The neurosurgical approach to the management of ischemic stroke has evolved dramatically over the past century with the bulk of these changes occurring over the past 25 years. While it is true that ischemic strokes continue to have devastating consequences, the modern neurosurgeon has become better equipped than-ever to make a significant impact on the lives of those affected. With recent advances in our fund of knowledge and with new tools in an updated armamentarium, neurosurgeons can now much more frequently not only prevent stroke, but restore blood flow and sometimes even completely restore neurological function to patients in the early stages of a stroke. The use of modern neurosurgical interventions in the management of stroke can be an extremely profound and rewarding experience. To continue to move forward and to fully appreciate the evolution of the newer neurosurgical approaches to the management of ischemic stroke it is important to review some of the historical events which have led to this point. It is also important to point out that a comprehensive review of the scientific and clinical contributions to the management of ischemic stroke would be very vast and would fill many chapters of many textbooks. With that notion in mind, the focus of this article will be specifically on reviewing both historical and current reports in the literature related to revascularization techniques, which are of interest to the field of neurosurgery.

Chiari firmly tied the association between occlusive disease of the carotid arteries and the symptoms of ischemic stroke in 1905 leading to further investigations of potential treatments.5)24) Chao at the Medical College of Peking performed the first successful surgery aimed at treating carotid occlusion on two people with carotid artery disease and anxiety and depression-like symptoms in 1938.4) The procedure he described was a carotid artery excision without restoring blood flow.4) Following the procedure both patient's mental conditions reportedly resolved leading to carotid excision becoming the neurosurgical treatment of choice for occlusion of the carotid artery.4) Very few subsequent patients improved and it is hypothesized that the improvement reported in successful cases came form prevention of repeat embolization. Although this procedure was infrequently performed it remained the treatment of choice throughout the 1940's.18)24) The first well-documented procedure that successfully restored blood flow to the internal carotid artery was done in Buenos Aires by Carrea, Molina, and Murphy.25) Angiography revealed severe narrowing of the internal carotid artery above the bifurcation in a patient with symptoms of ischemic stroke.25) The internal carotid and external carotid artery were cut 5 mm above the lesion. The proximal external carotid artery and distal internal carotid artery were anastomosed and patency was confirmed by angiography.25) This was the first reported internal-external carotid artery bypass.25) The patient recovered from hemiparesis and aphasia.25) This was the first demonstration that returning blood flow to the brain following ischemic stroke could return motor function. While this particular procedure was successful, carotid endarterectomy would soon surpass it to become the technique of choice in the coming years for the management of carotid stenosis.24)

DeBakey at Baylor University successfully performed the first carotid endarterectomy in 1953.8)9) Interestingly, DeBakey did not localize the lesion with angiography and performed his first endarterectomy based on reports that lesions were frequently localized to the carotid bifurcation.8)9) DeBakey described removing a partially occluded clot from the common carotid bifurcation and closing the vessel.8)9) This initial successful operation lead to a rapid increase in attempts to restore flow to occluded carotid artery segments. While DeBakey was the first to perform the procedure, Cooley became the first to publish on successful endarterectomy in 1956.7) He created a temporary polyvinyl shunt to be placed within the internal carotid bypassing the lesion until he could remove the plaque and became the first to successfully use this technique.7) Various techniques for this surgery developed over the ensuing years using varying degrees of temporary arterial bypass. Some surgeons choose not to use a bypass if the procedure will be quick and there is enough blood flow from the contralateral circulation. Over the next 40 years, surgical technique moderately improved although the indications for this procedure became less clear as negative reports on the procedure emerged.

The first of the randomized clinical trials regarding ischemic stroke and the effectiveness of carotid endarterectomy had negative results when compared to medical management leading to a relative decrease in procedural volume in the late 80's.11)28) The North American Symptomatic Carotid Endarterectomy Trial (NASCET) trial and the European Carotid Surgery Trial were large randomized controlled trials published in the 90's that both showed substantial benefit of carotid endarterectomy in symptomatic patients who had carotid stenosis of 70–99%.10)23) The NASCET trial demonstrated a 9% rate of ipsilateral stroke at two years in surgical patients with high-grade stenosis compared to a 26% rate in the medically managed patients with high-grade stenosis (absolute risk reduction [ARR] 17% ± 3.5%, p < 0.001).23) Medical management in this trial involved management of comorbid conditions plus aspirin at 1300 mg per day. The medically managed group of patients with high grade stenosis had a significantly higher rate of strokes that caused permanent disability or death compared to the surgically managed patients (13.1% vs. 2.5%; ARR 10.6% ± 2.6 (p < 0.001).23) While the perioperative mortality rate was slightly higher in the surgical group, this risk was negated by the significant reduction in mortality measures after a two year follow up.23) The European Carotid Surgery Trial was structured very similarly and showed that after 3 years there was a 12.3% rate of death from surgical complication, or stroke in the high grade stenosis group treated surgically compared to 21.9% percent in the medically managed group (ARR 9.6%, standard deviation 3.32, p < 0.01).10) While these studies left a large number of questions unanswered in particular, what to do with asymptomatic patients and with patients with moderate stenosis, this therapy was the first neurosurgical procedure that was proven with a randomized controlled trial to have a mortality benefit.

The early data regarding the efficacy and safety of mechanical thrombectomy supported its usage in patients in which t-PA could not be used. There were three studies done early in the development of mechanical thrombectomy that primarily looked at the benefit of endovascular treatment with the first and second generation mechanical thrombectomy devices instead of IV t-PA and as a follow up treatment for people who failed t-PA therapy which all failed to show any benefit to endovascular treatment.2)6)19) The Synthesis Expansion: A Randomized Controlled Trial on Intra-Arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke (SYNTHESIS Expansion) study compared intraarterial t-PA and mechanical thrombectomy as a substitute for initial treatment with IV t-PA and failed to show a benefit.6) Two later studies, Interventional Management of Stroke (IMS) III and Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE), examined the benefit of these treatments as follow up interventions in patients who continued to have large artery occlusion following the administration of t-PA.2)19) MR RESCUE and IMS III both failed to show any benefit using these interventions as follow up treatment for people who failed initial treatment.2)19) These studies achieved a rate of recanalization of 27–41%.2)19) As mechanical thrombectomy technology improved and became more widespread there has been renewed interest in research utilizing these therapies both as follow up therapies and as a primary therapy in lieu of IV t-PA.

From January 1, 2010 to December 23, 2015 there have been five significant positive trials that looked at utilizing stent retrievers in conjunction with t-PA, which have established mechanical thrombectomy and endovascular stroke therapy as the standard of care for proximal anterior occlusions.15) These five trials demonstrated a significant improvement of adequate recanalization (Thrombolysis in cerebral infarction grade 2b/3) in 59–88% of patients treated with t-PA in conjunction with stent retrievers compared to the 27–41% that was shown in the previous trials as well as a significantly reduced chance of disability at 90 days (Table 1). All 5 studies randomly assigned patients to receive thrombectomy plus medical care or medical care alone. Before randomization all patients were treated with a standard dose of IV t-PA if eligible. A recent Meta-analysis of patient data from 570 patients from all five trials and showed a significantly higher the National Institutes of Health Stroke Scale (NIHSS) score after 24 hours as well a greater improvement from baseline to 24 hours NIHSS among all patients assigned to thrombectomy.15) The Meta-analysis also reported that the 90-day mortality and risk of intraparenchymal hematoma and symptomatic intracranial hemorrhage did not differ between populations.15) Additionally, a subgroup analysis showed improved outcomes in several subgroups of special interest and typically excluded including patients older than 80 years, patients randomized more than 6 hours after symptom onset, and patients not receiving IV t-PA.15)