Noninvasive CA Monitoring Validation and Autonomic Modulation in Aneurysmal Subarachnoid Hemorrhage

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) affects approximately 35,000 Americans annually and carries a 30-day mortality of approximately 40%. Delayed cerebral ischemia (DCI) - caused by vasospasm, microvascular dysfunction, and impaired cerebrovascular regulation - complicates 25-35% of survivors during the 4-14 day post-rupture window. Cerebral autoregulation (CA) impairment predicts DCI onset and poor neurological outcome. Standard ICP-based CA indices cannot be computed through an open EVD - present in approximately 50-75% of aSAH patients - because the transducer is exposed to ambient pressure. This technical barrier has precluded CA-guided management in the most common clinical aSAH scenario for over two decades. The autonomic nervous system is a central, understudied regulator of CA in aSAH. Aneurysm rupture produces a massive catecholamine surge coinciding with the early window of CA impairment. We hypothesize that sympathetically-mediated cerebrovascular vasoconstriction contributes to CA failure, and that restoration of sympathovagal balance can shift CA parameters toward a more protective state. TWO-COMPONENT DESIGN: COMPONENT 1 - Validation and Natural History (activates immediately upon IRB approval): A standardized 15-minute EVD clamping protocol (5-minute equilibration plus 10-minute simultaneous invasive/noninvasive CA recording; ICP abort threshold greater than 20 mmHg sustained for 5 or more minutes) is used to validate B4C-derived CA indices (nPRx, nCPPopt, nMx) against invasive ICP-derived equivalents by Bland-Altman analysis and intraclass correlation. NIRS-based MAPopt (TOxA, COx) is characterized as an EVD-independent CA metric. Longitudinal multi-modal CA monitoring proceeds through ICU Day 14 for all enrolled participants. COMPONENT 2 - Autonomic Modulation (PI readiness-gated): Within-subject before-after assessment of right-sided cervical sympathetic block (CSB; ultrasound-guided, C6 approach, low-volume ropivacaine) and transcutaneous auricular vagal nerve stimulation (taVNS; 25 Hz, 200-500 microamps, 200 microsecond pulse width via TENS 7000 to cymba conchae; 20-minute sessions twice daily for up to 14 days) on CPPopt, MAPopt, Mx, and CPPopt-MAP deviation. Activation requires documented PI readiness attestation co-signed by a qualified co-investigator or Department Director. SAFETY (Component 2): CSB: Continuous cardiac monitoring; pre-procedure coagulation screening (INR 1.5 or less, platelets 50,000/uL or greater within 24 hours); real-time ultrasound guidance. Expected transient ipsilateral Horner syndrome lasting 2-6 hours. Serious adverse event rate less than 0.1% with low-volume technique. taVNS: Continuous cardiac telemetry; immediate device removal for HR below 50 bpm. Parameters consistent with NAVSaH trial and published taVNS literature. SIGNIFICANCE: Each aim is independently executable and generates independently publishable results. A positive Component 2 result directly motivates an NIH R01 for a powered randomized trial. A null result establishes the first causal evidence regarding non-modifiability of CPPopt by autonomic intervention, reorienting the field. The study cannot produce a non-informative result.