The journal of headache and pain · 2026
Blood-brain barrier integrity and brain entropy in reversible cerebral vasoconstriction syndrome.
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Wu Chia-Hung, Hsu Tun-Wei, Ling Yu-Hsiang, Wang Yen-Feng, Lin Chien-Yuan, Lee Chia-Wei, Lirng Jiing-Feng, Wang Shuu-Jiun, Chen Shih-Pin
Аннотация
BACKGROUND: Elucidating functional brain dynamics under different blood-brain barrier (BBB) permeabilities may resolve the enigmatic pathophysiology of reversible cerebral vasoconstriction (RCVS); however, relevant investigations are lacking. We aimed determine the relationship between brain functional dynamics and BBB permeability in patients with RCVS.
METHODS: We prospectively recruited RCVS patients and healthy controls (HCs) from November 2016 to January 2023 in Headache Center in a tertiary medical center (> 3000 beds) and adjacent communities. RCVS patients who were diagnosed according to the International Headache Society criteria, and age- and sex-matched HCs were enrolled. Normalized entropy, derived from resting-state fMRI (rs-fMRI), was compared at the network and parcel levels between RCVS patients with and without BBB disruption. Dynamic contrast-enhanced MRI (DCE-MRI)-derived Ktrans BBB permeability and ultrasonographic findings were analyzed.
RESULTS: In total, 188 subjects (100 RCVS + 88 HCs) were enrolled. Compared with the HCs, the RCVS patients had greater entropy (p = 0.014), which was greater in the RCVS patients without than in those with (adjusted p = 0.040) BBB disruption. Compared with HCs, patients without BBB disruption had greater entropy between 60 and 90 days after headache onset (adjusted p = 0.006). No significant differences in entropy were noted between disease stages in BBB-disrupted patients. Parcels within subnetworks of the Default mode network (Default A and C) exhibited higher entropy in patients without BBB disruption. In specific anatomical locations, entropy values were negatively correlated with ultrasonographic Lindegaard index vasoconstriction severity (p = 4.3 × 10- 6; within the Default A network) and DCE-MRI Ktrans BBB permeability (p = 0.005; within the Default C network).
CONCLUSION: The differential changes in normalized entropy suggest that increased rs-fMRI signal complexity may reflect a compensatory functional response to abrupt vasoconstriction. In contrast, the loss of entropy fluctuations in the context of severe BBB disruption indicates a state of impaired cerebral autoregulation in patients with RCVS. The compensatory capacity decreased as vasoconstriction or BBB disruption exacerbated.
METHODS: We prospectively recruited RCVS patients and healthy controls (HCs) from November 2016 to January 2023 in Headache Center in a tertiary medical center (> 3000 beds) and adjacent communities. RCVS patients who were diagnosed according to the International Headache Society criteria, and age- and sex-matched HCs were enrolled. Normalized entropy, derived from resting-state fMRI (rs-fMRI), was compared at the network and parcel levels between RCVS patients with and without BBB disruption. Dynamic contrast-enhanced MRI (DCE-MRI)-derived Ktrans BBB permeability and ultrasonographic findings were analyzed.
RESULTS: In total, 188 subjects (100 RCVS + 88 HCs) were enrolled. Compared with the HCs, the RCVS patients had greater entropy (p = 0.014), which was greater in the RCVS patients without than in those with (adjusted p = 0.040) BBB disruption. Compared with HCs, patients without BBB disruption had greater entropy between 60 and 90 days after headache onset (adjusted p = 0.006). No significant differences in entropy were noted between disease stages in BBB-disrupted patients. Parcels within subnetworks of the Default mode network (Default A and C) exhibited higher entropy in patients without BBB disruption. In specific anatomical locations, entropy values were negatively correlated with ultrasonographic Lindegaard index vasoconstriction severity (p = 4.3 × 10- 6; within the Default A network) and DCE-MRI Ktrans BBB permeability (p = 0.005; within the Default C network).
CONCLUSION: The differential changes in normalized entropy suggest that increased rs-fMRI signal complexity may reflect a compensatory functional response to abrupt vasoconstriction. In contrast, the loss of entropy fluctuations in the context of severe BBB disruption indicates a state of impaired cerebral autoregulation in patients with RCVS. The compensatory capacity decreased as vasoconstriction or BBB disruption exacerbated.