Cerebrospinal fluid volumetric net flow rate and direction in idiopathic normal pressure hydrocephalus

Abstract

The aim of the present study was to examine cerebrospinal fluid (CSF) volumetric net flow rate and direction at the cranio-cervical junction (CCJ) and cerebral aqueduct in individuals with idiopathic normal pressure hydrocephalus (iNPH) using cardiac-gated phase-contrast magnetic resonance imaging (PC-MRI). An in-depth, pixel-by-pixel analysis of regions of interest from the CCJ and cerebral aqueduct, respectively, was done in 26 iNPH individuals, and in 4 healthy subjects for validation purposes. Results from patients were compared with over-night measurements of static and pulsatile intracranial pressure (ICP). In iNPH, CSF net flow at CCJ was cranially directed in 17/22 as well as in 4/4 healthy subjects. Estimated daily CSF volumetric net flow rate at CCJ was 6.9 ± 9.9 L/24 h in iNPH patients and 4.5 ± 5.0 L/24 h in healthy individuals. Within the cerebral aqueduct, the CSF net flow was antegrade in 7/21 iNPH patients and in 4/4 healthy subjects, while it was retrograde (i.e. towards ventricles) in 14/21 iNPH patients. Estimated daily CSF volumetric net flow rate in cerebral aqueduct was 1.1 ± 2.2 L/24 h in iNPH while 295 ± 53 mL/24 h in healthy individuals. Magnitude of cranially directed CSF net flow in cerebral aqueduct was highest in iNPH individuals with signs of impaired intracranial compliance. The study results indicate CSF flow volumes and direction that are profoundly different from previously assumed. We hypothesize that spinal CSF formation may serve to buffer increased demand for CSF flow through the glymphatic system during sleep and during deep inspiration to compensate for venous outflow.

Keywords: Cerebral aqueduct; Cerebrospinal fluid; Cranio-cervical junction; Intracranial pressure; Phase-contrast MRI.

Graphical abstract

Fig. 1

The CCJ and cerebral aqueduct regions of interest in an iNPH individual (ID7). The ROIs are shown in blue and reference ROIs in red for (a) the CCJ and (b) the cerebral aqueduct. To the right is shown a zoomed in picture of the ROIs of the (a) CCJ and (b) cerebral aqueduct.

Fig. 2

Bidirectional CSF flow in CCJ of an iNPH patient (IDs 13). The CSF flow is presented in 2D and 3D showing (a) upward flow, (b) combined, and (c) downward flow.

Fig. 3

Bidirectional CSF flow in cerebral aqueduct of an iNPH patient (IDs 13). The CSF flow is presented in 2D and 3D showing (a) upward flow, (b) combined, and downward flow (c).

Fig. 4

Estimated CSF volumetric net flow rate in CCJ and cerebral aqueduct of iNPH patients and healthy subjects. The volume and direction of net CSF flow in (a) the CCJ and (b) cerebral aqueduct estimated for a 24 h interval is shown for the individual patients. Shunt responders are identified as R (Responders).

Fig. 5

Differences in estimated CSF volumetric net flow rates in CCJ and cerebral aqueduct between iNPH categories with different intracranial compliance indices. The volume and direction of CSF flow in (a) the CCJ and (b) cerebral aqueduct is present for iNPH categories with MWA below or above threshold values. MWA below threshold is indicative of normal intracranial compliance while MWA above threshold indicate impaired intracranial compliance. Differences between groups were determined by independent samples t-test.