Disproportionately Enlarged Subarachnoid-Space Hydrocephalus on MRI in Pathologically Confirmed Progressive Supranuclear Palsy

Several studies have shown that idiopathic normal-pressure hydrocephalus (iNPH) can mimic other neurodegenerative disorders, particularly progressive supranuclear palsy (PSP). In this study, we investigated iNPH clinical and neuroimaging features in patients with autopsy-confirmed PSP or Lewy body disease (LBD) by assessing the normal pressure hydrocephalus (NPH) triad of symptoms and imaging features of disproportionately enlarged subarachnoid-space hydrocephalus (DESH) and Evans index (EI) on antemortem MRI scans. Among our study participants (N = 190), the mean (SD) age was 76.8 (9.2) years and 134 (70.5%) were male. The patients had been followed at Mayo Clinic and had autopsy diagnosis of either PSP or LBD. Patients were excluded if they had Alzheimer disease or a history of a disorder that could cause hydrocephalus, such as chronic meningitis or neoplasia. The study included 101 patients with PSP and 89 with LBD. The frequency of DESH and a high EI on brain MRI were analyzed in PSP and LBD with logistic regression analyses, adjusting for age, sex, and brain weight. The NPH triad of symptoms was assessed relative to imaging findings. We found that DESH and high EI were similar between PSP and LBD. The mean age at death (PSP: 74.0 [8.2]; LBD: 80.0 [9.2]) and brain weight (PSP: 1,190 [123]; LBD: 1,300 [150]) were greater in LBD compared with PSP (p < 0.001 for each). The frequency of DESH was greater in LBD than PSP (13% vs 3%, p = 0.004), while a high EI was similar in PSP and LBD (36% vs 32%, p = 0.500). The adjusted odds ratios for DESH and high EI were similar between the 2 groups (DESH: adjusted ORs 0.3, 95% CI 0.06-1.25, p = 0.119; high EI: adjusted ORs 1.8, 95% CI 0.86-4.06, p = 0.120). These findings suggest that DESH and high EI, often considered biomarkers for iNPH, may lack specificity and may be found in a subset of patients with PSP or LBD leading to unnecessary neurosurgery for iNPH.