The actual impact of neurological complications on patient outcome during extracorporeal life support (ECLS) has emerged only since a few years (1,2) despite the use of such a temporary heart/lung support for more than four decades.The recent appraisal of the rather high incidence and ominous prognosis of these adverse events in ECLS patients have now alerted attending physicians and personnel upon continuous surveillance and early recognition. Nonetheless, it is increasingly evident that the mechanisms underlying the occurrence are not simply linked to embolization, bleeding, or low-flow related brain hypoxia (3-5) which were thought to represent the sole source of injury of the brain in ECLS patients.Following a study addressing the neurologic complications in the neonatal population (6), other two studies realized by analysing the Registry of the Extracorporeal Life Support Organization (ELSO), have recently investigated and clearly shown the entity of neurologic adverse events in veno-arterial (V-A) and veno-venous (V-V) ECLS configurations in adult patient populations (7,8). Incidence rates of brain injury were 15% in V-A and 7% in V-V patients, respectively, with an in-hospital survival of 10% in the first group, and 25% in the second, underlining the ominous prognosis once a neurological event occurs in the ECLS patients (7,8). These studies analyzed also the type of brain damage, according to the ELSO reporting system (embolism, hemorrhage, seizures, brain death) but also, more importantly, the trends of the overall CNS complications and of the single typerelated rates of such adverse events during a 20-year period whose assessment provided interesting findings (7,8).The difference of neurologic complication rates between V-A and V-V is not surprising. However, the two studies, as also highlighted by the comments provided by Pappalardo, Hirose, and Perico herewith enclosed (9-11), have provided several relevant clues for further interpretation and discussion. Interestingly, the incidence of CNS events in V-A ECLS patients steadily declined in the recent years, whereas no substantial change was observed in the V-V ECLS population (7,8). It is well-known that patients undergoing V-A ECLS, by definition and as also confirmed by the ELSO Registry data, are usually more prone to experience bleeding and hemodynamic instability after ECLS implant than V-V cases, therefore at higher risk also for brain injury. This is due to either the underlying disease, settings, and clinical conditions of the ECLS candidates or to the ECLS access (arterial cannulation certainly at higher risk of bleeding than venous access). V-A ECLS, indeed, is often applied nowadays in patients suffering from cardiac arrest, condition which is directly linked to brain hypoperfusion