Abstract
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. OBJECTIVES: This open-label study presents two novel neuroimaging biomarkers based on enlarged perivascular spaces (ePVS) of the sub-insular territory: the Hedgehog and Hedgehog-Halo (H-H) sign, designed to predict gait symptom severity and tap response in NPH. METHODS: We retrospectively reviewed 203 patients with possible NPH with baseline magnetic resonance imaging and gait analyses before and after lumbar puncture (LP). The Hedgehog/H-H sign was scored using T2-weighted images. 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 regression. The diagnostic performance of Hedgehog/H-H sign was compared with conventional radiological markers. RESULTS: Patients with H-H showed higher global disability and more severe gait impairment than those without any signs. Following LP, patients with Hedgehog/H-H sign significantly improved in various gait parameters, unlike those with neither sign. Additionally, sub-insular ePVS was significantly associated with post-tap gait improvement after adjusting covariates. Finally, the Hedgehog/H-H sign showed a higher performance than conventional markers in predicting post-tap gait response. CONCLUSIONS: The Hedgehog/H-H sign is a useful neuroimaging biomarker related to the severity and tap response in NPH. This biomarker can be readily applied in clinical practice before undergoing LP, independent of conventional radiological signs. Further research is warranted to determine applicability in predicting post-shunt gait response.