Heightened respiratory brain pulsations indicate fluid dynamic dysfunction in early multiple sclerosis

Multiple sclerosis (MS) is characterised by perivascular space inflammation and perivenous neuronal demyelination. Cerebrospinal fluid (CSF) is driven along these perivascular structures by vasomotor waves, respiratory and cardiovascular pulsations which also drive cerebral blood flow. As altered blood flow precedes lesion development in vivo, we used fast functional magnetic resonance imaging (fMRI) at 10 Hz and whole-brain statistical maps to investigate whether 25 patients without disease-modifying therapies and with recently diagnosed multiple sclerosis showed alterations in three physiological brain pulsations that drive brain fluid dynamics, compared to 25 age- and sex-matched healthy controls. In this observational study we show that respiratory pulsation's power (PP_Resp) is significantly higher in CSF spaces and widely in MS brain compared to the healthy controls. Neither arterial cardiovascular pulsations nor vasomotor waves showed significant differences between the groups. Furthermore, power of respiratory pulsation correlated with greater neurological disability especially in sensorimotor areas and thalamus, and with the higher MS lesion burden. The duration of MS correlated with the increased width range of variability in the autonomous respiratory rate. These findings indicate altered perivenous CSF and intravenous flow dynamics, consistent with the perivenous disposition of MS, and may provide target for new therapies.