Perfusion dynamics in reversible cerebral vasoconstriction syndrome

Elucidating the spatiotemporal dynamics of cerebral blood flow (CBF) may resolve the enigmatic pathophysiology of reversible cerebral vasoconstriction syndrome (RCVS), a condition with variable clinical and vascular manifestations, where the current understanding of perfusion is limited to inconsistent case report findings. We aimed to determine the spatiotemporal perfusion dynamics and their clinical and vascular correlations in RCVS. We prospectively recruited RCVS patients and age- and sex-matched healthy controls (HCs) over a 5-year period (June 2018 to April 2023) in the Headache center in a tertiary medical center (>3000 beds) and adjacent communities. RCVS patients were diagnosed according to the International Headache Society criteria. Voxelwise and whole-brain gray matter CBF on magnetic resonance imaging were compared between RCVS patients and HCs. The time-trend CBF dynamics in RCVS patients and correlations with ultrasonographic and clinical findings were analyzed. Totally, 316 participants (281 RCVS patients + 35 HCs) were enrolled. Acute RCVS (aRCVS; ≤30 days onset) patients presented lower global and regional CBF values (49.0 ± 10.2 vs. 53.9 ± 6.7 mL/100 g/min; p = 0.033) than HCs, but these values normalized by two weeks after headache onset and in the remission stage (rRCVS; ≥90 days onset; 52.8 ± 9.3 mL/100 g/min; p = 0.005), particularly in posterior regions. The distinct abrupt CBF fluctuations that occurred between days 2-16 and 7-21 in aRCVS were consistent across the different analytic models (significance as p < 0.05, 0.01, 0.005 or 0.001; sliding analytic time intervals of 5, 7 or 10 days). The ultrasonographic flow velocities of the middle cerebral (2nd week: r = 0.628; p < 0.001; 4th week: r = 0.471; p = 0.010) and internal carotid arteries (2nd week: r = 0.626; p < 0.001; 4th week: r = 0.381; p = 0.041) were positively correlated with CBF during similar periods in aRCVS patients. The unique CBF dynamics in patients with RCVS, particularly aRCVS, revealed potential roles of perfusion changes in RCVS pathophysiology.