Slow unsteady gait in a population-based cohort: links to ventriculomegaly and INPH-related imaging markers

Although clinical evaluation, radiological findings, and supplementary tests are routinely used to diagnose idiopathic normal pressure hydrocephalus (INPH), the large variability in surgical outcomes raises the question of whether diagnostic radiological markers truly reflect the typical clinical gait impairment. Gait disorder (GD) and ventriculomegaly (VM) are both common in older adults and may coincide by chance, potentially contributing to this inconsistency in results. This study aimed to determine the prevalence of typical INPH-related higher-level gait disorder (HLGD), diagnosed independently of imaging, and assess its association with VM and other MRI features.

In this case-control study, 6467 individuals age 65-84 years were screened for GD per questionnaire. Physicians with experience of neurological GD identified cases with HLGD and matched controls without GD through clinical evaluation of 1047 of these individuals. Subsequently, brain MRI (n = 909) or CT (n = 98) was performed. After exclusions, 81 with HLGD and 192 controls remained. Radiological hydrocephalus features were compared between the groups.

The prevalence of HLGD in the general older population was 5.8%. For HLGD combined with Evans Index (EI)>0.3, it was 3.7%, and 1.7% had HLGD with Disproportionately Enlarged Subarachnoid space Hydrocephalus (DESH). The estimated prevalence of asymptomatic VM, i.e. EI > 0.3 without GD, was 24%, and 4.1% had asymptomatic VM with DESH. Individuals with HLGD were older and performed worse on cognitive tests. Radiology revealed higher ventricular volumes and EI, and a more acute callosal angle in HLGD versus controls. DESH was also more frequent in HLGD (29% vs 7%, p < 0.001). Despite group-level differences, individual overlap was substantial. MRI markers showed poor to moderate ability to discriminate HLGD (AUC 0.614-0.765) from normal gait.

In this population-based case-control study, both HLGD and EI > 0.3 were common. EI > 0.3 occurred more frequently with HLGD, but it was also common in asymptomatic individuals, indicating that ventriculomegaly is not specific to HLGD. Most MRI biomarkers showed limited ability to distinguish HLGD from normal gait, although lateral ventricular volume divided by total intracranial volume (relative ventricular volume) was the most informative. The frequent occurrence of EI > 0.3 and DESH in asymptomatic individuals highlights the need for longitudinal studies to clarify prognosis in these individuals.