The Potential Role of Neuromodulation in Subarachnoid Hemorrhage

Aneurysmal subarachnoid hemorrhage (SAH) continues to be a difficult cerebrovascular disease with limited pharmacologic treatment options. Cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) are leading causes of morbidity and mortality after SAH. Despite the advances in the understanding of its pathophysiology and tremendous efforts to date, nimodipine is currently the sole Food and Drug Administration-approved treatment for patients with SAH, with benefits that are marginal at best. The neuromodulation therapies are promising, especially those that target CV and DCI to improve functional outcomes. The aim of this review is therefore to summarize the available evidence for each type of neuromodulation for CV and DCI, with a special focus on its pathophysiological mechanisms, in addition to their clinical utility and drawbacks, which we hope will lead to future translational therapy options after SAH.

We conducted a comprehensive review of preclinical and clinical studies demonstrating the use of neuromodulation for SAH. The literature search was performed using PubMed, Embase, and ClinicalTrials.gov. A total of 21 articles published from 1992 to 2021 and eight clinical trials were chosen.

The studies reviewed provide a compelling demonstration that neuromodulation is a potentially useful strategy to target multiple mechanisms of DCI and thus to potentially improve functional outcomes from SAH. There are several types of neuromodulation that have been tested to treat CV and DCI, including the trigeminal/vagus/facial nerve stimulation, sphenopalatine ganglion and spinal cord stimulation, transcranial direct electrical stimulation, transcutaneous electrical neurostimulation, and electroacupuncture. Most of them are in the preclinical or early phases of clinical application; however, they show promising results.

DCI has a complex pathogenesis, making the unique anatomical distribution and pleiotropic capabilities of various types of neuromodulation a promising field of study. We may be at the cusp of a breakthrough in the use of these techniques for the treatment of this stubbornly difficult disease.