Preoperative Prognostic Value of MRI Findings in 108 Patients with Idiopathic Normal Pressure Hydrocephalus

Discussion

In patients with suspected iNPH, MR imaging is used to aid in the diagnosis and selection of shunt candidates. In this retrospective study of 108 patients with iNPH who had undergone shunt surgery and clinical examination before and at 12 months after surgery, a small callosal angle, occurrence of DESH, and wide temporal horns on the preoperative MR imaging scans were significant predictors of positive shunt outcome.

A small callosal angle has previously been described as useful for separating patients with iNPH from those with Alzheimer disease and healthy controls.⁵ The results in this and a previous study of a smaller callosal angle in patients who responded to shunt surgery further support its prognostic value.³ The significant OR < 1 for the callosal angle can be interpreted as showing that 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 hydrocephalus^13,14 and has previously been reported to be more frequent in patients who improve after shunt surgery compared with nonresponders.¹² This finding was strengthened by the results of the present study. The dilation of the temporal horns in iNPH should not be mistaken for atrophy of the medial temporal lobe as is seen in Alzheimer disease,¹⁵ even though there are reports of diminished hippocampus volume in patients with NPH.¹⁶

In the present study, DESH was a predictor of a positive shunt outcome. The imaging feature was discussed in a publication from the Japanese Study of Idiopathic Normal Pressure Hydrocephalus on Neurological Improvement (SINPHONI), and was described as a morphologic hallmark of iNPH. In the SINPHONI study, a positive outcome was achieved in 80% of 100 patients by using an MR imaging–based diagnostic scheme.⁸ In SINPHONI, 96% of the patients had dilated Sylvian fissures and could be classified as having DESH compared with 67% in the present study. Because SINPHONI used narrow supra-Sylvian subarachnoid spaces as an inclusion criterion in contrast to the present study, the prognostic usefulness of DESH could not be calculated in that study. In CT studies, it has been reported that dilated Sylvian fissures are a sign of poor prognosis, and it has been argued that the dilation is caused by atrophy, which is at odds with the findings in the SINPHONI study.^12,17 The difference could be explained by the fact that the Sylvian fissure could only be evaluated on transverse images at that time, and it is much easier to visualize the dilation 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 a positive outcome. Nevertheless, in light of our study and the SINPHONI study, it seems as if DESH is a very common finding in iNPH and that it may aid in the selection of shunt candidates.

Several correlations between imaging findings were seen, and some patterns emerged. As expected, there were correlations between markers of the ventricular width and Evans index, and the temporal horns correlated with the diameter of the third ventricle. DESH correlated with a smaller callosal angle and focal bulging of the ventricular roofs.

There was a significant difference at baseline in the severity of motor symptoms and handicap levels between patients with and without PVH, dilated Sylvian fissures, and focal bulging of the ventricular roofs. Correlations were seen between the severity of motor symptoms and a smaller callosal angle or wider Sylvian fissures; and a correlation was seen between a larger Evans index and more impaired cognitive function.

White matter hyperintensities on MR imaging are often divided into PVH, adjacent to the ventricles, and DWMH, located in the deep white matter. Both DWMH and PVH have been reported to be associated with risk factors for vascular disease, such as hypertension and smoking. The origin of the hyperintensities is still debated, and DWMH has been reported to represent gliosis, chronic ischemia, or plasma leakage caused by diffuse cerebrovascular endothelial failure.¹⁸

In the present study, patients with severe DWMH had a similar positive outcome rate compared with the whole sample, which is in line with the results of Tullberg et al,¹⁹ who concluded that patients must not be excluded from shunt surgery on the basis of the DWMH findings. In NPH, the PVH around the lateral ventricles is probably caused by transependymal CSF passage into the adjacent white matter, and it has, in some studies, been reported to be a good prognostic sign.^20,21 We could not replicate that finding, but patients with PVH had more severe gait disturbances and handicap levels at baseline compared with patients without PVH. Because more severe PVH often extends far from the lateral ventricles into the deep white matter, it can sometimes be almost impossible to differentiate PVH from DWMH. This difficulty could be one explanation behind both the high frequency of severe DWMH and the good outcome rate in these patients. Some patients may have had both DWMH and advanced PVH. This possibility is further supported by a strong correlation between DWMH and PVH.

The focal bulging of the roof of the lateral ventricles is an MR imaging feature that, to our knowledge, has not been described previously in iNPH. We do not know the frequency of this finding in other types of ventricular enlargement, obstructive hydrocephalus, or healthy elderly. The focal bulging is best visualized on sagittal images in the section including the most cranial portions of the ventricles. The bulging may be caused by CSF pulsations in the lateral ventricles in a weakened spongiotic ependyma and edematous periventricular brain parenchyma,²² located between periventricular veins.

The interrater reliability between 2 observers of measures of flow void, focal bulging, and aqueductal stenosis was not satisfactory and neither was the reliability of the original description of the grading of the Sylvian fissure.^7,8 We showed that the reliability increased from κ = 0.36 to κ = 0.62 by defining the way the sections should be reconstructed and angulated. Dramatic differences in the height of the Sylvian fissure could be obtained depending on which coronal section was used and how it was angulated (Fig 2). All inconsistent grading scores were re-evaluated, and a consensus was reached between the 2 investigators. In accordance with our experience, Ishii et al⁵ illustrated differences in the callosal angle, depending on the angulation of the coronal section. These differences are important when these imaging features are used in clinical practice, and only well-defined grading scales with high reliability should be used.

In 3 of the cases in this study, there was a subtle focal narrowing of the Sylvian aqueduct. This did not obstruct the CSF flow and was not considered the cause of the hydrocephalus in these patients. It is advisable to evaluate the aqueduct thoroughly in patients with suspected iNPH—for example, by including a high-resolution, heavily T2-weighted 3D MR imaging sequence in the protocol to exclude obstructive causes of hydrocephalus.

An interesting finding is the diversity of different morphologic features in this study. All patients had similar symptomatology, but 67% had DESH, while 10% had neither dilated Sylvian fissures nor narrow high-convexity sulci; 25% had no PVH at all, while 13% had PVH extending all the way to the cortex. Previous studies in iNPH have found both heterogeneous patterns of metabolic disturbances in the cortex measured with FDG-PET and various patterns of CBF reduction measured with SPECT.^23,24 These findings raise the question: Are the morphologic differences different stages of the same disease or is iNPH a syndrome of several diseases with different etiologies? There were significant differences in symptom severity between patients with or without PVH, focal bulging, and dilated Sylvian fissures, indicating that these imaging features may be involved in the progression of the disease. However, this question should be addressed in a prospective longitudinal study.

It has recently been discussed that in studies of iNPH, it is important to present descriptive data of the sample, including comorbidity, to facilitate comparisons of different studies.²⁵ It seems to be equally important to also describe the radiologic findings in sufficient detail. Otherwise, we cannot know whether we are investigating and performing surgery in similar patients, and comparisons of studies become difficult.

Despite these findings, callosal angle, DESH, or temporal horns cannot be used to exclude patients from surgery. Of patients with a callosal angle of >90°, 4/7 (57%) improved; 23/36 (64%) patients without DESH improved; and 7/15 (47%) patients with temporal horns of <5 mm improved from shunt surgery. This illustrates one of the greatest problems with studies of prognostic or nonprognostic investigations in iNPH: The number of patients who do not improve after shunting are too few, even in samples as large as in this study, to draw any conclusions regarding in which patients shunting should not be performed.

Some limitations should be addressed. All patients had been diagnosed with iNPH by a specialized team and had undergone shunt surgery, and the MR imaging investigations used in this study had been used in the clinical evaluation of these patients. We had no control group of healthy individuals or patients with Alzheimer disease. Thus, the results in this study must be interpreted in the light of the highly selected sample, and no conclusions about the diagnostic value of the findings can be made. The clinical radiologic diagnosis was made by several different neuroradiologists without a defined protocol, which might have influenced the frequency of some of the retrospectively evaluated imaging findings. For example, all patients had an Evans index of >0.30, and no patient had severe cortical atrophy. However, several of the imaging features investigated in this study were not used clinically at the time of the study at our center. Because of missing sequences in some patients, we could not grade all imaging features in all patients. This gap was most evident for grading of the flow void because we chose to include only investigations from a single scanner to avoid any differences among scanners.²⁶ Because of the limited number of patients in whom flow void was graded, not a single patient with a small flow void was found, which probably affected the absence of significant correlations between flow void and other MR imaging findings. Although data were collected prospectively in a standardized way, the radiologic measurements and analyses of clinical data for this study were performed retrospectively. This feature limited the possibility of making corrections when specific MR imaging sequences or some clinical data were missing.