title: Sustained high-pressure in the spinal subarachnoid space while arterial expansion is low may be linked to syrinx development.
abstract: Syringomyelia (a spinal cord cyst) usually develops as a result of conditions that cause cerebrospinal fluid (CSF) obstruction. The mechanism of syrinx formation and enlargement remains unclear, though previous studies suggest that the fluid enters via the perivascular spaces (PVS) of the penetrating arteries of the spinal cord, and that alterations in the CSF pulse timing and pressure could contribute to enhanced PVS inflow. This study uses an idealised computational model of the PVS to investigate the factors that influence peri-arterial fluid flow. First, we used three sample patient-specific models to explore whether changes in subarachnoid space (SAS) pressures in individuals with and without syringomyelia could influence PVS inflow. Second we conducted a parametric study to determine how features of the CSF pulse altered perivascular fluid, including alterations to timing and magnitude of the peak SAS pressure, the timing of reversal from high to low pressure (diastolic phase), and the area under the pressure-time curve. The model for the patient with syringomyelia had higher net CSF inflow to the PVS than the two subjects without syringomyelia. In the parametric study, only increasing the area under the high pressure region of the SAS pulse substantially increased PVS inflow, when coupled with a temporal shift in arterial and SAS pulses. This suggests that a period of sustained high SAS pressure while arterial diameter is low may increase net CSF pumping into the PVS.
authors.affiliation: a Murray Maxwell Biomechanics Laboratory , Institute for Bone and Joint Research, Kolling Institute of Medical Research, Sydney Medical School - Northern, University of Sydney , Sydney , Australia.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Clarke
authors.affiliation: b School of Chemical and Biomolecular Engineering, University of Sydney , Sydney , Australia.
authors.forename: David F
authors.initials: DF
authors.lastname: Fletcher
authors.affiliation: c Neuroscience Research Australia, and Prince of Wales Clinical School , UNSW Medicine, University of New South Wales , Sydney , Australia.
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Bilston
mesh_terms: D001158:Arteries / Q000503:physiopathology*; D015170:Cerebrospinal Fluid Pressure / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D011674:Pulse; D013116:Spinal Cord / Q000503:physiopathology*; D013346:Subarachnoid Space / Q000503:physiopathology*; D013595:Syringomyelia / Q000503:physiopathology*
keywords: Biomechanics; Cerebrospinal fluid; Chiari malformation; computational fluid dynamics modelling; perivascular space; syringomyelia