A 68-year-old previously healthy woman experiences the acute onset of aphasia and right-sided hemiplegia. She is brought to the emergency department within the first hour after symptom onset, and emergency CT is performed.

Fig. 47.1 DSA. Left ICA angiogram in (A) AP and (B) lateral views demonstrates occlusion of the proximal middle branch of the left MCA.

CT

CT was unremarkable and did not demonstrate any signs of acute stroke, especially no hyperdense middle cerebral artery (MCA) sign. CTA demonstrated an M2 occlusion on the left side.

Acute left-sided MCA branch occlusion

EQUIPMENT

DESCRIPTION

Fig. 47.2 Unsubtracted gentle microcatheter injection in (A) AP and (B) lateral views reveals a filling defect, representing thrombus in the MCA branch.

Fig. 47.3 DSA. Left ICA angiogram in (A) AP and (B) lateral views after successful thrombolysis shows complete reopening of the entire MCA.

Stroke is one of the leading causes of death or long-term disability, and demographic changes are likely to result in an increase in both the incidence and prevalence of stroke. Stroke is a common cause of dementia, epilepsy, and depression in the elderly. More than 85% of all strokes are ischemic in nature. Up to 30 to 35% of ischemic strokes are due to extracranial or intracranial large-artery atherosclerosis. Cardioembolic strokes account for 25 to 30% of all cerebral ischemic events. Small-vessel disease accounts for 15 to 20% of all ischemic strokes. The remaining ischemic strokes have either another, uncommon cause or an undetermined origin. Nearly 10% of patients with acute stroke die, and of those who survive, about 50% are disabled. Older age, a poor neurologic score on admission, high blood levels of glucose, and a large clot burden increase the chance of a poor outcome.

Ischemic stroke is caused by a critical reduction in the blood supply to the brain for a prolonged period. Following the occlusion of a brain-supplying artery, a core of infarcted tissue will develop, surrounded by tissue that is initially only functionally impaired because of a reduced blood supply. The amount of functionally impaired tissue depends on the location of the occluded vessel and the collateral blood supply. Reperfusion can salvage those cells at risk for critical hypoperfusion.

In a recent Cochrane Database Review of more than 7000 patients, Wardlaw et al stated that thrombolytic therapy, mostly administered up to 6 hours after ischemic stroke, significantly reduced the proportion of patients who died or became dependent (modified Rankin Scale score of 3–6) at 3 to 6 months after stroke (odds ratio [OR], 0.81;95% confidence interval [CI], 0.73–0.90). However, the route of administration remains controversial (i.e., intravenous, intra-arterial, or bridging therapy, which is started with the intravenous administration and continued with the intra-arterial administration of a drug).

PHYSICAL EXAMINATION

CT/MRI

• Unenhanced CT is often the first-choice modality, given its wide availability. It can detect intracranial hemorrhage and may demonstrate early signs of ischemia, including hyperdense vessel signs (at the site of the vessel occlusion), and early markers of cytotoxic edema, including loss of the cortical ribbon, loss of gray/white differentiation at the level of the basal ganglia, and brain swelling.
  
• CTA can demonstrate the site of the occluded vessel, extent of the thrombus, and, if the carotid arteries are also imaged, potential sources of the acute thrombus.
  
• Perfusion CT can differentiate functionally impaired brain tissue from already infarcted brain tissue by differences in the cerebral blood volume (< 2 mL/100 g in the infarcted core). Compared with areas of the brain that are not impaired, both irreversibly and reversibly impaired brain tissue will show increases in mean transit time and decreases in blood flow.
  
• MRI is more sensitive than CT;however, it is not as widely available, and longer delays before imaging is completed may be encountered, depending on the clinical setting. A comprehensive MR stroke protocol comprises FLAIR-weighted scans to demonstrate old infarctions, diffusion-weighted scans to demonstrate the amount of acutely and irreversibly damaged brain tissue, perfusion-weighted MRI to evaluate the tissue at risk, and MRA to demonstrate the site of vessel occlusion.
  
• For many authors, a diffusion-perfusion mismatch serves as a rational criterion for the selection of therapeutic strategies. This concept is based on the assumption that diffusion-weighted imaging demonstrates irreversibly damaged brain tissue, whereas perfusion defects indicate the area that may progress to infarction if recanalization does not occur.
  
• Alternatives to diffusion-perfusion mismatch are diffusion-clinical findings mismatch (based on differences between the extent of diffusion-weighted imaging changes and the clinical severity of the stroke symptoms) and diffusion-MRA mismatch (in which MRA methods are used to estimate the tissue at risk).
  
• Infarctions are often first seen in subcortical areas (i.e., striatocapsular infarctions) because of the persistence of cortical collateral blood flow.

• DSA can demonstrate the site of occlusion and potential leptomeningeal collaterals, as well as collaterals from the anterior and posterior communicating arteries.
  
• If not already done during prior CTA or MRA, injections of the common carotid arteries and the subclavian arteries to evaluate the origins of the ICA and the vertebral artery are essential because high-grade stenoses in these regions may be the cause of the stroke.
  
• In most instances, invasive imaging is performed immediately before intra-arterial therapies are administered.

• Depending on the clinical findings, onset of symptoms, and imaging findings, the differential diagnosis of stroke (based on both clinical and imaging findings) can be extensive and includes neoplastic, inflammatory, and metabolic disorders.
  
• Rare causes of stroke must also be considered, especially in younger patients.

CONSERVATIVE OR MEDICAL MANAGEMENT

• Intravenous thrombolysis with rtPA within a 4.5-hour therapeutic window has proved to be beneficial for patients with acute ischemic stroke.
  
• Antiplatelet therapies have proved beneficial for patients with acute stroke, and most authors recommend starting acetylsalicylic acid within the first 48 hours after acute ischemic stroke.
  
• Anticoagulation is not associated with clinical benefits in most patients with acute ischemic stroke.
  
• Neuroprotective agents have not proved beneficial thus far.

ENDOVASCULAR TREATMENT

• Intra-arterial thrombolysis with either rtPA or urokinase may be administered.
  
• Different strategies of drug delivery may be chosen. The microcatheter can be positioned at the proximal aspect of the clot, into the clot, or beyond the clot. The protocol employed in our institution is described in greater detail in the earlier section, “Description of Treatment.”
  
• Mechanical treatments may be administered. (These are discussed in greater detail in later cases.)

• Reperfusion hemorrhage
  
• Distal embolism during recanalization
  
• Nonresponsiveness of the clot to the thrombolytic drug

It is beyond doubt that longer periods of time between the onset of symptoms of ischemic stroke and the initiation of treatment are associated with a progressively lower likelihood of clinical benefit. Likewise, the probability of a good clinical outcome decreases as the time to angiographic reperfusion increases. However, the way to reach the goal of rapid recanalization remains controversial.

In intra-arterial thrombolysis, the drug is given only to those patients who have an occluded artery; the dosage to be given is usually smaller and may therefore be safer. Further data in favor of endovascular therapies are derived from the Prolyse in Acute Cerebral Thromboembolism (PROACT) trials, which demonstrated good outcomes for patients with large-vessel occlusion given intra-arterial therapy. A significant 15% increase in the chance of a good outcome was noted when patients with M1 occlusion were treated with intra-arterial thrombolysis within a 6-hour time window without an increase in mortality in comparison with those who did not receive this intervention. In a recent observational study that compared data from two stroke units where the management of stroke was similar, except that one unit performed intra-arterial thrombolysis with urokinase and the other intravenous thrombolysis with plasminogen activator, intra-arterial thrombolysis was more beneficial than intravenous thrombolysis, even though intra-arterial thrombolysis was started later.

A bridging strategy between intravenous and intra-arterial thrombolysis has the advantage of not delaying lytic therapy while identifying nonresponders with persistent large-artery occlusion. Initial positive results for this treatment strategy have been reported by the RECANALISE study, which compared recanalization rates, neurologic improvement, and functional outcome in patients treated within the first 3 hours after stroke onset either with intravenous thrombolysis alone or with a combined intravenous-endovascular approach. The authors found that an intravenous-endovascular approach was associated with higher recanalization rates than intravenous alteplase in patients with stroke and confirmed arterial occlusion. The clinical outcome was more often favorable in the intravenous-endovascular group, whereas mortality rates and rates of hemorrhagic stroke were similar in the two groups. The bridging approach is currently being tested in the Interventional Management of Stroke (IMS III) trial, in which initial intravenous tPA is followed by artery reopening with thrombolytic agents or clot retrieval if vessel occlusion is demonstrated.

According to the presently available data, intravenous thrombolysis within the first 3 hours after stroke onset will result in less than a 30% chance of reopening large arteries with a large clot burden, versus a 60% to 70% chance of recanalization with intra-arterial thrombolysis. Given these data, one may be inclined to reassess current management strategies for patients with acute stroke in the 3-hour time period. If a patient has a major large-vessel occlusion and considerable mismatch, intra-arterial treatment may be considered. If significant delays in starting intra-arterial treatment are anticipated, intravenous thrombolysis can be initiated, followed by intra-arterial treatment if recanalization does not occur. For other cases in the early time window, intravenous thrombolysis may still be considered. After the 3- (or 4.5-) hour time window, treatment should be guided by the results of the PROACT II trial, which indicated a better outcome for patients treated with intra-arterial thrombolysis within up to 6 hours after stroke onset.

• Early recanalization can improve the prognosis in acute ischemic stroke.
  
• Although intra-arterial thrombolysis has been shown to be effective, the time delay required for cerebral angiography and microcatheter positioning is a handicap that can be overcome with “bridging” therapies.

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(21):2003–2011

Jahan R, Vinuela F. Treatment of acute ischemic stroke: intravenous and endovascular therapies. Expert Rev Cardiovasc Ther 2009;7(4):375–387

Mattle HP, Arnold M, Georgiadis D, et al. Comparison of intraarterial and intravenous thrombolysis for ischemic stroke with hyperdense middle cerebral artery sign. Stroke 2008;39(2):379–383

Mazighi M, Serfaty JM, Labreuche J, et al; RECANALISE investigators. Comparison of intravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and confirmed arterial occlusion (RECANALISE study): a prospective cohort study. Lancet Neurol 2009;8(9):802–809

Schonewille WJ, Wijman CA, Michel P, et al; BASICS study group. Treatment and outcomes of acute basilar artery occlusion in the Basilar Artery International Cooperation Study (BASICS): a prospective registry study. Lancet Neurol 2009;8(8):724–730

Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 1995;333(24):1581–1587

Wardlaw JM, Murray V, Berge E, Del Zoppo GJ. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev 2009;(4):CD000213

A 68-year-old woman presents to the emergency department 5 hours after the sudden onset of left hemiparesis. Her baseline National Institutes of Health Stroke Scale (NIHSS) score is 19. Risk factors include chronic hypertension and heavy smoking. Emergency CT, including CTA and CT perfusion, is performed.

Fig. 48.1 (A) Unenhanced axial CT scan demonstrates a hyperdense right MCA sign and (B,C) slight hypodensity within the right insular and fronto-opercular regions.

CT

MCA occlusion at the M1 (Thrombolysis in Cerebral Infarction [TICI] grade, 0).

EQUIPMENT

• Standard 8F access (puncture needle, 8F vascular sheath)
  
• Standard 8F multipurpose catheter (Cordis, Warren, NJ) with continuous flush and a 0.035-in hydrophilic guide wire (Terumo, Somerset, NJ)
  
• Preparation for the aspiration procedure
  
  
  
  • Penumbra Aspiration Catheter 041, curved at vapor (30 degrees) with continuous flush (Penumbra Inc, Alameda, CA)
    
  • A 0.016-in hydrophilic micro-guidewire
    
  • Connector to the pump (pretested at −20 mm Hg)
    
  • Penumbra Separator 041
  
  
• Contrast material
  
• Recombinant tissue plasminogen activator (Actilyse; Genentech, South San Francisco, CA) 1-mg/mL solution

DESCRIPTION

Fig. 48.4 (A) Unenhanced axial CT scan at 24 hours after treatment reveals no evidence of intracranial hemorrhage. There is mild effacement of the cortical sulci in the right fronto-opercular region. (B) Axial T2-weighted MR image 3 days after treatment shows a small right frontal infarction.

PHYSICAL EXAMINATION

MEDICAL OR SURGICAL TREATMENT

• The role of medical treatment was discussed in the previous case. There is no place for surgery in acute stroke except in extremely rare circumstances (e.g., removal of iatrogenic materials, coils).

ENDOVASCULAR TREATMENT

• Mechanical thrombectomy or intra-arterial medical thombolysis can be performed.
  
• For mechanical thrombectomy, many different devices are available. These can be placed proximal to the clot for aspiration or distally for retrieval.

Abbreviation: LOC, level of consciousness

Abbreviations: AOL, arterial occlusive lesion; TICI, Thrombolysis in Cerebral Infarction

• Thrombolytic therapy can be used primarily to dissolve the clot or at the end of a mechanical procedure to treat distal emboli. Although there is no consensus in the literature about what constitutes a safe dose, most authors quote a maximum of 22 mg of intra-arterial rtPA within the first 6 hours after stroke onset.

• Distal emboli (which can be treated with further intra-arterial injection of rtPA)
  
• Intracranial vascular dissection, subarachnoid hemorrhage, and vessel rupture
  
• Reperfusion syndrome and hemorrhagic transformation of acute stroke

The goal of recanalization therapy in acute ischemic stroke is to improve the clinical outcome by restoring antegrade perfusion and salvaging brain tissue at risk. Early vessel recanalization is linked to a good clinical outcome. Mechanical clot removal is an alternative to intravenous or intra-arterial medical thrombolysis, especially in patients with failed medical treatment, those with contraindications to rtPA (e.g., recent surgery), and those with a large clot burden. In this case, we focus on the two devices that are currently approved by the FDA;in the next case, we discuss additional new and promising devices for the mechanical treatment of stroke.

The MERCI device consists of a flexible, tapered nitinol wire with five helical loops that can be embedded within the thrombus for retrieval. Two major trials, Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI, have demonstrated its usefulness, especially in large-vessel occlusions. In these two trials, 48 to 68% of occluded vessels were recanalized, with a 5 to 7% rate of clinically significant procedural complications, an 8 to 10% rate of symptomatic hemorrhage, and a 34 to 44% mortality rate.

The present trials do not have a nontreatment arm and so cannot directly demonstrate the superiority of mechanical treatment versus no treatment or medical treatment. However, the rate of artery recanalization far exceeds the expected rate of spontaneous or drug-induced early recanalization. Therefore, mechanical thrombectomy for acute stroke is likely to be beneficial in appropriate patients.

• An intra-arterial procedure after intravenous thrombolysis requires careful attention to the puncture site. A one-wall technique or a micro-puncture set can be used. Heparin is not indicated when a previous dose of rtPA has been given because it increases the risk for hemorrhage.
  
• For aspiration procedures, the following should be noted:
  
  
  
  • Larger catheters work better and faster (Penumbra 041 and 054).
    
  • Do not allow the aspiration system to be blocked for a long time. Continuous reflux should be maintained to avoid the formation of clot inside the catheter system, which decreases the effcacy of aspiration or permanently blocks the catheter.
    
  • Always start aspirating at the proximal aspect of the clot, precisely at the zone between the clot and the vessel to be opened.
    
  • The separator is used to break up the clot, so that it enters the microcatheter more easily. It should never be used as a guidewire.
    
  • If the tip of the microcatheter is inside the thrombus and aspiration suddenly stops, the separator should be kept in position while the microcatheter is pulled back until reflux starts again.
    
  • For distal emboli, intra-arterial rtPA can be administered through the microcatheter or guiding catheter.

Further Reading

Gandhi CD, Christiano LD, Prestigiacomo CJ. Endovascular management of acute ischemic stroke. Neurosurg Focus 2009;26(3):E2

Nogueira RG, Liebeskind DS, Sung G, Duckwiler G, Smith WS; MERCI; Multi MERCI Writing Committee. Predictors of good clinical outcomes, mortality, and successful revascularization in patients with acute ischemic stroke undergoing thrombectomy: pooled analysis of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI Trials. Stroke 2009;40(12):3777–3783

Nogueira RG, Schwamm LH, Hirsch JA. Endovascular approaches to acute stroke, part 1: Drugs, devices,and data. AJNR Am J Neuroradiol 2009;30(4):649–661

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(8):2761–2768

Pexman JH, Barber PA, Hill MD, et al. Use of the Alberta Stroke Program Early CT Score (ASPECTS) for assessing CT scans in patients with acute stroke. AJNR Am J Neuroradiol 2001;22(8):1534–1542

Rha JH, Saver JL. The impact of recanalization on ischemic stroke outcome:a meta-analysis. Stroke 2007;38(3):967–973

Tomsick T, Broderick J, Carrozella J, et al ; Interventional Management of Stroke II Investigators. Revascularization results in the Interventional Management of Stroke II trial. AJNR Am J Neuroradiol 2008;29(3):582–587

A 48-year-old man with a known patent foramen ovale presents to the emergency department with left hemiparesis 2 hours after symptom onset. His baseline National Institutes of Health Stroke Scale (NIHSS) score is 12. Emergency CT is performed.

Fig. 49.1 (A) Unenhanced axial CT scan demonstrates a hyperdense right MCA sign and no evidence of hypodensity or intracranial hemorrhage. (B) CTA in coronal view shows occlusion of the right ICA bifurcation and the right MCA. (C,D) CT perfusion reveals hypoperfusion of the right MCA territory (blue).

CT

Acute occlusion of the carotid termination

EQUIPMENT

• Standard 8F access (puncture needle, 8F vascular sheath)
  
• Standard 8F balloon guide catheter (Concentric Medical, Mountain View, CA) with continuous flush and a 0.035-in hydrophilic guidewire (Terumo, Somerset, NJ)
  
• Preparation for acute stenting procedure
  
  
  
  • Rebar 18 Micro Catheter (ev3, Plymouth, MN), curved at vapor (30 degrees) with continuous flush
    
  • A 0.014-in hydrophilic micro-guidewire (Synchro2 14;Boston Scientific, Natick, MA)
    
  • Solitaire FR Revascularization Device 4 × 20 mm (ev3)
  
  
• Contrast material
  
• Recombinant tissue plasminogen activator (Actilyse;Genentech, South San Francisco, CA) 1-mg/mL solution

DESCRIPTION

Fig. 49.4 (A,B) Plain radiography in AP view during recovery of the device. Note inflation of the balloon guide catheter to stop flow in the ICA during recovery of the device. (C) The recovered device and retrieved clot.

Fig. 49.5 DSA. Right ICA angiogram in (A) AP and (B) lateral views after the procedure shows complete recanalization (TICI grade of 3). (C) Axial T2-weighted MR image 3 days after the procedure demonstrates a small residual infarction at the right basal ganglion.

In the treatment of acute stroke, the major concerns at present are the limited treatment window, the risk for hemorrhage associated with intravenous and intra-arterial thrombolytic agents, and the disappointing rates of recanalization reported with mechanical embolectomy. These shortcomings, together with the successful application of angioplasty and stenting in acute cardiac ischemia, have prompted the application of intracranial angioplasty and stenting in the acute phase of cerebral ischemia. However, caution must be exercised?because the vasculature and circulation of the cardiac system differ significantly from those of the cerebrovascular system. In the present case, a relatively new device is described that has demonstrated good recanalization rates without being overly aggressive.

TRANSCRANIAL DOPPLER ULTRASOUND

• Together with the clinical evaluation, transcranial Doppler ultrasound is a helpful tool to determine noninvasively at the bedside whether a vessel has reopened following the intravenous administration of rtPA.

CT/MRI

• Unenhanced CT is at present the most widely used screening tool for patients with acute stroke. However, modern MRI and CT techniques (i.e., diffusion- and perfusion-weighted imaging and perfusion CT) have been introduced that allow a comprehensive, noninvasive survey of patients with acute stroke. They accurately demonstrate the site of arterial occlusion and its hemodynamic and pathophysiologic effects on the brain parenchyma. After the onset of ischemic stroke, potentially viable tissue may be salvageable for as long as 48 hours. A combination of diffusion-weighted and perfusion-weighted MRI or perfusion CT may improve the selection of patients with potentially salvageable tissue and should therefore be used as soon as patients arrive in the emergency department.

ENDOVASCULAR TREATMENT

• Current reperfusion strategies are many, and some are still in the investigational phase. The following strategies are available.
  
  
  
  • Endovascular thrombectomy with distal devices:MERCI (Concentric), CATCH (Balt), Phenox clot retriever (Phenox), Neuronet (Guidant Endovascular), Attractor 18 (Target Therapeutics); endovascular thrombectomy with proximal devices:Alligator (ev3), InTime Retriever (Boston Scientific), snares
    
  • Endovascular mechanical aspiration with large catheters (Penumbra stroke system, Possis AngioJet) that have been shown to be effective in patients with a large clot burden (carotid T and M1 portion of the MCA)
    
  • Mechanical disruption of thrombus with micro-guidewires, snares, or balloon angioplasty
    
  • Transcranial augmented fibrinolysis (transcranial Dopper ultrasound) or endovascular augmented fibrinolysis (EKOS)
    
  • Endovascular entrapment of thrombus with balloon-expandable stents
    
  • Temporary endovascular bypass with resheathable stents

• Distal embolic events, intracranial vascular dissection, rupture with subarachnoid hemorrhage
  
• Reperfusion syndrome and hemorrhagic transformation of acute stroke