Current practices

Carotid artery stenting (CAS) is an approved treatment for symptomatic internal carotid artery stenosis and is the preferred intervention in high-risk cardiac patients [24]. Procedure-associated cerebral embolization of plaque (PCEP) from the carotid lesion is a known complication of CAS [25–31]. To prevent distal embolization events (DEE), cerebral embolic protection devices (CEPD) were developed for use in CAS [32, 33]. Although no direct comparison exists between CAS with and without CEPD use, numerous registries and series support CEPD’s neuroprotective benefit [34–37]. Historically, these devices were filter-based, but newer systems that utilize flow reversal technology have also become available [27]. Currently, three different types of CEPD are in routine use during CAS: filters, proximal occlusion balloons (POB), and distal occlusion balloons (DOB).

All devices are introduced after sheath placement. Filters and DOB devices are positioned distally to the carotid lesion treatment area. POB devices with flow reversal are placed proximally to the lesion of interest and are consequently the only devices that provide protected crossing of the stenotic lesion [38]. Filters are commonly favored in practice because of their ease of use, preservation of anterograde flow, and allowance for contrast injection to enable excellent vessel and lesion visualization during CAS [37, 39]. DOB methods, on the other hand, are less in favor due to their associated limitations and risks: interruption of anterograde flow, preclusion of adequate lesion visualization after occlusion, and known procedural risk of severe ischemia [40]. If either balloon occlusion method is chosen, determination of appropriate collateral flow to the brain should first occur to reduce risk of intra-procedural ischemic complications [40].

Device choice is operator dependent as it is undetermined which ones provide best protection and for which subpopulations of symptomatic internal carotid artery disease they are best indicated. Age, hypertension, lesion morphology, and aortic type have been found to be risk factors for DEE during CAS [41]. Additionally, stent type (open or closed) may also contribute differentially to DEE frequency and severity in CAS [30, 31].

CEPD may not be considered neuroprotective in all CAS cases. The decision to use a CEPD should be individually based and take into consideration other factors that may lead to poor outcome [34, 37].

Investigative practices

There are multiple clinical trials currently underway and in the pipeline to investigate the long-term clinical effects of DEE and which device systems may most effectively reduce PCEP/DEE occurrence in CAS:

Investigative practices

Magnesium functions in multiple capacities including as an antagonist to the N-methyl-d-aspartic acid (NMDA) and calcium channel receptors that aid in limiting ischemic effects. These, in addition to its excellent blood–brain barrier permeability and index of safety, have made it a potential neuroprotective therapy in hyperacute and acute stroke [46–48].

Although past large trials [7, 8] have not found intravenously delivered magnesium to provide a definite neuroprotective benefit in stroke, targeted delivery through endovascular means may. A multicenter phase I/II safety and feasibility evaluation of intra-arterial delivery of magnesium in endovascular treatment of hyperacute large-vessel occlusive ischemic stroke is currently enrolling patients [49]. In this study, magnesium is locally infused via catheter to the affected vascular territory prior to revascularization. If endovascular delivery of magnesium is determined safe and feasible, its phase III evaluation on clinical outcome is expected. Such evaluations may help determine the role for neurointervention in neuroprotection therapies and approaches in management of hyperacute ischemic stroke.

Investigative practices

Nimodipine’s success as an oral/intravenous prophylaxis against subarachnoid hemorrhage (SAH)-related vasospasm has led to its investigative crossover use in the endovascular management of SAH with promising outcomes. In multiple small, single-center series, intra-arterial delivery of nimodipine has been associated with improved clinical and radiographic outcomes especially in cases of refractory vasospasm [50, 51]. Drug delivery is achieved through intra-arterial infusion to the affected cerebral arteries after catheter placement in the relevant internal carotid or vertebral artery. Future trials are necessary to determine the role neurointervention will play in the management of SAH-related vasospasm.

Current practices

Hyperglycemia in acute stroke carries multiple deleterious effects. It augments multiple neurotoxic pathways of the ischemic cascade exacerbating neuronal injury in acute stroke [1, 52–55]. Furthermore, it worsens stroke-related morbidity and mortality outcomes and may negatively impact clinical responses to and complications of thrombolytic therapies [52–54]. Consequently, euglycemic control has been incorporated into standardized management of acute stroke at stroke centers because of its neuroprotective potential. In line with this, neurointervention periprocedural management for acute ischemic stroke should include a euglycemic goal range. This may be accomplished through adherence to approved protocols of care that address proper diet, intravenous fluids, and indications for aggressive insulin therapy.

Investigative practices

Although a great deal of evidence supports the neuroprotective benefits of euglycemic maintenance in acute stroke, past large, multicenter trials have shown only nonsignificant clinical benefits of aggressive glycemic regulation [54, 55].

The Stroke Hyperglycemia Insulin Network Effort (SHINE) is a phase III trial that may finally prove the neuroprotective benefits of euglycemia in acute stroke. The trial is currently enrolling patients to evaluate the role of euglycemic maintenance as a neuroprotective adjunctive therapy to thrombolytic and endovascular therapies in acute ischemic stroke [56, 57]. It is one of a few first-of-its-kind combination therapy studies in acute ischemic stroke and holds promise for improving on the clinical responses and complications seen with acute ischemic stroke therapies.

Current practices

Hypothermia is protective against cellular injury through its reduction of energy requirements and limiting of neurotoxic processes [1, 58, 59]. Past trials have supported hypothermia’s neuroprotective benefit [59–61] and have led to its use in critical care management of life-threatening neurological disease states such as SAH that may also require neurointervention. Hypothermia may be achieved and maintained through either device-based external or endovascular means. Critical care protocols guide hypothermic indication and management on a site-specific basis. Neurointervention periprocedural management may therefore necessarily include hypothermic regulation if clinically warranted.

Investigative practices

Although hypothermic regulation and neurointervention are used conjunctively in stroke management, it is undetermined how the two affect one another and clinical outcomes. Multiple clinical trials are currently underway to better understand hypothermia’s neuroprotective role in acute stroke treatment apart from and in combination with thrombolytic and endovascular therapies:

Current practices

Nimodipine is an L-type calcium channel antagonist that is one of the few well-established neuroprotective medical therapies in stroke. Indicated for the prevention of neurological injury related to vasospasm following SAH, it is a mainstay oral/intravenous therapy of critical care SAH management and should be used as clinically warranted in cases that include neurointervention therapies as well [68].

Investigative practices

Results support neuroprotective benefit on outcomes with periprocedural nimodipine in the neurointerventional management of SAH. One small case series showed reduced vasospasm and silent ischemia with long-term intravenous nimodipine after endovascular coiling [69]. Therefore, nimodipine in the periprocedural period appears to benefit neurointervention outcomes in SAH, but its indications and dosing require further evaluation.