles as is inthe reports on subjective sleep disturbance. However,subjective and objective discrepancies in sleep distur-bance, such as those observed in TBI patients, are notat all inconsistent with the general literature on insom-nia. Nonetheless, the largest studies in this section sug-gest that TBI patients do experience objective sleep dis-turbance and/or sleep disorders postinjury.21,22,26 Theother intriguing hypothesis that warrants more longitu-dinal research is the notion that preexisting sleep distur-bance may be associated with increased risk of TBI.23
TBI AND CIRCADIAN CHANGES
Recent research has provided evidence that, ratherthan insomnia per se, sleep disturbance following TBImay be associated with alterations in the timing andrhythm of sleep. Such alterations can result in a mis-match between an individuals biological sleep-wake
schedule and his or her desired 24-hour environmentaland social schedule.38,39 Of the circadian dysrhythmias,delayed sleep phase syndrome is the most common andis often misinterpreted as insomnia by patients and clini-cians alike. In fact, the estimated prevalence of circadiandisorders among patients who initially complain of in-somnia is 7% to 10%.38,39 Patients with circadian rhythmsleep disorders (CRSDs) often exhibit altered rhythmsof melatonin secretion and body temperature.40,41 Con-sistent with these notions, recent case studies of CRSDsfollowing TBI have reported evidence of delayed sleepphase,28 delayed sleep phase with delayed melatoninand body temperature rhythms,29 and a non24-hoursleep-wake pattern with abnormal melatonin rhythm.42
Recent work by Ayalon and colleagues30 found thatmTBI might actually contribute to the emergence ofCRSDs. In this latter study, 2 types of disturbanceswere observed: delayed sleep phase syndrome and irreg-ular sleep-wake pattern; these types differed in subjectivequestionnaire scores and had distinct profiles of mela-tonin and temperature circadian rhythms. The authorsalso reported that 15 of 42 patients (36%) with com-plaints of insomnia following mTBI were more properlydiagnosed with CRSDs. The frequency of CRSDs inthis sample is considerably higher than the prevalence ofthese disorders among the general population of patientsattending sleep clinics who complain of insomnia.38,39
Not all research, however, supports the idea that TBIleads to circadian disturbances. In a study of 10 patientsin a postacute TBI group compared with matched con-trols, Steele and colleagues31 found that the TBI and con-trol groups reported similar habitual sleep times as mea-sured with a Morningness-Eveningness questionnaire.Furthermore, the timing of melatonin onset did not dif-fer between the groups. While the small sample size mayhave contributed to the lack of group differences, thepreliminary conclusion of the authors is that this studyfailed to provide conclusive objective evidence of a shiftin circadian timing of sleep following acute TBI.
In summary, a growing body of evidence suggests thatfor some patients, circadian disturbances may play a rolein sleep problems subsequent to TBI. Unfortunately, theliterature in this area is sparse, and the 2 primary investi-gations reviewed here (studies of Ayalon et al and Steeleet al)30,31 came to opposite conclusions as to the roleof circadian dysrhythmia in TBI patients. It is obviousthat future studies are needed on this connection and itslimits.
TBI AND NEUROPHYSIOLOGIC/NEUROPSYCHOLOGIC DISTURBANCES
Recent research is beginning to demonstrate thatTBI may be implicated in neurophysiologic changesthat affect the regulation of sleep and wakefulness. For
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162 JOURNAL OF HEAD TRAUMA REHABILITATION/MAYJUNE 2009
example, Baumann and colleagues32 studied 44 consec-utive patients with acute TBI and controls and foundhypocretin-1 levels to be abnormally low in 95% ofpatients with moderate to severe TBI and in 97% ofpatients with posttraumatic brain changes as indicatedby computed tomographic scan. In a follow-up study,Baumann and colleagues33 observed low cerebral spinalfluid hypocretin-1 levels in 4 of 21 patients 6 monthsfollowing a TBI (mixed severities) as compared with 25of 27 patients in the first days after TBI. Furthermore,significantly lower levels of hypocretin-1 were associ-ated with posttraumatic excessive daytime sleepiness.These data suggest that hypocretin-1 deficiency afterTBI may reflect hypothalamic damage in patients withacute TBI. Such deficiencies would be expected to con-tribute to sleep disturbance via hypocretins role in pro-moting wakefulness (eg, the study of Mignot et al).43
More specifically, abnormally low levels of hypocre-tin would be expected to contribute to daytime sleepi-ness and fatigue, 2 common complaints in patients withmTBI.
Sleep-endocrine alterations have also been shown tobe present several months after severe TBI and ex-hibit a pattern of sleep EEG parameters and noctur-nal hormone secretions similar to that seen in patientswith remitted depression.34 Frieboes et al34 proposethat hypothalamic-pituitary-adrenal overdrive and long-term modulation of hypothalamic and pituitary recep-tors may lead to either permanent sleep-endocrine alter-ations (a neurobiologic scar) or perhaps hypothalamic-pituitary damage due to diffuse thinning out of neurons(eg, growth hormone secreting cells). Similar researchhas shown that patients with TBI are more likely thanhealthy, age-matched peers to report problems with theirmetabolic/endocrine and neurologic systems.35
Current research also indicates that deficits in cogni-tive performance may be related to the degree of sleepdisturbance resulting from TBI. In a study of 87 pa-tients with mild to severe TBI admitted to a compre-hensive outpatient neurorehabilitation program, hierar-chical regression analysis revealed that poor performanceon selected measures of cognitive functioning was signif-icantly related to sleep disturbance, accounting for 14%of variance beyond that accounted for by injury severityand gender.4 These results suggest that sleep disturbanceamong patients with mTBI may be associated with im-paired neuropsychologic functioning. Sleep disturbancehas also been shown to correlate with posttraumatic am-nesia. In a study of 9 patients in a rehabilitation unit,sleep efficiency was positively correlated with ratings oforientation and significantly predicted clearance of post-traumatic amnesia.36
Overall, it appears that TBI can induce measurableneurophysiologic changes that may lead to objective
alterations in sleep-wake regulation. In particular, theworks of Baumann et al32 and Friebos et al34 provide con-vincing evidence that TBI results in endocrine changesthat might explain sleep disturbance in this population.In addition, the literature reviewed here suggests thatsleep changes may contribute to cognitive performancedeficits in persons with TBI. While only a few studiesindicated a link among TBI, sleep problems, and neu-ropsychologic performance, such results should not besurprising, given the established role that sleep plays incognition. One issue in need of further investigation isthe amount of variance in neuropsychologic impairmentthat can be directly and uniquely attributed to sleep dis-turbance, independent of other factors.
TREATMENT OF SLEEP PROBLEMSASSOCIATED WITH TBI
As researchers debate the complex issues surroundingthe underlying etiology and course of symptoms result-ing from TBI, clinicians must focus on how best to treatsleep disturbance in this population. Overall, the TBI-related sleep disturbance most strongly supported in theliterature are consistent with insomnia and delayed sleepphase syndrome. Fortunately, there are many provenpsychologic and pharmacologic interventions that canhelp patients with these sleep disturbance. In fact, sev-eral cognitive-behavioral techniques (CBTs) have beeneffective in improving sleep in patients with insomniaand thus hold particular promise for persons with TBI.Unfortunately, we found only a single report in whicha CBT for insomnia was applied with individuals withTBI (ie, the work of Ouellet and Morin).44 In this casestudy, a patient treated with a CBT had reductions insleep-onset latencies from 47 to 18 minutes, nocturnalawakenings dropped from 85 to 28 minutes, and sleepefficiencies increased from 58% to 83%. These resultswere well maintained at 1- and 3-month follow-up assess-ment. Furthermore, there are several therapies that havebeen effective in the treatment of CRSDs and which mayhave applicability in this population. For example, brightlight therapy will aid in the consolidation of sleep in pa-tients with CRSDs.44 Given that alterations in melatoninfunctioning also lead to sleep-phase alterations seen inTBI patients, treatment with exogenous melatonin couldbe useful in adjusting sleep-phase problems seen in thispopulation.
Despite the effectiveness of CBTs for the treatmentof sleep disturbance, prescription and over-the-countermedication remain the most common and accessibleforms of treatment for most individuals recovering fromTBI. In fact, hypnotic medications may be prescribed inas many as 20% of TBI patients.45 While medications
Traumatic Brain Injury and Sleep Disturbance 163
have been effective in treating sleep disturbance inhealthy individuals, such treatment effects have notbeen studied in TBI patients. Use of hypnotic medica-tions may also be associated with daytime drowsiness,dizziness or lightheadedness, and cognitive and psy-chomotor impairments, all of which are likely to be par-ticularly detrimental for this population.
LIMITATIONS AND FUTURE DIRECTIONS
TBI is a common and economically costly health-care issue in the United States today, with sequelae thatare numerous and include both medical and psychiatricsymptoms. It is associated with frequent complaints ofsleep disturbance that likely result from and contributeto multiple interrelated factors associated with the in-jury, all of which complicate recovery and resolution ofsymptoms. While current research is beginning to elu-cidate the nature of the relationship between TBI andsleep disturbance, the literature is hampered by manymethodologic concerns. As seen in this review, studiesover the last decade vary considerably across importantfactors such as sample size, age, injury severity, types ofmeasures/assessments performed, and the length of timebetween injury and evaluation. In addition to variabilityin study design, reporting of important factors such asthe number of prior TBIs, patient treatment regimen,medication use, past/current medical and/or psychiatricstatus, etc varied considerably among articles (and oftenwere not reported at all), making it difficult to evaluatethe role of these variables in sleep-related outcomes andcomplicating comparisons between studies.
There are, of course, several other limitations to the lit-erature. For example, very little attention has been paidto symptoms associated with a specific type or locationof injury, making logical cross-comparisons of studiesalmost impossible. Second, studies have not adequatelyinvestigated the effects of TBI on sleep on the basis oftime since injury (immediate vs long term). Third, therelative role of physiologic and/or psychologic factorsin the emergence of sleep disorders (ie, due to physicalinjury in sleep/arousal brain regions vs trauma/stress)has not been fully explored. Fourth, whether impairedsleep is the result of or the cause of other TBI-relatedsymptoms and whether impaired sleep may even in-crease likelihood of injury is yet to be determined. Fifth,TBIs typically result in multiple sequelae, such as pain,mood problems, posttraumatic stress disorder, and sleepdisturbance. Hence, teasing apart comorbid symptomsand studying their contributory effects to illness and re-covery are difficult processes at best. Finally, for obviousreasons, premorbid sleep patterns in individuals who suf-fer a TBI are rarely assessed. Clearly, knowledge of such
status might have implications for the understanding ofpost-TBI functioning.
Another important limitation is the inability of re-search to explain why mTBI seems to be more com-monly associated with sleep disturbance than more se-vere forms of TBI. While this fact may seem counter-intuitive, it does appear that mTBI is correlated withincreased likelihood of insomnia or delayed sleep phasesyndrome. While no clear explanation for this link hasbeen established, one could speculate as to the potentialreasons for its occurrence. First, it may simply be a factthat more severe brain injuries result in more complexissues during the recovery process of patients. In suchcases, rehabilitation is focused on matters such as reestab-lishing the ability to conduct activities of daily livingand reduction of long-term disability. Thus, sleep distur-bance is less likely to become a focus of treatment and/orget reported. Second, differences in the nature of injuriesmay play a role in the development of sleep disturbance.Perhaps, more diffuse injuries (eg, axonal shearing) thatoccur in mTBI lead to impairment in global functioning(eg, arousal) more so than acute or focal traumas. Third,severe injuries may produce more permanent changes inbrain function, as opposed to mild injuries, and this dif-ference may alter in some meaningful way the recoveryprocess, causing sleep problems to occur more often inone group than another. Finally, differences in the waybrain injuries are treated may lead to differences in self-reported postinjury symptoms. Recent research by Cha-put et al13 has found that individuals with mTBI weremore likely to report mood and sleep problems 6 weeksafter injury than in the time immediately following theinjury. The author (personal communication) concludedthat sleep problems manifested at a later time becausepatients with mTBI are often rapidly discharged fromcare (as opposed to those with more severe injuries). Insuch cases, the appearance of sleep problems later inthe course of recovery might be due to patients runningout of medication and not receiving adequate follow-upservices.
In conclusion, it is obvious that TBI is associated withsleep disturbance. However, it is also clear that muchmore research needs to be done to understand the ex-tent of this relationship. More important, research needsto focus on uncovering the specific types, causes, andseverity of TBI that most often lead to sleep problems,as well as the most appropriate treatment strategies forthe resultant sleep-wake abnormalities. It is hoped thatrecent public attention regarding the significance of TBIwill spur support of research that is essential both to im-proving conceptualizations of this complex issue and toimproving therapeutic strategies that could benefit thosewho suffer from this debilitating condition.
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