This is a two-component prospective study of adult aneurysmal subarachnoid hemorrhage (aSAH) patients admitted to the Neurosciences Intensive Care Unit (NSICU) at UT Southwestern Medical Center. Component 1 (active upon IRB approval) validates Brain4Care (B4C) extensometry-derived noninvasive cerebral autoregulation (CA) indices against invasive ICP-derived equivalents in aSAH patients with open external ventricular drains (EVDs), and characterizes the prospective natural history of multi-modal CA parameter evolution through the delayed cerebral ischemia (DCI) window (admission through Day 14). Component 2 (activated upon PI readiness declaration) assesses the within-subject effect of cervical sympathetic block (CSB) and transcutaneous auricular vagal nerve stimulation (taVNS) on CA parameters in enrolled aSAH patients.

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.

Inclusion Criteria (Component 1 - All Enrolled Participants):

• Age 18 years or older
• Primary diagnosis of aneurysmal subarachnoid hemorrhage (aSAH), confirmed by imaging
• Admitted to the NSICU at Clements University Hospital, UT Southwestern Medical Center
• Informed consent obtained from subject or legally authorized representative (as defined under Texas Health and Safety Code Section 166.039)
• Brain4Care extensometry sensor placeable at an appropriate cranial site not occluded by surgical dressings or EVD hardware
• Open EVD with active continuous ICP monitoring (required for EVD clamping sub-protocol only; not required for Aims 2 or 3)

Exclusion Criteria (Component 1):

• Age younger than 18 years
• Prisoner status
• Primary NSICU admission diagnosis other than aSAH
• Active declination by subject or legally authorized representative
• Brain4Care sensor not placeable at any accessible cranial site
• Active clinical deterioration making research monitoring impractical at time of approach
• Physician-of-record declining research enrollment for clinical reasons
• Inability to provide informed consent in English
• Known pregnancy at time of enrollment

Additional Inclusion Criteria for Component 2 (Aim 3 - CSB and taVNS):

• At least one successful EVD clamping session completed
• PI documentation of Component 2 operational readiness, co-signed by qualified co-investigator or Department Director
• INR 1.5 or less and platelet count 50,000/uL or greater within 24 hours prior to each CSB procedure
• No active infection or cellulitis at right anterolateral neck
• No known allergy to ropivacaine or amide local anesthetics
• No contralateral phrenic nerve palsy or severe pre-existing respiratory compromise
• No cardiac pacemaker or implanted cardiac device contraindicating taVNS
• No allergy to electrode adhesive materials
• Continuous cardiac telemetry active and interpretable
• Resting HR 60 bpm or greater on two readings within 24 hours prior to session
• No current use of Class I or III antiarrhythmic medications
• No clinically significant AV conduction abnormality

Additional Exclusion Criteria for Component 2:

• Prior ipsilateral right-sided cervical surgery, radiation, or known anatomical distortion precluding safe C6 approach
• Hemodynamic instability with active vasopressor escalation at time of planned CSB
• Active uncontrolled tachyarrhythmia or bradyarrhythmia at time of taVNS session
• Physician-of-record declining autonomic modulation procedures for any clinical reason
• Known or suspected pregnancy