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

Abstract

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.

White matter hyperintensity mediating gait disorders in iNPH patients via neurofilament light chain

“…Hattori et al (2012) also obtained the same result in the conduction bundle specificity analysis of iNPH patients. Tang et al (2021) showed that iNPH patients with more WMH had poorer gait performance, and fiber bundles were most significantly correlated with gait index. In patients with iNPH, the white matter FA value in the prefrontal area is decreased.…”

Research Evidence of the Role of the Glymphatic System and Its Potential Pharmacological Modulation in Neurodegenerative Diseases

“…The exact aetiology of iNPH has yet to be fully understood [ 104 ]. It has recently been suggested that the glymphatic system may be implicated in iNPH pathogenesis [ 105 ], with studies showing a significant decrease in glymphatic clearance efficiency for subjects with iNPH relative to healthy controls [ 105 , 106 ].…”

Concussions and Idiopathic Normal Pressure Hydrocephalus: Is there a correlation?

“…BBB dysfunction has also been linked to impaired neurovascular functioning in iNPH patients, similar to concussion patients [9]. White matter structure abnormalities are observed in both iNPH and CTE, with studies demonstrating altered tissue diffusivities post-concussions [9,10]. Finally, ventricular dilation is common to both CTE and iNPH [6,10].…”

“…White matter structure abnormalities are observed in both iNPH and CTE, with studies demonstrating altered tissue diffusivities post-concussions [9,10]. Finally, ventricular dilation is common to both CTE and iNPH [6,10].…”