Neurocritical Care

7. Endovascular Recanalization in Acute Stroke

A 53-year-old man with history of hypertension and atrial fibrillation previously treated with ablation and currently not anticoagulated presented to an emergency department after developing sudden onset of speech difficulties and right-sided weakness. Initial head CT scan showed no acute abnormalities. The patient had no contraindications for thrombolysis. He was treated with 0.9 mg/kg of intravenous recombinant tissue plasminogen activator (rt-PA) starting 2 hours after symptom onset. He was then transferred to our hospital for further assessment.

On arrival to our emergency department he is alert, globally aphasic, and has a right hemianopia, left gaze preference and right hemiplegia. His NIH stroke scale sum score is 22.

What do you do now?

Intravenous thrombolysis with rt-PA within 4.5 hours after symptom onset is the only recanalization therapy supported by solid evidence and currently considered standard of care. However, commonly we encounter patients with severe deficits who fail to improve after intravenous thrombolysis or have contraindications for this treatment. In these cases we and many other centers around the world consider the option of attempting endovascular recanalization. Endovascular recanalization can be achieved by infusing drugs or using mechanical devices. Only a pharmacological approach has been shown effective in a randomized controlled trial. This trial (PROACT-II) tested intra-arterial pro-urokinase injected in the clot within 6 hours of stroke symptoms. This drug is no longer manufactured, and intra-arterial rt-PA is used instead. Currently, devices for mechanical embolectomy are used first when attempting endovascular recanalization while intra-arterial thrombolysis has become more often an adjuvant therapy. It is true that using whatever it takes to open an occluded major artery is justified because whether or not recanalization is achieved strongly predicts outcome in these patients. Yet it is unfortunate that the strategy of mechanical embolectomy was not evaluated more rigorously prior to their aggressive marketing. The field of endovascular stroke treatment is in flux, influenced by the newest (ingenious) device and without a consensus among “neurointerventionalists” on what should be the best practices. Randomized trials seem unlikely to be completed soon. Yet, there is a good reason to be optimistic that the emergent care of patients with severe ischemic stroke due to a major intracranial vessel occlusion may improve substantially in the future.

The major question, however, is what patients should be considered good candidates for endovascular therapies. We have incorporated CT angiogram and CT perfusion in our decision model to determine who has the best opportunity of improving after recanalization. Our selection criteria are summarized in Table 7.1.

We favor endovascular recanalization when there is a major intracranial vessel occlusion (M1 or large M2 branch of the middle cerebral artery, extracranial or intracranial carotid artery, dominant vertebral artery, or basilar artery) along with radiological evidence of ischemic penumbra (more than 25% mismatch between the area of perfusion abnormality and the area of reduced blood volume) in the absence of a large infarction (as estimated by the area of reduced cerebral blood volume). We tend to estimate the region of ischemic penumbra by the mismatch between the mean transit time and the cerebral blood volume. This model is more sensitive than comparing cerebral blood flow versus cerebral blood volume, but we realize it is less specific and might overestimate the area of salvageable tissue. Other groups use MRI scans (diffusion/perfusion mismatch) for patient selection. The two imaging techniques appear to be fairly comparable for decision-making.

TABLE 7.1 Conditions to be Met by Candidates for Endovascular Recanalization Therapy for Acute Ischemic Stroke

Severe, incapacitating neurological deficits

Large intracranial vessel occlusion

Presence of radiological penumbra

    Failure of intravenous thrombolysis*

    or

    Contraindications for intravenous thrombolysis, such as:

Time from symptom onset > 4.5 hours

Recent surgery

History of intracranial hemorrhage

Active anticoagulation

Good prestroke level of function

Good rehabilitation potential

*We occasionally proceed directly with endovascular recanalization attempt in cases of carotid artery occlusion or basilar artery occlusion.

Large areas of infarction (by restricted diffusion on MRI or reduced cerebral blood volume on CT perfusion scan) before the intervention strongly predict postprocedural bleeding. Therefore, patients with these findings should not be considered safe candidates for reperfusion therapy, and the rates of symptomatic hemorrhage may be as high as 50–80%. (To put this rate in perspective, among all patients, the rate of symptomatic intracranial bleeding after endovascular stroke therapy is approximately 10% regardless of the strategy used.)

The number of devices approved for mechanical removal of intracranial clots is increasing. Clot retrievers (MERCI device) and suction/separator catheters (PENUMBRA system) are currently most often used, but retrievable intracranial stents hold great promise. The selection of these devices varies (mostly determined by the personal preference of the neurointerventionalist), and more than one type may be tried in the same case. Intra-arterial rt-PA is frequently infused when devices fail to open the vessel or achieve only partial opening.

Studies publishing the experience with the use of certain devices have reported rates of recanalization in excess of 80%. It remains to be shown whether this can be reproduced in most practices. Of those patients who recanalize, a substantial proportion experience improved deficits but only a minority regains good function. While it is true that this can be explained because these patients start with large areas of ischemia and severe symptoms, there may be other factors apart from recanalization that affect the chances of recovery. For instance, it has been proposed that doing the intervention under general anesthesia rather than conscious sedation might worsen the chances of favorable functional recovery. Other factors associated with worse prognosis after endovascular stroke therapy are listed in Table 7.2.

TABLE 7.2 Indicators of Poor Prognosis after Acute Endovascular Stroke Therapy

Lack of recanalization or persistent distal occlusion

Worse initial stroke severity

Large area of diffusion restriction or reduced CBV before the intervention

Absence of large radiological penumbra before the intervention

Poor collateral arterial supply

Internal carotid artery occlusion

Postprocedural intracranial hemorrhage

Older age

Major comorbidities

General anesthesia

Atrial fibrillation

Diabetes mellitus

Admission hyperglycemia

CBV, cerebral blood volume.

Probable associations in italics

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FIGURE 7.1 CT perfusion revealing a large mismatch between the areas of reduced cerebral blood volume (A) and decreased cerebral blood flow (B).

Our patient represents a common clinical scenario—major deficit despite IV rt-PA and opportunity of an endovascular intervention. After confirming the presence of persistent left middle cerebral artery occlusion and a large area of ischemic penumbra in the left middle cerebral artery territory (Figure 7.1), the patient was taken to the angiography suite. The intervention started 3 hours and 30 minutes after symptom onset. Large amounts of clot were suctioned and the patient also received 6 mg of intra-arterial rt-PA. Recanalization was achieved after 80 minutes (Figure 7.2). The patient evolved favorably over the following days. He was initially discharged to the inpatient rehabilitation unit and then went home 21 days after the stroke. By that time, he had regained functional independence with mild residual expressive dysphasia, a right visual field deficit, and mild to moderate right hemiparesis. He could walk with a cane and climb a flight of stairs without assistance. His NIH stroke scale sum score was 5. Three months later he had mild residual deficits (modified Rankin score of 2). His brain infarctions are shown in Figure 7.3.

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FIGURE 7.2 A) Preprocedural cerebral catheter angiogram showing occlusion of the left middle cerebral artery. B) Recanalization after endovascular intervention.

As illustrated by this case, we have seen patients improving substantially after complete (Figure 7.4) or even partial endovascular recanalization. Other patients fail to get any better, and some others develop hemorrhagic conversion or a large intracerebral hematoma. Large territorial infarcts may go on to develop swelling, resulting in more complex decisions (discussed in chapter 8). In fact, the care of patients with a major ischemic stroke has become a specialized field, and there is proof that these patients do better when admitted to stroke units or neurosciences intensive care units manned by specialized teams.

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FIGURE 7.3 Brain infarctions on MRI (diffusion-weighted imaging sequence).

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FIGURE 7.4 Example of endovascular recanalization using the MERCI device. A) Preprocedural cerebral catheter angiogram showing occlusion of the right middle cerebral artery. B) Recanalization of the artery following endovascular intervention. C) Photograph of the clot retrieved from this patient by the MERCI device.

KEY POINTS TO REMEMBER REGARDING ENDOVASCULAR RECANALIZATION OF ACUTE STROKE

· Endovascular recanalization therapies are not part of the standard of care in acute stroke patients but can be useful in carefully selected candidates with territorial ischemia, large intracranial vessel occlusion, and absence of sizable established infarction.

· Evaluation of radiological penumbra (with CT perfusion or MRI) may help identify the most appropriate candidates for endovascular therapy.

· Recanalization by endovascular means can be attempted after failed intravenous thrombolysis or in patients with contraindications for intravenous thrombolysis.

· While recanalization can be achieved in a majority of patients, and patients who recanalize have better chances of recovery and often improve, one of ten patients will have a hemorrhage and get worse and only one in three or four patients will regain full functional independence.

Further Reading

Baker WL, Colby JA, Tongbram V et al. Neurothrombectomy devices for the treatment of acute ischemic stroke: state of the evidence. Ann Intern Med 2011; 154:243–252.

Brinjinkji W, Rabinstein AJ, Kallmes DF et al. Patient outcomes with endovascular embolectomy therapy for acute ischemic stroke: A study of the national inpatient sample 2006–2008. Stroke 2011; in press.

Casta o C, Dorado L, Guerrero C et al. Mechanical thrombectomy with the Solitaire AB device in large artery occlusions of the anterior circulation: a pilot study. Stroke 2010; 41:1836–1840.

Furlan A, Higashida R, Wechsler L et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. PROlyse in Acute Cerebral Thromboembolism. JAMA 1999; 282:2003–2011.

Hallevi H, Barreto AD, Liebeskind DS et al; UCLA Intra-Arterial Therapy Investigators, Grotta JC, Savitz SI. Identifying patients at high risk for poor outcome after intra-arterial therapy for acute ischemic stroke. Stroke 2009; 40:1780–1785.

Molina CA. Reperfusion therapies for acute ischemic stroke: current pharmacological and mechanical approaches. Stroke. 2011;42:S16–S19.

Penumbra Pivotal Stroke Trial Investigators. The penumbra pivotal stroke trial: safety and effectiveness of a new generation of mechanical devices for clot removal in intracranial large vessel occlusive disease. Stroke 2009; 40:2761–2768.

Smith WS, Sung G, Saver J et al. Mechanical thrombectomy for acute ischemic stroke: final results of the Multi Merci trial. Stroke 2008; 39:1205–1212.

Wintermark M, Meuli R, Browaeys P et al. Comparison of CT perfusion and angiography and MRI in selecting stroke patients for acute treatment. Neurology 2007; 68: 694–697.