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STATE-OF-THE-ART REVIEW

PERIPHERAL

Endovascular Reperfusion Strategiesfor Acute Stroke

Panagiotis Papanagiotou, MD, PHD,a,b Christopher J. White, MD, MSCAIc

ABSTRACT

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Stroke is the most common cause of permanent disability, the second most common cause of dementia, and the third

most common cause of death in the Western world. About 10% to 20% of strokes are due to large-artery occlusions

causing severe disabling strokes. Recently, 5 randomized controlled trials established mechanical thrombectomy in

stroke treatment in patients with large-vessel occlusions. The current intra-arterial reperfusion therapies allow high

recanalization rates, high rates of favorable clinical outcome, and low complication rates. This review discusses the

results of recent randomized trials and describes the current state-of-the-art endovascular treatment in acute ischemic

stroke. (J Am Coll Cardiol Intv 2016;9:307–17) © 2016 by the American College of Cardiology Foundation.

S troke is the most common cause of permanentdisability, the second most common cause ofdementia, and the third most common cause

of death in the Western world (1). The World HealthOrganization estimates that 5.7 million people die ofstroke each year. On average, every 40 seconds,someone in the United States has a stroke. Eachyear, w795,000 people experience a new or recurrentstroke in the United States and 1 million people in theEuropean Union (2). Stroke survivors are oftenburdened with exorbitant rehabilitation costs, lostwages and productivity, limitations in their dailysocial activity, and significant residual disability. Asthe world’s population continues to age, the inci-dence of stroke will increase proportionately.Between 2012 and 2030, total direct medical stroke-related costs are projected to triple, with the majorityof the increase arising from patients between 65 and79 years of age (3).

The majority (>80%) of acute strokes are ischemic.The primary principle driving treatment of ischemicstroke is that “time is brain.” The following are vari-ables that affect the extent of ischemic brain injury:1) the time from the onset of symptoms to reperfusion;

m the aClinic for Diagnostic and Interventional Neuroradiology, Hospital B

scular Simulation Unit, Anglia Ruskin University, Cambridge, England; an

hsner Clinical School, University of Queensland, Ochsner Medical Center,

e principal investigator of the SWIFT PRIME study. Dr. White has reported

this paper to disclose.

nuscript received June 18, 2015; revised manuscript received October 29,

2) the presence of collateral circulation including anintact circle of Willis; and 3) the “penumbra ofviability” surrounding the infarcted brain tissue. Thepenumbra is the region of brain surrounding theinfarct area where the blood supply is significantlyreduced, but energy metabolism is maintained due tocollateral flow. The viability of this area is dependenton both the severity and duration of ischemia. If bloodflow is rapidly restored, some ischemic brain tissuewill be saved. This puts a premium on the rapidassessment of patients presenting with stroke.

Previous trials of endovascular therapy includedthe intracranial administration of thrombolysis andthe use of early generation mechanical thrombectomydevices (Merci [Concentric Medical, Mountain View,California] and Penumbra [Penumbra Inc., Alameda,California] devices) (4–7). The initial trials did notdemonstrate conclusive benefit for endovasculartherapy, although there were promising signals.There seemed to be a balance between early andeffective mechanical reperfusion balanced against therisk of intracranial hemorrhage (ICH) that wasperhaps related to reperfusion of nonviable brain.The next step was to deliver rapid, safe, and effective

remen-Mitte, Bremen, Germany; bNeuroscience and

d the cJohn Ochsner Heart & Vascular Institute, The

New Orleans, Louisiana. Dr. Papanagiotou was local

that he has no relationships relevant to the contents

2015, accepted November 3, 2015.

ABBR EV I A T I ON S

AND ACRONYMS

ASPECTS = Alberta Stroke

Program Early CT score

CT = computed tomography

CTA = computed tomography

angiography

D2D = door-to-device

IAT = intra-arterial

thrombectomy

ICA = internal carotid artery

ICH = intracranial hemorrhage

IV t-PA = intravenous tissue-

type plasminogen activator

MCA = middle cerebral artery

NIHSS = National Institutes of

Health Stroke Scale

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reperfusion therapy in stroke patients withviable brain tissue at risk (penumbra),determined by pretreatment brain imaging.

Between December 2014 and April 2015,5 randomized, controlled trials providedcompelling evidence that intra-arterialthrombectomy (IAT) improves outcomes af-ter acute ischemic stroke. Endovasculartreatment significantly improved clinicaloutcome in patients with proximal intracra-nial occlusion of the anterior circulationcompared with intravenous tissue-type plas-minogen activator (IV t-PA), indicating thatthe preferred treatment of these patients is nolonger IV t-PA, but endovascular techniques(8–12).

This review discusses the results of recentrandomized trials and describes the current

state-of-the-art endovascular treatment for acuteischemic stroke.

RESULTS OF RECENT RANDOMIZED

CLINICAL TRIALS

A large number of prospective trials studying me-chanical thrombectomy for acute ischemic stroke thatpredate “stent retriever” devices have been negative orinconclusive. The results of the IMS-III (InterventionalManagement of Stroke III) trial, published in 2013,showed no benefit of endovascular therapy after theuse of intravenous (IV) thrombolysis over IV throm-bolysis alone in the treatment of moderate to severeacute ischemic stroke (1,13). However, thereweremajorweaknesses in this study. First, computed tomographyangiography (CTA)was not required,which allowed theinclusion of patients who did not have intracraniallarge-vessel occlusion. Second, the new technology,stent retrievers, were used only in 5 patients.

Between December 2014 and April 2015, 5 multi-center randomized clinical trials were published withpositive results with endovascular therapy. The majordifferences between these positive endovascular tri-als and past trials were the use of CTA to select pa-tients with proximal intracranial occlusion and theuse of stent retrievers for thrombectomy in themajority of cases (Central Illustration).

The MR CLEAN (Multicenter Randomized ClinicalTrial of Endovascular Treatment for Acute IschemicStroke in the Netherlands) (2,11), ESCAPE (Endovas-cular Treatment for Small Core and Anterior Circula-tion Proximal OcclusionWith Emphasis onMinimizingCT to Recanalization Times) (3,10), EXTEND-IA(Extending the Time for Thrombolysis in EmergencyNeurological Deficits-Intra-Arterial) (8–12), SWIFT

PRIME (SolitaireWith the Intention for Thrombectomyas Primary Endovascular Treatment) (8), and REVAS-CAT (Endovascular Revascularization With SolitaireDevice Versus Best Medical Therapy in Anterior Cir-culation Stroke Within 8 Hours After Symptom Onsetin Ischemic Stroke) (9) have demonstrated the efficacyof endovascular therapy versus IV-tPA alone in treat-ing patients with acute anterior circulation ischemicstroke. The last 3 studies were terminated early bytheir Data Safety Monitoring Boards after the MRCLEAN results were published (Tables 1 and 2).

INCLUSION CRITERIA AND TIME WINDOW. All 5 tri-als used CT imaging to select patients. In MR CLEAN,patients were selected based on plain CT imagingusing the Alberta Stroke Program Early CT score(ASPECTS). In other trials, patients were selected forhaving a small ischemic core at baseline and eitheradequate collaterals (using CTA in ESCAPE) orsalvageable brain (using CT perfusion) in EXTEND-IAand SWIFT PRIME.

The documentation of a proximal anterior circula-tion intracranial occlusion with CTA was required inall trials, which is a major difference from the nega-tive endovascular reperfusion trials in the past.

The baseline age and sex were comparable in alltrials. The baseline National Institutes of HealthStroke Scale (NIHSS) score was high, at w16. In theEXTEND-IA study, the NIHSS was lower in the con-servative group compared with the interventiongroup (13 vs. 16). Patients older than 80 years of agewere included in all but SWIFT PRIME trial.

The SWIFT PRIME treated patients up to 4.5 h fromthe onset of stroke, whereas MR CLEAN and EXTEND-IA included those up to 6 h after onset, REVASCAT upto 8 h, and ESCAPE up to 12 h. In practice, however,only a few patients who could not have groin punctureby 6 h were actually included. Therefore, the positiveresults of the trials mainly apply to patients treatedwithin 6 h from symptom onset. A combined approachwith IV thrombolysis and thrombectomy was requiredin the SWIFT PRIME and was used in the majority ofpatients in the other studies. Most patients in thecontrol groups received IV thrombolysis if they pre-sented within the 4.5-h time window (Table 1).

FAVORABLE CLINICAL OUTCOME. All 5 randomized,controlled trials showed a benefit for endovasculartreatment compared with IV t-PA alone with regardto functional outcomes. The percentage of patientsachieving a favorable clinical outcome with IATvaried between 33% and 71%; there was a consistentpositive difference across all studies with a favorableclinical outcome (defined as a modified RankinScale score of 0 to 2 at 90 days) between the

CENTRAL ILLUSTRATION Current Reperfusion Techniques in Acute Intracranial Artery Occlusions

Papanagiotou, P. et al. J Am Coll Cardiol Intv. 2016; 9(4):307–17.

(a) Acute occlusion of middle cerebral artery due to a clot. (b) Stent retriever technique: the placement of the stent retriever, a self- expandable

stent, produces immediate flow restoration. The device is pulled back to remove the thrombus. (c) Aspiration technique: the thrombus is being

removed with a large-lumen aspiration catheter.

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interventional and control arms favoring IAT by 14%to 31%. The difference between the groups was morepronounced in the trials in which penumbral imagingwith CT perfusion was used. However, even withoutimaging selection beyond the unenhanced CT, suchas the MR CLEAN study, there was a clear benefit

favoring IAT. Importantly, IAT was consistentlyeffective overall and among important pre-specifiedpatient subgroups of sex, age, stroke severity, andtime of presentation.COMPLICATION AND MORTALITY RATES. In all ofthe studies, IAT added no additional risk of bleeding

TABLE 1 Recent Randomized Trials for Endovascular Treatment of Acute Stroke: Important Inclusion/Exclusion Criteria, Primary Endpoints, and Devices Used

Trial Comparison Inclusion Criteria Exclusion Criteria

No. of Patientsin IAT/Control

Groups Primary Endpoint Devices Used

MR CLEAN IAT þ standard carevs. standard care

Age $18 yrs, NIHSSscore >2 at 6 hfrom onset

233/267 mRS score at 90 days Retrievable stents in81%, IA thrombolysisin 10%

SWIFT PRIME Thrombectomy þ IVt-PA vs. IV t-PA

Age, 18–80 yrs, NIHSSscore $8 and <30,IV t-PA within 4.5 h

Extracranial cervicalcarotid occlusion

98/98 mRS score at 90 days Retrievable stents(Solitaire FR, ev3Endovascular Inc.,Plymouth, Minnesota)

ESCAPE Thrombectomy þ standardcare vs. standard care

Age $18 yrs, NIHSSscore >2 at 12 hfrom onset, groinpuncture within60 min of baseline CT

ASPECTS 0–5, poorcollaterals on CTA,large infarct coreon CT perfusion

165/150 mRS score at 90 days Retrievable stents in 86%

EXTEND-IA Thrombectomy þ IVt-PA vs. IV t-PA

Age $18 yrs, IV t-PAwithin 4.5 h,penumbral imagingusing CT or MRI

Groin puncture after6 h from onset

35/35 Early neurologicalimprovement inNHISS score,reperfusion at 24 h

Retrievable stents(Solitaire FR)

REVASCAT Thrombectomy þ medicaltherapy vs. medicaltherapy

Age 18-85 yrs, NIHSSscore >6 at 8 hfrom onset

ASPECTS <7 103/103 mRS score at 90 days Retrievable stents(Solitaire FR)

ASPECTS ¼ Alberta Stroke Program Early CT score; CT ¼ computed tomography; CTA ¼ computed tomography angiography; IA ¼ intracranial administration; IAT ¼ intra-arterial thrombectomy; IV t-PA ¼intravenous tissue-type plasminogen activator; MRI ¼ magnetic resonance imaging; mRS ¼ modified Rankin Scale; NIHSS ¼ National Institutes of Health Stroke Scale.

TABLE 2 Results of

Trial n

MR CLEAN 50

SWIFT PRIME 19

ESCAPE 31

EXTEND-IA 70

REVASCAT 20

NS ¼ not significant; sICH

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over standard management with IV t-PA. The intra-cerebral hemorrhage risk in both the interventionaland control arms ranged from 0% to 7%. The factthat in all trials IAT carried no higher bleedingrisk compared with IV t-PA demonstrates thatthrombectomy is safe and any bleeding risk is causedmainly by thrombolysis. There was an overall trendtoward a reduction in mortality with IAT.

RECANALIZATION RATES. Successful recanalizationwas defined as a Thrombolysis In Cerebral Infarctionscore of 2b or 3. The use of stent retrievers in the trialsled to recanalization rates of between 59% and 88%.The trials showed also that the likelihood of a goodoutcome increased with better recanalization. Thehighest recanalization rates were achieved in SWIFTPRIME (88%) and EXTEND-IA (86%), correlating withthe high rates of good clinical outcomes seen in thesetrials (60% and 71%, respectively). The lowest recana-lization rate was in MR CLEAN at 59% with a favorableclinical outcome occurring in only 33% of the patients.

Recent Randomized Trials for Endovascular Treatment of Acute Stroke

TICI 2B/3, %

mRS Score 0–2

IAT, % Control, % p Value IAT, %

0 59 33 19 <0.001 7.7

6 88 60 36 <0.001 0

5 72 53 29 <0.001 3.6

86 71 40 0.01 0

6 73 44 28 <0.001 1.9

¼ symptomatic intracerebral hemorrhage; TICI ¼ Thrombolysis In Cerebral Infarction; other

ENDOVASCULAR TECHNIQUE/THROMBECTOMY DEVICES.

The major difference between these randomized tri-als and the mechanical thrombectomy trials in thepast was the use of stent retrievers in the majority ofthe patients (Table 1). Retrievable stents are self-expandable stentlike devices that are fully re-trievable. Therefore, these devices combine theadvantages of prompt flow restoration and mechani-cal thrombectomy (Figure 1). The excellent recanali-zation results with the low complication rates of thestent retriever devices in registries suggested a highrate of favorable clinical outcome (14–16). This wasconfirmed in all 5 randomized trials.

INDICATIONS AND PATIENT SELECTION FOR

ENDOVASCULAR TREATMENT

Important features of the patient’s clinical presenta-tion that affect endovascular treatment decisionsinclude the patient’s clinical status, time of presen-tation, and imaging characteristics.

sICH Mortality

Control, % p Value IAT, % Control, % p Value

6.4 NS 21 22 NS

3 0.12 9 12 0.50

2.7 0.75 10 19 0.04

6 0.49 9 20 0.18

1.9 1.00 18 16 0.60

abbreviations as in Table 1.

FIGURE 1 Stent Retriever

Example of large thrombus that was extracted by a stent

retriever. Stent retrievers are self-expandable stentlike devices

that are fully retrievable.

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CLINICAL STATUS. The NIHSS, a quantitative mea-sure of the severity of a stroke, should be performedat the initial examination in all stroke patients, butespecially in patients being considered for IV t-PA(17). Patients with significant deficits manifesting asscores between 8 and 20 are more likely to benefitfrom reperfusion, making them better candidates fortreatment (18,19). Patients with minor to mild symp-toms (NIHSS score <8) and an existing intracraniallarge vessel occlusion were not included in the trials.In these patients, the decision to perform additionalIAT is based on the operator’s experience and theestimated risk of the procedure.

TIME OF PRESENTATION. IV t-PA and IAT reperfu-sion therapies have both been shown to improve pa-tient outcome. However, the time window fortreatment of both approaches is limited. IV throm-bolysis can be given up to 4.5 h after stroke onset;additional or primary IA therapies can be used up to12 h after stroke onset. In anterior circulation strokes,the impact of successful thrombectomy is greater inthe first 3 to 4.5 h after stroke compared with laterecanalization after 5 to 8 h (20–22).IMAGING OF ACUTE STROKE. Imaging helps identifytarget intracranial thrombi and measures the extentof salvageable brain tissue. Imaging the brain and thevasculature that supplies it is therefore a vital firststep in evaluating patients with acute ischemic stroke.A comprehensive evaluation may be performed withCTA or magnetic resonance imaging. The majoradvantages of CTA compared with magnetic reso-nance imaging are that CTA is widely available, and astroke imaging protocol that consists of unenhancedCT, CTA, and CT perfusion imaging can be performedin 5 min for the comprehensive evaluation of the ex-tra- and intracranial circulation, the amount ofinfarcted brain tissue, and the penumbra.

Computed tomography . With its widespread avail-ability, short scan time, noninvasiveness, and safety,CT has been the traditional first-line imaging modal-ity for the evaluation of acute ischemic stroke.Multimodal CT includes unenhanced CT, CTA, and CTperfusion. Noncontrast CT can identify ICH anddetect early signs of acute ischemic stroke (Figure 2).CTA can identify the occlusion site, detect arterialdissection, and grade collateral blood flow, whereasCT perfusion can differentiate between tissue at risk(the so-called penumbra) and irreversibly damagedbrain tissue (Figures 3 and 4) (17,23,24). MultimodalCT offers rapid data acquisition and can be performedwith modern CT equipment.Noncontrast CT. In the acute ischemic strokesetting, noncontrast CT has been used to rule out ICH(a contraindication to thrombolysis) or other strokemimics (e.g., tumor, infection), which preclude theuse of thrombolytic therapy and also used to measurethe extent of early ischemic changes within ischemicbrain. The Alberta Stroke Program Early CT Score(ASPECTS) is a simple and systematic approach toevaluating stroke patients (25). Patients with a highASPECTS of 8 to 10 seem to benefit more from IAT. InMR CLEAN included patients with an ASPECTS of 5 to7 had an odds ratio of 1.97 for benefit, whereas thosewith an ASPECTS of 8 to 10 had a beneficial odds ratioof 1.61. Those with an ASPECTS of 0 to 4 had nobenefit (odds ratio: 1.09), suggesting that mechanicalthrombectomy has less efficacy in patients with alarge ischemic core (11).CT angiography . CTA is widely available, with fast,thin-section, volumetric spiral CT images acquiredduring the injection of a time-optimized bolus ofcontrast material for vessel opacification. The entireregion from the aortic arch to the circle of Willis canbe covered in a single image acquisition. CTA allows adetailed evaluation of the intra- and extracranialvasculature (26,27). Its utility in acute stroke lies in itsability to detect large-vessel occlusion within intra-cranial vessels and to evaluate the carotid andvertebral arteries in the neck.

CTA can also depict the leptomeningeal collateralsand can identify large-vessel occlusions with “good”and “poor” collaterals. Good collateral circulationimproves the chance of a good neurological outcomeby limiting the extent of brain infarction (28). TheESCAPE trial used collateral assessment to select pa-tients; the exclusion of participants with a largeinfarct core and poor collateral circulation was one ofthe reasons for the high rate of favorable clinicaloutcomes (53%) (10).CT per fus ion . CT perfusion allows rapid, noninva-sive, quantitative evaluation of cerebral perfusion. CT

FIGURE 2 CT Imaging in Acute Stroke

(A) Computed tomography (CT) of intracerebral hemorrhage.

(B) Hyperdense artery sign (arrow).

FIGURE 3 CTA in Acute Stroke

Computed tomography angiography (CTA) depicts occlusion of

the left middle cerebral artery (arrows). (A) Coronary and

(B) transversal reconstructions.

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perfusion differentiation of the infarct core from thepenumbra is based on the concept of cerebral vascularautoregulation. In the penumbra, autoregulation ispreserved, the mean transit time is prolonged, but thecerebral blood volume is preserved because of vaso-dilation and collateral recruitment as part of theautoregulation process. In the infarct core, auto-regulation is lost, the mean transit time is prolonged,

and the cerebral blood volume is reduced (29). Thus,using appropriate mean transit time and cerebralblood volume thresholds, infarct core and penumbracan be distinguished on CT perfusion maps (Figure 5)(30). Direct assessment of an individual patient’sischemic penumbra may allow more personalized,appropriate selection of candidates for interventionthan generalized time criteria because individualsmay have different timelines for conversion of pen-umbra into infarct tissue. CT perfusion was used toselect patients for the EXTEND-IA trial, which ach-ieved an impressive rate of good clinical outcomes at71% (12).

PRE-PROCEDURE PLANNING

Despite the fact that the efficacy of IV thrombolysisdecreases with duration from the onset of symptoms,less than one-third of the patients meet the goal of a“door-to-needle time” of #60 min due to in-hospitaldelays (31). Improvements in pre-hospital and in-hospital stroke management can translate into fastertreatment (32). Every stroke center should have anoptimized stroke management protocol to reduce the“door-to-treatment” time. An on-demand, 24-7-365,stroke reperfusion service, is also required (19).

FIGURE 4 CT Perfusion in Acute Stroke

CT perfusion-map of a right MCA occlusion. (A) CBV is slightly reduced on the right side compared to the left side; (B) CBF is reduced;

(C) TTP is prolonged. (D) The area in which the cerebral blood volume is decreased corresponds to the infarct core (red area). There exists

a penumbra because there is a large area of the middle cerebral artery territory in which mean transit time is prolonged and cerebral

blood volume is preserved (green area). CT ¼ computed tomography; CBF ¼ cerebral blood flow; CBV ¼ cerebral blood volume;

MCA ¼ middle cerebral artery; TTP ¼ time to peak.

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OPTIMIZED STROKE MANAGEMENT. Emergency ser-vices are instructed to bring patients with a suspectedstroke directly to the stroke treatment room, whichshould be located in proximity to the CT scanner.After the neurological examination, an unenhancedCT scan is obtained. If an ICH can be ruled out, CTA

and CT perfusion are performed. Within the 4.5-htime window, patients are treated with IV t-PAimmediately after exclusion of clinical and neurora-diological contraindications.

If an occlusion of a large intracranial vessel isfound, the decision to perform endovascular therapy

FIGURE 5 Endovascular Stroke Treatment

(A) Acute middle cerebral artery occlusion (arrow). (B) Placement of the stent retriever with immediate flow restoration. Distal marker of the

device (thin black arrow), the thrombus is pressed to the vessel wall (thick black arrow). (C) Successful recanalization of the artery.

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is based on the clinical condition of the patient, thetime window (up to 6 h after stroke onset) as wellas imaging criteria of the CTA and CT perfusion(presence of leptomeningeal collaterals and ofischemic penumbra). If the decision to proceed withendovascular therapy is made, the patient is trans-ferred immediately to the angiography suite.

At this point, the decision regarding the need forgeneral anesthesia and ventilation is made, depend-ing on the patient’s clinical condition. A subgroupanalysis from MR CLEAN indicated that the advan-tage of IAT may disappear with general anesthesia.One advantage of conscious sedation compared withgeneral anesthesia is time saving, which allows theprocedure to start more quickly. Another majoradvantage of conscious sedation is to be able to assessthe clinical status of the patient during the procedure

and to evaluate the success of treatment. The disad-vantage of conscious sedation is the patient’s move-ments, which require experienced operators for a safeand successful procedure.

With an optimized stroke protocol, we defined inaprospective study (ReFlow [Mechanical Recanaliza-tion With Flow Restoration in Acute Ischemic Stroke]study) the door-to-device (D2D) time (the time fromarrival at the hospital until the thrombectomy device isplaced in the target lesion). Patients with a D2D timeof <100 min had a favorable outcome rate of 66%comparedwith 44%of patientswith aD2D time of>100min (15). By analogy, the D2D time should playan important role in the outcome of these patients as itdoes for the door-to-balloon time in the outcome ofpatients with ST-segment elevation myocardialinfarction (33).

FIGURE 6 Aspiration Catheter

Example of large thrombus aspirated with the Penumbra ACE 64

aspiration catheter (Penumbra Inc.).

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DESCRIPTION OF PROCEDURE

FROM FIRST-GENERATION DEVICES TO THE FLOW-

RESTORATION DEVICES (STENT RETRIEVER). Quickrecanalization is the goal of treatment of patients withacute ischemic stroke as a result of large-vessel oc-clusion. In the past decade, mechanical recanalizationdevices were developed to achieve better results thanIAT. The Merci device (Concentric Medical) and thePenumbra aspiration system (Penumbra Inc.) are thefirst devices for which a large amount of clinicalexperience has been reported (6,34).

However, the breakthrough in interventionaltreatment of acute stroke was achieved by the use ofstentlike thrombectomy devices (stent retriever)(35,36). The stent retriever devices allow high recan-alization rates with a reduction in the recanalizationtime and low complication rates (14,15).

In cases of a large thrombus load, a combination ofaspiration through a large lumen reperfusion cathetercan be used. In the special groups of patients withextracranial carotid occlusion, arterial dissection, andintracranial stenosis, carotid stentingwill be necessary(37).

STENT RETRIEVER TECHNIQUE. Stent retrievers areself-expandable stentlike devices that are fullyretrievable. Therefore, these devices combine theadvantages of prompt flow restoration and mechani-cal thrombectomy. The improved clinical outcomewith flow-restoration devices is due to fast andeffective clot removal and the possibility of tempo-rarily restoring flow (35). Recanalization rates ofThrombolysis In Cerebral Infarction of 2a/b or 3 floware high, as high as 90%. The results of prospectivestudies showed high rates of favorable clinical out-comes at 3 months, a low rate of symptomatic ICH,and a low mortality rate (15). The low mortality ratereflects the low rate of symptomatic ICH and shows

the safety of flow-restoration devices compared withreperfusion devices in the past (34,38).

STENT RETRIEVER RECANALIZATION TECHNIQUE.

Vascular access, catheter, and sheaths. The commonfemoral artery is the most common vascular accesssite with placement of a 6-F sheath. The brachial ar-tery may be also used in cases in which puncture ofthe femoral arteries is not possible. To perform anintracranial thrombectomy, it is necessary to place along (90 to 100 cm) 6-F sheath or an 8-F guide cath-eter in the internal carotid artery (ICA). To place thesheath in the ICA, the use of a coaxial 125-cm longcatheter over a guidewire is required. Two cathetersthat can be used are the multipurpose catheter andthe SIM2 catheter for types II and III aortic archconfigurations.Guidewires, microcatheters, and retriever devices.Typically, a 0.014-inch guidewire is used to traversethe intracranial circulation; based on the size of thethrombectomy device, a microcatheter between 0.018and 0.027 inch is required. The size of the stentretriever devices range from 3.0� 15 mm up to 6.0� 30mm. The size of the retriever device is based on the sizeof the occluded artery. Typically, a 4- to 4.5-mmdevicehas been used for themiddle cerebral artery (MCA) anda 6.0-mm device for occlusions in the terminal ICA.

INTRACRANIAL RECANALIZATION PROCEDURE. After theplacement of the long 6-F sheath in the ICA, the oc-clusion of the target vessel is verified angiographically.The target vessel is entered with a 0.014-inch guide-wire and a microcatheter. The thrombus is crossedwith the guidewire, and the microcatheter is placeddistal to the thrombus. The device is placed with theproximal third of the thrombus. A control angiogram isperformed after successful unfolding of the stentretriever device to evaluate re-establishment of flow.After a short period of time, the device is pulled backwith continuous aspiration. The procedure is repeateduntil a Thrombolysis In Cerebral Infarction score of 2bor 3 is reached (Figure 5).

THE ASPIRATION PROCEDURE. Despite the impres-sive results of the stent retrievers with successfulrecanalization results of up to 95%, there are somevessel occlusions and thrombi that are resistant to thistechnique even after repeated recanalization at-tempts. These vessel occlusions include cases of ter-minal ICA occlusions. Moreover “hard” thrombi inother locations, such as the MCA, can also been resis-tant to the stent retriever technique. For these cases,direct aspiration of the thrombus can be used as analternative technique. For direct thrombus aspiration,themost common aspiration catheters that are used forthese purposes are 5-F systems, e.g., the Penumbra

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ACE 64 reperfusion catheter (Penumbra Inc.), whichhas a 0.64-inch inner lumen and is significantly largerthan the previous generation of aspiration catheters(Figure 6) (Central Illustration, panel c) (39).

POST-PROCEDURE MANAGEMENT

The use of vascular closure devices can be routinelyused with low complication rates, especially in pa-tients who received IV thrombolysis (40). During theintervention, there is no need for any antiplateletmedication. In cases of emergency stent implantationof occlusions at the origin of the ICA, antiplatelettherapy is necessary to prevent acute stent throm-bosis. In these cases, administration of IV aspirinwould be possible (41). Post-procedure guidelinesrecommend 325 mg aspirin orally within 24 to 48 h ofischemic stroke onset (42).

Although hypertension is common in acuteischemic stroke and associated with poor outcomes,studies of antihypertensive treatment in this settinghave produced conflicting results. A theoreticaldrawback of blood pressure reduction is that elevatedblood pressure may counteract dysfunctional cerebralautoregulation from stroke, but limited evidencesuggests that antihypertensive treatment in acutestroke does not change cerebral perfusion (43). OnceIV t-PA or thrombectomy are performed, the bloodpressure must be maintained below 180/105 mm Hg tolimit the risk of ICH (42).

POTENTIAL COMPLICATIONS. Complications thatcan occur during or after the procedure include distalembolization to the same or other vessel territories,dissection of the arteries, and subarachnoid or intra-cerebral hemorrhage. MR CLEAN reported a 5.6%incidence of new symptomatic embolism. With distalembolization, the management depends on howrelevant it is estimated that the occluded branch is. Ifthe patient is not intubated, a clinical examinationcan show whether the persistent occlusion is

relevant. If the occluded branch is a relevant one, astent retriever can be used, even in M3 branches ofthe MCA or in the A2 segment of the anterior cerebralartery.

Dissections of the vessels mostly occur in the ICAwhen a distal access catheter is used. Dissectionswithout flow restriction do not require any therapy.In cases of a flow-limiting dissection, stenting of theaffected vessel can be performed.

Small subarachnoid hemorrhages are often seen onthe control CT and do not require specific therapy.Intracerebral hemorrhage can occur during the pro-cedure due to the intervention or even within 48 hafter the procedure as a result of reperfusion injury(44). Therefore, blood pressure control is a criticalelement of post-procedure management. The occur-rence of any worsening of neurological status shouldbe considered a possible sign of ICH, warrantingimmediate clinical evaluation and emergency CT scanof the brain. Should ICH be found, reversal of allantithrombotic agents should be carried out.

CONCLUSIONS

Recently completed randomized controlled trialshave established mechanical thrombectomy in stroketreatment in patients with large-vessel occlusions.The current endovascular reperfusion therapies allowhigh recanalization rates, high rates of favorableclinical outcomes, and low complication rates. How-ever, to optimize clinical results, image-guided pa-tient selection and the use of an optimized strokemanagement protocol are required.

REPRINT REQUESTS AND CORRESPONDENCE: Prof.Panagiotis Papanagiotou, Clinic for Diagnostic and Inter-ventional Neuroradiology, Hospital Bremen-Mitte, St.-Jürgren-Strasse 1, Bremen 28205, Germany; Neuroscienceand Vascular Simulation Unit, Anglia Ruskin University,Cambridge, England. E-mail: papanagiotou@me.com.

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KEY WORDS acute stroke, aspiration,Penumbra, recanalization, stent-retriever,thrombectomy