Key-words: Disproportionately enlarged subarachnoid space hydrocephalus - Evans' Index - idiopathic
normal pressure hydrocephalus - interobserver variability - ventriculoatrial shunt
Introduction
Idiopathic normal-pressure hydrocephalus (iNPH) is a syndrome mainly found in elderly
people and comprises a triad of gait disturbance, dementia, and urinary incontinence
that can be improved by cerebrospinal fluid (CSF) shunting.[[1 ]] In the image diagnosis of iNPH, ventriculomegaly is a mandatory condition that
is defined as Evans' Index (EI) >0.3 in both international and Japanese guidelines[[2 ]],[[3 ]] until 2012 when the revised Japanese guidelines introduced disproportionately enlarged
subarachnoid space hydrocephalus (DESH) as a necessary component in the image diagnosis
of iNPH.[[4 ]]
EI in the diagnosis of iNPH is defined as a frontal horn ration calculated at the
maximum frontal horn ventricular width divided by the transverse inner diameter of
the skull at the same horizontal plane.[[4 ]],[[5 ]] As the shapes of the cranium and the lateral ventricle differ depending on the
level of the horizontal plane, there is a possibility of error in the selection of
the level for EI calculation. Furthermore, the judgment of DESH is subjective and
therefore poses a potential risk of interobserver variability. Therefore, both parameters
may vary from one evaluator to another (interobserver variability).
The criteria of EI >0.3 were derived from the previous definition of ventriculomegaly
for child hydrocephalus studied by means of pneumoencephalogram.[[6 ]] It was not a result of a direct comparison between iNPH patients and healthy controls.
DESH was proposed as a unique morphological configuration to iNPH,[[7 ]] and Hashimoto et al. confirmed its diagnostic value for iNPH.[[8 ]] However, many elderly people are known to show asymptomatic ventriculomegaly with
imaging features of iNPH on magnetic resonance imaging (MRI) (AVIM)[[9 ]] but without presenting symptoms of iNPH.[[10 ]] In addition, it is known that there are many iNPH patients who do not show the
expected DESH findings, but whose symptoms improved by CSF shunting.[[11 ]] As for EI, about 20%–30% of the healthy elderly people are known to have EI >0.3.[[12 ]],[[13 ]] These studies suggest that neither EI nor DESH might be appropriate image diagnostic
criteria for iNPH. A very recent study showed that DESH and other morphologic MRI
markers including sharp callosal angle[[14 ]] are not proper diagnostic image criteria.[[15 ]]
Before the publication of the guidelines for diagnosis and management of iNPH,[[2 ]],[[3 ]] there had not been a clear definition of ventriculomegaly for iNPH. One of the
authors (KT, who is also the neurosurgeon in this study: NS) started ventriculoatrial
(VA) shunt for iNPH before the publication of Japanese guidelines in 2004.[[3 ]] He placed VA shunt only for the patients with a positive lumbar tap test whose
brain computed tomography or MRI showed anterior horn rounding, third ventricular
ballooning, sylvian fissure enlargement, or convexity subarachnoid space enlargement,
which are not commonly observed in normal adults [[Figure 1 ]]. He found that some of these cases did not meet the criteria of either EI >0.3
or DESH, but he nevertheless observed satisfactory postoperative outcomes for these
iNPH patients.
Figure 1: Normal (a) and representative magnetic resonance imaging images (b-e) of the patients
operated by ventriculo-atrial shunt with clinical improvement. (a) Normal magnetic
resonance imaging of healthy person. (b) Third ventricular ballooning. (c) Anterior
horn rounding. (d) Sylvian fissure dilatation. (e) Enlarged convexity subarachnoid
space
After the publication of the guidelines,[[2 ]],[[3 ]] neurologists and neurosurgeons again came to recognize iNPH as a possible cause
of gait disturbance, dementia, and urinary incontinence. Once the image diagnostic
criterion of ventriculomegaly is defined as EI >0.3, the patients who do not fulfill
this criterion would not be diagnosed as iNPH and be left untreated even though they
show the typical triad of the disease without other responsible disorders. Since 2011,
DESH has been accepted as a conjunct image indicator of iNPH along with EI in Japan.[[4 ]] This may further narrow the window for the chance to receive shunt surgery for
the possibly treatable iNPH patients.
The purpose of this study was to assess the reliability of EI and DESH in diagnosing
iNPH by estimating retrospectively the MR images of definite iNPH patients. The second
objective of the study was to examine the variability and agreement between the evaluators
for their judgments of EI and DESH criteria.
Materials and Methods
From April 2007 to December 2014, we had 288 definite iNPH patients out of 330 VA
shunts for probable iNPH at Kashiwatanaka Hospital NPH Center. All the shunted patients
were installed with a programmable valve. Of these definite iNPH patients, 84 patients
had clear preoperative axial and coronal brain MRI scans as well as follow-up period
of over 1 year. These were the definite iNPH patients included in this study because
their scans could be used to assess both EI and DESH.
The NS who performed the VA shunts had evaluated EI and DESH before the surgery. All
patients except one received a lumbar tap test with a positive response. One patient
had an unruptured cerebral aneurysm and the lumbar tap test was not performed. However,
his MRI findings fulfilled the revised Japanese guideline. A neuroradiologist (NR)
and a physical therapist (PT) who were blind to the patients' clinical information
independently calculated EI and evaluated DESH for these cases. EI was computed using
an axial section of MRI T1 images according to the calculation method described in
the guideline,[[4 ]] not by the original method.[[6 ]] DESH was judged based on the original paper by Kitagaki et al.[[7 ]]
The mean EIs evaluated by three raters were compared by means of one-way ANOVA. The
rate of a positive finding for iNPH was calculated for the three raters. Student's
t-test was used to compare the means of baseline variables. Paired sample t-test was
used to compare scores before shunt surgery and at 3 months. Fleiss kappa test was
used to assess the agreement between all the three raters, and Cohen's kappa was used
to assess the significance of difference/disagreement between the raters. P < 0.05
was set as statistical significance. The results were showed in mean (standard deviation).
Ethical considerations
The data collection was approved by the Institutional Review Board of Kashiwa Takana
Hospital and informed consent was obtained in a written form.
Results
There were 49 males and 35 females. The overall mean age was 78.4 (6.3) years, while
the mean age for males was 78.1 (6.8) years, and for females, it was 78.7 (5.6) years.
There was no gender difference in the mean age (P = 0.66) [[Table 1 ]].
Table 1: Demographic data of the 84 patients
With all patients being definitive iNPH patients, an improvement was observed in the
clinical rating scales of the patients after the shunt surgery. [[Table 2 ]] briefly demonstrates the changes in clinical scores before shunt procedure and
the best scores after surgery for the Modified Rankin Scale, mini-mental state examination,
and Japanese idiopathic normal-pressure hydrocephalus Grading Scale.[[16 ]]
Table 2: Pre- and postoperative modified Rankin scale, mini-mental state examination, and
total score of Japanese idiopathic normal-pressure hydrocephalus Grading Scale
The mean EI was 0.33 (0.04), 0.32 (0.04), and 0.31 (0.03) for NS, NR, and PT respectively
(P < 0.0001). [[Table 3 ]] shows the numbers and percentages of the cases correctly diagnosed as iNPH patients
(EI >0.3) by three evaluators. The percentage of the cases correctly diagnosed as
iNPH with EI >0.3 criteria was between 61% and 74%, and the level of agreement was
moderate (κ = 0.59).
Table 3: The numbers and percentages of the cases correctly diagnosed idiopathic normal-pressure
hydrocephalus with Evans’ Index >3 by three evaluators
[[Table 4 ]] shows the numbers and percentage of cases correctly diagnosed as iNPH with DESH
evaluated by the same three evaluators. The percentage of cases correctly as iNPH
using the DESH criteria was 50% or less, with a moderate level of agreement between
them (κ = 0.522).
Table 4: The numbers and percentages of the cases correctly diagnosed idiopathic normal pressure
hydrocephalus with disproportionately enlarged subarachnoid space hydrocephalus by
three evaluators
[[Table 5 ]] shows the numbers and percentages of cases by their EI and DESH status as determined
by the NR. The percentage of the patients fulfilling both the diagnostic criteria
proposed in Japanese guidelines was lower than 30%. When we compared the clinical
rating scales of these cases before shunt and the best scores over 3-month follow-up
after VA shunt, they were very similar to the overall mean differences and significance
level, indicating that this group of patients was not different from the total group.
Table 5: Cross-mach table for Evans’ Index and disproportionately enlarged subarachnoid space
hydrocephalus by neuroradiologist
Interobserver agreement was assessed between the pairs of raters. In all evaluations,
NS had the highest rate of correctly identifying iNPH. Therefore, using NS as the
reference point, the NS-NR agreement and NS-PT agreement for EI scores were moderate
(κ = 0.58 and 0.66, respectively), while the disagreement was significant between
NS and PT (P = 0.003). For DESH, the NS-NR agreement was good (κ = 0.79), but the
NS-PT agreement was poor (κ = 0.41), and disagreement was again significant between
NS-PT (P < 0.001). When the combined score was examined, NS-NR agreement was again
moderate (κ = 0.68), but NS-PT agreement further worsened (κ = 0.30) and disagreement
remained significant (P < 0.001).
Discussion
This study suggests that DESH cannot be a reliable diagnostic image criterion for
iNPH because over 50% of definite iNPH patients did not show DESH [[Table 4 ]]. Furthermore, it also indicates that over 30% of definite iNPH patients can be
overlooked even by applying EI >0.3 for iNPH diagnosis [[Table 3 ]]. We also disclosed that there were not negligible interobserver differences for
both calculating EI and evaluating DESH.
Recent studies from outside Japan support our findings on DESH.[[15 ]],[[17 ]],[[18 ]] However, many recent studies from Japan support the diagnostic validity of DESH.[[10 ]],[[19 ]],[[20 ]],[[21 ]] Since the publication of the guidelines in 2004,[[3 ]] Japanese neurosurgeons have operated on almost exclusively the iNPH patients with
DESH. The patients with iNPH triad without DESH had only a small chance to be operated
on or even to receive lumbar tap test for the diagnostic examination. This biased
situation in Japan may explain the discrepancy between the conclusions on the validity
of DESH from outside Japan and from Japan. The diagnostic value of DESH for iNPH has
been derived from comparing the images of only 11 iNPH cases and the images of the
corresponding number of patients with Alzheimer's disease and vascular dementia.[[7 ]] The MRI images of the healthy elderly were not included. Iseki et al. disclosed
that there are many asymptomatic cases with DESH.[[9 ]] DESH is a unique morphological configuration. Therefore, apart from the diagnostic
standpoint, it is necessary to investigate the underlying mechanisms that create this
image finding.
EI >0.3 has been a universally accepted definition of ventriculomegaly and the most
frequently used diagnostic criterion.[[2 ]],[[3 ]],[[4 ]],[[5 ]] However, not all the iNPH patients with EI >0.3 improved by shunt surgery.[[8 ]],[[15 ]],[[22 ]] Agerskov et al. reported only 68.5% improvement rate for the iNPH patients with
EI >0.3.[[15 ]]
The definition of ventriculomegaly of EI >0.3 is derived from the study of pediatric
hydrocephalus.[[6 ]] It was modified for CT or MRI to define the ventriculomegaly of iNPH.[[2 ]],[[3 ]],[[4 ]],[[5 ]] Again, we had no direct comparisons between iNPH patients and healthy controls.
About 20%–30% of the healthy elderly people are known to have EI >0.3.[[12 ]],[[13 ]]
As we stated in the materials and methods part, we had 288 definite iNPH cases of
330 probable iNPH cases received VA shunt. Although not all of them did not fulfill
the criterion of EI >0.3, the improvement rate was 87.3%. Although Agerskov et al.
did not state the type of surgery in their article,[[15 ]] ventriculoperitoneal (VP) shunt was used as surgical treatment. We can expect this
from other European studies.[[23 ]],[[24 ]],[[25 ]] Our improvement rate was significantly better than that reported by Agerskov et
al.[[15 ]] (P < 0.0001, Fisher's exact test) despite that our study included the patients
with EI ≤0.3. Hashimoto et al.[[8 ]] reported an improvement rate of 80% for VP shunt in iNPH fulfilling both EI >0.3
and DESH. Kazui et al. reported 75% improvement for lumboperitoneal (LP) shunt[[22 ]] for iNPH fulfilling both EI >0.3 and DESH. Although it is easy to just list the
improvement rate of the reported studies, it is not fair to compare the improvement
rates since the study designs were different. However, our study was quite different
from others which contained definite iNPH without EI >0.3, and we applied VA shunt.
Liu et al. reported 78% improvement rate for VA shunt (EI >0.3).[[26 ]] Since they did not mention to DESH, they operated on the patients without DESH.
VA shunt may be a better treatment modality than VP or LP shunt for iNPH.
Taking these facts together into consideration, ventriculomegaly defined as EI >0.3
cannot be a mandatory condition to diagnose iNPH. However, since it covered about
70% of the definite iNPH, it can still have some diagnostic value for iNPH.
To our knowledge, this is the first study to investigate the interobserver variability
for both calculating EI and evaluating DESH. We have several image diagnostic criteria
and clinical rating scales in the neurosurgical field. Rating scales commonly used
in neurosurgery for subarachnoid hemorrhage (SAH) are coma scales[[27 ]],[[28 ]] and image criteria.[[29 ]] These scales and criteria are used to predict the outcome of the disease or to
make a treatment plan. We do not make the diagnosis of SAH by means of these scales
and criteria. In addition, a high level of accuracy and consistency among evaluators
is confirmed for these scales and diagnostic criteria.[[30 ]],[[31 ]],[[32 ]]
Quite different from these scales and criteria, EI >0.3 and DESH are diagnostic image
criteria for iNPH. Being directly involved in the diagnostic procedure, these scales
need to be highly accurate and consistent individually and in combination (as per
the current Japanese guidelines) in making the diagnosis of iNPH. However, we observed
the contrary. To calculate EI, it is necessary to select a proper slice of CT or MRI.
Each slice has different sizes and shapes of the cranial circumference, and it is
possible to induce the Delboeuf illusion.[[33 ]] It is also necessary to set boundaries CSF and brain parenchyma. The boundary between
the ventricle and brain parenchyma is not always clear cut. These facts may be the
cause of interobserver variability of EI. Evaluating DESH is subjective, and the possibility
of interobserver variability is inevitably involved. Interobserver variability can
be avoided by introducing computer-assisted automated measurement system.[[34 ]] However, the reliability of EI and DESH to diagnose iNPH is a quite another problem.
Our study indicates that the reliability of DESH and EI may not improve.
Conclusion
In conclusion, the results of this study suggest that the paradigm shift is inevitable
in the diagnosis and treatment of iNPH. The current image diagnostic criteria of the
Japanese guidelines are not reliable in diagnosing iNPH patients, and there is an
urgent need to revise them. Using the current guidelines, the vast majority of treatable
iNPH patients will remain untreated and suffer unnecessarily even though they clearly
have the typical iNPH triad. The results of this study also request the randomized
controlled trial to determine the best surgical modality for iNPH.
