Abstract

Background: Idiopathic normal pressure hydrocephalus (iNPH) is suspected by clinical symptoms and enlarged ventricles on imaging (Evans index [EI] >3.0). However, it remains unclear how to deal with patients who present with clinical symptoms but have no ventricular enlargement.

Case Description: A 77-year-old man, whose symptoms were diagnosed as age-related (because of no ventriculomegaly and negative tap test) at a hospital visited 3 months prior, came to our clinic presenting with gait disturbance, cognitive decline, and urinary incontinence (iNPH triad). His responses to questions were very slow, and his Mini–Mental State Examination (MMSE) score was 11/30. The patient was unable to stand up from his wheelchair without assistance and had difficulty in taking the first step. On examination, his EI was 0.26 and tap test was negative. However, iNPH was strongly suspected because imaging showed unclear cerebral sulci at the parietal level, a narrow callosal angle, and a disproportionately enlarged subarachnoid space. Lumbar drainage was performed for 2 days, which improved his gait ability and increased his MMSE score to 17/30. We then performed shunt surgery. At 2 months after surgery, he was able to walk freely and independently around the hospital, his MMSE score improved to 25/30, and he was discharged home.

Conclusion: Ventricle size is only an indicator for iNPH, and an EI cut-off of 0.3 is not an absolute indicator. Thus, even in the absence of ventricular enlargement, a thorough assessment is crucial in suspected iNPH cases.

Keywords: Callosal angle, Disproportionately enlarged subarachnoid space, Evans index, Hydrocephalus, Spinal drainage

INTRODUCTION

The diagnostic criteria for hydrocephalus are generally based on ventricular size, with an Evans index (EI) >3.0.[ 3 , 10 , 15 ] The Japanese guidelines for idiopathic normal pressure hydrocephalus (iNPH) also describe enlarged ventricles as the most important findings in hydrocephalus.[ 13 ] However, enlarged ventricles do not always indicate hydrocephalus because hydrocephalus is a functional disorder, and asymptomatic ventricular enlargement should just be considered ventriculomegaly. iNPH is suspected in patients with enlarged ventricles presenting with gait disturbance, cognitive decline, and urinary incontinence (iNPH triad).[ 3 , 10 , 13 ] The potential for iNPH further increases when periventricular lucency (PVL), narrowing of the high convexity/midline subarachnoid spaces, an enlarged Sylvian fissure, a callosal angle <90°, or a disproportionately enlarged subarachnoid space is identified on imaging.[ 6 , 8 , 13 , 16 ] For patients with these clinical symptoms and imaging features, the tap test is applied as a functional assessment to clarify whether surgery is indicated, which is evaluated using a timed up and go (TUG) test, a 10-m walking test, and a Mini–Mental State Examination (MMSE).[ 2 , 13 , 17 , 19 ] Conversely, if a patient presents with the iNPH triad in the absence of enlarged ventricles, can iNPH be strongly suspected? Presumably, Parkinson’s disease and other degenerative diseases would be preferentially suspected in such a patient. Herein, we report a case who markedly recovered from the iNPH triad following a shunt procedure but who had no evidence of ventricular enlargement and a negative tap test. Note that the term “disproportionately enlarged subarachnoid-space hydrocephalus (DESH)” is commonly used in cases of hydrocephalus. In this report, we used the term “disproportionately enlarged subarachnoid space” as an imaging feature because the patient did not show an enlarged ventricle.

CASE DESCRIPTION

A 77-year-old man visited a local certain hospital 3-month prior, complaining of worsening forgetfulness and a narrower stride than ever. He could walk steadily and his MMSE score was 19/30. Head magnetic resonance imaging (MRI) showed opening of the subdural space without ventriculomegaly and moderate leukoaraiosis in the deep white matter [ Figure 1 ] (coronal imaging was not performed). A tap test was performed but was negative, and his symptoms were considered age-related. However, 3-month later, his wife took him to our hospital because he could not walk without help, demonstrated strange behaviors, and had urinary incontinence. His responses to questions were very slow, and his MMSE score had decreased to 11/30. He could not stand up from his wheelchair without assistance, and he had difficulty taking the first step. Although he walked with assistance, his stride was extremely narrow, and he wobbled and almost fell. Head computed tomography (CT) showed no evidence of enlarged ventricles, with an EI of 0.26. However, imaging showed obscure parietal sulci, a callosal angle of 78.3°, enlarged bilateral Sylvian fissures, and a disproportionately enlarged subarachnoid space, which strongly indicated iNPH [ Figure 2a ]. Perfusion CT displayed decreased cerebral blood volume (CBV) and cerebral blood flow (CBF) in the deep white matter around the lateral ventricles and at the parietal cortex, and mean transit time (MTT) was delayed except in the high frontal lobes [ Figure 2b ]. There was no reflux of contrast media to the third and lateral ventricles on CT cisternography [ Figures 3a and 3b ], and after 24 h, the contrast media had diffused into the basal cisterns, Sylvian fissures, and cerebral sulci, with minimal diffusion into the disproportionately enlarged subarachnoid space [ Figure 3b ]. His cerebrospinal fluid (CSF) pressure measured by lumbar tap was 9.0 cmH₂O, and 40 mL of CSF was drained by spontaneous dripping. Examination of the CSF revealed the number of leukocyte 5 (mononuclear 4 and polymorphonuclear 1), protein 40.6 mg/dL, glucose 61mg/dL, and phosphorylated tau protein <25 pg/mL. Tap test evaluated 3 and 24 h after the lumbar puncture was both negative, showing no improvement in gait ability in either the TUG test or the 10-m walking test and no significant increase in MMSE score [ Table 1 ]. TUG was defined as the time taken to stand up from sitting in a wheelchair, walk back and forth for 3 m, and finish sitting in the wheelchair again. Ten-meter (10-m) walk was defined as the time taken to walk back and forth for 5 m. Based on the report that prolonged external lumbar drainage in excess of 300 mL is associated with high sensitivity and high positive predictive value for shunt surgery in iNPH patients,[ 11 ] evacuation of 300 mL CSF/day for 2 days by continuous lumbar drainage was performed. As a result, his walking ability dramatically improved and MMSE score increased to 17/30 [ Table 1 ]. Under the conviction that shunt surgery could improve his symptoms, ventriculoperitoneal (VP) shunt was performed on the patient (Codman Hakim programmable valve, Integra Japan, Tokyo). A shunt valve pressure control was initiated at 110 mmH₂O and a final shunt pressure was set at 70 mmH₂O, and his symptoms markedly improved [ Table 1 ]. Follow-up CT showed shrinkage of the ventricle size (EI of 0.23), fading of the PVL, narrowing of the Sylvian fissure, clarification of the parietal sulci, and widening of the callosal angle (91.5°) [ Figure 4a ]. A definitive increase in CBV and CBF, and shortening of the MTT, was also identified on postoperative perfusion CT, especially in the deep white matter [ Figure 4b ]. At 2 months after the VP shunt, the patient had an MMSE score of 25/30 [ Table 1 ]. The patient also showed a wider stride, and a faster and more stable gait, after shunt surgery [ Figure 5 ]. Furthermore, the presentation of urinary incontinence became very infrequent, and the patient was discharged home.

Figure 1:

Magnetic resonance imaging (MRI) before surgery. (a) T-2 weighted (T2W) MRI shows no enlargement of the anterior horn of the lateral ventricles but opening of the Sylvian fissure and a mild opening of the frontotemporal subdural space. A wedge-shaped disproportionately enlarged subarachnoid space is observed in the right parietal region. (b) High signal areas around bilateral lateral ventricles are identified on fluid-attenuated inversion recovery MRI.

Figure 2:

Computed tomography (CT) and perfusion CT before surgery. (a) Simple CT scan demonstrates an Evans index of 0.26 and a callosal angle of 78.3°. The Sylvian fissures are wide with clear evidence of periventricular lucency around the lateral ventricles. (b) Cerebral blood volume and (CBV) cerebral blood flow (CBF) are widely reduced, especially in the deep white matter. The mean transit time (MTT) also tends to be delayed, but the bilateral high frontal regions show normal range in blood flow times.

Figure 3:

Computed tomography (CT) cisternography. (a) CT at 6 h after administration of contrast medium into the lumbar subarachnoid space demonstrates flow of the contrast media into the cerebral aqueduct of Sylvius but no reflux into the third ventricle. (b) The contrast medium spreads into the basal cistern and subarachnoid spaces at 24 h, but not into the disproportionately enlarged subarachnoid space in the right parietal region.

Table 1:

Pre-and post-operative assessments of gait and cognitive functions

Figure 4:

Computed tomography (CT) and perfusion CT after surgery. (a) The tip of the shunt tube was placed into the left anterior horn of the lateral ventricle. The Evans index decreases to 0.23, the periventricular lucency is diminished, the Sylvian fissures become narrower, and the callosal angle increases to 91.5°. However, there is minimal improvement in the disproportionately enlarged subarachnoid space in the right parietal region. (b) Cerebral blood volume (CBV) increases diffusely in the bilateral cerebral cortex. Cerebral blood flow (CBF) also increases sporadically, particularly around the lateral ventricles. The delayed mean transit time (MTT) is improved in bilateral deep white matter.

Figure 5:

Walking before and after surgery. Before surgery, the patient was unable to stand in the wheelchair by himself and was unable to walk without assistance because it was hard for him to move his legs forward. At 2 months after surgery, he was able to stand from his chair without assistance and could walk in a stable posture with wider strides and swinging of his upper limbs.

DISCUSSION

iNPH is generally diagnosed by symptoms of ventricular enlargement without increased intracranial pressure.[ 13 ] Hamidu et al. stated that an EI cut-off value of 0.3 was a suitable indicator of ventricular enlargement, with a mean EI of 0.28 for patients ≥60 years old.[ 4 ] By contrast, Brix et al. reported that a mean EI cut-off of 0.37 should be used in men 75−79 years old.[ 1 ] It is important to note that an EI cut-off of 0.3 is an indicator and not an absolute value. Indeed, the Japanese guidelines for iNPH recommend closer examinations in patients with suspected iNPH and an EI <3.0.[ 13 ] However, only one case of iNPH without ventricular enlargement has been reported, although the patient had an EI of 0.29 and a positive tap test, which simplified the iNPH diagnosis.[ 18 ] In the present case (77-year-old man), the EI of 0.26 was too small to suspect hydrocephalus, and the negative tap test made a diagnosis of iNPH difficult. An enlarged Sylvian fissure and opening of the frontal-to-temporal subdural space in an axial view may suggest brain atrophy [ Figure 1 ], but hydrocephalus should never be ruled out without a coronal section on CT or MRI. Our strong suspicion of iNPH was based on the tightness of the subarachnoid space at the high convexity and the narrowing of the callosal angle, which are only observed in the coronal view and are considered key findings in iNPH diagnosis.[ 13 , 15 ] In our case, narrowing of the callosal angle was not associated with enlarged ventricles. The authors considered that the widening of the bilateral Sylvian fissures causes vertical elevation of the temporal lobes and pushes the lateral ventricles superiorly and medially, which results in narrowing of the callosal angle. After surgery, the callosal angle increased as the Sylvian fissure narrowed [ Figure 2a and 4a ].

It is difficult to distinguish PVL in hydrocephalus from age-related periventricular leukoaraiosis on CT or MRI. Furthermore, significant periventricular leukoaraiosis is frequently associated with gait disturbance, mental decline, and urinary incontinence reminiscent of the iNPH triad.[ 5 ] However, obvious age-related leukoaraiosis in the absence of ventricular enlargement associated with cerebral atrophy is also inconsistent.[ 5 ]

A disproportionately enlarged subarachnoid space is strongly indicative of iNPH. Recently, when DESH is identified in addition to iNPH triad, the patient is considered eligible for shunt surgery even with a negative tap test,[ 12 , 13 ] although it is reported that a positive response to the tap test is expected if a patient has at least one of the iNPH triad and DESH on imaging.[ 9 ] Probably, the theory might be correct. Our case with iNPH triad demonstrated disproportionately enlarged subarachnoid space on CT and dramatically recovered from the iNPH triad after shunt surgery although EI was <3.0 and the tap test was negative. However, disproportionately enlarged subarachnoid space never normalized after shunt surgery even when clinical symptoms are improved, which seems to be inconsistent with DESH being a key finding for surgical indication. Otherwise, narrowing of the callosal angle and enlargement of the Sylvian fissures were definitely improved. On CT cisternography, in contrast to the finding of definite diffusion of contrast medium into the Sylvian fissures, there was minimal influx of contrast medium into the disproportionately enlarged subarachnoid space, which is isolated from the normal CSF circulation and is different from a simply enlarged subarachnoid space. This may contribute to the observation that DESH hardly disappears after shunting. According to the previous report, CT cisternography could demonstrate diverse pattern in iNPH patients, and stasis of the contrast medium at the lateral ventricles is one of the important findings.[ 7 ] However, no reflux of contrast medium into the lateral ventricles occurred in our case, and CSF backflow into the ventricles may not occur in a case with poor nonenlarged ventricle iNPH. Nonreflux phenomenon would usually occur in the obstructive hydrocephalus, but it was not radiologically identified whether check-valve structure existed or not in the aqueduct of Sylvius in our case.

Compared to healthy individuals, CBF in iNPH patients is known to be reduced. However, the CBF pattern in iNPH is not well defined, and the pattern varies according to the methods being assessed.[ 20 ] Evaluation of CBF on single-photon emission CT displays increased CBF at the high parietal lesion, which is called convexity apparent hyperperfusion (CAPPAH),[ 14 ] and CAPPAH in the shunt-effective group was lower than that in the shunt-noneffective group.[ 13 ] However, CAPPAH is not real parietal hyperperfusion and is considered to reflect the increased gray matter density of the high-convexity area.[ 14 ] In our case, CBV and CBF, which were reduced in all anatomical areas in the brain before surgery, definitely increased after surgery in periventricular white matter and occipital and parietal areas. Although it is common that CBF increases after shunt surgery in iNPH patients, this increased effect is not always associated with clinical improvement. It is reported that the shunt-effective group showed recovery of CBF in all anatomical regions after surgery on perfusion CT; however, CBF increase in the caudate head, the lentiform nucleus, and the periventricular thalamus was observed in shunt-nonresponders.[ 20 ] Since the pattern of abnormal CSF dynamics in iNPH patients varies from person to person, it is assumed that the areas of ischemic changes and metabolic abnormalities might also vary from patient to patient. Therefore, a more detailed region-specific CBF evaluation is needed.

Our report has limitations since the findings in our single case may not be common to all cases. Nevertheless, the authors speculate that the number of patients with nonenlarged ventricle iNPH may be much higher than that reported. Such cases could be included in the category of “Possible iNPH” in the Japanese iNPH guideline because an EI > 3.0 is not included in the mandatory criteria. There might be many patients in whom hydrocephalus is ruled out because of the absence of ventricular enlargement or who are excluded from shunt surgery because of a negative tap test. Thus, it is important to make every effort to prove that surgery is indicated in iNPH-suspected patients, especially in those with nonenlarged ventricle iNPH. With further case reports, we believe that nonenlarged ventricle iNPH may become an established category of iNPH.

CONCLUSION

Preoperative evaluations for efficacy of shunt surgery are necessary for a patient with no ventriculomegaly (EI>3.0) when iNPH is suspected based on clinical symptoms. Even though the tap test is negative in the patient, a thorough pursuit should be achieved, including lumbar drainage, cerebral perfusion evaluation, and cisternography.

Ethical approval:

Institutional review board approval is not required.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.

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