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Publications

Journal Article Ahead of print

PubMed: 42271210 DOI: 10.1186/s10194-026-02409-9

Blood-brain barrier integrity and brain entropy in reversible cerebral vasoconstriction syndrome.

J Headache Pain

Authors: Chia-Hung Wu, Tun-Wei Hsu, Yu-Hsiang Ling, Yen-Feng Wang, Chien-Yuan Lin, Chia-Wei Lee, Jiing-Feng Lirng, Shuu-Jiun Wang, Shih-Pin Chen

Affiliations

  • Department of Radiology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd. Beitou District, Taipei, 112201, Taiwan.
  • School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Department of Radiology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd. Beitou District, Taipei, 112201, Taiwan. School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
  • School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
  • Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • GE Healthcare, Taipei, Taiwan.
  • Department of Radiology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd. Beitou District, Taipei, 112201, Taiwan.
  • School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
  • Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Institute of Clinical Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong St. Beitou Dist, Taipei, 112304, Taiwan.
  • Division of Translational Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.

Abstract

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 K trans 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 K trans 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.

MeSH

Headache, Blood-Brain Barrier, Blood, Vasoconstriction, Brain, Dynamic Contrast Enhanced Magnetic Resonance Imaging