To the Editor:
We are grateful for the opportunity to respond to the thoughtful commentary1 stemming from our publication, “Surgical Performance Determines Functional Outcome Benefit in the Minimally Invasive Surgery Plus Recombinant Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation (MISTIE) Procedure.”2
We would like to first highlight that the efficacy of intracerebral hematoma (ICH) evacuation in the MISTIE III (Minimally Invasive Surgery Plus Recombinant Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation) clinical trial was high, achieving a mean end of treatment hematoma volume of 12.6 mL (compared to a mean initial ICH volume of 48.7 mL), and a mean 73.9% hematoma evacuation in surgical cases. A greater evacuation efficacy was achieved when protocol adherence was optimal, and this translated into improved mortality and functional outcomes.
New devices have emerged, some gaining Food and Drug Administration (FDA) approval recently, to improve fibrinolytic activity, such as ultrasonic tipped, endoscopic or aspiration catheters. These new and additional adjuncts or drugs have not been subjected to the same rigorous safety and protocol performance testing as was done with the MISTIE procedure. Progress in ICH treatment will likely be incremental, including patient selection, optimized intensive care unit (ICU) care, optimized timing of intervention, novel techniques/technology with precision execution, and ultimately a platform with wide generalizability.
A key lesson of the MISTIE trial should highlight that MISTIE is much more than just a catheter and recombinant tissue plasminogen activator (rtPA). It includes careful patient selection with etiology screening, bleeding stabilization, surgeon training and experience, state-of-the-art ICU care, and enforced protocol adherence.3 It is difficult to assess the contribution of any single element of this intricate process. It will be equally challenging to evaluate pharmacological adjuncts, unless all other elements are standardized and controlled.
Neutrophil extracellular traps (NETs) present a biologically plausible and interesting avenue to enhance clot lysis, or to target those clots that present a challenge to lyse. Preclinical data are needed to confirm this, and prospective clinical data will be needed to understand their potential role in ICH/intraventricular hemorrhage (IVH)/subarachnoid hemorrhage (SAH), and different impacts with those various bleeds. Hypotheses must be clearly articulated about the specific bleed type, potential hematologic criteria of resistance to fibrinolysis, goals of maintaining catheter patency versus enhancement of ICH/IVH/SAH thrombolytic clearance, and criteria for superiority in comparative effectiveness.
We remain enthusiastic that many investigators are eager to expand the armamentarium for the treatment of ICH with improvements in current treatment paradigms at all levels.
The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.
1. Feng Z, Tan Q, Chen Z. Letter: surgical performance determines functional outcome benefit in the minimally invasive surgery plus recombinant tissue plasminogen activator for intracerebral hemorrhage evacuation (MISTIE) procedure. Neurosurgery. 2020;86(4):E410.
2. Awad IA, Polster SP, Carrion-Penagos J, et al. Surgical performance determines functional outcome benefit in the minimally invasive surgery plus recombinant tissue plasminogen activator for intracerebral hemorrhage evacuation (MISTIE) procedure. Neurosurgery. 2019;84(6):1157-1168.
3. Dey M, Stadnik A, Awad IA. Spontaneous intracerebral and intraventricular hemorrhage: advances in minimally invasive surgery and thrombolytic evacuation, and lessons learned in recent trials. Neurosurgery. 2014;74(Suppl_1):S142-S150.