Abstract Introduction Harlequin syndrome is a critical complication of peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) characterized by differential upper-body hypoxemia when deoxygenated native cardiac output mixes with oxygenated ECMO flow. It can lead to cerebral and coronary hypoxia despite seemingly adequate systemic oxygenation. Early detection is crucial. We hypothesized that noninvasive multimodal neuromonitoring—near-infrared spectroscopy (NIRS), transcranial Doppler (TCD), and intracranial compliance monitoring (Brain4Care®)—could detect cerebral blood flow and compliance changes before systemic oxygen saturation declined. We present a case illustrating this early warning approach for impending Harlequin syndrome. Case Presentation A 42-year-old woman on peripheral femoro-femoral VA-ECMO and an intra-aortic balloon pump for cardiogenic shock underwent continuous neuromonitoring with NIRS, TCD, and Brain4Care®. On ECMO day 4, neuromonitoring revealed early signs of cerebral hypoperfusion while peripheral oxygenation remained stable. Right-sided cerebral oximetry (rSO2) dropped from 64% to 52%, whereas systemic and right radial arterial saturations stayed above 94%. TCD showed an elevated pulsatility index with reduced diastolic flow in the right middle cerebral artery, consistent with impaired cerebral autoregulation. Simultaneously, Brain4Care® waveforms shifted from normal (P1P2P3) to abnormal (P2P1), indicating reduced intracranial compliance. Notably, these cerebral changes preceded any peripheral desaturation. Later, a drop in right radial saturation confirmed Harlequin syndrome. The patient was promptly converted to veno-arterio-venous (VAV) ECMO with the addition of a right internal jugular return cannula, which restored cerebral oxygenation and normalized all neuromonitoring parameters. Discussion Cerebral autoregulation normally maintains constant cerebral blood flow despite systemic blood pressure fluctuations, but it can be disrupted by hypoxemia or other insults. Noninvasive multimodal neuromonitoring (NIRS, TCD, and intracranial compliance monitoring) provides real-time detection of changes in cerebral oxygenation, blood flow dynamics, and intracranial pressure waveforms, serving as a surrogate measure of autoregulatory function. Harlequin syndrome is traditionally diagnosed by noting a significant oxygenation gradient between the upper-body and lower-body arterial circulations. However, by the time this differential hypoxemia is recognized, cephalic (upper-body) oxygen deprivation may have already compromised cerebral perfusion. In our case, continuous neuromonitoring identified compromised cerebral oxygen delivery and compliance well before peripheral oxygen saturation dropped. This early warning facilitated timely conversion to VAV-ECMO before severe hypoxic injury could occur. This case underscores the novel clinical utility of multimodal neuromonitoring in VA-ECMO as an early warning tool for Harlequin syndrome, potentially enabling earlier intervention and improved outcomes. This abstract is funded by: N/A
J A Carrizosa (Fri,) studied this question.