Somatosensory Evoked Potentials (SEP) Monitoring in Patients With Acute Ischemic Stroke (AIS) and Large Anterior Vessel Occlusion (LVO) Undergoing Endovascular Thrombectomy (EVT). A Clinical Validation of the BraiN20® Medical Device.

EVT is the gold standard treatment in patients with AIS and LVO (1). However, currently, the probability of severe functional dependence or death at 3 months remains between 14-31% according to the results of the five large clinical trials that demonstrated efficacy and safety of EVT (2). There are two fundamental problems that need to be overcome to bring this treatment to more patients. First, patients need to seek help more often and sooner after their symptoms start. Second, once the alert occurs, the patients who may benefit from this treatment need to be identified and triaged to the appropriate facility. Unmet needs are the development of a portable, accurate, user-friendly device to quickly determine in real-time along the stroke journey if there is salvageable brain. This would be especially useful at prehospital levels to accelerate the transfer to comprehensive stroke centers and in the angio-room to monitor potential complications of the EVT.

Biomarkers could be useful to determine a priori patients who could most likely benefit from treatment from those in whom EVT would probably be futile. Multiple predictive factors of clinical response have been described (3). Clinical variables include age, baseline NIHSS score, systolic blood pressure, and hyperglycemia (3-7). Relevant radiological parameters are early ischemic signs in non-contrast CT (NCCT) assessed by the ASPECT score (3,8), thrombus extension and location,9 collateral status on CT or /MR angiography(10) and perfusion parameters such as infarct core and penumbra volume (11). Most of these factors require evaluation in a stroke center and are not available at previous levels of care, such as the pre-hospital setting or local hospitals.

SEP, and in particular the N20 response to peripheral nerve stimulation, reflect the electrical activity of different areas and tracts of the nervous system and correlate with cortical cerebral perfusion(12). SEP recording is a fast, non-invasive and reproducible technique that can be performed at the patient's bedside and provides real-time data on the functional status and perfusion of brain even when the patients are anesthetized or in an induced coma(13).

The PROMISE (Prognostic Accuracy of N20 Somatosensory Potential in Patients With Acute Ischemic Stroke and Endovascular Thrombectomy) trial (Stroke: Vascular and Interventional Neurology. 2023;3:e000735) investigated the presence and amplitude of the N20 response of SEP recorded before EVT in the ischemic hemisphere of 223 patients with anterior LVO undergoing EVT. N20 predicted functional independence at day 7 with a sensitivity of 93% (95%CI, 78-98%) and negative predictive value of 93% (80-98%), which increased to 100% after the EVT. Indeed, its predictive performance before treatment was superior to that of common factors used in clinical routine and added 0.07 points to the predictive model combining clinical variables, NIHSS score and ASPECT score (AUC of 0.84 versus AUC 0.77). Furthermore, N20+ had a higher predictive value of good outcome than advanced imaging variables recorded at baseline, such as the volume of infarct core, volume of hypoperfusion and collateral circulation. Taken together, these findings indicate that N20 might be a neurophysiological surrogate of salvageable brain and highlight the concept that ischemic brain tissue may remain viable from the perspective of cortical electrical function. Therefore, N20 SEP monitoring is a novel neurophysiological biomarker in acute stroke with the potential of having a major impact on the way stroke patients are managed throughout the world.

A major limitation of the PROMISE study was that N20 recording in the angio-room was interfered by electromagnetic artifacts precluding the blinded correct evaluation of the SEP in 25% of patients. These artifacts occurred in available commercial multifunction equipment not designed for the particular detection of N20 avoiding potential artifacts such as movements, electromagnetic interferences, noise, etc.