White Matter Microstructural Damage Associated With Gait Abnormalities in Idiopathic Normal Pressure Hydrocephalus

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a common disease in elderly adults. Patients with iNPH are generally characterized by progressive gait impairment, cognitive deficits, and urinary urgency and/or incontinence. A number of radiographic studies have shown that iNPH patients have enlarged ventricles and altered brain morphology; however, few studies have focused on the relationships between altered brain structure and gait dysfunction due to iNPH. Thus, this study aimed to evaluate the abnormalities of white matter (WM) correlated with gait impairment in iNPH patients and to gain a better understanding of its underlying pathology. Methods: Fifteen iNPH patients (five women, 10 men) were enrolled in this study, and each patient's demographic and gait indices were collected. First, we performed a correlation analysis between the demographic and gait indices. Then, all gait indices were grouped according to the number of WM hyperintensities (WMH) among each WM tract (JHU WM tractography atlas), to perform comparative analysis. Results: Considering sex and illness duration as covariates, correlation analysis showed a significantly negative correlation between step length (r = -0.80, p = 0.001), pace (r = -0.84, p = 2.96e-4), and age. After removing the effects of age, sex, and illness duration, correlation analysis showed negative correlation between step length (r = -0.73, p = 0.007), pace (r = -0.74, p = 0.005), and clinical-grade score and positive correlation between 3-m round trip time (r = 0.66, p = 0.021), rising time (r = 0.76, p = 0.004), and clinical-grade score. Based on WMH of each white matter tract, gait indices showed significant differences (p < 0.05/48, corrected by Bonferroni) between fewer WMH patients and more WMH in the middle cerebellar peduncle, left medial lemniscus, left posterior limb of the internal capsule (IC), and right posterior limb of the IC. Conclusions: Our results indicated that iNPH patients exhibited gait-related WM abnormalities located in motor and sensory pathways around the ventricle, which is beneficial to understand the underlying pathology of iNPH.