The potential of closed-loop endovascular neurostimulation as a viable therapeutic approach for drug-resistant epilepsy: A critical review

Over the last few decades, biomedical implants have successfully delivered therapeutic electrical stimulation to reduce the frequency and severity of seizures in people with drug-resistant epilepsy. However, neurostimulation approaches require invasive surgery to implant stimulating electrodes, and surgical, medical, and hardware complications are not uncommon. An endovascular approach provides a potentially safer and less invasive surgical alternative. This article critically evaluates the feasibility of endovascular closed-loop neuromodulation for the treatment of epilepsy. By reviewing literature that reported the impact of direct electrical stimulation to reduce the frequency of epileptic seizures, we identified clinically validated extracranial, cortical, and deep cortical neural targets. We identified veins in close proximity to these targets and evaluated the potential of delivering an endovascular implant to these veins based on their diameter. We then compared the risks and benefits of existing technology to describe a benchmark of clinical safety and efficacy that would need to be achieved for endovascular neuromodulation to provide therapeutic benefit. For the majority of brain regions that have been clinically demonstrated to reduce seizure occurrence in response to delivered electrical stimulation, vessels of appropriate diameter for delivery of an endovascular electrode to these regions could be achieved. This includes delivery to the vagus nerve via the 13.2 +/- 0.9 mm diameter internal jugular vein, the motor cortex via the 6.5 +/- 1.7 mm diameter superior sagittal sinus, and the cerebellum via the 7.7 +/- 1.4 mm diameter sigmoid sinus or 6.2 +/- 1.4 mm diameter transverse sinus. Deep cerebral targets can also be accessed with an endovascular approach, with the 1.9 +/- 0.5 mm diameter internal cerebral vein and 1.2-mm-diameter thalamostriate vein lying in close proximity to the anterior and centromedian nuclei of the thalamus, respectively. This work identified numerous veins that are in close proximity to conventional stimulation targets that are of a diameter large enough for delivery and deployment of an endovascular electrode array, supporting future work to assess clinical efficacy and chronic safety of an endovascular approach to deliver therapeutic neurostimulation.