The significance of developing a safe and effective therapy for aneurysmal subarachnoid hemorrhage (aSAH) patients suffering cerebral vasospasm (CVS) cannot be overstated. Vasospasm - a clamping down of normal arteries in the days following rupture - remains incredibly challenging to treat.1,2 Current drugs and minimally invasive surgical therapies are helpful, yet woefully insufficient. Symptomatic cerebral vasospasm afflicts about 30% of aneurysmal subarachnoid hemorrhage patients and nearly half will go on to suffer a stroke, despite aggressive medical care.1-3 The autonomic nervous system is a balance between sympathetic (fight or flight) and parasympathetic (rest and digest) influence with sympathetic overactivity and inflammation shown to play an important role in the development and severity of cerebral vasospasm.4,5,17-20 Prior studies of autonomic nervous system neuromodulation highlight its promise as a promising potential avenue to improve morbidity and mortality from CVS in aSAH.6-15 Despite progress, continued high levels of CVS morbidity and mortality stress the urgent need for exploration of neuromodulation therapy.
In this proposal, the study team will modulate the autonomic nervous system function in aSAH patients using transcutaneous vagal nerve stimulation (tVNS). tVNS involves placement of a stimulation electrode on the external ear to non-invasively stimulate a branch of the vagal nerve and increase parasympathetic influence. This device has FDA approval for epilepsy and cluster headache.
The study hypothesis is that neuromodulation of the autonomic nervous system with tVNS (increasing parasympathetic influence) reduces sympathetic overactivity and inflammation in aSAH resulting in decreased morbidity of CVS.
Provision of signed and dated informed consent
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or Female
18-65 years of age
Medically unfit to undergo endovascular treatment (e.g., Hunt Hess grade 5)
Does not provide consent
Posterior circulation aneurysmal subarachnoid hemorrhage
Initial aneurysm treatment after post bleed day 1
Single group
Transcutaneous Vagal Nerve Stimulation
DeviceParticipants will receive up to 4 sessions per day of up to 20-minute stimulation, over the next 10 days of their inpatient hospital stay, following endovascular treatment. Stimulation will be provided by the tVNS device through a small electrode placed around the ear that will send low intensity, pulsed, electrical pulses the vagus nerve.
Number of participants affected by cerebral inflammation during the course of the study as assessed by laboratory markers in blood and cerebral spinal fluid
Rate of blood flowing through the brain as assessed by transcranial doppler imaging
Number of participants experiencing sudden health issues during the study as determined by the need for ventriculoperitoneal shunt placement prior to discharge, length of hospital stay, and disposition upon discharge.
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Marshall Holland
Lead sponsor
University of Alabama at Birmingham
Sponsor institution
