Neuropathology of Idiopathic Normal Pressure Hydrocephalus: A Study of Three Autopsy Cases and a Literature Review

Abstract

We present neuropathological findings in three autopsy brains from patients diagnosed clinically with idiopathic normal pressure hydrocephalus (iNPH) in Japan; still, specific findings of iNPH remain unclear. Comorbid atherosclerosis and hypertensive microvascular diseases, including arterio- and arteriolosclerosis and ischemic changes in the brain parenchyma, are frequently (65%) observed in autopsy brain tissue from patients with iNPH, which has drawn attention to the clinicopathological similarities and differences between iNPH and Binswanger's disease. Additionally, Aβ protein deposition and phosphorylated tau-positive neurofibrillary tangles and neuropil threads are observed in cerebral cortical biopsy specimens obtained during intracranial pressure monitoring or shunt surgery among a subset of patients with iNPH. These findings are as frequent as those reported in autopsy data of the age-matched general population. Alterations in aquaporin-4 expression in the cerebral cortex have also been reported, suggestive of a possible association with altered volume or composition of the interstitial fluid in the microenvironment, particularly in the vicinity of capillaries, or glymphatic system dysfunction and consequent altered interstitial fluid drainage. Greater understanding of the normal anatomical structures and pathways involved in cerebrospinal fluid circulation, particularly in absorption and drainage, in the craniospinal region is essential for better clarity regarding iNPH neuropathology.