Intracranial Intervention and Acute Stroke

Introduction

The management of cerebrovascular disease has often lagged behind the advances made in the management of cardiovascular disease. However those same technological advances in cardiovascular devices have facilitated the development of dedicated neurovascular devices, which have resulted in a narrowing of the treatment gap. Still there remain major differences primarily due to anatomical and physiological differences between the coronary and cerebral vasculatures.

Cerebrovascular Disease

The Cerebral Vasculature

The brain and cerebral circulation have several unique characteristics and are histologically different from other vessels in the body. Shortly after penetrating the skull base (~1 cm) the cerebral arteries lose the external elastic lamina and the tunica muscularis and adventitia thin considerably. As a consequence they become significantly more fragile and prone to injury during interventional procedures. Furthermore, after penetrating the dura matter the arteries enter the subarachnoid space that overlies the surface of the brain. Any injury that results in vessel rupture or perforation (e.g., dissection) can lead to catastrophy because the resultant SAH and/or ICH can result in a rapid and marked elevation of intracranial pressure (ICP) leading to either herniation or reduction/cessation of cerebral blood flow. The elevated ICP and its consequences are difficult to manage pharmacologically and sometimes require emergent neurosurgical decompression. Another important consideration is that embolization or occlusion of distal branches or perforators, even if nearly microscopic, can result in major disability. Finally, the cerebral vessels are also extremely tortuous and prone to vasospasm. For example, the internal carotid arteries (ICAs) have 180-degree turns in their cavernous segments. The proximal segments of the intracranial ICA run through the densest bone in the human body, the petrous bone, and are subsequently anchored within the cavernous sinus and the layers of the leathery dura matter. These factors, combined with their fragility, make the navigation of endovascular devices intracranially particularly difficult and potentially hazardous.

The brain is supplied blood by the paired ICA and vertebral arteries (VAs). The ICAs are branches of the common carotid artery and have no extracranial branches. Their first important intracranial branch is the ophthalmic artery. Shortly thereafter they (variable) give off the posterior communicating artery (PCom), which is the major anterior-posterior circulation collateral. They then give off the very important anterior choroidal artery before dividing into the MCA and anterior cerebral arteries (ACAs) ( Figure 25-1 ). The VAs are the first branches of the subclavian arteries and have many muscular branches in the neck as well as collaterals to the spinal cord. They enter the foramen magnum and join together to form the single basilar artery (BA) after giving off the (usually) large posterior inferior cerebellar artery. The BA has numerous perforators and branches supplying the pons, midbrain, and remainder of the cerebellum ( Figure 25-1 ). The BA then divides into the bilateral posterior cerebral arteries (PCAs), which supply the occipital lobes. The PCom joins the ipsilateral PCA and in combination with the bilateral ICA, bilateral ACA, and single anterior communicating artery (ACom) complete the Circle of Willis. The Circle is an inherent source of collaterals and (when present) can completely supply CBF to the territory of an occluded ICA or BA. Unfortunately, a complete Circle exists in only 25% to 40% of humans.

There are essential perforating arteries that emanate from the MCA, BA, and PCA trunks ( Figure 25-1 ). These vessels supply critical structures and, although small (50-200 µm), their occlusion can cause major and disabling neurological deficits. These vessels are at risk of occlusion during intracranial interventions, especially if they were the etiology of the presenting symptoms. Furthermore, they are particularly vulnerable to wire perforation. They arise from the dorsal (superiorly in anterior-posterior view) aspect of the MCA and (posteriorly in anterior-posterior view) BA.

Acute Ischemic Stroke Treatment

Current acute stroke therapies include intravenous (IV) tissue plasminogen activator (tPA), which is effective in both small and large vessel strokes and endovascular therapy (EVT), which is used for large vessel strokes. The former was approved in 1996 by the Food and Drug Administration (FDA) based mainly upon the results of the National Institute of Neurologic Disorders and Stroke (NINDS) study. More than a decade later, on average, only 5% to 10% of patients with ischemic stroke receive IV-tPA treatment. The major limiting factors are the strict criteria for the administration of IV-tPA, in particular the narrow time window for administration of only 3 hours from clear symptom onset. Furthermore, IV-tPA is poorly effective at recanalizing larger vessels. The middle cerebral artery (MCA) recanalization rate is approximately 30% while the larger ICA is successfully recanalized in <10% of cases. Consequently, EVT has been studied as an adjunctive/alternative treatment for large vessel acute ischemic stroke. Endovascular therapy (AKA Intraarterial thrombolysis [IAT]) is not an FDA-approved treatment. The only FDA-approved treatment for acute ischemic stroke (IS) remains IV-tPA.

The indications for EVT are evolving and since there is no approved EVT for stroke, there is a great deal of variability between practitioners in the field with regards to the indications. In general, patients with acute IS presenting less than 4.5 hours meeting criteria should be offered IV-tPA, and EVT should be offered to all others, and to those who refuse IV-tPA. It is important to note that treatment with IV-tPA does not reduce stroke mortality and patients with large vessel occlusions, large thrombus burden (i.e., thrombi longer than 8 mm), and those with more severe strokes respond less well to IV thrombolysis. For these patients EVT may be considered as an (unproven) alternative to IV thrombolysis. In one observational study of 112 patients with hyperdense middle cerebral artery (MCA) sign, half of whom received IV-tPA and the other EVT, favorable outcome was doubled and risk of death reduced by two thirds in patients treated with EVT.

The traditional time window for EVT is up to 6 hours for thrombolysis and 8 hours for mechanical embolectomy. The duration of ischemia is a leading predictor of neurological outcome, but with modern penumbral imaging selection of patients for EVT may be time-independent (see further on).

Patients must also have a significant clinical deficit that warrants intervention since mild deficits (i.e., National Institutes of Health Stroke Score [NIHSS] <4) are less likely to be associated with a visible proximal large arterial occlusion; such milder strokes have an excellent prognosis on average even without treatment. On the other end of the spectrum patients with severe strokes (NIHSS >20) generally do not benefit as much from treatment. Multimodal imaging techniques such as perfusion imaging may help select patients with major deficits who have small infarct cores and large penumbral zones who may still benefit from treatment. A recent prospective cohort study (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 [DEFUSE 2]) tested whether an MRI perfusion-based definition of target mismatch (TMM) could appropriately detect who would benefit from EVT within 12 hours of stroke onset. Of the 99 patients with perfusion imaging, 78 had a TMM, and 42 of whom were treated beyond the 6-hour time window. With recanalization and a TMM there was an odds ratio (OR) of 8.5 for good neurological outcomes in patients treated >6 hours along with a 2.9 OR for those treated <6 hours, compared with those without a TMM. Importantly, no reperfusion led to infarct growth and patients without a TMM did not benefit from recanalization (OR 0.2; p = 0.004). Unfortunately there is a paucity of level 1 evidence on the use of and parameters for defining penumbra with these techniques. An alternative is to select patients using the Alberta Stroke Program Early CT score (ASPECTS): a 10-point scale with 10 representing a normal CT and 0 a complete infarct of the entire MCA territory. A baseline ASPECTS score of ≥8 is an excellent predictor of clinical response to treatment.

The contraindications for IAT are generally any that would increase the risk of ICH. A history of spontaneous ICH or an untreated ruptured aneurysm or arteriovenous malformation are contraindications to thrombolysis although mechanical embolectomy may be performed in selected patients. A history of dementia, unless mild, should be a contraindication as those patients have a low probability of recovering. Relative contraindications are active anticoagulation with any class of anticoagulant, including antiplatelet agents; one small study has shown that mechanical embolectomy may be safe.