J Vet Intern Med 2017

Y.Tanaka

Transcranial Doppler Ultrasound Examination in Dogs with Suspected Intracranial Hypertension
Caused by Neurologic Diseases
K. Sasaoka	
 （神経疾患による頭蓋内圧亢進が疑われる犬における経頭蓋ドプラ超音波検査）
はじめに	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
 
◯ 頭蓋内圧亢進(IH)は様々な頭蓋内疾患によって生じ、脳血流減少と機械的圧迫により脳に致命的な障害を生じう	 るため、迅速な診断と適切な治療が必要である。

◯ IH の診断は臨床症状(※1)と MRI 所見(※2)によってなされるが非特異的である。
◯ 経頭蓋ドプラ超音波検査(TCD)は脳動脈血流を評価する迅速、非侵襲的な方法でありヒトにおいては利用されているが、犬の IH における臨床的有用性は報告されていない。
◯ 目的：⑴ TCD 血管抵抗変数と IH を疑う MRI 所見の存在が相関するかを決定する。
	
  	
  	
  	
 

⑵ TCD 血管抵抗変数と頭蓋内構造性疾患の存在が相関するかを決定する。

Materials and M ethods

	
  	
  	
  	
  	
  	
  	
  	
 

◯ 2011 年 10 月~2012 年 10 月、北海道大学、前向き研究◯ 組み入れ基準 - 頭蓋内疾患が疑われ、全身麻酔下にて MRI 検査を実施した犬
◯ IH の診断基準 - IH を疑う MRI 所見(※2)のうち 2 つ以上満たす症例を IH と診断◯ MRI 所見に基づき 3 つのグループに分類(右表)GroupⅠGroupⅡGroupⅢ◯ TCD は MRI 撮影後に実施(TCD の方法は※3)

非構造性疾患IH(−)の構造瀬疾患

IH(+)の構造性疾患

Results◯ n=50、Table 1、Table2◯ TCD 血管抵抗変数のうち Sm/Dm のみがグループ間に有意差が認められ、GⅢは GⅠ、GⅡと比べて有意に高値。
◯ Sm/Dm と IH を示唆する MRI 所見の数との間に有意な正の相関が認められた。
◯ GⅢを特定するための ROC 解析では Sm/Dm のカットオフ値 1.78 とした場合、感度 62%、特異度 92%。
◯ IH を示唆する神経学的異常の有無において TCD 変数の有意差はなかった。
Discussion◯ Sm/Dm は GⅢにおいて有意に高く、Sm/Dm が IH の診断に有用であることを示唆する。
	 脳圧亢進により収縮期血流速度が維持される一方、拡張期血流速度が減弱するためにこのような変化が生じる。

◯ 頭蓋内容積の増加が緩徐な場合、代償メカニズムから脳圧上昇が起きずに脳灌流圧が維持され、結果として GⅠ、
	 

GⅡの間に TCD 変数の有意差を欠いた可能性がある。TCD は頭蓋内圧上昇が軽度では検出できない可能性。

◯ TCD は神経学的検査よりも感度よく簡易的に IH を診断することができる。
批評	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
 
◯ 一次診療において頭蓋内疾患に伴う IH を疑う術は臨床症状のみであり、低侵襲かつベッドサイドで実施可能な
	 TCD(Sm/Dm)は IH 診断精度を上げ、神経疾患のエマージェンシー対応の一助となり得る。

◯ 麻酔薬とマンニトールの脳圧への影響、重篤例に関しては省かれているため、Sm/Dm の実数値、カットオフ値の	
 

利用には注意が必要で、個々の症例の Sm/Dm を経時的に測定し、脳圧の変化を観察する利用方法が有用。

◯ 重症例を含め研究を進めることで Sm/Dm 以外の TCD 変数である RI、PI の有用性も明らかになる可能性はある。

(range). Determination of the norm
evaluated by means of a Shapiro–W
the homogeneity of variances wasIf the data distribution was determvariance homogeneous, the overall
determined by 1-way analysis of v
意識レベルの低下、歩行異常、姿勢反応低下、瞳孔サイズの異常、瞳孔対光反射の欠如、威嚇反応の低下、
hoc multiple comparisons were madtest. When the distribution was det
variance not homogeneous, the ove
クッシング反応
was determined by the Kruskal–Wa
ANOVA), and post hoc multiple co
脳溝の不明瞭化、脳ヘルニア、脳脊髄液腔の圧迫、中脳蓋の変位
Steel-Dwass test. Categorical variab
exact test. Spearman’srank correla
描出方法	
  4-11Mhz のコンベックスプローブを使用、左側横臥位、頚部を 90 度に屈曲、経椎間、Bモード、
gate correlations between variables.
istic (ROC) analysis with the
	
  	
  	
  	
 
矢状断面、カラードプラにより脳底動脈を特定
Bonferroni correction for multiple tability to use TCD variables to
4 TCD 変数	  最大収縮期速度(PSV)、拡張末期速度(EDV)、平均速度(Vm)、収縮期平均速度(Sm)Sasaoka et al
intracranial hypertension among tho
compression of the CSF space in 16 dogs (third ventriComparison of the TCD Variables
area under the ROC curve (AUC)	
 拡張期平均速度(Dm)、血管抵抗指数(RI=(PSV-EDV)/PSV)、拍同指数(PI=(PSV-EDV)/Vm)、Sm/Dm
TCD
inIntracranial
Hypertension
3
cle in 13 dogs; fourth ventricle in 9 dogs); and displaceOf the TCD vascular resistance variables, only Sm/Dm(CI) were calculated for each variab
ment of the lamina quadrigemina in 10 dogs (Table 1).
wassignificantly
different
the groupsof (Table
2,(range).
Determinationof the amongnormal distribution
data wasAny 1 of the MRI findings was recorded in 9 dogs:
chosen for each TCD variable ba
Fig
2, P by= 0.01).
Sm/Dm wastest,
significantly
higher
A dogs were categorized into group II. Meanwhile,evaluatedmeans Theof a Shapiro–Wilkand assumptionofThese
index. For the optimal cutoff valuin
III (median,
1.78;
1.44–2.58)
thantest.
inthegroup
homogeneityof variances
wasrange,
determinedby Bartlett’s
among dogs in group III, 6 had any 2 of the MRI findBgroup(controlgroup:
1.63;
range,
1.43–1.75;
If the Idata
distribution
wasmedian,determined
to benormaland theand specificity were calculated. For
ings; 3 had any 3 of the MRI findings; and 4 had all of
overall difference
among groups
wasPvariance= 0.02)homogeneous,and group theII (median,
1.62; range,
1.27–2.10;
環椎
the 4 小脳findings.
at P < 0.05.
analysishand,of variance(ANOVA),difference
and post
Pdetermined= 0.02). by
On1-way
the otherno significant
The proportion of the dogs that had abnormalities
hoc multiple
comparisonswere madeHSD
wasfound between
groupsI andbyIIthe(PTukey–Kramer= 0.96). RegardIntraobserver repeatability was aon neurologic examination in each group was depentest. When the distribution was determined not to be normal oring the other variables, including RI and PI, no signifident on the distribution of clinical diagnosis in thevariance not homogeneous, the overall difference among groups
variation (CV) and intraclass ccantdifferenceswereobserved
amonggroups.
was determined by the Kruskal–Wallis test (nonparametric 1-way
group. Five dogs (5/22, 23%) in group II and 4 dogs
Repeatability was considered to be
No differencesin multiple
TCD comparisonsvariables were
weremade
identified
ANOVA),and post hocby the(4/13, 31%) in group III exhibited neurologic abnormalbetween
dogs
neurologic
Steel-Dwass
test. with
Categoricalvariablesabnormalities
were compared suggestive
by Fisher’s
ities suggestive of intracranial hypertension, such as low<15%26 and the ICC was >0.70.27

A

※1

※2
※3

level of consciousness, pupil size abnormalities, absenceof pupillary light reflexes, and deficits in 脊髄
the menace
response. No dogs showed the Cushing response. Noneof the data on the study population except for clinicaldiagnosis was different amonggroups (Table 1). All
脳底動脈
6
dogs
diagnosed with idiopathic epilepsy were classified
髄質
into group I (control group).

ofintracranial
hypertension(n = 10)withoutsuch
exact
test. Spearman’srank correlation
test andwas used
to investigate correlations
between variables.
Receiverneurologic
abnormalities(n = 40).
The operating
medians character(ranges)
istic
(ROC)
analysiswiththeMann–Whitney
U-testandof RI were 0.73 (0.59–0.81) and 0.72 (0.57–0.89) in dogs
Bonferroni
correction thefor neurologic
multiple testing
was used to assessthewithand withoutabnormalities,
respecability to use TCD variables to detect dogs with suspected
tively.
The medians (ranges) of PI were 1.60 (1.02–2.74)
intracranial hypertension among those with neurologic signs. The
andin (AUC)dogs withand confidence
without interval
neuroSasaokaet(1.03–4.41)
al ROC curvearea 1.55
undertheand 95%logic
abnormalities,
The medians(ranges)(CI) were
calculated for respectively.
each variable. Optimal
cutoff values
were

ResultStudy Popu

chosen for each TCD variable based on the highest Youden
index. For the optimal cutoff value of each variable, sensitivity
Band specificity
were calculated.
For all tests,ultrasoundsignificance was setexamination
Fig 1.
Transcranial
Doppler(TCD)
Table 1. Demographic data, physiologic variables, neurologic
findings, clinical diagnoses, and MRI
at Pexamination< 0.05.
Basilarartery flow
is identified
belowofmedulla on a sagittal
Intraobserver
repeatability
was assessedby the coefficient
findings of 50 dogs that underwent transcranial Doppler images.
ultrasoundexamination.
(CV) flow
and intraclasscorrelation
coefficient (ICC).
viewvariationof color
Doppler(A). Measurementof basilar arterialGroup I (Control Group)Group
IIGroup IIIwhen the CV
Overall
Repeatability wasconsidered
to be acceptablewasflow<15%
by 26pulsed
Doppler(B). Systolic
meanP-value
velocity (Sm) and diasVariable(n = 15)= 22)(n = 13)and the(nICC
was >0.70.27

Age (years)
7 (2–13) tolic mean velocity
6 (3–13) (Dm) are
8 (2–13)0.88by an end-T wave of
discriminatedBody weight (kg)5.9 (2.4–24.1)
5.5 (1.7–33.3) Results
5.2 (1.3–20.6)
0.50
ECG.
0.43
Sex
Study Population
Male (No. intact)
9 (4)15 (9)
6 (1)Female (No. intact)
6 (2)
7 (2)
7 (3)
Fifty-nine client-owned dogs with neurologic signs
Physiologic
variables during TCD
Fig 1. Transcranial Doppler ultrasound examination (TCD)
were recruited.
Six dogs were excluded
Mean arterial(mmHg)
75 (55–98)
70 (56–94)because sedation
0.43
images.
Basilarpressure
artery flow
is identified below medulla on65a (58–80)
sagittalor anesthesia (23.0–43.0)
for MRI was considered
to be contraindiEnd-tidal
CO2flow(mmHg)
36.0 (32.0–38.0)
33.0 (26.0–38.0)=(PSV–
EDV)/PSV,
and PI0.09= (PSV – EDV)/Vm.20
viewof color
Doppler (A). Measurement of basilar
arterialfollows: RI34.5
cated. Of 75.6
the (48.5–125.0)
remaining 53 dogs,
dogs (Golden RetrieHeartbyrate
(rpm)
76.3
(58.3–147.4)
82.13(40.7–158.7)
0.89
flow
pulsedDoppler (B). Systolic mean velocity (Sm)anddiasTheratioofsystolictodiastolicmeanvelocity(Sm/Dm) also was
ver,
28.7
kg;
FrenchBulldog,
12.4
kg;
and
American
Neurologic
examination
tolic mean velocity (Dm) are discriminated by an end-T wave ofFig
3. level
Correlations
between the TCD variables ((A)
and Spaniel,(C) Sm/Dm)
andwerenumberMRIfindings indicativeofCocker
9.7 kg)excludedbecause
DopplerLowof consciousness
0 RI, (B) PI,
1
2 of identified
ECG.
calculated
asavascularresistancevariable(Fig1B).19 Heart rate
intracranial
hypertension(horizontalaxis).
The
MRI
findings
indicativeof
intracranial
hypertension
were
effacementofthecerebral sulci,
Gait abnormalities
0
63
waveforms could
not be obtained
from the basilar
was artery.
calculatedusing theR-R
intervals
onP-value
simultaneous
Posturalreaction deficits
0
9 quadrigemina.
4 waveforms
brain
herniation,
compression of CSF space, and displacementofthe lamina
Spearman’s
rho andforConsequently,
Doppler
could
be are includedelectrocarPupilplot.
size abnormalities
0
1 50 dogs (50/53, 94%).
1
eachobtained The
from
Of the 50cardiac
finally cycles were calcudiograms.
means of 5 consecutive
20
follows:(PSV – light
EDV)/PSV,
Absence RIof =pupillaryreflexes and PI = (PSV – EDV)/Vm.
1
1 there were 14 intact
1 males, 16 castrated
enrolled dogs,
The
ratioinofthesystolic
to response
diastolic mean velocity (Sm/Dm) also
waslated for all 4TCD variables.3 During TCD, physiologic variables
Deficits
menace1males, 8 intact females, and 12 spayed females. The
calculated
as a vascular resistance variable (Fig 1B).19 Heart rate
<0.001
Clinicaldiagnosis
median age
was 7involving
years (range,
2–13 years),
andmedian
RI,
0.61
(95%
forsimultaneous
PI, and 0.79
(95%
CI,
studiespatients
withintracranial
hypertension
includingmeanarterialpressureandend-tidal
CO2 also were
wascalculatedusingCI,the 0.40–0.82)
R-R
intervals onelectrocarIdiopathic
epilepsy
15
2
0
てんかん
17,28
body
weightwas
5.8
kg(range,1.3–33.3
kg).
The
most
The discordance
0.63–0.95)
for
Sm/Dm
(Table
3,
Fig
4).
after
traumaticbrain
injury.
diograms.
The
means of 5腫瘍
consecutive cardiac cycles were
Intracranial
neoplasia
0 calcu-recorded.
77commonly
represented
breed
was
Miniature
Dachshund
lated
for all TCD variables. During TCD, physiologic variables
Encephalitis
063
between our results and these findings may have been
脳炎
(n = 8), followedby Chihuahua0 (6), mixed breed (5),includingmean arterialpressure and end-tidal CO2 also
Cerebrovasculardisease 血管性0 were6causedby a differencein thestudy population: Dogs
Toy Poodle 1(4), Maltese (4), Shetland
Sheepdog (3),recorded.
Hydrocephalus Assessment
3
水頭症 of Repeatability 0
withsevere (3),clinicalstatusprecluding
general anesthesia
Miniature
Schnauzer
GoldenRetriever(2), French
MRI findings
excludedTerrier
from (2),thestudy.
The TCD
could
besulci
performed
in all laboratory
dogs
Bulldog were(2), 0Yorkshire
1 each of AusEffacementof thecerebral0
7 andAssessmentof 脳溝の不明瞭化
Repeatability
tralianShepherd,
BeardedCollie,Cavalier
King
CharlesBrain herniation
3
10
Our
findings indicatethat intracranial hypertension
undergeneral anesthesia.脳ヘルニア
All CV values 0were <10%,
laboratory
dogsSpaniel,(2 males4 offemales;ages,
2–12 years;
Six laboratory
dogs (2 males and 4 females; ages, 2–12
Foramen
0 years; Six
2 beCocker
8Japanese
Spaniel,EnglishSpitz,
Labramaydiagnosedontheandbasis
increased
Sm/Dm.
whereasallmagnum
ICC
values were >0.70 (Table 4).
bodyweight, 10.3–12.4 kg) were used. All dogs were confirmed
Transtentorial
00 10.3–12.4
5were
dorweight,
Retriever,
Norfolk
Terrier,
Papillon,
Shiba,
Shih
body
kg)
used.
All
dogs
confirmed
The1 Sm/Dm in the ophthalmicarteryhas
beenwerereportedas Subfalcine
healthy on the basis of physical, neurologic, and blood0 exam3
Tzu, and Welsh Corgi. Clinical diagnoses included idio19
asonanindicatorofsystemic
atherosclerosis
inandhumans.
inations.
Eachofdog
wasanesthetizedwith isoflurane as describedas healthy
physical,neurologic,
blood
examCompression
CSF
space
0
4 the
12
脳脊髄腔の圧迫
Discussion
pathic epilepsy(n basis= 17), ofintracranial
neoplasia(14),
above.
a stabilization period, each dog underwent
ThirdAfter
ventricle
0 TCD
4atherosclerosis
In (9),
in9disease
humans,highvaluesof Sm/Dm
encephalitis
cerebrovascular(6), andhydroinations.
Each
dog
was
anesthetizedwithisofluraneasdescribed
performedby1
observer
(KS)
3
times
at
15-minuteintervals.
Fourthventricle
00
9
Our results suggest that TCD vascular resistance varia decrease in diastolic flow because of decreased
cephalusreflect
(4).
Each
time, theTCD
variables
were 中脳蓋の変位
determined as describedabove.
After
TCD
Displacementof thelaminaquadrigemina
0
2 a stabilization8 period, each dog underwent
19,29
ables
basis of compliance
the MRI findings,
22, and 13systolicdogs velocity.
with15,preserved
above. can be used to detect dogs with intracranialOn thearterial
performedby1
observer(KS)
3 times
at of15-minute
wereclassified
into
groupsII,
andreport
III,
respectively.
hypertension.
no significant
differences in
Our study
is the I,firsttothe use
Sm/Dm as intervals.
aCSF, cerebrospinalAlthough
fluid; MRI, magnetic
resonance imaging.
As time,for were
MRI
findings
indicativeof intracranial
hypertenContinuous
data are expressedas thevariables
median (range).
AlloverallP-values
determinedby thevariables
Kruskal–Wallis
test(continuous
TCD
in Intracranial
Hypertension
5
TCD
vascularresistancewere
detected
variable
of
TCD
in
dogs.
Wewerehypothesizedthat Sm/Dm
Each
the
TCD
determined
as described
Statistical
Analysis
sion, effacement of the cerebral sulci was identified in 7
variables)
test (categoricalvariables).
betweenor Fisher’sdogs exact
without
intracranial
structural diseases
also would reflect the alterations in cerebral blood flow
above.
dogs; brain herniation in 13 dogs (foramen magnum in
Statistical analysis was performed using commercially available(groupI) and those withintracranial
structuraldiseases
in inintracranial
hypertension:
10 dogs;observed
transtentorial
5 dogs; subfalcine
in 4 dogs);As intracranial
software.e,f All continuous
variables
were expressed as
median ultrasoundTable
2. Transcranial
Doppler
examination
variablesfor
3 groups.

Assessment of Repeatability

without suspected intracranial hypertension (group II),
pressure increases, the resultant decrease in cerebral
we found that Sm/Dm wassignificantly
higher inGroupdogsII blood flow Group
alters III
the Doppler waveforms
Group
I
ANOVA orof the cerebral
OverallStatistical
Analysiswith suspected intracranial
hypertension
Variable(Control Group)(n = 15) (group III).
(n = 22)(n =the13)diastolic velocity
Kruskal–Wallis
P-valueartery so thatis decreased with
the
15,16
our study, RI, 76.4
PI, (41.5–97.9)
and Sm/Dm
increasedtheaa systolic velocity beinga preserved.
Considering that
64.2as(34.3–99.3)
81.7 (46.9–111.3)
A commercially
0.24
PSVIn(cm/s)
Statisticalanalysiswasperformed
using
availableaanumber
MRI findings
indicativeof a no significant
differencesin Dm were Aobserved among0.84
the19.9 (8.6–39.4)
17.3 (8.9–39.0)
EDV(cm/s) of identified
20.1 (13.4–33.1)e,faa groups,
avariables
software.
All continuous
wereas medianintracranial
hypertension
increased.
However,33.5
RIandthe (13.9–68.4)
relative changes
in diastolicvelocity mightVm(cm/s)
34.2 (19.1–49.9)(13.7–56.8)
27.7
K expressed
0.68
aa occur in individual Doppler
PI (cm/s)
did not significantly
differ between
dogs 44.9
with(18.4–78.2)
andwaveforms,
wasSm
47.6 (24.9–64.7)
41.5 (22.0–95.8)aA and Sm/Dm 0.60
awithout
hypertension.
Previousas a(11.8–50.9)
ratio of athese relative changes.
Dm(cm/s) suspected intracranial
30.0 (17.5–44.6)
28.0(11.4–48.2)a reflected23.6
A
0.79
a
a
a
RI
(0.62–0.78)(0.57–0.80)
0.75 (0.59–0.89)
A may be a more
0.16
experimental studies 0.72
in dogs
have shown that 0.71
increased
Our findings
indicate that Sm/DmaaPI(1.09–2.12)directly
1.47 (1.03–2.41)a sensitive1.84(1.02–4.41)
K
0.47
intracranial pressures1.57
measured
are associatedvariableto detect intracranial
hypertension
a
a
b
20
Sm/Dm
1.63
(1.43–1.75)
1.62(1.27–2.10)
1.78(1.44–2.58)
K
0.01
with an increase in RI obtained by TCD. In humans,
compared with RI and PI. A previous study evaluatinga correlation between directly measured intracranial
Doppler waveforms of the ophthalmic artery showed
A, ANOVA; Dm, diastolic mean velocity; EDV, end diastolic velocity; K, Kruskal–Wallis test; PI, pulsatility index; PSV, peak systolicpressures and PI has been shown in neurointensive carethat Sm/Dm can be more sensitive for the detection ofvelocity; RI, resistive index; Sm, systolic mean velocity; Sm/Dm, ratio of systolic to diastolic mean velocity; Vm, mean velocity.
Continuous data are expressed as the median (range). Values with different superscript letters indicate significant differences amonggroups.

Table 3. Area under the receiver operating characteristic curve (AUC) and optimal diagnostic cutoffs to detect dogs
with suspected intracranial hypertension among dogs with neurologic diseases.
Variable

AUC

95% CI

Sensitivity

Specificity

CutoffP-value

RI
PI
Sm/Dm

0.66
0.61
0.79

0.47–0.85
0.40–0.82
0.63–0.95

0.38
0.38
0.62

0.95
0.92
0.92

0.79
2.21
1.78

0.09
0.23
0.002

AUC, area under the receiver operating characteristic curve; CI, confidence interval; PI, pulsatility index; RI, resistive index; Sm/Dm,
ratio of systolic to diastolic mean velocity.

Fifty-nine client-owned dog
were recruited. Six dogs were eor anesthesia for MRI was concated. Of the remaining 53 dogver, 28.7 kg; French Bulldog,
Cocker Spaniel, 9.7 kg) were ewaveforms could not be obartery. Consequently, Doppl
obtained from 50 dogs (50/53
enrolled dogs, there were 14 imales, 8 intact females, andmedian age was 7 years (range
body weight was 5.8 kg (range
commonly represented breed w(n = 8), followed by Chihuah
Toy Poodle (4), Maltese (4),Miniature Schnauzer (3), Gold
Bulldog (2), Yorkshire Terrier
tralian Shepherd, Bearded Coll
Spaniel, English Cocker Spanie
dor Retriever, Norfolk TerrieTzu, and Welsh Corgi. Clinica
pathic epilepsy (n = 17), intr
encephalitis (9), cerebrovascula
cephalus (4).
On the basis of the MRI findwere classified into groups I,
As for MRI findings indicative
sion, effacement of the cerebra
dogs; brain herniation in 13 d
10 dogs; transtentorial in 5 do