Preoperative Prognostic Value of MRI

Findings in 108 Patients with Idiopathic

Normal Pressure Hydrocephalus
J. Virhammar, K. Laurell, K.G. Cesarini and E.-M. Larsson
AJNR Am J Neuroradiol 2014, 35 (12) 2311-2318
This information is current as doi: https://doi.org/10.3174/ajnr.A4046
of December 20, 2023. http://www.ajnr.org/content/35/12/2311
 ORIGINAL RESEARCH
BRAIN

Preoperative Prognostic Value of MRI Findings in 108 Patients

with Idiopathic Normal Pressure Hydrocephalus
J. Virhammar, K. Laurell, K.G. Cesarini, and E.-M. Larsson

ABSTRACT
BACKGROUND AND PURPOSE: MR imaging is used in the diagnostic evaluation of patients with idiopathic normal pressure hydroceph-
alus. The aim of this study was to describe the prevalence of several imaging features and their prognostic use in the selection of shunt
candidates with idiopathic normal pressure hydrocephalus.

MATERIALS AND METHODS: Preoperative MR imaging scans of the brain were retrospectively evaluated in 108 patients with idiopathic normal
pressure hydrocephalus who had undergone a standardized, clinical evaluation before and 12 months after shunt surgery. The MR imaging
features investigated were the Evans index, callosal angle, narrow sulci at the high convexity, dilation of the Sylvian fissure, diameters of the third
ventricle and temporal horns, disproportionately enlarged subarachnoid space hydrocephalus, flow void through the aqueduct, focal bulging of the
roof of the lateral ventricles, deep white matter hyperintensities, periventricular hyperintensities, and focal widening of sulci and aqueductal stenosis.

RESULTS: In logistic regression models, with shunt outcome as a dependent variable, the ORs for the independent variables, callosal angle,
disproportionately enlarged subarachnoid space hydrocephalus, and temporal horns, were significant (P ⬍ .05), both in univariate analyses
and when adjusted for age, sex, and previous stroke.

CONCLUSIONS: A small callosal angle, wide temporal horns, and occurrence of disproportionately enlarged subarachnoid space hydro-
cephalus are common in patients with idiopathic normal pressure hydrocephalus and were significant predictors of a positive shunt
outcome. These noninvasive and easily assessed radiologic markers could aid in the selection of candidates for shunt surgery.

ABBREVIATIONS: DESH ⫽ disproportionately enlarged subarachnoid space hydrocephalus; DWMH ⫽ deep white matter hyperintensities; ICC ⫽ intraclass correlation
coefficient; iNPH ⫽ idiopathic normal pressure hydrocephalus; NPH ⫽ normal pressure hydrocephalus; PVH ⫽ periventricular hyperintensities; SINPHONI ⫽ Study of Idiopathic
Normal Pressure Hydrocephalus on Neurological Improvement

I diopathic normal pressure hydrocephalus (iNPH) is a disease of

the elderly population, with symptoms of balance and gait dis-
turbances, dementia, and urinary incontinence; and in approxi-
aging are of prognostic value is controversial, and there is no
consensus regarding which MR imaging sequences and variables
to evaluate in the selection of shunt candidates. In addition, it is
mately 8 of 10 patients, the symptoms are reversible after shunt not fully clear how the radiologic features are related to each other
insertion.1,2 Several imaging methods have been used in the and to the symptoms. Previous studies have often involved a lim-
diagnosis and selection of shunt candidates, but the standard ited number of patients and a mixed sample of both idiopathic
method at present is MR imaging. Even though advanced func- normal pressure hydrocephalus and normal pressure hydroceph-
tional imaging methods are being considered, the clinical eval- alus (NPH) secondary to a brain insult.
uation of patients with iNPH still often relies on morphologic Therefore, we investigated 108 patients who had undergone
findings. shunt surgery for iNPH, with the aim of describing the occurrence
However, whether morphologic findings on preoperative im- and prognostic value of 13 different radiologic variables and the
relation between MR imaging findings and clinical symptoms.
Received March 30, 2014; accepted after revision May 23.
From the Departments of Neuroscience and Neurology (J.V., K.L.), Neuroscience
and Neurosurgery (K.G.C.), and Radiology (E.-M.L.), Uppsala University, Uppsala,
MATERIALS AND METHODS
Sweden; and Department of Pharmacology and Clinical Neuroscience (K.L.), Öster- Materials
sund, Umeå University, Umeå, Sweden. The sample consisted of 108 patients with iNPH who underwent
Please address correspondence to J. Virhammar, MD, PhD, Department of Neuro-
science and Neurology, Uppsala University, Akademiska Sjukhuset, ing 85, 751 85
shunt surgery between 2006 and 2010 at the authors’ hospital.
Uppsala, Sweden; e-mail: johan.virhammar@neuro.uu.se; @johanvirhammar. Median age at the time of surgery was 74 years (range, 54 – 88
http://dx.doi.org/10.3174/ajnr.A4046 years); 58 (54%) were men and 50 (46%) were women. Inclusion
AJNR Am J Neuroradiol 35:2311–18 Dec 2014 www.ajnr.org 2311
criteria were a preoperative MR imaging examination of the brain ratio between the maximum diameter of the frontal horns of the
and a clinical evaluation before and at 12 months after shunt lateral ventricles and the maximum inner diameter of the skull in
surgery. All patients had ventricular enlargement and gradually the same section (Fig 1A).
evolving symptoms, including a gait disturbance with or without The callosal angle measured on MR imaging is the angle be-
cognitive decline or urinary incontinence. Patients with second- tween the lateral ventricles on a coronal image through the pos-
ary NPH were excluded. During the follow-up period, 29 patients terior commissure, perpendicular to the anterior/posterior com-
had various types of shunt complications and 5 patients had com- missure plane (Fig 1B).5
plications related to comorbidity. The sample is described in de- Compression of the medial and/or high convexity cortex sulci
tail in a previous study.3 (narrow sulci) was evaluated on coronal and transverse images.6 It
was graded as the following: 0 ⫽ normal or wider than normal,
Clinical Evaluation 1 ⫽ slight compression, 2 ⫽ definitive compression (Fig 1C, -D).
Patients referred to Uppsala University Hospital because of clin- Dilation of the Sylvian fissure was graded in 3 different ways.
ical and radiologic symptoms of NPH were evaluated prospec- The first method was described by Kitagaki et al7 and later illus-
tively before surgery and at follow-up 12 months postoperatively trated with coronal images by Hashimoto et al.8 We graded dila-
by a multidisciplinary team specialized in hydrocephalus. A neu- tion as the following: 0 ⫽ normal or narrow, 1 ⫽ mildly moder-
rologist performed a clinical and neurologic evaluation, including ately enlarged, 2 ⫽ highly enlarged.7,8 When we used this method,
a medical history covering intracranial hemorrhage, meningitis, the reliability between the 2 investigators was not sufficient (␬ ⫽
or trauma or other causes of secondary hydrocephalus. All pa- 0.36, Fig 2 and Table 1). Therefore, we created a new grading scale,
tients were assessed according to a prospective, standardized pro- the Sylvian fissure ordinal, an ordinal scale with 3 levels and grad-
tocol developed to follow symptoms with time and to measure the ing still based on the images of Hashimoto et al but with a more
outcome after shunt surgery. The cognitive function was tested precise definition of how to reconstruct the coronal images to
with the Mini-Mental State Examination; urinary symptoms, attain a higher reproducibility. The coronal images used for the
with 1 ordinal continence scale4; motor function, with 1 ordinal Sylvian fissure ordinal were reconstructed at the level of the cen-
balance scale4 and 1 ordinal gait scale4; and we also used 3 tests in tral part of the brain stem and angulated along the brain stem (Fig
which time and the number of steps were measured. The latter 2B). In the third method, the height of the Sylvian fissure was
included walking 10 m at a self-chosen speed, a Timed Up and Go measured quantitatively on a sagittal image located at the mid-
Test, and walking backward 3 m. point between the skull and the insular cortex. The height was
A shunt responder was defined as a patient improved in any of measured in millimeters in 5 different locations perpendicular to
the following 3 criteria: the direction of the Sylvian fissure. The median value of the 5
1) Motor function of ⱖ1 level on the gait or balance scale or locations was calculated for each side, and the average of right and
ⱖ20% reduction in the time or the number of steps in left was recorded.
ⱖ50% of the 3 tests Disproportionately enlarged subarachnoid space hydroceph-
2) Cognition ⱖ4 levels in the Mini-Mental State Examination alus (DESH) refers to a communicating hydrocephalus with en-
3) Continence scale ⱖ1 level and improvement in the Mini- larged ventricles and a disproportionate distribution of the CSF
Mental State Examination score of ⱖ2 levels. between the inferior and superior subarachnoid spaces.8 It was
A dichotomous variable shunt outcome was created and graded as present if both narrow sulci at the high convexity and
used as a dependent variable in the logistic regression. The the Sylvian fissure ordinal were graded as ⱖ1 (Fig 1D).
modified Rankin Scale was used as a measure of general hand- Flow void phenomenon through the aqueduct and fourth ven-
icap level. tricle (flow void) was graded by a modified version of the ordinal
scale described by Algin et al.9 It was graded as follows: 0 ⫽ no
Imaging flow in the aqueduct, 1 ⫽ flow void only in the aqueduct, 2 ⫽ flow
Forty-one (38%) of the preoperative MR imaging examinations void in the aqueduct and the upper half of the fourth ventricle,
were performed at the authors’ hospital, and 67 (62%), at the 3 ⫽ flow void that extends to the caudal part of the fourth ventri-
referring hospitals. Ten (9%) were performed on a 3T scanner; 75 cle. It was graded on T2-weighted sagittal images without flow
(70%), on a 1.5T scanner; 15 (14%), on a 1T scanner; and 8 (7%), compensation. Only examinations from 1 scanner (Avanto 1.5T;
on a 0.5T scanner. Siemens, Erlangen, Germany) were included to avoid scanner dif-
Evaluation of MR images was performed retrospectively, with ferences with regard to flow compensation (n ⫽ 36, Fig 1E).
the investigators blinded to the patients’ clinical data. Multiplanar Focal bulging of the roof of the lateral ventricles was eval-
reconstruction of the images was used as described below. For uated on sagittal images and was graded as present or not pres-
continuous variables, 2 investigators analyzed 20 randomly se- ent (Fig 3).
lected patients, and intraclass correlation coefficients (ICCs) were The diameter of the third ventricle was measured in millimeters
calculated to obtain inter-rater reliability. For the ordinal and on transverse T1-weighted images in the center of the ventricle in the
dichotomous variables, 2 investigators independently analyzed all anteroposterior direction but in the widest part in the inferior-supe-
patients; and to test reliability, Cohen ␬ was calculated. In cases of rior direction (Fig 1F). The maximal diameter of the temporal horns
discrepancy in the evaluation, the images were re-evaluated, and a was measured in millimeters on each side on transverse images, and
consensus was reached. the average of left and right was calculated (Fig 1G).
The Evans index was measured on transverse images as the Deep white matter hyperintensities (DWMH) were evaluated
2312 Virhammar Dec 2014 www.ajnr.org
FIG 1. Nine different patients with iNPH. A, Evans index ⫽ x/y. B, Callosal angle. C, Narrow medial sulci and 2 focally dilated sulci on the left side.
D, DESH. E, A flow void in the aqueduct and fourth ventricle graded as 2. In addition, a flow void in the foramina of Monro. F, Large diameter of
the third ventricle. G, Dilated temporal horns. H, DWMH graded as 3 in a patient who also has PVH. I, PVH graded as 2.

on T2 FLAIR images by the ordinal scale described by Fazekas et ventricular wall and small caps around the frontal horns), 1 ⫽
al10 as follows: 0 ⫽ no lesions, 1 ⫽ punctate foci, 2 ⫽ beginning increased PVH, 2 ⫽ irregular large symmetric hyperintensities
confluence of foci, 3 ⫽ large confluent areas (Fig 1H). All clearly extending out into the deep white matter and, on at least 2 loca-
visible single lesions were graded as punctate foci. tions, all the way from the ventricles to the cortex (Fig 1I).10
Periventricular hyperintensities (PVH) along and always in Accumulation of CSF in focally enlarged sulci, previously
contact with the frontal and parietal portions of the lateral ventri- called “transport sulci,” was evaluated as present or not present
cles were evaluated on T2 FLAIR images. They were graded as (Fig 1C).11,12
follows: 0 ⫽ normal (including a “pencil-thin lining” along the Focal narrowing of the aqueduct with suspicion of aqueductal
AJNR Am J Neuroradiol 35:2311–18 Dec 2014 www.ajnr.org 2313
FIG 2. T1-weighted 3D images of a patient with iNPH. A and B, Coronal images illustrate the different heights of the Sylvian fissure that can be
achieved depending on the angulation of the section. B, The Sylvian fissure ordinal. C, Sagittal image with orientation lines represented by the
coronal images A and B.

Table 1: Interrater reliability between 2 independent was set at P ⬍ .05. No corrections for multiple analyses were done.
investigators for all imaging findings Analyses were performed by using SPSS Version 21.0, (IBM, Ar-
Imaging Feature Reliability
monk, New York).
Evans index (ICC) 0.93
Callosal angle (ICC) 0.95
Narrow sulci (␬) 0.64 RESULTS
Sylvian fissure original (␬)a 0.36 At 12-month follow-up, 82 of the 108 patients (76%) had im-
Sylvian fissure ordinal (␬)b 0.62 proved after shunt surgery. Mean values ⫾ SD at preoperative MR
Sylvian fissure height (ICC) (mm) 0.89
DESHc NA imaging were the following: Evans index, 0.38 ⫾ 0.04; callosal
Flow void (␬) 0.33 angle, 61 ⫾ 17°; diameter of the third ventricle, 12 ⫾ 3 mm;
Focal bulging (␬) 0.28 diameter of the temporal horns, 7 ⫾ 2 mm; and the mean height
Third ventricle (ICC) 0.96 of the Sylvian fissures, 6 ⫾ 3 mm. Prevalence and grading of
Temporal horns (ICC) 0.80
imaging features measured on ordinal or dichotomous scales are
DWMH (␬) 0.67
PVH (␬) 0.72 presented in Table 2.
Focally enlarged sulci (␬) 0.54 The predictive value of the imaging findings is presented as a
Aqueductal stenosis (␬) 0.32 sex-adjusted OR in Fig 4. For callosal angle, DESH, and temporal
Note:—NA indicates not applicable. horns, the ORs were significant in the univariate analyses, and
a
The original method to measure the Sylvian fissure.7
b when adjusted for sex or when adjusted for sex, age, and previous
Ordinal scale of 0 –2.
c
Calculated from Sylvian fissure ordinal and narrow sulci. stroke in the 3 separate multivariate logistic regression models. If
only patients without complications (n ⫽ 76) were included in the
logistic regression, the ORs for callosal angle, DESH, and tempo-
stenosis was evaluated on sagittal and coronal images and graded
as present or not present. ral horns were still significant.
There were several correlations among different imaging fea-
tures at the preoperative MR imaging investigations in the range
Statistics
ICC and ␬ were used to test for reliability between 2 investigators. of r ⫽ 0.26 – 0.68 (Table 3).
Univariate associations and associations adjusted for sex, between Patients without PVH performed better at baseline in the
shunt outcomes, and all imaging features were assessed with lo- modified Rankin Scale and in the stride length in the Timed Up
gistic regression models. Imaging markers significant in the uni- and Go Test and 10 m walk compared with patients with PVH
variate analyses were adjusted for age, sex, and previous stroke in (P ⬍ .05). Patients without focal bulging performed better in the
multiple logistic regression models. Results from the logistic re- walking backward 3 m test compared with patients with the im-
gression models were presented in a forest plot as estimated ORs aging feature present (P ⬍ .05). Patients with normal Sylvian fis-
with a 95% CI of 1 SD increase for continuous variables and a 1 sures performed better in the modified Rankin Scale (P ⬍ .01),
unit increase for dichotomous and ordinal variables. The differ- balance scale (P ⬍ .01), 10 m walk, and the walking backward 3 m
ence in the proportion of shunt responders or the level of im- test (P ⬍ .05) compared with patients with dilated Sylvian fis-
provement between patients with or without dichotomous imag- sures. At baseline, Sylvian fissure height (millimeters) correlated
ing findings was tested with the ␹2 test and the Mann Whitney U with both impaired speed and step length in the walking backward
test, respectively. Correlations were tested by using the Spearman 3 m test at baseline (r ⫽ 0.61, P ⬍ .001 and r ⫽ 0.66, P ⬍ .0001,
rank correlation coefficient (r) or the ␾ coefficient when appro- respectively). A smaller callosal angle correlated with more im-
priate. The correlations tested were exploratory and were not de- paired scoring in the balance scale (r ⫽ 0.26, P ⬍ .01), and the
cided before the study, and the level of significance was set at P ⬍ Evans index correlated negatively with the Mini-Mental State Ex-
.01 for correlations. For other analyses, the level of significance amination score (r ⫽ ⫺0.27, P ⬍ .01).
2314 Virhammar Dec 2014 www.ajnr.org
 patients with a larger angle are less likely
to benefit from shunt surgery.
Dilation of the temporal horns of the
lateral ventricles is an established finding
in hydrocephalus13,14 and has previously
been reported to be more frequent in pa-
tients who improve after shunt surgery
compared with nonresponders.12 This
finding was strengthened by the results of
the present study. The dilation of the tem-
poral horns in iNPH should not be mis-
taken for atrophy of the medial temporal
lobe as is seen in Alzheimer disease,15
even though there are reports of dimin-
FIG 3. Two patients with focal bulging of the roof of the lateral ventricles. Sagittal images ished hippocampus volume in patients
include the most cranial portions of the lateral ventricles. A, T2-weighted image. B, T1-weighted with NPH.16
image. In the present study, DESH was a pre-
Table 2: Prevalence and grading of imaging findings measured on dichotomous and dictor of a positive shunt outcome. The
ordinal scales imaging feature was discussed in a publica-
Imaging Feature Frequency of Different Grading (No.) (%)a Sample tion from the Japanese Study of Idiopathic
(Grading Range) 0 1 2 3 (No.) Normal Pressure Hydrocephalus on Neu-
Sylvian fissure ordinal (0–2) 23 (21) 77 (71) 8 (8) NA 108 rological Improvement (SINPHONI), and
DESH (0–1) 36 (33) 72 (67) NA NA 108 was described as a morphologic hallmark
Flow void (0–3)b 0 (0) 0 (0) 9 (25) 27 (75) 36
of iNPH. In the SINPHONI study, a pos-
Narrow sulci (0–2) 24 (22) 22 (20) 62 (58) NA 108
Focal bulging (0–1) 13 (12) 95 (88) NA NA 108 itive outcome was achieved in 80% of 100
DWMH (0–3) 5 (5) 11 (10) 31 (29) 60 (56) 107 patients by using an MR imaging– based
PVH (0–2) 27 (25) 66 (62) 14 (13) NA 107 diagnostic scheme.8 In SINPHONI, 96%
Focally enlarged sulci (0–1) 45 (42) 63 (58) NA NA 108 of the patients had dilated Sylvian fissures
Aqueductal stenosis (0–1) 105 (97) 3 (3) NA NA 108
and could be classified as having DESH
Note:—NA indicates not applicable.
compared with 67% in the present study.
a
Dichotomous variables: 0 ⫽ not present, 1 ⫽ present.
b
Flow void in the aqueduct and fourth ventricle. Because SINPHONI used narrow supra-
Sylvian subarachnoid spaces as an inclu-
There was no difference in the proportion of patients with a pos- sion criterion in contrast to the present study, the prognostic use-
itive outcome or level of improvement in relation to the Fazekas score fulness of DESH could not be calculated in that study. In CT
among patients with DWMH. The proportion of patients with severe studies, it has been reported that dilated Sylvian fissures are a sign
DWMH (Fazekas 3) that improved after shunting was 45/60 (75%) of poor prognosis, and it has been argued that the dilation is
compared with 36/47 (77%) in patients with less severe DWMH. caused by atrophy, which is at odds with the findings in the
In Table 1, the interrater reliability is presented. For continu- SINPHONI study.12,17 The difference could be explained by the
ous variables, the reliability had the range of 0.80 – 0.96 (ICC), and fact that the Sylvian fissure could only be evaluated on transverse
for variables on an ordinal scale, it had a range of 0.33– 0.72 (␬). images at that time, and it is much easier to visualize the dilation
The interrater reliability of dichotomous variables was 0.28 – 0.67 of Sylvian fissures on reconstructed coronal sections as in modern
(␬). studies. In the present study, the finding of only dilated Sylvian
fissures or only narrow sulci at the high convexity did not predict
DISCUSSION a positive outcome. Nevertheless, in light of our study and the
In patients with suspected iNPH, MR imaging is used to aid in the SINPHONI study, it seems as if DESH is a very common find-
diagnosis and selection of shunt candidates. In this retrospective ing in iNPH and that it may aid in the selection of shunt
study of 108 patients with iNPH who had undergone shunt sur- candidates.
gery and clinical examination before and at 12 months after sur- Several correlations between imaging findings were seen, and
gery, a small callosal angle, occurrence of DESH, and wide tem- some patterns emerged. As expected, there were correlations be-
poral horns on the preoperative MR imaging scans were tween markers of the ventricular width and Evans index, and the
significant predictors of positive shunt outcome. temporal horns correlated with the diameter of the third ventricle.
A small callosal angle has previously been described as useful DESH correlated with a smaller callosal angle and focal bulging of
for separating patients with iNPH from those with Alzheimer dis- the ventricular roofs.
ease and healthy controls.5 The results in this and a previous study There was a significant difference at baseline in the severity of
of a smaller callosal angle in patients who responded to shunt motor symptoms and handicap levels between patients with and
surgery further support its prognostic value.3 The significant without PVH, dilated Sylvian fissures, and focal bulging of the
OR ⬍ 1 for the callosal angle can be interpreted as showing that ventricular roofs. Correlations were seen between the severity of
AJNR Am J Neuroradiol 35:2311–18 Dec 2014 www.ajnr.org 2315
FIG 4. Forest plot with sex-adjusted odds ratios for all imaging features. OR with a 95% CI of 1-SD increase for continuous variables and a 1-U
increase for dichotomous and ordinal variables. An arrow indicates that the confidence interval extends beyond the range of the plot. The
Sylvian fissure ordinal is the ordinal scale 0 –2; the Sylvian fissure height is measured in millimeters. The asterisk indicates P ⬍ .05.

Table 3: Correlations among different imaging markers at chronic ischemia, or plasma leakage caused by diffuse cerebrovas-
baselinea cular endothelial failure.18
Imaging Feature Significant Correlations In the present study, patients with severe DWMH had a similar
Evans index Third ventricle (r ⫽ 0.39b) positive outcome rate compared with the whole sample, which is
Callosal angle DESH (r ⫽ ⫺0.27c), focal bulging (r ⫽ ⫺0.28c),
in line with the results of Tullberg et al,19 who concluded that
temporal horns (r ⫽ ⫺0.33d)
DESH Focal bulging (r ⫽ 0.34d), focally enlarged sulci patients must not be excluded from shunt surgery on the basis of
(r ⫽ 0.32d), callosal angle (r ⫽ ⫺0.27c) the DWMH findings. In NPH, the PVH around the lateral ventri-
Focal bulging Temporal horns (r ⫽ 0.26c), callosal angle cles is probably caused by transependymal CSF passage into the
(r ⫽ ⫺0.28c), DESH (r ⫽ 0.34d) adjacent white matter, and it has, in some studies, been reported
Third ventricle Temporal horns (r ⫽ 0.38b) to be a good prognostic sign.20,21 We could not replicate that
DWMH PVH (r ⫽ 0.68b)
finding, but patients with PVH had more severe gait disturbances
Note:—r indicates Spearman correlation coefficient.
a
Measurements of Sylvian fissure and narrow sulci at the high convexity were not
and handicap levels at baseline compared with patients without
included because they are components of DESH. PVH. Because more severe PVH often extends far from the lateral
b
P ⬍ .0001. ventricles into the deep white matter, it can sometimes be almost
c
P ⬍ .01.
d
P ⬍ .001.
impossible to differentiate PVH from DWMH. This difficulty
could be one explanation behind both the high frequency of se-
vere DWMH and the good outcome rate in these patients. Some
motor symptoms and a smaller callosal angle or wider Sylvian patients may have had both DWMH and advanced PVH. This
fissures; and a correlation was seen between a larger Evans index possibility is further supported by a strong correlation between
and more impaired cognitive function. DWMH and PVH.
White matter hyperintensities on MR imaging are often di- The focal bulging of the roof of the lateral ventricles is an MR
vided into PVH, adjacent to the ventricles, and DWMH, located imaging feature that, to our knowledge, has not been described
in the deep white matter. Both DWMH and PVH have been re- previously in iNPH. We do not know the frequency of this finding
ported to be associated with risk factors for vascular disease, such in other types of ventricular enlargement, obstructive hydroceph-
as hypertension and smoking. The origin of the hyperintensities is alus, or healthy elderly. The focal bulging is best visualized on
still debated, and DWMH has been reported to represent gliosis, sagittal images in the section including the most cranial portions
2316 Virhammar Dec 2014 www.ajnr.org
of the ventricles. The bulging may be caused by CSF pulsations in samples as large as in this study, to draw any conclusions regard-
the lateral ventricles in a weakened spongiotic ependyma and ing in which patients shunting should not be performed.
edematous periventricular brain parenchyma,22 located between Some limitations should be addressed. All patients had been
periventricular veins. diagnosed with iNPH by a specialized team and had undergone
The interrater reliability between 2 observers of measures of shunt surgery, and the MR imaging investigations used in this
flow void, focal bulging, and aqueductal stenosis was not satisfac- study had been used in the clinical evaluation of these patients.
tory and neither was the reliability of the original description of We had no control group of healthy individuals or patients with
the grading of the Sylvian fissure.7,8 We showed that the reliability Alzheimer disease. Thus, the results in this study must be inter-
increased from ␬ ⫽ 0.36 to ␬ ⫽ 0.62 by defining the way the preted in the light of the highly selected sample, and no conclu-
sections should be reconstructed and angulated. Dramatic differ- sions about the diagnostic value of the findings can be made. The
ences in the height of the Sylvian fissure could be obtained de- clinical radiologic diagnosis was made by several different neuro-
pending on which coronal section was used and how it was angu- radiologists without a defined protocol, which might have influ-
lated (Fig 2). All inconsistent grading scores were re-evaluated, enced the frequency of some of the retrospectively evaluated im-
aging findings. For example, all patients had an Evans index of
and a consensus was reached between the 2 investigators. In ac-
⬎0.30, and no patient had severe cortical atrophy. However, sev-
cordance with our experience, Ishii et al5 illustrated differences in
eral of the imaging features investigated in this study were not
the callosal angle, depending on the angulation of the coronal
used clinically at the time of the study at our center. Because of
section. These differences are important when these imaging fea-
missing sequences in some patients, we could not grade all imag-
tures are used in clinical practice, and only well-defined grading
ing features in all patients. This gap was most evident for grading
scales with high reliability should be used.
of the flow void because we chose to include only investigations
In 3 of the cases in this study, there was a subtle focal narrow-
from a single scanner to avoid any differences among scanners.26
ing of the Sylvian aqueduct. This did not obstruct the CSF flow
Because of the limited number of patients in whom flow void was
and was not considered the cause of the hydrocephalus in these graded, not a single patient with a small flow void was found,
patients. It is advisable to evaluate the aqueduct thoroughly in which probably affected the absence of significant correlations
patients with suspected iNPH—for example, by including a high- between flow void and other MR imaging findings. Although data
resolution, heavily T2-weighted 3D MR imaging sequence in the were collected prospectively in a standardized way, the radiologic
protocol to exclude obstructive causes of hydrocephalus. measurements and analyses of clinical data for this study were
An interesting finding is the diversity of different morphologic performed retrospectively. This feature limited the possibility of
features in this study. All patients had similar symptomatology, making corrections when specific MR imaging sequences or some
but 67% had DESH, while 10% had neither dilated Sylvian fis- clinical data were missing.
sures nor narrow high-convexity sulci; 25% had no PVH at all,
while 13% had PVH extending all the way to the cortex. Previous
CONCLUSIONS
studies in iNPH have found both heterogeneous patterns of met- The callosal angle, diameter of the temporal horns, and presence
abolic disturbances in the cortex measured with FDG-PET and of DESH were predictors of a positive outcome after shunting in
various patterns of CBF reduction measured with SPECT.23,24 this sample of patients with iNPH. We recommend that these
These findings raise the question: Are the morphologic differ- noninvasive imaging features be assessed in the preoperative eval-
ences different stages of the same disease or is iNPH a syndrome of uation of patients with iNPH because they may aid in the selection
several diseases with different etiologies? There were significant of shunt candidates.
differences in symptom severity between patients with or without
PVH, focal bulging, and dilated Sylvian fissures, indicating that
ACKNOWLEDGMENTS
these imaging features may be involved in the progression of the
We thank Lisa Wernroth for statistical consultation and the staff
disease. However, this question should be addressed in a prospec-
of our NPH team at Uppsala University Hospital for their com-
tive longitudinal study.
mitment to all the patients.
It has recently been discussed that in studies of iNPH, it is
important to present descriptive data of the sample, including Disclosures: Johan Virhammar—RELATED: Grant: Selanders Stiftelse,* Comments:
comorbidity, to facilitate comparisons of different studies.25 It Selanders Stiftelse is an independent foundation in Sweden. The institution received
seems to be equally important to also describe the radiologic find- a grant to support the cost of this study. Katarina Laurell—RELATED: Grant: Seland-
ers Stiftelse.* *Money paid to the institution.
ings in sufficient detail. Otherwise, we cannot know whether we
are investigating and performing surgery in similar patients, and
comparisons of studies become difficult.
REFERENCES
Despite these findings, callosal angle, DESH, or temporal
1. Adams RD, Fisher CM, Hakim S, et al. Symptomatic occult hydro-
horns cannot be used to exclude patients from surgery. Of pa- cephalus with “normal” cerebrospinal-fluid pressure: a treatable
tients with a callosal angle of ⬎90°, 4/7 (57%) improved; 23/36 syndrome. N Engl J Med 1965;273:117–26
(64%) patients without DESH improved; and 7/15 (47%) patients 2. Klinge P, Hellstrom P, Tans J, et al. One-year outcome in the Euro-
with temporal horns of ⬍5 mm improved from shunt surgery. pean multicentre study on iNPH. Acta Neurol Scand 2012;126:
145–53
This illustrates one of the greatest problems with studies of prog- 3. Virhammar J, Laurell K, Cesarini KG, et al. The callosal angle mea-
nostic or nonprognostic investigations in iNPH: The number of sured on MRI as a predictor of outcome in idiopathic normal-pres-
patients who do not improve after shunting are too few, even in sure hydrocephalus. J Neurosurg 2014;120:178 – 84

AJNR Am J Neuroradiol 35:2311–18 Dec 2014 www.ajnr.org 2317

 4. Hellström P, Klinge P, Tans J, et al. A new scale for assessment of relates with severe cognitive impairment in elderly patients with
severity and outcome in iNPH. Acta Neurol Scand 2012;126:229 –37 suspected normal pressure hydrocephalus. J Neurol Neurosurg Psy-
5. Ishii K, Kanda T, Harada A, et al. Clinical impact of the callosal angle chiatry 1994;57:590 –93
in the diagnosis of idiopathic normal pressure hydrocephalus. Eur 17. Benzel EC, Pelletier AL, Levy PG. Communicating hydrocephalus in
Radiol 2008;18:2678 – 83 adults: prediction of outcome after ventricular shunting proce-
6. Sasaki M, Honda S, Yuasa T, et al. Narrow CSF space at high convex- dures. Neurosurgery 1990;26:655– 60
ity and high midline areas in idiopathic normal pressure hydro- 18. Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cere-
cephalus detected by axial and coronal MRI. Neuroradiology bral small vessel disease: insights from neuroimaging. Lancet Neu-
2008;50:117–22 rol 2013;12:483–97
7. Kitagaki H, Mori E, Ishii K, et al. CSF spaces in idiopathic normal 19. Tullberg M, Jensen C, Ekholm S, et al. Normal pressure
pressure hydrocephalus: morphology and volumetry. AJNR Am J hydrocephalus: vascular white matter changes on MR images must
Neuroradiol 1998;19:1277– 84 not exclude patients from shunt surgery. AJNR Am J Neuroradiol
8. Hashimoto M, Ishikawa M, Mori E, et al. Diagnosis of idiopathic 2001;22:1665–73
normal pressure hydrocephalus is supported by MRI-based 20. Poca MA, Mataro M, Del Mar Matarin M, et al. Is the placement of
scheme: a prospective cohort study. Cerebrospinal Fluid Res 2010; shunts in patients with idiopathic normal-pressure hydrocephalus
7:18 worth the risk? Results of a study based on continuous monitoring
9. Algin O, Hakyemez B, Taskapilioglu O, et al. Morphologic features of intracranial pressure. J Neurosurg 2004;100:855– 66
and flow void phenomenon in normal pressure hydrocephalus and 21. Børgesen SE, Gjerris F. The predictive value of conductance to out-
other dementias: are they really significant? Acad Radiol 2009;16:
flow of CSF in normal pressure hydrocephalus. Brain 1982;105:
1373– 80
65– 86
10. Fazekas F, Chawluk JB, Alavi A, et al. MR signal abnormalities at 1.5
22. Milhorat TH, Clark RG, Hammock MK, et al. Structural, ultrastruc-
T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol
tural, and permeability changes in the ependyma and surrounding
1987;149:351–56
brain favoring equilibration in progressive hydrocephalus. Arch
11. Holodny AI, George AE, de Leon MJ, et al. Focal dilation and para-
Neurol 1970;22:397– 407
doxical collapse of cortical fissures and sulci in patients with nor-
23. Ishii K, Hashimoto M, Hayashida K, et al. A multicenter brain per-
mal-pressure hydrocephalus. J Neurosurg 1998;89:742– 47
fusion SPECT study evaluating idiopathic normal-pressure hydro-
12. Wikkelsö C, Andersson H, Blomstrand C, et al. Computed tomogra-
cephalus on neurological improvement. Dement Geriatr Cogn Dis-
phy of the brain in the diagnosis of and prognosis in normal pres-
sure hydrocephalus. Neuroradiology 1989;31:160 – 65 ord 2011;32:1–10
13. Svendsen P, Duru O. Visibility of the temporal horns on computed 24. Tedeschi E, Hasselbalch SG, Waldemar G, et al. Heterogeneous cere-
tomography. Neuroradiology 1981;21:139 – 44 bral glucose metabolism in normal pressure hydrocephalus. J Neu-
14. Tans JT. Differentiation of normal pressure hydrocephalus and ce- rol Neurosurg Psychiatry 1995;59:608 –15
rebral atrophy by computed tomography and spinal infusion test. 25. Malm J, Graff-Radford NR, Ishikawa M, et al. Influence of comor-
J Neurol 1979;222:109 –18 bidities in idiopathic normal pressure hydrocephalus: research and
15. Scheltens P, Leys D, Barkhof F, et al. Atrophy of medial temporal clinical care—a report of the ISHCSF task force on comorbidities in
lobes on MRI in “probable” Alzheimer’s disease and normal INPH. Fluids Barriers CNS 2013;10:22
ageing: diagnostic value and neuropsychological correlates. J Neu- 26. Bradley WG Jr, Scalzo D, Queralt J, et al. Normal-pressure
rol Neurosurg Psychiatry 1992;55:967–72 hydrocephalus: evaluation with cerebrospinal fluid flow measure-
16. Golomb J, de Leon MJ, George AE, et al. Hippocampal atrophy cor- ments at MR imaging. Radiology 1996;198:523–29

2318 Virhammar Dec 2014 www.ajnr.org