Diagnosis of idiopathic normal pressure hydrocephalus is supported by MRI-based scheme: a prospective cohort study

Abstract

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a treatable neurological syndrome in the elderly. Although the magnetic resonance imaging (MRI) findings of tight high-convexity and medial subarachnoid spaces and the ventriculo-peritoneal (VP) shunt with programmable valve are reportedly useful for diagnosis and treatment, respectively, their clinical significance remains to be validated. We conducted a multicenter prospective study (Study of Idiopathic Normal Pressure Hydrocephalus on Neurological Improvement: SINPHONI) to evaluate the utility of the MRI-based diagnosis for determining the 1-year outcome after VP shunt with the Codman-Hakim programmable valve.

Methods: Twenty-six centers in Japan were involved in this study. Patients aged between 60 and 85 years with one or more of symptoms (gait, cognitive, and urinary problems) and MRI evidence of ventriculomegaly and tight high-convexity and medial subarachnoid spaces received VP shunt using the height/weight-based valve pressure-setting scheme. The primary endpoint was a favorable outcome (improvement of one level or more on the modified Rankin Scale: mRS) at one year after surgery, and the secondary endpoints included improvement of one point or more on the total score of the iNPH grading scale. Shunt responder was defined by more than one level on mRS at any evaluation point in one year.

Results: The full analysis set included 100 patients. A favorable outcome was achieved in 69.0% and 80.0% were shunt responders. When measured with the iNPH grading scale, the one-year improvement rate was 77.0%, and response to the surgery at any evaluation point was detected in 89.0%. Serious adverse events were recorded in 15 patients, three of which were events related to surgery or VP shunt. Subdural effusion and orthostatic headache were reported as non-serious shunt-related adverse events, which were well controlled with readjustment of pressure.

Conclusions: The MRI-based diagnostic scheme is highly useful. Tight high-convexity and medial subarachnoid spaces, and enlarged Sylvian fissures with ventriculomegaly, defined as disproportionately enlarged subarachnoid-space hydrocephalus (DESH), are worthwhile for the diagnosis of iNPH. This study is registered with ClinicalTrials.gov, number NCT00221091.

Figure 1

Typical iNPH findings on MRI. Illustrative coronal sections of coronal T1-weighted images selected from an included patient showing enlarged ventricles (*), tight high-convexity and medial surface subarachnoid spaces (oval ring), and expanded Sylvian fissures (arrow).

Figure 2

Trial profile showing flow chart of patient numbers from initial screening to final analysis.

Figure 3

Two cases excluded by the central MRI review. MRIs of two illustrative cases excluded by the central MRI review board because of deviation from the pre-set MRI criteria. Note the enlarged subarachnoid spaces (arrow) proportionate to ventriculomegaly indicating brain atrophy (A), and the open high-convexity and medial subarachnoid spaces (arrow) despite disproportionately expanded ventricles (*) suggesting chronic occlusive hydrocephalus (B).

Figure 4

Bar chart showing the distribution of Evans' index in the patient population. The mean Evans' index was 35.6 ± 4.0% ranging 0.30 to 0.48, which indicated that the dilation of lateral ventricle in this group was mild to moderate, and marked dilation was rare.

Figure 5

Dilatation of Sylvian fissures. A) Illustrative MRI sections showing the variable size of Sylvian fissure. A: narrowing, B: normal, C: mildly-moderately enlarged, D: highly enlarged, A (C): Arrow indicating focal sulcal dilatation. B) Bar chart showing patient distribution of the four dilation categories described above. The Sylvian fissures were dilated in 96% of patients.

Figure 6

Flow chart showing the outcome for all patients analysed. There were 80 shunt responders with 69 having a favourable outcome. There were 20 non-responders, 12 of which had some adverse event. Serious adverse events are listed. * Functional improvement (≥ 1 improvement on mRS) at some point during one year. † Functional improvement (≥ 1 improvement on mRS) at one year. mRS: modified Rankin Scale. SAE: Serious adverse event. AE: Adverse event.

Figure 7

Bar charts of patients' functional status based on the modified Rankin scale (mRS). A: Distribution at baseline and one year. B: Change between baseline and one year.