Objective: We aimed to present two novel neuroimaging biomarkers based on enlarged perivascular spaces (ePVS) of the sub-insular territory: the Hedgehog and Hedgehog-Halo (H-H) sign to predict gait symptom severity and tap response in NPH.

Background: Reduced cerebrospinal fluid (CSF) clearance may play a vital role in the pathogenesis of normal pressure hydrocephalus (NPH), but the radiologic marker is yet to be elucidated.

Method: We retrospectively reviewed 203 patients with possible NPH with baseline magnetic resonance imaging and detailed gait analyses before and after lumbar puncture. The Hedgehog/H-H sign was scored using T2-weighted images. Gait was assessed using time-up-and-go test and objective gait analysis. The clinical severity at baseline and post-tap gait improvement was compared in patients with and without Hedgehog/H-H sign. The association between Hedgehog/H-H sign and post-tap gait outcomes was assessed using multivariate linear regression analysis.

Results: Patients with H-H showed higher modified Rankin Score (mRS) and more severe gait impairment than those without any signs. Following therapeutic lumbar puncture, patients with Hedgehog/H-H sign significantly improved in various gait parameters on objective gait analysis, unlike those without Hedgehog/H-H sign. Finally, the degree of alleged glymphatic dysfunction (H-H > Hedgehog > none) was significantly associated with post-tap gait improvement after adjusting for age, sex, disease duration, total basal ganglia-ePVS burden, and pre-tap mRS.

Conclusion: The Hedgehog/H-H sign is a useful neuroimaging biomarker related to the severity and tap response in NPH potentially implying glymphatic dysfunction. This biomarker can be readily applied in clinical practice, independent of conventional radiological signs.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/sub-insular-enlarged-perivascular-spaces-are-associated-with-gait-symptom-severity-and-tap-response-in-normal-pressure-hydrocephalus/