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The success of the 2015 stroke trials changed the indications for mechanical thrombectomy and the landscape of acute stroke care.1–5 A treatment we have always believed to be beneficial was shown, without doubt, to be effective. Systems of care have been designed around IA therapy for acute stroke. Procedural volumes have increased dramatically. Most importantly, a large number of patients have directly benefitted from this procedure. The 2015 mechanical thrombectomy studies succeeded for many reasons. The trials were thoughtful and well designed. The operators were experienced. Recanalization rates have now improved drastically. Thrombolysis in Cerebral Infarction 2b or 3 is now the expectation, and short procedural times the norm. Regardless of specific recanalization methods, we, as a field, have become very good at opening occluded blood vessels quickly. There remains room for improvement, but the margin is decreasing. Device development and procedural adaptations have been the bell cow thus far; tools have evolved from the Merci device to aspiration and stentrievers. Balloon guide catheters and direct carotid access have played a role. We have all recognized that we need to shift some of our attention to other aspects of the delivery model. Systems of care devoted to stroke delivery have recently come into focus. We recognize that reducing procedural times is of little value if symptom recognition is delayed and transfer times are long. Diversion of large vessel strokes and stroke center accreditation are at the forefront of our literature reviews and discussions at the national meetings.
Efficient delivery of patients with emergent large vessel occlusion to appropriate stroke treatment centers is critical. Designing effective systems of care is a large undertaking that is well worth the effort. However, another variable in the equation also deserves our time and effort. While we are working to move patients through the system more quickly, we are also developing strategies to preserve brain function. We all, rightfully, operate under the dogma that ‘time is brain’ and make every attempt to shift left on the time from symptom onset to revascularization versus good functional outcome curve.6 Moving our patients quickly through the system achieves this goal.
However, administration of effective neuroprotective strategies would allow us to shift the entire curve upward along the y-axis, allowing for a better functional outcome at every time point. Neuroprotective therapies may also increase the volume of tissue that is affected by our recanalization methods. We recognize that there is a difference between ‘recanalization’ and ‘reperfusion’. Microvascular failure and a ‘no-reflow’ phenomenon may prevent blood from reaching the capillary level even after the large vessels are opened. Despite showing great promise in animal models, translating effective neuroprotective strategies to the clinical arena has failed in the past. However, we have never had an efficient/effective method of opening blood vessels quickly that did not require medication, such as tissue plasminogen activator, that could alter/affect the properties of putative neuroprotective agents. Further, we have lacked the effective delivery platforms that we now have.
Neuroprotective strategies before, during, and after mechanical thrombectomy procedures have great relevance. Field administration of neuroprotective agents by paramedics is an attractive paradigm. Saver et al7 pioneered, and refined, this delivery platform in their Fast-Mag trial. This allows a treatment to begin working on route to the hospital. This probably provides the earliest point at which we could slow, or diminish, the deleterious cellular processes resulting from large vessel occlusion and ensuing ischemia. Imagine the positive impact we could derive from actively treating our patients while they are in transit to the emergency room or from a primary stroke center to one with endovascular capabilities. We can also now leverage regional and local delivery of therapeutic agents to the intracranial circulation and the ischemic tissue bed. Catheter-based infusion of neuroprotectants is intuitive. This type of delivery could allow medications to reach previously inaccessible tissue and reduce systemic dose effects. Even if the sole purpose of an intra-arterial neuroprotective therapy were to reduce the rate of hemorrhagic conversion following thrombectomy, it would be invaluable.
Treatments that were once considered failures or have never been attempted can gain relevance once new procedures, technologies, or delivery routes become available. This is evident in our own field. Endovascular techniques allow IA chemotherapy delivery for retinoblastoma. Aneurysm coiling was facilitated by the advent of microcatheters. Clip ligation of cerebral aneurysms would not be safe without the surgical microscope.
Discussion of specific neuroprotective therapies that might prove effective is beyond the scope of this column. Rigorous preclinical testing and adherence to the Stroke Treatment Academic Industry Roundtable (STAIR) recommendations are important.8 We, as a group, must form a partnership with translational scientists and stroke neurologists to leverage optimal methods and delivery platforms. Mechanical thrombectomy procedures, and the neuroendovascular surgeons performing them, will probably play a central role in these advances. Our endovascular suites will provide the portals/facilities for application of these therapies. While neuroendovascular surgeons have occupied prominent roles in device development and computational fluid dynamics research, these new delivery platforms open exciting doors for involvement and leadership in neuroprotection research. Attempts to combine IV neuroprotectants and mechanical thrombectomy procedures are underway in Escape NA-1, a pivotal phase 3 trial. We hope this trial will generate further enthusiasm to realize the potential synergies of combination therapies. If efforts such as this are feasible, safe, and potentially effective, they will be just the beginning.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.