Acute Stroke Management

Pierre Y. Gobin and Edward D. Greenberg

Stroke is the leading cause of disability and the third leading cause of death in the United States, with approximately 795,000 patients a year experiencing a stroke, at an annual cost of $40.9 billion.¹ Almost 90% of strokes are ischemic and arise from arterial thrombotic or thromboembolic occlusion. Loss of cerebral blood flow results in cerebral ischemia, which cascades to infarction if brain perfusion is not rapidly restored. The goal of acute ischemic stroke (AIS) intervention is to minimize cerebral damage by restoring blood flow to ischemic brain tissue as efficiently and safely as possible. In 1995, results from the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study Group² demonstrated that in carefully selected ischemic stroke patients, significant clinical benefit at 3 months is observed after intravenous (IV) administration of tissue plasminogen activator (tPA) performed within 3 hours of AIS onset. More recent studies have shown that the window for treatment could be extended to 4.5 hours in certain patients.^3,4 Despite the benefits of IV tPA, which resulted in U.S. Food and Drug Administration (FDA) approval for the treatment of AIS, the utility of the drug for the vast majority of AIS patients is limited in actual practice. Because of the limited time window and other stringent exclusion criteria (Table 92-1), only 2% to 6% of stroke patients are administered IV tPA.^5,6 When treated with IV tPA alone, patients with large-vessel ischemic stroke, which carries the highest morbidity and mortality rate, still have overall poor clinical outcomes, most likely because IV tPA fails to recanalize up to 70% of large artery occlusions.⁷ Endovascular stroke intervention is aimed at treating these large-vessel strokes and expanding the proportion of the AIS population eligible for acute treatment.

TABLE 92-1

Exclusion Criteria for Intravenous Administration of Tissue Plasminogen Activator (tPA)

• 3 hours from stroke onset

• Minor or resolving deficits, NIHSS score < 4

• Sustained hypertension (systolic BP > 185 mmHg/diastolic BP > 110 mmHg)

• Seizure at onset

• International normalized ratio > 1.7

• Intravenous heparin with partial thromboplastin time > 40 s or low-molecular-weight heparin in past 48 hours

• Platelet count < 100,000/mm³

• Glucose > 400 mg/dL or < 50 mg/dL

• Stroke, myocardial infarction, or head trauma in past 3 months

• Major gastrointestinal or genitourinary hemorrhage in past 3 weeks

• Major surgery in past 2 weeks

• Noncompressible arterial puncture in past 7 days

• Past intracerebral hemorrhage, subarachnoid hemorrhage, or intraventricular hemorrhage

• CT scan with intracerebral hemorrhage or hypodensity in greater than one third of middle cerebral artery territory

BP, Blood pressure; CT, computed tomography; NIHSS, National Institutes of Health Stroke Scale.

Indications

Careful patient selection for endovascular acute stroke treatment is paramount to successful clinical outcome. Ideally, at the time of the intervention, the patient should have minimal cerebral infarction, with a large ischemic penumbra that will revitalize once cerebral blood flow is restored. This should ensure maximal clinical benefit and help minimize the principal risk of endovascular AIS therapy, namely intracerebral hemorrhage (ICH). Table 92-2 summarizes the indications, which represent common knowledge within the neuro-interventional community at the time of this writing. It is important to note that mechanical embolectomy using the MERCI and Penumbra devices is not FDA-approved for the specific clinical indication of AIS. Use of these devices is based on single-arm trials sponsored by the respective companies (Concentric Medical and Penumbra), designed to gain 510K clearance from the FDA for the purpose of vessel recanalization and/or thrombus removal. As for intraarterial (IA) thrombolysis, although such treatment is based on the positive results of the randomized PROACT II trial (Prolyse in Acute Cerebral Thromboembolism),⁸ these results were not sufficient to achieve FDA approval.

TABLE 92-2

Indications for Endovascular Acute Stroke Therapy

NIHSS, National Institutes of Health Stroke Scale; tPA, tissue plasminogen activator.

^*Internal carotid artery (including bifurcation, or “T” occlusions), middle cerebral artery (first and second divisions), vertebral artery, basilar artery, or proximal posterior cerebral artery.

^†≤12 hours for basilar artery occlusion, although efficacy not proved.

Patients eligible for interventional stroke therapy include those arriving within 3 hours of stroke onset who have systemic contraindications to IV tPA treatment, as listed in Table 92-1. Endovascular stroke therapy is also indicated for patients arriving after 3 to 8 hours from stroke onset, because mechanical embolectomy and IA thrombolysis theoretically carry a lower risk of ICH than IV tPA after recanalization if performed under the same conditions. The likelihood of postrevascularization ICH depends on both temporal and tissue factors, as well as the extent of the induced coagulopathy. Large tissue infarctions, especially involving the basal ganglia, and prolonged duration of ischemia both elevate the risk of reperfusion hemorrhage. The duration and extent of ischemia determine the degree of neuronal death and cerebral tissue infarction, which progress in a time-dependent fashion.⁹ Although these factors are present regardless of treatment, it is the minimalization and even omission of a thrombolytic drug that enables the prolonged time window associated with IA therapy. The upper limit of this time window, however, is not certain. Data from the PROACT II trial, a randomized controlled trial of IA prourokinase, suggest that the upper limit for recanalization should be 8 hours after symptom onset. In the special case of basilar artery occlusion, these time-to-treat guidelines may not apply, and some centers will treat aggressively up to 24 hours after stroke onset, given the dismal 80% to 90% mortality rate associated with untreated acute basilar artery occlusion and the numerous series showing some positive outcomes after late endovascular recanalization.¹⁰ A key concept to consider when treating AIS, besides the time from symptom onset, is the amount of viable brain tissue at risk for infarction (penumbra) and the amount of core infarction present. Most would agree that patients with minimal or no core infarction and a large amount of penumbra are good candidates for endovascular treatment, regardless of the time from symptom onset, whereas patients with a large amount of core infarction (>100 mL) are not considered to be good candidates for endovascular treatment, owing to the higher risk of hemorrhage. Higher risk of hemorrhage may make even patients with greater than 70 mL of core infarction unsuitable candidates for endovascular treatment.

Interventional stroke treatment is limited to patients with significant neurologic deficits, namely patients with National Institutes of Health Stroke Scale (NIHSS) scores greater than 4, except for patients with isolated aphasia or hemianopsia. In addition, patients with fluctuating symptoms and evidence of a large-vessel occlusion, even with little deficit at the time of treatment, may qualify for endovascular therapy. These patients typically have sufficient collateral circulation to maintain adequate cerebral blood flow to minimize neurologic deficits, but this compensation is nearly invariably temporary. IA stroke treatment is also indicated for patients who fail to recanalize after IV tPA administration. Finally, endovascular revascularization requires the angiographically demonstrable arterial occlusion of an accessible artery. Appropriate target vessels include the internal carotid artery (ICA), the first (M1) and second (M2) division of the middle cerebral artery (MCA) (Fig. 92-1), the vertebral artery, the basilar artery, and the first (P1) segment of the posterior cerebral artery.

FIGURE 92-1 A, Right carotid artery angiogram, intracranial anteroposterior view, demonstrating acute occlusion of proximal M1 segment of right middle cerebral artery (MCA) in a 77-year-old man. B, After mechanical embolectomy with the Merci L6 Retriever, right MCA is recanalized. Note dissection flap, seen in proximal M1 segment, that occurred as a consequence of clot retrieval.

Contraindications

Endovascular stroke therapy is contraindicated in patients with ICH, large established infarction (>one third MCA territory computed tomography [CT] hypodensity or magnetic resonance imaging [MRI] diffusion-weighted abnormality), or completed infarction without salvageable territory. CT perfusion, MRI diffusion/perfusion-weighted (DWI-PWI) mismatch, and MRI diffusion-weighted/clinical mismatch are all useful in determining the extent of the latter and aid in patient selection, especially when contemplating late recanalization (>3 hours). A DWI-PWI mismatch may be found in up to 70% of patients imaged within 6 hours from stroke onset,¹¹ and it is hypothesized that these patients may derive the most clinical benefit from endovascular intervention. Some relative contraindications to IA therapy include rapidly improving neurologic examination, NIHSS over 30, and a history of anaphylaxis to thrombolytic drugs or iodinated contrast material.

Equipment

Digital biplane angiography with road-mapping capability is optimal for the safe and efficient performance of endovascular acute stroke intervention. General endotracheal anesthesia is required for most procedures, although monitored conscious sedation is at times adequate for cooperative patients. Our experience is that patients with left hemisphere strokes are paradoxically more cooperative than right hemisphere stroke patients. The patient should have an arterial line placed for blood pressure management, which may become crucial after recanalization to prevent reperfusion hemorrhage. In the time before vessel recanalization, it is critical to maintain adequate perfusion pressure by elevating the patient’s blood pressure to significantly above the patient’s baseline values, particularly during administration of general anesthesia. A recent study comparing outcomes of AIS patients ¹² showed that patients placed under general anesthesia during endovascular treatment for anterior circulation had higher rates of poor neurologic outcome and mortality, a difference that could potentially be due to lack of adequate blood pressure support during general anesthesia. Common femoral artery access requires a minimum of a 5F sheath for IA thrombolysis and up to a 9F sheath for the Merci Retrieval System. A 5F diagnostic catheter is used for cerebral angiography to demonstrate and characterize the arterial occlusion. The catheter and sheath are maintained under continuous heparinized saline flush (5000 units heparin per liter normal saline), and nonionic iodinated contrast (Omnipaque [GE Healthcare, Piscataway, N.J.]) is used for angiography. Once an intervention is deemed appropriate, minimal systemic anticoagulation is initiated with 2000 to 3000 units of IV heparin.

A guide catheter is required for device support during thrombolysis and embolectomy. A microcatheter and microwire facilitate navigation past the occlusion, and the microcatheter provides a conduit for IA thrombolytic infusion. More specific details about the basic equipment required for IA treatment are summarized in Table 92-3.

TABLE 92-3

Basic Equipment for Acute Stroke Management

Device	Example	Company
Femoral sheath	5F-9F, 11-90 cm*	Cordis Corp., Miami Lakes, Fla.
Diagnostic catheter	TempoVert	Cordis
Guide catheter*	6F Envoy	Cordis
	Guider Softip XF guide catheter	Boston Scientific, Natick, Mass.
	Shuttle Introducer	Cook Inc., Bloomington, Ind.
	Balloon Guide Catheter	Concentric Medical Inc., Mountain View, Calif.
Intermediate catheter	DAC	Concentric Medical
Microcatheter	Excelsior SL10	Boston Scientific
	Excelsior 1018	Boston Scientific
	Prowler Plus	Cordis
Microguidewire	Transend-14	Boston Scientific
	Synchro-14	Boston Scientific
Thrombolytic	tPA	Genentech Inc., San Francisco, Calif.
	Abciximab (ReoPro)	Eli Lilly, Indianapolis, Ind.