8/12/2019 Changes in the Volumes of the Brain and Cerebrospinal Fluid Spaces After Shunt
1/6
Changes in the volumes of the brain and cerebrospinal uid spaces after shunt
surgery in idiopathic normal-pressure hydrocephalus
Kotaro Hiraoka a,, Hiroshi Yamasaki a,Masahito Takagi a, Makoto Saito a, Yoshiyuki Nishio a, Osamu Iizuka a,Shigenori Kanno a, Hirokazu Kikuchi a, Takeo Kondo b, Etsuro Mori a
a Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japanb Department of Physical Medicine and Rehabilitation, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
a b s t r a c ta r t i c l e i n f o
Article history:
Received 7 December 2009
Received in revised form 22 June 2010
Accepted 23 June 2010
Keywords:
Idiopathic normal-pressure hydrocephalus
Cerebrospinaluid shunt
Magnetic resonance imaging
Volumetry
Objectives:To investigate volumetric changes of the brain and cerebrospinal uid (CSF) spaces after shunt
surgery in shunt-responsive idiopathic normal-pressure hydrocephalus (iNPH), and correlations between
the changes and postoperative clinical improvements.
Methods: Twenty-one patients with shunt-responsive iNPH were studied. Magnetic resonance imaging
(MRI) of the brain was performed before and 1 year after surgery, and clinical symptoms were assessed by
the iNPH Grading Scale, a validated assessment tool of the triad of iNPH, the Modied Rankin Scale, the
Timed Up and Go Test, and neuropsychological tests including the Mini-Mental State Examination. The
volumes of the left cerebral hemisphere, infratentorial brain, ventricles, and suprasylvian and infrasylvian
subarachnoid CSF spaces were measured using an MRI-based volumetric technique.
Results: The volumes of the cerebral hemisphere and infratentorial brain did not change signi cantly after
shunt surgery (p =0.231, 0.109, respectively). The volumes of the ventricles and infrasylvian subarachnoid
CSF spaces were signicantly decreased (pb0.0001, b 0.05, respectively), with a mean change rate of26.1%
and 4.5%, respectively. The volumes of the suprasylvian subarachnoid CSF spaces increased signicantly
(pb0.0001), with a mean change rate of 43.5%. The decrease in ventricular volumes was signicantly
correlated with clinical improvement.
2010 Elsevier B.V. All rights reserved.
1. Introduction
Idiopathic normal-pressure hydrocephalus (iNPH) is a syndrome
manifesting as a triad of dementia, gait disturbance, and urinary
impairment, with ventricular enlargement and normal cerebrospinal
uid (CSF) pressure, and without preceding events such as subarach-
noid hemorrhage and meningitis. It is characterized by clinical
improvement following shunt placement[14]. Although the cause
and pathophysiology of iNPH remain unclear, the conventional view is
that it is due to obstruction of CSF circulation and/or absorption. The
effectiveness of shunt placement for the treatment of iNPH has been
established[14], but the mechanism of its effect has not yet been
claried.
Radiological studies have led to clarication of the morphological
features of iNPH, and dilation of the ventricles and sylvianssures as
well as narrowing of the subarachnoid CSF spaces on the high
convexity and interhemispheric ssure is seen on magnetic
resonance imaging (MRI)[5]. However, there have been few studies
investigating morphometric changes of the intracranial components
after shunt surgery. Kitagaki et al. showed that the mean postop-
erative CSF volume of ve patients with iNPH was signicantly
decreased in the sylvian space and in the ventricle, marginally
decreased in the basal cistern, and signicantly increased in the
suprasylvian space as compared with the preoperative volume [5]. In
the study by Anderson et al. [6], the ventricular volumes of 10 (91%)
out of 11 iNPH patients who underwent shunt surgery were
decreased, with a mean change rate of 39%. Volume changes of the
brain and the association between changes in volume of the
intracranial components and clinical outcomes after shunt surgery
remain to be claried.
In thisstudy, we investigated volumetric changesof the brain and
CSF spaces and their association with clinical outcomes after shunt
surgery. The CSF spaces were segmented into the ventricles and
suprasylvian and infrasylvian subarachnoid spaces, as previous
study[5] showed volume decrease of the ventricles, sylvian space,
and basal cistern, and volume increase of the suprasylvian
subarachnoid spaces. We assumed that cerebral volume increases
postoperatively along with the clinical improvements and as the
offset of ventricular volume decreases after shunt surgery. In
addition, we expected to nd a correlation between the volumetric
changes of the intracranial components and clinical improvement
after shunt surgery. We aimed to elucidate the pathophysiology of
Journal of the Neurological Sciences 296 (2010) 712
Corresponding author. Tel.: +81 22 717 7358; fax: +81 22 717 7360.
E-mail address:[email protected](K. Hiraoka).
0022-510X/$ see front matter 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jns.2010.06.021
Contents lists available at ScienceDirect
Journal of the Neurological Sciences
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
http://dx.doi.org/10.1016/j.jns.2010.06.021http://dx.doi.org/10.1016/j.jns.2010.06.021http://dx.doi.org/10.1016/j.jns.2010.06.021mailto:[email protected]://dx.doi.org/10.1016/j.jns.2010.06.021http://www.sciencedirect.com/science/journal/0022510Xhttp://www.sciencedirect.com/science/journal/0022510Xhttp://localhost/var/www/apps/conversion/tmp/scratch_9/Unlabelled%20imagehttp://dx.doi.org/10.1016/j.jns.2010.06.021http://localhost/var/www/apps/conversion/tmp/scratch_9/Unlabelled%20imagemailto:[email protected]://dx.doi.org/10.1016/j.jns.2010.06.0218/12/2019 Changes in the Volumes of the Brain and Cerebrospinal Fluid Spaces After Shunt
2/6
iNPH and the mechanism of shunt effect by precisely measuring
morphometric changes after shunt surgery in patients with denite
iNPH.
2. Methods
2.1. Subjects and study design
Patients who had been diagnosed as having iNPH and who hadundergone shunt surgery between March 2005 and November 2007
were enrolled in a prospective follow-up program. The patients were
diagnosed by neurologists as probable iNPH based on the diagnostic
criteria published by the Guidelines Committee of Idiopathic Normal
Pressure Hydrocephalus, the Japanese Society of Normal Pressure
Hydrocephalus [7], i.e., (1) individuals who develop symptoms in
their 60 s or older, (2) the presence of more than one of the triad of
gait disturbance, cognitive impairment, and urinary incontinence, (3)
MRI featuresof iNPH (i.e., both ventricular dilation (Evans IndexN0.3)
and narrowing of the subarachnoid CSF spaces on the high convexity
and interhemispheric ssure), (4) CSFpressureof 200 mm H2O orless
and normal CSF content, (5) positive CSF tap test, (6) clinical
symptoms that cannot be completely explained by other neurological
or non-neurological diseases, and (7) no obvious preceding diseasesthat could possibly cause ventricular dilation, including subarachnoid
hemorrhage, meningitis, head injury, congenital hydrocephalus, and
aqueductal stenosis. Routine laboratory tests and single photon
emission computed tomography (SPECT) of the brain were performed
for differential diagnosis, and MRI and clinical evaluations were
performed as a baseline assessment. After conrmation that there was
no contraindication to the surgical procedure, patients who fullled
the criteria underwent ventriculoperitoneal (VP) or lumboperitoneal
(LP) shunt surgery. After surgery, the patients were followed up for
1 year, and the pressure settings of their programmable valves were
adjusted in the outpatient clinic. One year after surgery, the patients
were re-admitted to the hospital for re-assessment of their clinical
symptoms and for radiological investigations.
In this study, only baseline and 1-year follow-up data were used.Only data from those patients who completed the 1-year follow-up
program and who had denite iNPH (i.e., those who showed clinical
improvements as described below) were included in order to avoid
contamination of the results with data from patients with unspecied
diagnosis. Clinical improvement after shunt surgery was dened as a
decrement of more than 1 point in total score on the iNPH Grading
Scale (iNPHGS)[8] compared to the baseline score. The iNPHGS is a
validated tool for assessment of the clinical triad. It is rated according
to theclinician'sobservation andinterview with thepatient and hisor
her caregiver in order separately to assess the severity of each
component of the triad. The score for each domain ranges from 0 to 4,
and higher scores indicate worse symptoms. Patients who dropped
out from the 1-year follow-up program and patients who did not
show clinical improvements 1 year after surgery were excluded from
volumetry.
The procedure followed the clinical study guidelines of the Ethics
Committee of Tohoku University Hospital and was approved by the
Internal Review Board. Written informed consent was obtained from
the patients or their families.
2.2. Clinical assessment
Clinical symptoms were assessedat baseline and 1 year after shunt
surgery. In addition to the iNPHGS, the modied Rankin Scale (mRS)
[9], Timed Up and Go (TUG) test[10], Mini-Mental State Examination
(MMSE) [11], Frontal Assessment Battery (FAB) [12], and the
modied version of the Neuropsychiatric Inventory (NPI) [1315]
were administered. In the TUG test, patients are timed while they rise
from an arm chair, walk 3m, turn, walk back, and sit down again, and
the number of steps is counted.
2.3. Shunt surgery and programmable valve adjustments
The operative procedure either VPshunt orLP shunt was selected
according to thecondition of the patient'scervicaland lumbarvertebrae
when investigated by spinal MRI and the preference of the patient and
his or her family. In cases of VP shunt, a catheter was placed in theanterior horn of the right lateral ventricle, and in cases of LP shunt
surgery, a catheter was placed in the lumbar subarachnoid space. The
abdominal-side catheter was guided to the abdomen subcutaneously
and inserted in the peritoneal cavity. We used the Codman-Hakim
programmable valve system in all shunt surgery. The initialpressure for
the shunt system was set before surgery, based on the patient's height
and weight [16,17]. Postoperatively, patients were followed up in
outpatient clinics; the pressure settings of their programmable valves
were adjusted step by step and clinical improvements and adverse
effects were noted. If clinical improvement was absent or insufcient,
the pressure setting was lowered by 1030 mm H2O over a period of1
2 weeks. If orthostatic headache or subdural effusion/hematoma was
observed by computed tomography (CT), the pressure setting was
increased by 30 mm H2O. Pressure adjustments were repeated until
optimal pressure for each patient was attained.
2.4. MR volumetry
Brain MRI was performed at baseline and 1 year after surgery.
Axial, three-dimensional spoiled gradient echo (SPGR) images were
obtained for volumetry. The images were generated with a 1.5-T MRI
unit (Signa Horizon LX CV/i; GE Healthcare, Milwaukee, WI).
Operating parameters were as follows: eld of view, 250 mm; matrix,
256256; contiguous sections, 1081.5 mm; repetition time, 20 ms;
echo time, 4.1 ms; and ip angle, 30. Axial T2-weighted images and
uid-attenuated inversion recovery (FLAIR) images were also
obtained for diagnosis. The volumes of the left cerebral hemisphere,
infratentorial brain, ventricles, and subarachnoid CSF spaces on the
left side were measured on the MR image (Fig. 1). The reason for notmeasuring the right cerebral hemisphere and subarachnoid space on
the right side was that there were artefacts caused by the shunt valve
on the postoperative images in the cases of VP shunt surgery. The
subarachnoid CSF spaces were segmented into two parts supra-
sylvian and infrasylvian as mentioned below.
The MRI data sets of all images were transmitted to a personal
computer from the MRI unit. Measurements were performed by one
investigator(K.H.), whowas blinded to (1)all clinicalinformation, (2)
the order (pre-surgery and post-surgery) of MRIs, and (3) the time of
enrolment. The right side of cerebral convexity and circumferential
tissues such as dura mater, cranium, subcutaneous fat, and scalp were
masked in both the pre-surgery and post-surgery images, sparing the
right lateral ventricle for volumetry, so that the investigator could not
discriminate by means of artefacts between the pre-surgery and post-surgery images in cases of VP shunt surgery. The MRI data sets were
analyzed using ImageJ 1.37 (NIH, Washington, USA), based on built-in
functions[18]. For volumetry, we used a combination of semiauto-
matic segmentation technique through density thresholding and
manual tracing, thereby avoiding partial voluming and observer bias.
The volume of each structure was obtained by automatically counting
the number of pixels within the segmented regions and then
multiplying the number by voxel size (0.9821.50= 1.44 mm3).
The reliability and validity of this method have been established and
described elsewhere[19].
The left cerebral hemisphere and infratentorial brain were
outlined and the ventricles were extracted with surrounding brain
parenchyma by tracing with a manually driven mouse cursor. The
boundary between the cerebral hemispheres and infratentorial brain
8 K. Hiraoka et al. / Journal of the Neurological Sciences 296 (2010) 712
8/12/2019 Changes in the Volumes of the Brain and Cerebrospinal Fluid Spaces After Shunt
3/6
was the plane of the intercollicular level of the midbrain. The
boundaries between the right and left hemispheres were traced
manually in the middle of the corpus callosum, septum pellucidum,
body of fornix, and anterior and posterior commissures. The ventral
boundary of the infratentorial brain was the plane including the apex
of the odontoid process. The ventricles included the bilateral lateral
ventricles, third ventricle, cerebral aqueduct of Sylvius, and fourth
ventricle. For the segmentation of the subarachnoid CSF spaces, the
ventricles were blacked out from the original MR images. The external
boundary of the subarachnoid CSF spaces was outlined by tracing the
dura mater with a manually driven mouse cursor. The boundary
between the right and left halves of the subarachnoid spaces was
determined on the basis of landmarks such as the falx cerebri and
cerebral aqueduct of Sylvius. The subarachnoid CSF spaces were
segmented into upper and lower parts along the intermediate plane
between the plane through the nasion and the external occipital
protuberance and the cranial top point of the dura mater, so that theupper part included the subarachnoid CSF spaces above the sylvian
ssure, and the lower part included the subarachnoid CSF spaces in
the sylvian ssure and below it.
Subsequently, each intracranial component was automatically
segmented on the extracted images using density threshold set at a
range between minimum and maximum pixel values. For volumetry
of the cerebral hemisphere and infratentorial brain, the maximum
value was the largest pixel value of the brain, and the minimum
value was half the mean pixel value of the gray matter (the caudate
head) and the mean value of the CSF, since the gray matter and CSF
are predominant constituents of the brainextrabrain interface. For
volumetry of the ventricles and subarachnoid CSF spaces, the
maximum value was half the value of the mean pixel value of the
gray matter (the caudate head) and the mean value of the CSF, andthe minimum value was the minimum pixel value of the CSF (lateral
ventricles).
The testretest reliabilities of the volumetry were expressed as
intraclass correlation coefcients (ICCs), which werecalculated from
MRIs repeated after a 1-week interval and volumetry by a single
rater (K.H.) under blind conditions for 10 subjects. The ICCs for the
cerebral hemisphere, infratentorial brain, ventricles, and suprasyl-
vian and infrasylvian subarachnoid CSF spaces were 0.987, 0.992,
0.995, 0.987, and 0.984, respectively. Coefcients of variation
(standard deviation/mean, where standard deviation indicates the
square-root value of the arithmetic mean of 10 variance estimates)
were 0.662%, 0.775%, 1.593%, 1.720%, and 1.661% for the cerebral
hemisphere, infratentorial brain, ventricles, and suprasylvian and
infrasylvian subarachnoid CSF spaces, respectively.
2.5. Statistical analysis
The volumetric change rate of each intracranial component was
dened as the percentage change, which was calculated as postop-
erative volume minus baseline volume divided by baseline volume
(100). The changes of iNPHGS, mRS, MMSE, FAB, and modied NPI
were calculated by subtracting baseline scores from postoperative
scores. The change rates of time and steps in TUG test were calculated
as postoperative value minus baseline value divided by baseline value
(100). Two-tailed Student's t test was used for comparison of
volume change rates of each intracranial component between VP
shunt cases and LP shunt cases. Paired, two-tailed Student'sttest was
used for comparison of baseline and postoperative volumes of each
intracranial component. Spearman's correlation was used for explor-
atory correlation analysis between volumetric change rates of
intracranial components and change (rate) of clinical assessments.
All statistical analyses were performed on the statistical softwarepackage SPSS, version 11.0.1 J (SPSS Inc., Chicago, IL). The statistically
signicant level was set atpb0.05. The signicance level for multiple
comparisons was not corrected because of the explorative nature of
this study.
3. Results
During the study period, 38 patients with probable iNPH
underwent shunt surgery. Of these 38 patients, 12 dropped out due
to: ischemic stroke (n =3), malignancy (n =2), severe infectious
disease (n =2), chronic subdural hematoma (n =2), withdrawal of
consent (n = 1), institutionalization (n =1), and femoral fracture
(n =1). Therefore 26 patients completed the 1-year follow-up
program and were re-assessed 1 year after surgery. Of these 26patients, 21 showed clinical improvements and were selected for
Fig. 1. Segmentation of the intracranial components. The intracranial components were segmented into the left cerebral hemisphere, infratentorial brain (both sides), bilateral
ventricles, and suprasylvian and infrasylvian subarachnoid CSF spaces (left side).
Table 1
Demographic characteristics of the patients (n =21).
Sex (male/female) 8/13
Operative procedure (VP/LP) 15/6
Mean SD
Age at baseline (years) 76.2 3.6
Education (years) 9.7 2.9
Duration of disease (years) 3.1 1.4
Interval between operation and postoperative MRI (months) 12.8 0.8
VP, ventriculoperitoneal; LP, lumboperitoneal; MRI, magnetic resonance imaging; SD,
standard deviation.
9K. Hiraoka et al. / Journal of the Neurological Sciences 296 (2010) 712
http://localhost/var/www/apps/conversion/tmp/scratch_9/image%20of%20Fig.%E0%B1%808/12/2019 Changes in the Volumes of the Brain and Cerebrospinal Fluid Spaces After Shunt
4/6
volumetry. All these 21 patients were right-handed. Their demo-
graphic characteristics are summarized inTable 1,and the results of
their clinical assessments at baseline and 1 year after shunt surgery
are shown inTable 2.
Initially, we analyzed the volumetric changes of VP cases and LP
cases separately (Table 3). As both cases showed similar volumetric
changes, VP cases and LP cases were brought together for further
analysis. Volumetric results for the patients are shown in Table 4. The
volumes of the cerebral hemisphere and infratentorial brain did not
change signicantly after shunt surgery (p =0.231 and 0.109,
respectively). The ventricular volumes decreased signicantly
(pb0.0001) after shunt surgery, with a mean change rate of26.1%
(range 5.9% to 82.0%). There was a signicant increase in
suprasylvian subarachnoid CSF spaces (pb0.0001), with a mean
change rate of 43.5%, and the infrasylvian subarachnoid CSF spaces
showed a signicant decrease (pb0.05), with a mean change rate
of4.5%. The total volumes of the cerebral hemisphere, infratentorial
brain, ventricles, and suprasylvian and infrasylvian subarachnoid CSF
spaces showed a signicant decrease (pb0.001), with a mean change
rate of
3.4%.The results of the correlation analysis between volumetric changes
and changes in clinical assessments are shown inTable 5. The change
rates of the ventricular volume showed a signicant correlation with
changes in scores of the MMSE, FAB, scores for the gait domain in the
iNPHGS, and the mRS, and change rates related to time in the TUG test
(pb0.05).The correlations indicated that the patients whose ventricular
volume decreased most showed more clinical improvements than the
patients with less substantial ventricular volume decrease. Change rates
in the volume of the cerebral hemisphere, infratentorial brain, and
suprasylvian and infrasylvian subarachnoid CSF spaces did not show a
signicant correlation with changes in clinical parameters.
4. Discussion
In this study, we did not include subjects in whom no improvement
was noted after shunt surgery. While the exclusion of patients with
iNPH who showed no improvement because of treatment failure or
other problems possibly causes a selection bias, the exclusion of those
with an ambiguous diagnosis (including misdiagnosis and comorbidity
of other diseases)makesit possible to obtainuncontaminated datafrom
patients with a denite diagnosis, which is suitable for the pathophys-
iological study of iNPH.
Initially, we hypothesized that the volume of the brain increases
after shunt surgery as the symptoms of iNPH improve and
ventricular volume decreases. However, the results revealed that
the volumes of the cerebral hemisphere and infratentorial brain did
not change signicantly after shunt surgery. Previous longitudinal
MRI studies of Alzheimer's disease have indicated that the 1-year
whole-brain volume decrease was 0.98% to 2.8% [20,21], whereas the
1-year brain volume decrease in normal aging was 0.4% to 0.45%
[20,22].In this study, the rate of hemispheric volume change after
shunt surgery was compatible with the 1-year brain volumedecrease in normal aging. The results suggest that the volumes of
the cerebral hemisphere and infratentorial brain do not increase
after shunt surgery.
The volume of suprasylvian subarachnoid CSF increased, whereas
the volumes of the infrasylvian subarachnoid CSF spaces and
ventricles decreased signicantly. If the CSF in each part is
proportionally drained by shunt surgery, the CSF volumes in both
parts should have been reduced. Thecontrastingchanges maysuggest
the preoperative existence of a pressure gradient, i.e., the pressure of
the ventricles and infrasylvian subarachnoid CSF spaces is likely to be
higher than that of the suprasylvian subarachnoid CSF spaces. Shunt
surgery may relieve the pressure gradient, evacuate CSF from the
ventricles and the infrasylvian subarachnoid CSF spaces, and
consequently increase the CSF in the suprasylvian subarachnoidspaces. The existence of a transmantle pressure gradient in iNPH,
which is a pressure gradient between the ventricles and subarachnoid
CSF spaces, has not yet been established, as it has been found in some
studies[23,24]and not in others [25]. However, the ndings of this
study support the existence of such a pressure gradient. The pressure
gradient is against Pascal's principle, which states that pressure
exerted anywhere in a conned uid is transmitted equally in all
directions throughout the uid. However, the principle may not be
applicable in cases in which CSF ows through the complex
subarachnoid spaces synchronized with heart beats.
The total volume of cerebral hemisphere, infratentorial brain,
ventricles, and subarachnoid CSF spaces decreased signicantly after
shunt surgery. This may seem anomalous considering that the total
intracranial volume is unalterable in the elderly. The decrease of the
Table 2
Results of clinical assessment at baseline and 1 year after surgery (n =21).
Baseline Post-op p
valueMean SD Mean SD
TUG test Time (s) 20.8 11.0 14.3 6.8 0.001
Steps 27.5 12.9 22.3 8.6 0.030
MMSE (/30) 20.5 5.3 23.0 6.2 0.022
FAB (/18) 8.9 2.9 11.5 3.7 0.002
iNPHGS Gait (/4) 2.5 0.6 1.7 0.9 b0.001
Cognition (/4) 2.6 0.8 1.8 1.0 b0.001
Urination (/4) 1.9 1.1 0.8 0.9 b0.001
Total (/12) 6.9 1.9 4.1 2.2 b0.001
mRS (/6) 3.0 0.9 2.0 0.9 b0.001
Modied NPI (/144) 9.1 6.6 4.3 3.9 b0.001
Post-op, postoperative results; SD, standard deviation; TUG test, Timed Up and Go test;
MMSE, Mini-MentalState Examination;FAB, Frontal Assessment Battery;iNPHGS, iNPH
Grading Scale; mRS, modied Rankin Scale; NPI, Neuropsychiatric Inventory.
Table 3
Volumetric change rates for patients following VP shunt surgery (n =15) and LP shunt
surgery (n =6).
Change rate (%) p
VP shunt
surgery
(n =15)
LP shunt
surgery
(n =6)
Mean SD Mean SD
Cerebral hemisphere 0.9 2.3 0.1 2.0 0.35
Infratentorial brain 1.0 3.7 1.9 3.2 0.63
Ventricles 27.5 21.4 22.5 15.6 0.61
Subarachnoid CSF spaces Suprasylvian 41.2 44.2 49.4 21.8 0.67
Infrasylvian 4.4 10.6 5.0 7.7 0.90
Two-tailed Student'sttest.
VP, ventriculoperitoneal; LP, lumboperitoneal; SD, standard deviation; CSF,
cerebrospinaluid.
Table 4
Volumetric results for the patients (n =21).
Baseline Post-op pvalue Change
rate (%)
Mean SD Mean SD Mean SD
Cerebral
hemisphere
446.3 54.4 443.8 57.0 0.231 0.6 2.2
Infratentorial
brain
131.6 12.5 133.2 13.4 0.109 1.3 3.5
Ventricles 124.1 24.1 90.8 25.9 b0.0001 26.1 19.7
Subarachnoid
CSF spaces
Suprasylvian 33.5 11.8 44.8 9.5 b0.0001 43.5 38.8
Infrasylvian 103.1 18.2 97.5 13.6 b0.05 4.5 9.7
Total 838.5 89.9 810.2 89.0 b0.001 3.4 3.2
Unit: cm3.
SD, standard deviation; post-op, postoperative results; CSF, cerebrospinal uid.
The total indicates the sum of volumes of the cerebral hemisphere, infratentorial brain,
ventricles, and subarachnoid CSF spaces.
10 K. Hiraoka et al. / Journal of the Neurological Sciences 296 (2010) 712
8/12/2019 Changes in the Volumes of the Brain and Cerebrospinal Fluid Spaces After Shunt
5/6
total volume may be explained by volume increase of the venous
sinuses in the cranium. In most of our cases, expansion of the cross-
section of thesagittal sinus after shunt surgery was observed by visual
assessment of MRIs, although the volume of the venous sinuses was
not measured in this study.
The results were similar whether the catheters were insertedin the lateral ventricles (VP shunt surgery) or in the lumbar
subarachnoid space (LP shunt surgery), which indicates that the
shunt effect on CSF dynamics is the same whether CSF is drained
from the lateral ventricles or lumbar subarachnoid space. Relief of
the abnormal pressure gradient by shunt surgery altered the
distribution of CSF in the cranium, and deformation of the
cerebral hemisphere caused by the pressure of CSF in the
ventricles was reduced, which may contribute to the improve-
ment in symptoms.
The clinical improvements after shunt surgery correlated with the
decreaseof ventricular volumes. As postoperative clinical assessments
and MRI were performed in a single time point for each patient, it
cannot be concluded that the clinical symptoms improved in
proportion to the ventricular volume decrease in individual patients.However, the correlation may suggest an association between the
ventricular volume decrease and improvement of the symptoms.
With reference to the pathophysiology of iNPH, the correlation may
also suggest some association between the ventricular enlargement
and the manifestation of symptoms. Some previous studies have
raised concerns about the role of frontal lobe dysfunction in the
pathophysiology of iNPH[2632]. A study of iNPH by Momjian et al.
showed autoregulation disturbance of cerebral blood ow in para-
ventricular white matter, which may be caused by the abnormal
pressure of theCSF in theventricles [33]. Theabnormalpressureof the
CSF in the ventricles towards the cerebrum deforms the cerebrum,
which probably leads to neural dysfunction, especially of the frontal
lobe.
In conclusion, the ndings in this study suggest the existence of atransmantle pressure gradient, which enlarges the ventricles, deforms
the cerebral hemispheres, and causes symptoms in iNPH. Shunt
surgery may relieve the abnormal pressure gradient and reduce the
deformation of the cerebrum, which may contribute to the improve-
ment in symptoms.
5. Conclusions
Shunt surgery changed the distribution of CSF in the cranium,
but did not change brain volume. It also reduced the deformation of
the cerebral hemisphere, which may result from the pressure of CSF
in the ventricles and may contribute to the development of
symptoms.
Acknowledgment
This work was partly supported by a Research Grant from the
Ministry of Health, Labour and Welfare of Japan (2008-Nanchi-17).
References
[1] Boon AJ, Tans JT, Delwel EJ, Egeler-Peerdeman SM, Hanlo PW, Wurzer HA, et al.The Dutch normal-pressure hydrocephalus study. How to select patients forshunting? An analysis of four diagnostic criteria. Surg Neurol 2000;53:2017.
[2] Raftopoulos C, Deleval J, Chaskis C, Leonard A, Cantraine F, Desmyttere F, et al.Cognitive recovery in idiopathic normal pressure hydrocephalus: a prospectivestudy. Neurosurgery 1994;35:397404.
[3] WeinerHL, Constantini S, Cohen H, Wisoff JH.Current treatmentof normal-pressurehydrocephalus:comparisonofow-regulatedand differential-pressureshunt valves.Neurosurgery 1995;37:87784.
[4] Krauss JK, Droste DW, Vach W, Regel JP, Orszagh M, Borremans JJ, et al.Cerebrospinaluid shunting in idiopathic normal-pressure hydrocephalus of theelderly: effect of periventricular and deep white matter lesions. Neurosurgery1996;39:2929.
[5] Kitagaki H, Mori E, Ishii K, Yamaji S, Hirono N, Imamura T. CSF spaces in idiopathicnormal pressure hydrocephalus: morphology and volumetry. AJNR Am J
Neuroradiol 1998;19:127784.[6] Anderson RC, Grant JJ, de la PazR, FruchtS, Goodman RR. Volumetric measurements
in the detection of reduced ventricular volume in patients with normal-pressurehydrocephalus whose clinical condition improved after ventriculoperitoneal shuntplacement. J Neurosurg 2002;97:739.
[7] IshikawaM, HashimotoM, Kuwana N, Mori E, Miyake H, WachiA, etal . Guidelinesfor management of idiopathic normal pressure hydrocephalus. Neurol Med Chir(Tokyo) 2008;48:S1S23 Suppl.
[8] Kubo Y, Kazui H, Yoshida T, Kito Y, KimuraN, Tokunaga H, et al.Validation of gradingscalefor evaluatingsymptomsof idiopathicnormal-pressurehydrocephalus.DementGeriatr Cogn Disord 2008;25:3745.
[9] Rankin J. Cerebral vascular accidents in patients over the age of 60. III Diagnosisand treatment Scott Med J 1957;2:25468.
[10] Podsiadlo D, Richardson S. ThetimedUp & Go: a testof basic functional mobilityfor frail elderly persons. J Am Geriatr Soc 1991;39:1428.
[11] Folstein MF, Folstein SE, McHugh PR.Mini-mental state. A practical method forgrading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:18998.
[12] Dubois B, Slachevsky A, Litvan I, Pillon B. The FAB, a Frontal Assessment Battery atbedside. Neurology 2000;55:16216.
[13] Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. TheNeuropsychiatric Inventory: comprehensive assessment of psychopathology indementia. Neurology 1994;44:230814.
[14] Hirono N, Mori E, Ikejiri Y, Imamura T, Shimomura T, Hashimoto M, et al. Japaneseversion of the Neuropsychiatric Inventorya scoring system for neuropsychiatricdisturbance in dementia patients. No To Shinkei 1997;49:26671.
[15] Mori S, Mori E, Iseki E, Kosaka K. Efcacy and safety of donepezil in patients withdementia with Lewy bodies: preliminary ndings from an open-label study.Psychiatry Clin Neurosci 2006;60:1905.
[16] Miyake H, Ohta T, Kajimoto Y, Nagao K. New concept for the pressure setting of aprogrammable pressure valve and measurement of in vivo shuntow performedusing a microowmeter. Technical note J Neurosurg 2000;92:1817.
[17] Miyake H, Kajimoto Y, Tsuji M, Ukita T, Tucker A, Ohmura T. Development of aquick reference table for setting programmable pressure valves in patients withidiopathic normal pressure hydrocephalus. Neurol Med Chir (Tokyo) 2008;48:42732 discussion 32.
[18] Rasband W. ImageJ. [http://rsb.info.nih.gov/ij/] website National Institutes of
Health, Bethesda, Maryland, USA; 1997.
Table 5
Correlation matrix contrasting volumetric change rates against clinical changes and change rate ( n =21).
( Chan ge r ate) (Change)
TUG test MMSE FAB iNPHGS mRS Modied
NPITime Steps Gait Cognition Urination Total
(Change rate)
Cerebral hemisphere 0.04 0.12 0.10 0.24 0.02 0.20 0.25 0.02 0.09 0.06
Infratentorial brain 0.12 0.00 0.11 0.13 0.03 0.12 0.08 0.01 0.05 0.04
Ventricles 0.45
0.47
0.49
0.58
0.48
0.35 0.32 0.50
0.46
0.26
Subarachnoid CSF spaces Suprasylvian 0.03 0.25 0.02 0.10 0.16 0.20 0.13 0.05 0.02 0.24
Infrasylvian 0.03 0.15 0.04 0.31 0.01 0.16 0.15 0.02 0.18 0.27
Spearman's correlation, pb0.05.
TUG test, Timed Up and Go test; MMSE, Mini-Mental State Examination; FAB, Frontal Assessment Battery; iNPHGS, iNPH Grading Scale; mRS, modied Rankin Scale; NPI,
Neuropsychiatric Inventory.
Change rate (%)=(postoperative valuepreoperative value)/preoperative value100.
Change=postoperative valuepreoperative value.
11K. Hiraoka et al. / Journal of the Neurological Sciences 296 (2010) 712
8/12/2019 Changes in the Volumes of the Brain and Cerebrospinal Fluid Spaces After Shunt
6/6
[19] Mori E, Hirono N, Yamashita H, Imamura T, Ikejiri Y, Ikeda M, et al. Premorbidbrain size as a determinant of reserve capacity against intellectual decline inAlzheimer's disease. Am J Psychiatry 1997;154:1824.
[20] Fotenos AF, Snyder AZ, Girton LE, Morris JC, Buckner RL. Normative estimates ofcross-sectional and longitudinal brain volume decline in aging and AD. Neurology2005;64:10329.
[21] Chan D, Janssen JC,Whitwell JL,WattHC, Jenkins R,FrostC, etal. Change inratesofcerebral atrophy over time in early-onset Alzheimer's disease: longitudinal MRIstudy. Lancet 2003;362:11212.
[22] Enzinger C, Fazekas F, Matthews PM, Ropele S, Schmidt H, Smith S, et al. Riskfactors for progression of brain atrophy in aging: six-year follow-up of normal
subjects. Neurology 2005;64:1704
11.[23] Conner ES, Foley L, Black PM. Experimental normal-pressure hydrocephalus isaccompanied by increased transmantle pressure. J Neurosurg 1984;61:3227.
[24] Hoff J, Barber R. Transcerebral mantle pressure in normal pressure hydrocephalus.Arch Neurol 1974;31:1015.
[25] Stephensen H, Tisell M, Wikkelso C. There is no transmantle pressure gradient incommunicating or noncommunicating hydrocephalus. Neurosurgery 2002;50:76371.
[26] Sakakibara R, Kanda T, Sekido T, Uchiyama T, Awa Y, Ito T, et al. Mechanism ofbladder dysfunction in idiopathic normal pressure hydrocephalus. NeurourolUrodyn 2008;27:50710.
[27] Iddon JL, Pickard JD, Cross JJ, Grifths PD, Czosnyka M, Sahakian BJ. Specicpatterns of cognitive impairment in patients with idiopathic normal pressurehydrocephalus and Alzheimer's disease: a pilot study. J Neurol NeurosurgPsychiatry 1999;67:72332.
[28] Stolze H, Kuhtz-Buschbeck JP, Drucke H, Johnk K, Illert M, Deuschl G. Comparativeanalysis of the gait disorder of normal pressure hydrocephalus and Parkinson'sdisease. J Neurol Neurosurg Psychiatry 2001;70:28997.
[29] Miyoshi N, Kazui H, Ogino A, Ishikawa M, Miyake H, Tokunaga H, et al. Associationbetween cognitive impairment and gait disturbance in patients with idiopathicnormal pressure hydrocephalus. Dement Geriatr Cogn Disord 2005;20:716.
[30] Lenfeldt N, Larsson A, Nyberg L, Andersson M, Birgander R, Eklund A, et al.
Idiopathic normal pressure hydrocephalus: increased supplementary motoractivity accounts for improvement after CSF drainage. Brain 2008;131:290412.[31] OginoA, Kazui H, Miyoshi N, HashimotoM, Ohkawa S, TokunagaH, et al.Cognitive
impairment in patients with idiopathic normal pressure hydrocephalus. DementGeriatr Cogn Disord 2006;21:1139.
[32] Sakakibara R, Hattori T, Yasuda K, Yamanishi T. Micturitional disturbance afteracute hemispheric stroke: analysis of the lesion site by CT and MRI. J Neurol Sci1996;137:4756.
[33] Momjian S, Czosnyka Z, Owler BK, Czosnyka M, Pena A, Pickard JD. Pattern ofwhite matter regional cerebral blood ow and autoregulation in normal pressurehydrocephalus. Brain 2004;127:96572.
12 K. Hiraoka et al. / Journal of the Neurological Sciences 296 (2010) 712