From: Pathophysiology of reversible cerebral vasoconstriction syndrome
Key elements | Main mechanism | Strength of evidence | Possible treatment strategiesa |
---|---|---|---|
Dysregulation of cerebral vascular tone | • Suddenly increased sympathetic drive • Passive autoregulatory response against blood pressure surge • Consequences of endothelial dysfunction, oxidative stress, and BBB disruption • Dysregulated circulating miRNAs associated with vasomotor regulation | +++ | • Early identification and avoidance of triggers or secondary causes with heightened sympathetic drive • Cerebrovascular-selective calcium channel blockers? |
Sympathetic overactivity | • Predisposing sympatho-vagal imbalance • Triggers or secondary causes associated with heightened sympathetic drive | ++ | • Early identification and avoidance of triggers or secondary causes |
Endothelial dysfunction | • Impaired endothelial repairing capacity (i.e., reduced endothelial progenitor cells) • Systemic endotheliopathy caused by secondary causes | +++ | • Avoidance or early removal of secondary causes |
Excessive oxidative stress | • Increased reactive oxygen species and lipid peroxidation upon increased shearing stress and endothelial dysfunction | ++ | • Antioxidants? |
Blood–brain barrier disruption | • Excessive blood pressure surge and pulsatile flow exceeding autoregulatory capacity • Oxidative stress • Circulating microRNAs (miR-130a) | +++ | • Avoid blood pressure surge • Antioxidants? |
Altered trigeminovascular nociception | • Sudden stretch of perivascular trigeminal nociceptors (by dilatation of distal arteriole or meningeal artery) • Increased BBB permeability • Altered circulating microRNAs | ? | • The cerebrovascular-selective calcium channel blocker nimodipine • CGRP-targeting therapy? (with risk of vasoconstriction) |
Genetic predisposition | • Genetic contribution to disease vulnerability | + | • Gene-based mechanism targeting therapy? |
Sex hormones | • Hormonal modulation of cerebral vascular tone | + | • Avoid abrupt hormonal fluctuation in vulnerable subjects? |
Inflammation | • Systemic or perivascular inflammation causing endothelial dysfunction | + | • Anti-inflammatory therapy? (Of note, steroid may be associated with poor prognosis) |