Introduction
The occurrence of obstructive hydrocephalus (ObH) as sequelae of deep midline brain
tumors (third and lateral ventricles, thalamic, pineal region, brainstem, and fourth
ventricle) can be estimated up to 90% of cases. The Evans' index (EI) proposed in
1942 by William Evans remains the most popular index of ventricular dilatation,[[1]] and EI >0.3 is accepted in many international recommendations as the criterion
of ventriculomegaly.[[2]],[[3]],[[4]],[[5]]
The EI is an easy, fast, and a strong linear method, which does not require special
software. It shows the ratio of the maximum width of the anterior horns of the lateral
ventricles and the maximum internal diameter of the skull at the same level in the
axial magnetic resonance imaging (MRI) and computed tomography (CT) scans. However,
the EI cannot be accurate in cases of asymmetric or uneven expansion of the lateral
ventricles,[[6]] which is one of the limitations of its application in cases of occlusive hydrocephalus
of tumor origin. Hence, recent studies using volumetric analysis have suggested that
EI is not an ideal method in the diagnostics of ventricular dilatation, its values
vary significantly depending on the CT/MRI slice within the same scan.[[7]],[[8]] Despite this, the EI is routinely used in clinical practice [[9]] and has shown that it correlates well with ventricular volume.[[10]]
In modern neurosurgery, volumetric ventricular volume analysis provides the most accurate
information about ventricular volume, but it is labor-intensive, technically complex
(as it requires specialized software) that is not always available in every hospital
(especially in rural and developing countries) and is not suitable for general neurosurgical
practice, as it is not financially affordable. It has been proven that simple, reliable,
and easily reproducible linear measurements, including EI, can be effective alternatives
to volumetric analysis to determine the size of the ventricles.[[10]],[[11]]
We believe that the mamillopontine distance (MPD) – the distance between the lower
surface of the mammillary body and the upper surface of the pons in the sagittal images
– can be a sufficiently reliable alternative to the EI for the diagnosis of ObH.
The purpose of this study was to study the results of CT/MRI images in patients with
tumor-associated occlusive hydrocephalus and to compare the significance of differences
in MPD, angle of corpus callosum (ACC), and EI with the control group and the correlation
of MPD, ACC, and EI with various other indicators of increased intracranial pressure
(periventricular edema [PvE], papilledema, and Karnofsky scale [KS]).
Pathological changes in MRI or CT scan of the brain with intracranial hypertension
can be explained pathophysiologically, which is well understood by the Monro–Kelly
doctrine.[[12]] According to this theory, the volume of intracranial and intraspinal spaces is
constant, and these spaces consist of (1) cerebrospinal fluid (CSF), (2) brain and
spinal cord, that is, -parenchyma, and (3) arteries and veins. If one of the components
changes in volume, CSF, or blood volume, therefore, there will be compensatory decrease
on the other parts. Thereby, increasing ventricular CSF leads to increasing intraventricular
pressure, consequently, PvE develops. Ventricular dilation and PvE of white matter
due to transependymal resorption of CSF are characteristic features of hypertensive
hydrocephalus.[[13]],[[14]],[[15]],[[16]] This is the reason we included an objective quantitative assessment of PvE in our
study as an indicator of increased intracranial pressure in the obstructive form of
hydrocephalus. We also included an assessment of the state of the optic disc (OD)
in ophthalmoscopy, as one of the objective signs of increased intracranial pressure.[[17]],[[18]] We assume that a comprehensive approach to comparing these indicators of morphometric
analysis with objective and clinical data such as the quantitative parameters of PvE
and the condition of OD at ObH can serve to create a classification of the degree
of severity of ObH, depending on the most reliable and sensitive morphometric parameters.
Materials and Methods
All patients underwent a comprehensive examination, including clinical-neurological,
instrumental, and laboratory methods of investigation. The leading clinical sign of
the disease was hypertensive-hydrocephalic syndrome, the severity of focal symptoms
depended on the level of occlusion of the CSF pathways, the etiology and phase of
the clinical course of the disease, and the patient's age. The inclusion criteria
were as follows:
-
Presence of a brain tumor which causes compression of the CSF pathways
-
Clinical presentation of ObH.
The work is based on a retrospective analysis of the results of clinical and laboratory
examination and observation of 43 patients with ObH of different origin-etiology,
who were on treatment at the Republican Scientific Center of Neurosurgery of the Republic
of Uzbekistan during the period 2013–2016. Age of patients ranged from 1.5 months
to 60 years. Most predominantly: By age group amount of patients older and younger
12 years were 27 (62.8%) and 16 (37.2%) respectively. By gender there were no critical
different, 53.5% (n = 23) were female and 46.5% (n = 20) male.
The control group consisted of individuals who underwent MRI and/or CT examination
in the private clinics “Diyor” and “Jacksoft Medical Service,” the inclusion criterion
was absence of brain pathology on MRI and/or CT examinations. Age varied from 5 to
72 years, of which number of younger children 12 years were n = 7 (23.3%) and older
n = 23 (76.7%). Men – 16 (53.3%) and women – 14 (46.7%).
Measurement methods
The MRI study was included an assessment of the following morphometric parameters:
-
MPD – the distance between the lower surface of the mammillary body and the upper
surface of the pons in the sagittal images [[19]],[[20]] [[Figure 1]]a
-
ACC – ideally the angle should be measured in a coronary projection perpendicular
to the line between the anterior and posterior commissure at the level of the posterior
commissure [[21]],[[22]] since the angle of the corpus callosum is very different, depending on the level
of the scan in which the measurement was performed. The normal value is usually between
100° and 120°[[22]] [[Figure 1]]b
-
EI – The ratio of the maximum width of the anterior horns of the lateral ventricles
and the maximum internal diameter of the skull at the same level in the axial MRI
and CT scans [[8]],[[23]] [[Figure 1]]c
-
PvE – The prevalence of PvE was measured from the anterior side of the anterior horn
of the lateral ventricles in millimeter. [[Figure 1]]d.
Figure 1: Types of linear measurement methods on magnetic resonance imaging images: (a) mamillopontine
distance; (b) angle of corpus callosum; (c) Evans' index; (d) periventricular edema
Clinical correlation
A study of the ocular fundus (OF) for the presence of papilledema was also performed,
and its degree was determined as a clinical indicator of increased intracranial pressure
to make subsequent correlation with the above-mentioned morphometric parameters. During
OF examination, the condition of the optic nerve disc was assessed as follows, starting
from the absence of papilledema to a severe stage; we have used popular papilledema
grading system (Frisen Scale):
-
Stage 0: Normal OD – absence of papilledema, retinal angiopathy can be observed in
ophthalmoscopy
-
Stage 1: Very early papilledema
-
Stage 2: Early papilledema
-
Stage 3: Moderate papilledema
-
Stage 4: Marked papilledema
-
Stage 5: Severe papilledema.
Furthermore, we carried out an integrative assessment of the patient's state according
to the KS, which serves to assess the patient's quality of life and take into account
the dynamics during treatment, is also widely used by neurosurgeons in clinical practice.
Statistical analysis
The relationship between the indicators was analyzed using the appropriate coefficient
or criterion: the Pearson's correlation and the Spearman's correlation. The analysis
was made using Student's t-criteria for two groups. All results were corresponded
statistically strong P value (≤0.05 or ≤ 0.01). The statistical calculations were
performed using the IBM SPSS Statistics 22.0.0.0, (IBM, Armonk, NY, USA), based on
the Mac OS operating system.
Results and Discussion
We considered it is rational to compare the morphometric parameters of MRI studies
in patients with occlusive hydrocephalus with a control group, and we divided the
group with pathology into two: 1st group: children under 12-year-old, and 2nd group:
12–60 years. Age of patients ranged from 1.5 months to 60 years. Most predominantly:
adults were 27 (62.8%) and children under 12 years – 16 (37.2%). Women were 23 (53.5%)
and men were 20 (46.5%).
The results of the study of all four morphometric parameters, the status of the fundus
and the KS showed that the differences in the mean values of all the indicators between
the group with pathology and control are statistically significant. All examined in
the control group had no PvE, pathology of the optic nerve disc, and there were also
100 pts on the KS [[Table 1]]. The mean value of the EI was equal to 0.299 ± 0.005, at 0.242 ± 0.003 in the control
group. In 19 patients, EI et al.[[20]] and differ from the results published by El Gammal et al. (11.5 mm), probably because,
that our reference point was the center of the mammillary body and not the top of
their anterior part.[[24]]
Table 1: The average values of IE, MPD, ACC, PvE, OD and KS in all patients and control group
(Mean-standard deviation). The maximum and minimum values are in brackets
When analyzing the indexes of ACC, a narrowing of the angle was revealed in many patients
– 97.7 ± −3.3, with an average value in the control group – 125.3 ± 1.2. When dividing
patients into two groups due to anthropometric age differences, the following differences
were found in (1) children under 12 years (37.2%) and (2) adults and children over
12 years of age: MPD and ACC rates were significantly lower in children in comparison
with the 2nd group. Furthermore, children have a relatively large PvE – 8.3 mm ± 1.1
mm than in adults (6.0 ± 0.9). Furthermore, in children, a significantly poor condition
of OD and KS was observed in the 2nd group.
The greatest statistically significant differences in morphometric parameters were
in the MPD (P < 0.001) between patients with pathology and the control group, and
it was also the highest in children under 12 years of age (P < 0.001), and the remaining
patients were older than 12 years (P < 0.001) [[Table 2]].
Table 2: Results of the statistical significance of differences in mean values between groups
with pathologies and control (t-test of Student)
We also investigated the correlation between the morphometric parameters and the data
of air defense, OD, and KS. For this, we used the two-sided Spearman correlation analysis
method, which is most often used in medicine. The analysis data showed that the EI
has the strongest inverse correlation with MPD (r = −0.725, P = 0.01) [[Table 3]], followed by UMR (r = −0.690; P = 0.01) and PvE (r = 0.362; P = 0.05). We did not
reveal a statistically significant correlation of EI with KS and OD.
Table 3: Results of the correlation analysis of Spearman's morphometric data (2-sided)
In the study of the correlation of MPD with the rest of the indices, a strong correlation
was observed with the indices of ACC (r = 0.698, P = 0.01) and PvE (r = −0.588, P
= 0.01), except for the strong inverse correlation with the EI described above. Furthermore,
the MPD correlates with the KS (r = 0.356; P = 0.05). When analyzing ACC data, the
greatest correlation with MPD is determined (r = 0.698, P = 0.01) and EI (r = −0.690;
P = 0.01). The greatest correlation of PvE is observed with MPD (r = −0.588, P = 0.01)
and ACC (r = −0.608; P = 0.01).
In medical practice, the sensitivity and specificity of the diagnostic method is important,
as far as it determines truly positive and negative results. We determined and compared
the sensitivity and specificity of the most popular and often used in practice method
of morphometric analysis – EI and MPD. The specificity of both linear methods in our
sample is 100% since the absence of pathology is reliably determined. The sensitivity
of the EI is equal to 55.8% since the criterion proposed by many authors of ventriculomegaly
– EI > 0.30, then the data of 24 patients (0.327 ± 0.005) corresponded to the criterion,
and in the remaining 19 patients, the mean EI was 0.265 + 0.006. When studying the
parameters of MPD in patients, we found 100% sensitivity of the method, as in all
patients according to our criteria the MPD values were more than 9 mm. In [[Figure 2]], a visual interpretation of the MPD and EI indicators of all patients and control
group is presented, with each point corresponding to a single patient. It is clearly
seen that EI often gives a significant number of false-negative results.
Figure 2: The values of the Evans' index and the mamillopontine distance of each examined person
in the control group and in the group with occlusive hydrocephalus. The dotted line
shows the mamillopontine distance (=9.0 mm) and the Evans index (=0.30)
As a result of the analysis of all the data of the study, we found that MPD is a worthy
and strong alternative to EI in the diagnosis of ventricular hydrocephalus of occlusive
genesis, in favor of this conclusion say:
-
The highest statistically significant differences between the control group and the
patients (P < 0.001)
-
The strongest inverse correlation was between EI and MPD (r = −0.725, P = 0.01), which
indicates the tightness of the relationship between these indicators
-
MPD accurately separates 43 patients with obstructive hydrocephalus from 30 ones of
control group, which proves high sensitivity and specificity of this method and 30
of them had MPD < 9 mm from all 30 examined in the control group
-
Ease of use, MPD is measured in the sagittal scan MRI/CT and does not require any
arithmetic calculations and special equipment.
We believe that these MPD data can serve to assess the degree of hydrocephalus, and
we propose our classification of the degrees of hydrocephalus based on the MPD, and
we divide it into three degrees:
-
I – degree: MPD from 5.1 to 8.9 mm
-
II – degree: MPD from 2.1 to 5.0 mm
-
III – degree: MPD from 0 to 2.0 mm.
In the study of patients, we divided them into three groups, depending on the MPD,
and studied their relationship to other indicators. A direct proportional relationship
between the MPD and ACC and KS indices was found, as well as an inverse proportional
relationship with the results of EI, PvE, and OD [[Figure 2]]. We also found that MPD is the most sensitive method that shows the patient's clinical
condition, correlating with air defense, OD, and KS data.
I – degree was revealed in 10 (23.2%) patients, 8 (80%) of them are older than 12
years old. It differed significantly in the high index of the KS – 74 ± 2.2. MPD was
7 ± 3 and EI was 0.28 ± 0.01.
II – degree was detected in 22 (51.2%) patients, of which 16 (72.72%) patients were
older than 12 years. The MPD was 3.1 ± 0.2 and the PvE was 7.6 ± 0.9.
III – degrees were revealed in 11 (25.6%) patients, 8 (72.7%) of them were children
under 12 years old. MPD was 0.9 ± 0.1, PvE was 9.3 ± 1.5; and OF was 2.5 ± 0.4. The
lowest indications of KS were in the 1st group – 65.5 ± 1.6.
From the above-mentioned results of the study, it follows that the division of the
degree of hydrocephalus, depending on the MPD, makes it possible to clinically assess
the overall condition of the patient with a single morphometric measurement that correlates
well with other objective indicators of intracranial hypertension (OD and PvE), ventriculomegaly
(EI and ACC), and patient status.
This is understandable with the advent of a new technology for image processing and
the introduction of more complex calculations, that older methods of linear measurements
can be eliminated in favor of three-dimensional volumes. Nevertheless, it should be
taken into account that in the current economic climate of healthcare and with an
increasing emphasis on cost-saving procedures, MPD and EI are simple measurements
that reliably determine the increase in ventricles and do not require the expensive,
laborious and technically complex software required for volumetric analysis. In addition,
these linear measurements may be the only way available in some medical institutions,
such as rural areas and developing countries that do not have access to the latest
imaging technology.
Conclusions
MPD is a strong and reliable alternative to the EI in all age groups and may be useful
in rural areas and developing countries that do not have access to the latest imaging
technology. MPD has high specificity and sensitivity in the diagnosis of occlusive
hydrocephalus. The EI has the strongest inverse correlation with the MPD (r = −0.725,
P = 0.01). The greatest statistically significant differences in morphometric indicators
among patients and the control group were in MPD (P < 0.001). The use of the proposed
classification of the degree of severity of hydrocephalus, depending on the MPD, makes
it possible to clinically assess the patient's overall condition with a single morphometric
measurement that correlates well with other objective indicators of intracranial hypertension
(OD and PvE), ventriculomegaly (EI and ACC), and patient's status.
