Aging and Disease

Interthalamic Adhesion as a Potential Structural Regulator of Cerebrospinal Fluid Dynamics in the Third Ventricle

Cohort study in peopleMechanisms
Follow

Abstract

The interthalamic adhesion (ITA), located at the center of the brain, may influence ventricular morphology and cerebrospinal fluid (CSF) dynamics. Its role in Hakim's disease, renamed idiopathic normal pressure hydrocephalus (iNPH), remains unclear. To investigate the relationship between ITA morphology and CSF dynamics in the third ventricle using three-dimensional (3D) and four-dimensional (4D) flow MRI in healthy individuals and patients with Hakim's disease. The study participants were 83 patients with Hakim's disease (mean age, 77.0 ± 6.2 years) and 226 healthy volunteers (mean age, 58.2 ± 18.2 years) were analyzed. 3D T1-weighted MRI was used to evaluate the morphology of the third ventricle and ITA, and 4D flow MRI (velocity encoding = 5 cm/sec) was used to assess CSF streamlines and vorticity throughout the cardiac cycle. ITA width increased and ITA area decreased with third ventricle enlargement. Compared with younger healthy volunteers, older volunteers had approximately two-fold greater mean ITA width and one-third smaller mean ITA area, whereas patients with Hakim's disease had four-fold greater width and one-eighth smaller area. ITA absence was more frequent in Hakim's disease (14%) than in healthy volunteers, though this difference was not statistically significant. In healthy volunteers, downward systolic and upward diastolic streamlines with paired vortices behind the ITA were consistently observed, irrespective of age. In contrast, 63 patients with Hakim's disease (81%) lacked these flow patterns and instead exhibited abnormal bidirectional flows in the cerebral aqueduct, with some showing marked upward flow extending into the third ventricle. The ITA functions as a potential structural regulator of third-ventricular morphology and CSF dynamics. In Hakim's disease, physiological streamlines and vortices within the third ventricle are absent, and abnormal aqueductal flow predominates.