Low interstitial fluid in patients with spontaneous intracranial hypotension

Background CSF loss in spontaneous intracranial hypotension (SIH) has been related to alterations in glymphatic flow, which is poorly understood in this disease. Advanced multi-shell diffusion-weighted MRI (dMRI) enables quantification of the interstitial free water fraction, serving as a possible surrogate marker for glymphatic system function in patients with SIH. Methods SIH Patients underwent dMRI before and after closure of a spinal CSF leak. The microstructural free water compartment (V-CSF) of the whole brain gray and white matter, corona radiata, amygdala, hippocampi and parahippocampal gyri was compared to 23 age-matched normal controls. Pre- and post-therapeutic volumetry encompassed the total ventricular, total gray and white matter compartments and mesial temporal structures. Results 23 SIH patients (50.3 ± 13.1 years, 15 women) were included. After leak closure, V-CSF increased in the global gray matter (mean pre 0.140 vs. mean post 0.151; p = 0.029), posterior corona radiata (mean pre 0.103 vs. mean post 0.108; p = 0.0055), hippocampi (mean pre 0.100 vs. mean post 0.105; p = 0.001), and parahippocampal gyri (mean pre 0.156 vs. mean post 0.177; p = 0.009). Compared to normal controls, V-CSF was decreased before leak closure in the hippocampi (mean pre 0.100 vs. mean NC 0.211; p = 0.0019) and posterior corona radiata (mean pre 0.103 vs. mean NC 0.118; p = 0.011). No significant change of total gray or white matter volume occurred after leak closure. Conclusion Closure of the spinal CSF leak leads to an increase of interstitial fluid in gray matter, corona radiata, hippocampi, and parahippocampal gyri, respectively. Our results suggest, that SIH patients may have less interstitial fluid in the hippocampi and posterior corona radiata compared to normal controls. Whether shifts in brain interstitial fluid in eloquent cerebral regions contribute to cognitive decline in patients with CSF loss should be topic of further research.