Predictors of Recovery from Traumatic Brain Injury-Induced Prolonged Consciousness Disorder

12 Pages·2017·1.16 MB·English

Hindawi
Neural Plasticity
Volume 2017, Article ID 9358092, 11 pages
https://doi.org/10.1155/2017/9358092
Research Article
Predictors of Recovery from Traumatic Brain Injury-Induced
Prolonged Consciousness Disorder
HiroakiAbe,1,2KeigoShimoji,3YoshihideNagamine,4
SatoruFujiwara,5andShin-IchiIzumi2,6
1DepartmentofRehabilitationMedicine,KohnanHospital,TohokuRyogoCenter,Sendai,Japan
2DepartmentofPhysicalMedicineandRehabilitation,GraduateSchoolofMedicine,
TohokuUniversity,Sendai,Japan
3DepartmentofDiagnosticRadiology,TokyoMetropolitanGeriatricHospital,Tokyo,Japan
4DepartmentofNeurosurgery,KohnanHospital,TohokuRyogoCenter,Sendai,Japan
5DepartmentofNeurosurgery,KohnanHospital,Sendai,Japan
6GraduateSchoolofBiomedicalEngineering,TohokuUniversity,Sendai,Japan
CorrespondenceshouldbeaddressedtoHiroakiAbe;[email protected]
Received28October2016;Revised19January2017;Accepted22January2017;Published23February2017
AcademicEditor:Cheng-ShengChen
Copyright©2017HiroakiAbeetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,
whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
Weinvestigatedtheclinicalpredictorsofthedegreeofrecoveryinpatientswithprolongeddisordersofconsciousness(PDC)caused
bytraumaticbraininjury.FourteenpatientswithPDCunderwenttwodiffusiontensorimaging(DTI)studies;thefirstandsecond
scanswereperformedat345.6±192.6and689.1±272.2daysaftertheinjury,respectively.Inadditiontothetemporalchangesin
eachofthesediffusionparameters,fractionalanisotropy(FA),meandiffusivity,axialdiffusivity(AD),andradialdiffusivitywere
assessedovera1-yearperiod.RelationshipofclinicalandDTIparameterswithrecoveryfromPDC(RPDC)wasevaluatedusing
Spearman’srank-correlationandstepwisemultiplelinearregressionanalysis.ThemeanFAandnumberofvoxelswithFAvalues>
0.4(VsFA0.4)weresignificantlydecreasedatthesecondscan.Asignificantpositivecorrelationwasobservedbetweenthedegree
ofRPDCandmeanFA(𝑟=0.60)andVsFA0.4(𝑟=0.68)aswellasbetweenthedifferenceinVsFA0.4(𝑟=0.63)andAD(𝑟=0.54)
betweenthefirstandsecondscans.Onmultiplelinearregressionanalysis,initialseverityofPDCandthedifferenceinADremained
significantlyassociatedwiththedegreeofRPDC.Themicrostructuralwhitematterchangesobservedinthisstudyindicatetheir
potentialrelationwiththedegreeofRPDCoverthelongerterm.
1.Introduction patientswhoremainedinavegetativestateafterTBIuntilthe
timeoftheirdeath[3,4].Thus,severeTBIcommonlyinvolves
Diffuseaxonalinjury(DAI)isacommonformoftraumatic multiplediffuselesionsinbothwhiteandgraymatter.
brain injury (TBI) sustained in motor vehicle collisions. Diffusion tensor imaging (DTI) has been useful in
The injury involves rotational forces and is characterized describing the microstructure changes in the chronic stage
by extensive white matter damage [1]. The neuropathology of DAI [5]. Several studies have documented posttraumatic
of disorders of consciousness (coma, vegetative state, and findingsofaxotomyanddemyelination,monthstoyearsafter
minimallyconsciousstate)hasbeenextensivelydescribedat injury. These include findings of increased water diffusion
postmortem [2–4]. Diffuse disruption of subcortical white as measured by mean diffusivity (MD) and a reduction
matteris the most commonpostmortemfindingin victims in the directionality of diffusion as measured by fractional
of TBI associated with impaired consciousness [2]. DAI anisotropy (FA) on DTI [5]. These findings, in conjunction
and thalamic damage were the most common postmortem with the apparent loss of subcortical white matter volume,
structural abnormalities reported in a case series of 35 suggest that acute edema may be a potential early marker
2 NeuralPlasticity
ofposttraumaticdeteriorationthatultimatelyimpairsaxonal daysaftertheinitialinjury);thesecondscanwasperformed
integrity in the chronic state [5]. Few longitudinal studies approximately1yearafteradmission(689.0±272.2daysafter
have examined temporal evolution of white matter damage theinitialinjury).
after DAI in humans [6–9]. However, the acute scans were Furthermore, we prospectively recruited 8 healthy nor-
collected,onaverage,withintwomonthsafterinjury;smaller malvolunteers(2malesand6females)forcomparison.The
time windows are necessary to obtain a more thorough agerangeofthehealthyparticipantswas32–60(45.5±9.1)
understandingoftheevolutionofwhitematterdamage.Fur- years(Table2).
ther, several studies have documented correlation between
decreased FA in several brain regions and unfavorable out- 2.2. Standard Protocol Approvals, Registrations, and Patient
comesinpatientswithsevereTBI[8,10,11].Arecentwhole Consent. This study was conducted in compliance with the
brain WM analysis of DTI parameters revealed an increase ethicalprinciplesforbiomedicalresearchonhumansubjects
in axial diffusivity (AD) and radial diffusivity (RD) in the enshrined in the Declaration of Helsinki and informed
acute phase and a positive correlation of RD with severity consent regulations. Approval from the institutional ethics
ofinjury[5].LongitudinalanalysisshowedreductioninFA committee was obtained prior to the initiation of the
and AD, but not in RD [5]. This study [5] examined the study.
evolution of white matter integrity from acute to chronic
stages of DAI due to TBI. Data from this study suggest
2.3. PDC Assessment. PDC was assessed using the Kohnan
complicatedmild-to-severeTAIresultsinsignificantedema
score,whichmeasurestheseverityofconsciousnessdisorder
thateventuallyresolvesleavingbehindacompromisedwhite
fromasevere,persistentvegetativestate(Appendix[12]).The
matter microstructure. The data [5] also suggest that white
Kohnanscorewasdevelopedatourinstitutiontoresolvethis
matter compromise after DAI is a process involving white
issue.Theunidimensionalityandhigherintra-andinterrater
matterdemyelinationaswellasaxonaldamagethatmaybe
reliability of this score have previously been reported [12].
present not only in the early stage but also in the chronic
The score is based on seven parameters, each of which is
stage[5].However,themechanismthatexplainsthisfinding
subdivided into 5 grades: extreme (10 points), severe (9
is still unclear. DTI still appears to be capable of detecting
points),moderate(7or8points),mild(5points),andslight(0
microstructuralchangesafterDAI.
points).Weadditionallyassessedgeneralfunctionalrecovery
Patients with severe PDC, such as those in a vegetative
usingtheExtendedGlasgowOutcomeScale(GOSE)(range
state,typicallyhaveunfavorableoutcomesalthoughgradual,
1–8; higher scores indicate superior functional outcomes).
subtle,andminorclinicalchangesareonrecord.Inthelast
These assessments were performed at admission and at 2
2 years, our institution provided inpatient care to patients
yearsafteradmission.
with prolonged disorders of consciousness (PDC) due to
TBI. The therapeutic modalities include standard nursing
2.4. Image Acquisition. MRI was performed using a 3.0T
care, physical therapy, and occupational therapy, as well as
Signa Excite HD scanner (General Electric, Milwaukee,
otheralternativetreatmentmodalitiessuchasmusictherapy,
WI, USA). The parameters for DTI were as follows: echo
aroma massage, and exposure to natural environment (i.e.,
∘
time, 59ms; repetition time, 9,000ms; flip angle, 90 ; slice
feelingthesunlight,blowingwind,andexposuretoseasonal
thickness, 3mm with no gap; field of view, 28.8 × 28.8cm;
temperature changes). Indeed, a few patients have shown
acquisitionmatrix,96×96;imagematrix,256×256witha
slight positive reactions during inpatient residency at our
voxel size of 1.125 × 1.125 × 3.0mm; number of excitations,
institution.
1;andbandwidth,250kHz.Imageswereobtainedusing15-
In this study, we sought to identify potential predictors
of the degree of recovery from PDC over a period of 2 directionaldiffusionencoding(𝑏value,1,000s/mm2ineach
years,usingDTIparametersinwholebrain.Weexaminedthe direction)andonesetofimageswith𝑏=0s/mm2.
longitudinal alterations in anatomical connections of white Atotalof46axialsectionscoveringtheentirecerebrum
matter in these patients and explored potential association wereobtained.ThemostinferiorDTIsliceswerepositioned
ofmicrostructuralimagingbiomarkersinwholebrainwhite atthemedullaoblongataduringacquisition.
and gray matter with clinical markers of potential clinical
relevance. 2.5.ImagePreprocessing. AllDTIdatawereprocessedusing
theFSLsoftwarepackage(theOxfordCentreforFunctional
2.Methods MagneticResonanceImagingoftheBrainSoftwareLibrary
[13]). DTI images were skull-stripped using the Brain
2.1.Patients. Weretrospectivelyrecruited14patientsatour ExtractionTool(BET)intheFSL.Theimageswerecorrected
institution that had chronic severe PDC resulting from usingtheEddyCorrectprogramoftheFSLpackagetoadjust
traffic accident-related brain injury. All patients with PDC fortheeffectsofheadmovementandeddycurrents.FA,MD,
underwent3TMRIstudiesatadmissionandaftercompletion AD, and RD maps were generated using dtifit program in
of1yearoftreatmentatourinstitution.Meanage(±SD)of theFSL.Lastly,wecalculatedthemeanFA,MD,AD,andRD
patientswas58.6±19.3years;themeanduration(±SD)from andcountedthenumberofvoxelsinwhichFAvalueswere
admissiontostudyrecruitmentwas339.8±191.7days.The >0.4 in the whole brain (VsFA0.4) using fslstats program
clinicalcharacteristicsofpatientsarepresentedinTable1.The implementedintheFSL.Weassumedthatusingwholebrain
first DTI scan was performed at admission (345.6 ± 192.6 methodaffectednotonlywhitematterchangesbutalsogray
NeuralPlasticity 3
Degreeofimprove-mentfromprolongedconscious-ness∗disorders2 29 −1 7 2 421 29 1 3 10 1 2 21
rmn
Kohnancoreafteyearfrodmissio 63 5 68 56 62 6434 0 62 64 52 64 65 34
s1a
n
Kohnanscoreatdmissio 65 34 67 63 64 6855 29 63 67 62 65 67 55
a
ermn
ftoo
ury. GCSEa1yearfradmissi 2 3 2 2 2 23 3 2 2 2 2 2 3
nj
ni aton
ai Esi
br CSmis 2 3 2 2 2 22 3 2 2 2 2 2 2
eto Gad
u
disordersd Daysuntilthesecondscanfrominjury 768 548 636 416 885 591396 286 580 1173 779 849 1200 540
s
nsciousnes Daysuntilthefirstscanfrominjury 415 266 311 135 629 158232 149 228 490 360 400 807 258
o
prolongedc Daysuntiladmissionfollowinginjury 407 264 296 126 629 155230 147 226 482 350 391 798 256
Table1:Clinicalprofilesofpatientswith Diagnosis Rightacutesubduralhematoma,cerebralcontusionTraumaticsubarachnoidhemorrhage,pneumocephalus,diffuseaxonalinjuryTraumaticsubarachnoidhemorrhage,diffuseaxonalinjury,brainstemcontusionCerebralcontusion,traumaticsubarachnoidhemorrhage,diffuseaxonalinjury,brainstemcontusionLeftsubduralhematoma,traumaticsubarachnoidhemorrhage,intracerebralhemorrhageTraumaticsubarachnoidhemorrhageTraumaticsubarachnoidhemorrhage,diffuseaxonalinjuryTraumaticsubarachnoidhemorrhage,leftintracerebralhemorrhageTraumaticsubarachnoidhemorrhage,cerebralcontusion,leftintracerebralhemorrhageLeftintraventricularhemorrhage,leftintracerebralhemorrhage,diffuseaxonalinjuryCerebralcontusion,intraventricularhemorrhage,brainstemcontusionTraumaticsubarachnoidhemorrhage,diffuseaxonalinjury,cerebralcontusionRightacutesubduralhematoma,traumaticsubarachnoidhemorrhage,cerebralcontusion,diffuseaxonalinjuryTraumaticsubarachnoidhemorrhage,cerebralcontusion,leftcerebralhemorrhage hnanscorefromadmissiontoafter1year.
o
Gender Female Male Male Female Female MaleFemale Male Female Male Male Male Female Male nceinK
e
Age(y) 75 60 68 68 78 8644 58 77 31 56 64 23 33 differ
e
h
t
1 2 3 4 5 67 8 9 10 11 12 13 14 ∗is
4 NeuralPlasticity
DifferenceinRD−32×[10mm/s]fromthefirsttothesecondscan −0.120.06−0.05−0.05−0.05−0.10−0.04−0.040.01−0.070.05−0.07−0.020.30
2m/s]ond
RD−3×[10matthesecscan 1.491.251.301.271.441.331.051.231.491.391.141.341.361.28 diffusivity.
2m/s]scan adial
RD−3mefirst 1.371.311.261.221.391.231.011.191.491.331.181.281.341.58 RD:r
etobraininjury. DifferenceinAD−32×[10mm/s]×[10fromthefirstatthtothesecondscan −0.170.11−0.03−0.05−0.07−0.060.020.140.01−0.090.18−0.060.040.41 AD:axialdiffusivity;
ssdisordersdu AD−32×[10mm/s]atthesecondscan 2.001.711.771.711.971.891.461.672.001.831.621.801.821.86 meandiffusivity;
onsciousne AD−320mm/s]hefirstscan 1.831.821.741.661.901.841.481.812.021.741.801.741.862.27 brain;MD:
dc ×[1att ole
e h
withprolong DifferenceinMD−32×[10mm/s]fromthefirsttothesecondscan −0.140.08−0.04−0.05−0.06−0.09−0.020.020.01−0.070.09−0.070.000.34 an0.4inthew
s h
arameterofpatient MD−32×2[10mm/s]m/s]atthesecondscanscan 1.661.401.461.411.621.521.181.381.661.541.301.501.511.47 otropyvaluegreatert
2:Eachdiffusionp DifferenceinMDVsFA0.4−3×fromthe[10mfirsttotheatthefirstsecondscan−15191.5281921.4849831.4235771.369651.56219771.431.178618444801.39−19871.671.476167322121.3935801.4385241.5297381.81 withafractionalanis
Table VsFA0.4atthesecondscan 2341439756307502669030802555012909439949260242184440235338541771046882 ofvoxels
VsFA0.4atthefirstscan 2189547948357333026731767774783771284429240372801172447374342623456620 4:number
DifferenceinFAfromthefirsttothesecondscan 0.000.010.010.010.000.040.020.070.000.000.050.010.030.00 py;VsFA0.
o
FAatthesec-ondscan 0.210.220.210.210.220.250.220.210.210.190.240.210.200.25 nisotr
a
FAatthefirstscan 0.210.240.220.220.220.290.240.280.210.190.290.220.220.26 onal
ber acti
m r
f
Nu 1234567891011121314 FA:
NeuralPlasticity 5
matter and ventricles. To eliminate these effects, we chose No significant correlations were observed between the
themethodofVsFA0.4thatselectsonlythevoxelwithhigh degree of recovery from PDC and age. Kohnan score was
FAvalues. stronglyassociated(𝑟=−0.76,𝑃=0.002)withthedegreeof
recoveryfromPDC.AmongtheDTIparameters,significant
2.6. Statistical Analysis. Statistical analyses were performed correlations were observed between the degree of recovery
using the Statistical Package for the Social Sciences (SPSS) from PDC and FA (𝑟 = 0.60, 𝑃 < 0.05) and VsFA0.4 at
24.0 for Mac (IBM SPSS, Chicago, IL, USA). Comparisons thefirstscan(𝑟 = 0.68,𝑃 = 0.008);however,nosignificant
over time for group Kohnan scores, GOSE, FA, VsFA0.4, correlationwasobservedbetweentheMD,AD,andLDatthe
MD, AD, and RD were conducted using the paired 𝑡-test first scan (Table 6). In the longitudinal DTI parameters, no
or Wilcoxon rank-sum test according to the results of the significantcorrelationswereobservedbetweenthedegreeof
Shapiro–Wilk test. The Spearman rank-correlation coeffi- recoveryfromPDCanddifferenceinFA,MD,andRDover
cientwasusedtoevaluatetherelationshipsbetweenage,time time(Table6).However,asignificantpositivecorrelationwas
ofadmissionfrominjury,degreeofrecoveryfromPDC(as observedbetweenthedegreeofrecoveryfromPDCandtime-
determinedbychangeintheKohnanscoreduringthe2-year dependentchangesinAD(𝑟=0.544,𝑃<0.05)andVsFA0.4
periodafteradmission),andthediffusiontensorparameters. (𝑟 = 0.624, 𝑃 < 0.05) between the first and second scans
These diffusion tensor parameters used for comparisons (Table6).
were FA, VsFA0.4 MD, AD, and RD in the first scan and Variablesshowingasignificantassociation(Pvalue<0.1)
the differences in the same parameters between the first were included in the Spearman correlation analysis. Thus,
and the second scan. All univariate potential factors with day of institution admission from injury, Kohnan score at
a 𝑃 value < 0.1 were entered into the multivariate linear thefirstassessment,FAatthefirstscan,VsFA0.4atthefirst
regression model. In addition, variance inflation factors scan,differenceinVsFA0.4,andMDandADfromthefirstto
werecomputedtoexaminethepossiblecollinearityproblem thesecondscanwereincludedinthemultivariateregression
amongthepredictors.Stepwisemultipleregressionanalyses analysis. Stepwise multiple regression analysis revealed that
wereperformedtoidentifythevariablesassociatedwiththe theKohnanscoreatthefirstscan(standardized𝛽 = −0.723,
degreeofrecoveryfromPDC.Thealphalevelwassetto0.05 95% CI: 32.7–63.0, 𝑃 < 0.0001) and difference in AD over
for all statistical tests and adjusted for multiple tests (e.g., time (standardized 𝛽 = 0.337, 95% CI: 4610.7–46541.3, 𝑃 <
𝑛 = 5,𝑃 > 0.01,comparisonofthemeanFA,MD,AD,and 0.05)accuratelypredictedthedegreeofrecoveryfromPDC
RD)withBonferronicorrection. [adjusted𝑅2=0.841].
3.Results 4.Discussion
In this study, 12 patients had a GOSE score of 2 (vegetative We explored potential clinical predictors of the degree of
state),and2patientshadGOSEscoreof3(severedisorder) recovery from PDC after 2 years of admission, with a
atadmission.However,Kohnanscoresatadmissionshowed particularfocusontheDTIparameters.Ourresultsshowed
morevariability(range:29–68).Theserangedfromminimum significantly decreased FA values and number of voxels
consciousness disorder (<39) to complete vegetative state in which FA values were >0.4 (VsFA0.4) in whole brain,
(>65).After2years,therewasnosignificantchangeinGOSE but MD, AD, and RD showed no significant change. In
scores(𝑃 = 0.16,Wilcoxonrank-sumtest):10patientshad contrast, healthy participants did not exhibit such changes.
aGOSEscoreof2,while4patientshadaGOSEscoreof3. Oncorrelationanalysis,KohnanscoreandFAandVsFA0.4,
In contrast, a subset of PDC patients showed a significant thedifferenceofVsFA0.4,andADweresignificantlycorre-
recoverybasedontheKohnanscore(58.9±12.3versus48.7± lated in monovariable analysis. Multiple regression analysis
22.7,𝑃<0.01;Wilcoxonrank-sumtest)(Table3).Themean revealed that each Kohan score in the first assessment and
differenceinKohnanscoresatadmissionandatcompletion the difference in AD over time have statistically significant
of2yearswas10.14±11.10. contributiontothedegreeofrecoveryfromPDC.Currently,
In patients with PDC, FA, VsFA0.4, MD, AD, and RD tothebestofourknowledge,therearenoknownpredictors
valuesinthefirstscanwere0.24±0.03,43715.14±20913.54, of long-term positive clinical response in patients with
1.47 ± 0.15 [×10−3mm2/s], 1.82 ± 0.18 [×10−3mm2/s], and PDC. Several clinicians were forced to provide long-term
1.30±0.14[×10−3mm2/s],respectively,whereasthoseinthe care without established specific clinical goals for patients
second scan were 0.22 ± 0.02, 33036.07 ± 10413.59, 1.47 ± with PDC. Therefore, it is critical to develop predictors of
0.01 [×10−3mm2/s], 1.79 ± 0.15 [×10−3mm2/s], and 1.31 ± long-term changes elicited through long-term therapeutic
0.13[×10−3mm2/s],respectively(Table3).PatientswithPDC interventioninthesepatients.Ourresultsdemonstratethat
showedsignificantchangesinFA(𝑃 = 0.006,paired𝑡-test) microstructural white matter changes occurred in patients
and VsFA0.4 (𝑃 = 0.003, Wilcoxon rank-sum test) over with PDC, which suggests that the assessment of white
time.However, therewere no significantdifferences in MD matter changes may help identify valid long-term outcome
(𝑃 = 0.993,paired𝑡-test),AD(𝑃 = 0.506,paired𝑡-test),and predictorsinthesepatients.
RD (𝑃 = 0.650, paired 𝑡-test) values between the first and DTI is based upon the diffusivity of water molecules,
second scans (Table 4). In contrast, any significant change which varies in different tissues [14]. In white matter, it is
of DTI parameters was not shown in the 8 normal healthy morelimitedinthedirectionsofdiffusion.Inhealthytracts,
participants(Table5). theanisotropy(limiteddirectionalityofdiffusion)ishigher
6 NeuralPlasticity
DifferenceinRD−32×mm/s][10fromthefirsttothesecondscan 0.880.920.890.880.830.850.920.86
2m/s]ond
RD−3×m[10atthesecscan 1.251.311.261.281.221.231.311.26 usivity.
ff
RD−32×mm/s][10atthefirstscan 1.001.051.011.010.960.981.050.99 RD:radialdi
DifferenceinAD−32×mm/s][10fromthefirsttothesecondscan 96457111993123996122068150473118282111993144917 xialdiffusivity;
ants. AD−32×mm/s][10atthesecondscan 0.260.260.260.270.270.260.260.28 ffusivity;AD:a
yparticip AD−32mm/s]0hefirstscan 0.890.910.880.880.860.860.750.86 D:meandi
nnormalhealth DifferenceinMD−32×mm/s][10×[1fromthefirstatttothesecondscan 1.271.301.271.281.261.251.141.26 ewholebrain;M
i h
parameter MD−32×mm/s]10atthesecondscan 1.021.041.011.010.990.990.880.99 than0.4int
Eachdiffusion MD[−32×[10mm/s]atthefirstscan 97531115720125776125151149240122442135897145240 pyvaluegreater
Table3: DifferenceinVsFA0.4fromthefirsttothesecondscan 0.260.260.260.270.280.270.290.27 alanisotro
VsFA0.4atthesecondscan 0.880.920.890.880.830.850.920.86 fraction
a
VsFA0.4atthefirstscan 1.251.311.261.281.221.231.311.26 elswith
x
DifferenceinFAfromthefirsttothesecondscan 1.001.051.011.010.960.981.050.99 berofvo
m
FAatthesecondscan 96457111993123996122068150473118282111993144917 0.4:nu
FAatthefirstscan 0.260.260.260.270.270.260.260.28 y;VsFA
p
Gender FemaleFemaleFemaleFemaleFemaleFemaleMaleMale nisotro
a
Agember(years) 6049444354463236 fractional
Nu 12345678 FA:
NeuralPlasticity 7
Table4:Comparisonofdiffusiontensorparametersandconsciousnessdisorders.
Firstscan Secondscan
Diffusionparameters Standard Standard 𝑃values
Mean Mean
deviation deviation
Kohnanscore∗ 58.86 12.30 48.71 22.69 0.001
GSCE∗ 2.14 0.36 2.29 0.47 0.157
Fractionalanisotropy 0.24 0.03 0.22 0.02 0.006
Numberofvoxelswithafractionalanisotropyvaluegreater
∗ 43715.14 20913.55 33036.07 10413.59 0.003
than0.4inthewholebrain
Meandiffusivity(MD)[×10−3mm2/s] 1.47 0.15 1.47 0.01 0.993
Axialdiffusivity(AD)[×10−3mm2/s] 1.82 0.18 1.79 0.15 0.506
Radialdiffusivity(RD)[×10−3mm2/s] 1.30 0.14 1.31 0.13 0.65
∗
Wilcoxonranktest.
Table5:Comparisonofdiffusiontensorparametersinnormalhealthyparticipants.
Firstscan Secondscan
Diffusionparameters Standard Standard 𝑃values
Mean Mean
deviation deviation
Fractionalanisotropy 0.26 0.07 0.27 0.01 0.13
Numberofvoxelswithafractionalanisotropyvaluegreaterthan0.4
122522.38 17745.24 127124.63 16594.75 0.15
inthewholebrain
Meandiffusivity(MD)[×10−3mm2/s]∗ 1.01 0.03 0.99 0.05 0.40
Axialdiffusivity(AD)[×10−3mm2/s]∗ 1.26 0.03 1.25 0.05 0.23
Radialdiffusivity(RD)[×10−3mm2/s]∗ 0.88 0.03 0.09 0.05 0.57
∗
Wilcoxonranktest.
Table6:Correlationbetweenthedegreeofrecoveryfromprolongedconsciousnessdisorderandeachvalue.
DegreeofrecoveryfromPCD
Variable 𝑟
𝑃values
(Spearmancorrelationcoefficient)
Atthefirstscanorassessment
Age −0.24 0.41
Dayofinstitutionadmissionfrominjury −0.48 0.086
Kohnanscore −0.76 0.002
Fractionalanisotropy 0.60 0.023
Numbersofvoxelswithafractionalanisotropyvaluegreaterthan0.4 0.68 0.008
Meandiffusivity −0.22 0.459
Axialdiffusivity −0.01 0.976
Radialdiffusivity −0.34 0.241
Thedifferencebetweenthefirstandthesecondscan
Fractionalanisotropy 0.38 0.177
Numbersofvoxelswithafractionalanisotropyvaluegreaterthan0.4 0.62 0.017
Meandiffusivity 0.48 0.086
Axialdiffusivity 0.54 0.044
Radialdiffusivity 0.40 0.162
than that in the gray matter. This difference allows for the havedemonstratedthepotentialutilityofDTIforproviding
calculationoffractionalanisotropy(FA)valuesfortissueand quantitative assessments of microstructural damage in TBI,
thegenerationofwhitematterfibermaps.FArangesfrom0 inwhichDAIiscommon[1–11,14–16].Althoughthespecifics
to1,where0representsisotropicdiffusion(orlackofdirec- arestillnotwellunderstood,FAisbelievedtobeinfluenced
tional organization) and 1 represents anisotropic diffusion by many factors, including the degree of myelination and
(ororganizedtissuesuchaswhitemattertracts)[15].Studies axonaldensityand/orintegrity[9,17–19].
8 NeuralPlasticity
Slight(0)(1)Capableofmovementwithintention(2)Capableofunassistedposturechange(partialchangeinclusive)(3)Movingwheelchairunassisted,evenifawkwardly Ingestingonownusingspoonawkwardly Exceptduringthenight,preevacuationandpreurinationcommunicationispossible (1)Capableofreadingeasywords(2)Capableofunderstandingsimplenumbers(3)WhenwatchingTV,responseandlaughterareapparent
Mild(5)(1)Occasionalmovementtomeetanobject(2)Capableofraisingthearmsupwardormovingthemintheintendeddirection,thatis,faceorhead,imitatingapostureofthetester(1)Capableofunassistedingestionbyswallowing;masticationcouldbeawkward(2)Capableofingestingallthericegruelservedorchoppedfoodwithassistance(3)Attemptingtoreachmouthwithapassedspoonorputthefoodintomouthawkwardly(1)Forcedregularevacuatingandurinatingleadtothepreventionoffecalandurinaryincontinence(2)Communicatingthefactinacertainwayafterincontinence (1)Discriminatingcloserelativesfollowedbyafacialexpression(2)Favoritepicture,amongotherthings,inducesafacialexpression
able7 GradeModerate(8/7) (1)Occasionalall/partialextremitymovementwithnointention(2)Extremitycouldbeparetic(3)Brushingawayreactionforpain (1)Capableofmasticating;evenifnot,almostcapableofassistedauroralingestionbyswallowing,thoughsometimeschoking(2)Insufficientperoralingestionrequirestubenutrition Afterincontinence,adispleasedlookorsomesignalisobserved,thatis,frequentsomaticmovement (1)Lookingstraighttowardthedirectionofthecall(2)FollowingamovingobjectorstaringataTV,althoughunderstandingisimpossible
T
Severe(9)(1)Almostabsentbutpartsoftheextremitiesmoveminutely(2)Partoftheextremityflexedandpartparalyzed(3)Painreflexornopainreflexwithclearlyfrowningface (1)Almostontubenutrition(2)Salivaswallowingormasticationisfound(3)Capableofattemptingslightperusalingestion,thatis,fruitjuice,custardpudding,andsoforth Slightsomaticmovementwhenevacuating/urinating (1)Eyesopened,blinkreflex(2)Nofollowingocularmovementandnofocusingeyesonanobject
Extreme(10) (1)Absent(2)Acrocontracture(3)Painreflexbutslighttremblingandroughbreathing Totallyincapableofmasticatingandswallowing;ontubenutrition(gastric/nasalfeeding) Noobservedsomaticmovementwhenevacuating/urinating (1)Eyesnotopened(2)Eyesopened,noblinkreflex
ms y hy
Clinicalsympto Voluntarymovement Voluntaryingestion Fecalandurinarincontinence Ophthalmograpandvisualrecognition
NeuralPlasticity 9
Slight(0) (1)Capableofvocalizingasimplewordresponse(2)Lipmovementcorrespondstowhatisasked Changeofexpression,suchascryingandsmiling,exactlymatchesanexpectedresponsetotheambientstimulation
Mild(5) (1)Occasionalvocalizingofameaningfulword(2)Vocalresponsetocalls(3)Imitatingtalkingbythetesterundertracheostomy Changeofexpression,suchassmiling,crying,andanger,closelymatchesanexpectedresponsetotheambientstimulation
7:Continued. GradeModerate(8/7)(1)Ashortutterancethoughnotunderstandable(2)Occasionalinarticulatevocalresponsetocalls(3)Undertracheostomy,responsetocallsisthroughlipmovement Changeofexpressionisoccasionallyfoundinresponsetoambientstimulations
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Ta Severe(9) (1)Groaning,amongothers,withoutmeaningfulutterances(2)Lipmovementobservedundertracheostomy Changeofexpression,suchassmiling,crying,andanger,isnotduetoambientstimulations
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Clinical Vocaliziutteranc Changeexpressi
10 NeuralPlasticity
FAhasbeenshowntodecreaseinpatientswithmildand asaprognostictoolneedsfurtherinvestigationinstudieswith
moderate/severebraininjury[1,4,5,11,14–16,19–28].Perez alargernumberofsubjects.
etal.[5]reportedsignificantlylowerFAinthechronicphase In conclusion, on stepwise multiple linear regression
of TBI as compared to that in healthy controls; in contrast, analysis, Kohnan score and the difference in AD showed
AD, MD, and RD in chronic patients were significantly a significant association with the degree of recovery from
higher than in healthy controls. Additionally, chronic FA PDC.Inotherwords,wedemonstrateevidenceoftemporal
showed a positive correlation with processing speed [28]. microstructuralwhitematterchangesinpatientswithPDC;
In this study, patients with chronic PDC had significantly DTI parameters are useful indices for assessment of white
lower FA and VsFA0.4 at 2 years as compared to those at matteralterationsinthesepatients.Asanoninvasivemodal-
admission. Our first scan data were collected 345.6 ± 192.6 ity, DTI provides in vivo quantitative pathophysiological
daysafterinjury,whichcorrespondstothechronicstageof information.Trackingwhitemattermicrostructuralchanges
whitematterdamage.Thus,ourresultssuggestoccurrenceof over time has the potential to measure neuroplasticity and
microstructuralchangeoverthelongerterm.Onunivariate repair after TBI and may eventually be utilized to monitor
correlationanalysis,FAandVsFA0.4atthefirstscansignifi- therapeuticresponses.Furtherresearchisrequiredtoinves-
cantlycorrelatedwiththedegreeofrecoveryofPDC,whichis tigatetheleadsidentifiedinthisstudy.
consistentwithpreviousstudies[5–8,10,11,14,20–29]where
patients with higher FA showed good recovery. Temporal
Appendix
changeinVsFA0.4andADsignificantlycorrelatedwiththe
degree of recovery from PDC. This probably indicates that SeeTable7.
minor microstructural changes correlate with the degree of
recovery from PDC. Several previous studies [6, 8, 10, 11,
CompetingInterests
20, 25–29] have reported a positive association of FA with
higher cognitive function and outcomes. However, in this
Theauthorsdeclarethattheyhavenocompetinginterests.
study,higherdifferenceofVsFA0.4,MD,andADpositively
correlated with the degree of recovery from PDC. In other
Acknowledgments
words, a time-dependent decrease in VsFA0.4, MD, and
AD may be related to a better outcome in PDC. In this
This study was supported by a medical research grant on
respect,ourresultsarenotinconsistentwiththoseofseveral
traffic accidents from the General Insurance Association of
previous reports [6, 8, 10, 11, 20, 25–29], which indicated
Japan. This work was also supported by JSPS KAKENHI
that a time-dependent decrease in FA was associated with
Grantno.JP16H06280,Grant-in-AidforScientificResearch
pooroutcomesasassessedbycognitivefunctionandGOSE.
on Innovative Areas-Resource and Technical Support Plat-
These contradictory findings may reflect the difference in
forms for PromotingResearch “Advanced Bioimaging Sup-
PDC severity between studies; most of our patients had
GOSE scores of ≤3 and showed subtle and minor clinical port.” The authors would like to thank the patients and
normalhealthyvolunteerswhoparticipatedinthisstudy.The
changes.Althoughsignificantrecoverieswereobservedbased
authorswouldalsoliketothanktheimagingstaff,particularly
on Kohnan scores, the changes were not significant when
TomohiroChiba,fortheirskilledMRIacquisition.Theyalso
based on GOSE scores, which suggests that improvement
thankEnagofortheEnglishlanguagereview.
in our patients was lower than that reported in previous
studies [6, 8, 10, 11, 20, 25–29]. Our subjects generally had
more severe outcomes; all our patients had GOSE scores ≤ References
3, which indicates more severe disability than that among
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