The Effect of Sympathetic Modulation on Cerebral Vasospasm Secondary to Aneurysmal Subarachnoid Hemorrhage

The Investigators' overarching hypothesis is that sympathetic innervation plays a substantial role in conferring cerebral vasospasm (CVS) risk to aneurysmal subarachnoid hemorrhage (aSAH) patients and is associated with severity of clinical features and outcomes. Specifically, the Investigators surmise that central (hypothalamic) and local (arterial adventitia) sympathetic inputs are upregulated following SAH and integrate at the level of the neuromuscular junction to abnormally increase cerebrovascular tone. The long-term goal of this program is to use orthogonal approaches to undertake a comprehensive electrophysiological, functional genomics, and advanced imaging analysis of CVS. The Investigators hope is these data inform therapeutic pathways to modulate implicated pathogenic mechanisms and reduce CVS incidence and severity, thereby improving overall clinical outcomes in aSAH. In the short-term, the Investigators will focus on elucidating the modulatory role of cervical spinal cord stimulator (SCS) on sympathetic innervation to the cerebral vasculature.

This is a Phase 2 prospective, randomized single center study assessing the safety and efficacy of SCS for reducing vasospasm. aSAH patients who meet inclusion criteria and provide informed consent will be randomly assigned to SCS or a sham procedure. Subjects will be blinded until the end of the study, with no allowance for crossover. Temporary leads will stimulate, utilizing a paradigm established from prior human studies and the effect measured with daily transcranial doppler (TCD). Leveraging prior experience in vascular and functional neurosurgery, the Investigators' group is poised to make a substantial impact. Below the Investigators outline a feasible framework to modulate sympathetic drivers of CVS.

Aim 1: Perform feasibility analysis of SCS placement and operation in the aSAH setting. It is presently unknown how temporary SCS will impact the workflow and care of patients with acutely ruptured cerebral aneurysms. Given the rate of new aSAH cases at the Investigators' center (~50 per year), initiation of prospective data collection and longitudinal study are required. The Investigators will comprehensively assess operative time for electrode implantation, lead function and data transmission efficiency in the ICU, site infection/pressure injury and untoward systemic effects (hypotension, arrhythmia) for all patients enrolled at the Investigators' center.

Aim 2: Quantify the sympathetic modulating effect of SCS on cerebral blood flow during CVS. Further characterization of the sympathetic contribution to CVS will establish a rationale for functional/neuromodulatory therapies such as SCS. The Investigators will perform cervical epidural stimulation through temporary leads and monitor effects on cerebral blood flow by daily TCD. Experiments will continue throughout the 14-day CVS window to capture longitudinal changes in sympathetic tone and vascular response. Quantitative TCD metrics (velocity, resistance, Lindegaard ratio) will be compared between on- and off-stimulation epochs. The Investigators' study will not only fundamentally advance the Investigators' understanding of vasospasm, but also provide a framework to elucidate mechanisms of other cerebrovascular conditions.

Inclusion criteria

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Diagnosed with Fisher grade 3 or 4 aneurysmal subarachnoid hemorrhage (1)
• Ability to undergo endovascular treatment of aneurysmal subarachnoid hemorrhage
• For females of reproductive potential: Negative pregnancy test at time of treatment
• Plan to undergo standard of care and follow-up

Exclusion criteria

• Medically unfit to undergo endovascular treatment (e.g., Hunt Hess grade 5)
• Does not provide consent for the procedure.
• Posterior circulation aneurysmal subarachnoid hemorrhage.
• Initial aneurysm treatment after post bleed day 1