Thrombectomy for Distal, Medium Vessel Occlusions a Consensus Statement on Present Knowledge and Promising Directions

Stroke

SPECIAL REPORT Thrombectomy for Distal, Medium Vessel Occlusions A Consensus Statement on Present Knowledge and Promising Directions

Jeffrey L. Saver, MD; Rene Chapot, MD; Ronit Agid, MD; Ameer Hassan, DO; Ashutosh P. Jadhav, MD; David S. Liebeskind, MD; Kyriakos Lobotesis, MD; Dan Meila , MD; Lukas Meyer, MD; Guy Raphaeli, MD; Rishi Gupta, MD; for the Distal Thrombectomy Summit Group*†

ndovascular thrombectomy (EVT) is well established and thromboaspiration devices suggest EVT for DMVOs as a highly effective treatment for acute ischemic is safe, technically efficacious, and potentially clinically Estroke (AIS) due to proximal, large vessel occlusions beneficial. Collaborative investigations are desirable to (PLVOs). With iterative further advances in catheter tech- enhance imaging recognition of DMVOs; advance device nology, distal, medium vessel occlusions (DMVOs) are now design and technical efficacy; conduct large registry stud- emerging as a promising next potential EVT frontier. This ies using harmonized, common data elements; and com- consensus statement integrates recent epidemiological, plete formal randomized trials, improving treatment of this anatomic, clinical, imaging, and therapeutic research on frequent mechanism of stroke. DMVO-AIS and provides a framework for further studies. Rapid EVT to restore cerebral perfusion is now the DMVOs cause 25% to 40% of AISs, arising as primary cornerstone of treatment for AIS due to PLVOs. Multiple Downloaded from http://ahajournals.org by on August 7, 2020 thromboemboli and as unintended consequences of EVT randomized trials demonstrated dramatically improved performed for PLVOs, including emboli to new territories patient outcomes with EVT among broadly selected (ENTs) and emboli to distal territories (EDTs) within the patients within the first 6 hours and imaging-selected initially compromised arterial field. The 6 distal medium patients 6 to 24 hours after last known well. With PLVOs arterial arbors (anterior cerebral artery [ACA], M2–M4 well established as a treatment target, DMVOs have middle cerebral artery [MCA], posterior cerebral artery emerged as a promising next potential frontier for EVT, [PCA], posterior inferior cerebellar artery [PICA], anterior for several reasons. First, the overwhelming benefit mag- inferior cerebellar artery [AICA], and superior cerebellar nitude of EVT for PLVOs suggests thrombectomy would artery [SCA]) typically have 25 anatomic segments and also be beneficial for DMVOs. Second, the advent of EVT give rise to 34 distinct branch arterial segments nourish- as a standard PLVO therapy has triggered rapid, iterative ing highly differentiated, largely superficial cerebral neu- advances in endovascular retriever and aspiration tech- roanatomical regions. DMVOs produce clinical syndromes nology, leading to more navigable and smaller devices that are highly heterogenous but frequently disabling. able to reach more distal, narrower vessels. Third, a recog- While intravenous fibrinolytics are more effective for dis- nized unintended event during EVT for PLVO is thrombus tal than proximal occlusions, they fail to recanalize one- fragmentation and escape from retrieval devices, lead- half to two-thirds of DMVOs. Early clinical series using ing to emboli in distal arteries. For EVT of PLVO-AIS to recently available, smaller, more navigable stent retriever achieve maximal benefits, effective rescue endovascular

Key Words: animals ◼ brain ischemia ◼ dogs ◼ embolism ◼ Hong Kong

Correspondence to: Jeffrey L. Saver, MD, Department of Neurology, Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095. Email [email protected] This manuscript was sent to Kazunori Toyoda, Guest Editor, for review by expert referees, editorial decision, and final disposition. *A list of Distal Thrombectomy Summit Group collaborators is given in the Appendix. †Institutions of Distal Thrombectomy Summit Group collaborators are listed in Table I in the Data Supplement. The Data Supplement is available with this article at https://www.ahajournals.org/doi/suppl/10.1161/STROKEAHA.120.028956. For Sources of Funding and Disclosures, see page XXX. © 2020 American Heart Association, Inc. Stroke is available at www.ahajournals.org/journal/str

Stroke. 2020;51:00–00. DOI: 10.1161/STROKEAHA.120.028956 September 2020 1 Downloaded from http://ahajournals.org by on August 7, 2020 7, August on by http://ahajournals.org from Downloaded Special Report 2 (3.2 mm), and the vertebral artery (2.8 mm). the M1 segment of the (2.7 MCA mm), the basilar artery typicaldiameter,internal carotidartery(ICA; 3.8 mm), old placesintothelargevessel categorytheintracranial between 0.75 and2.0mm.The upper2.0-mmthresh- ally definedascerebral arterieswith lumendiameters the intermediate,“mediumvessels”canbeoperation- far toosmallforendovasculartargeting.Consequently, are thoseoccurringwithinpenetratingarteries,currently lar literature.Accordingly, smallvesselocclusions[SVOs] label of“smallvessel”diseaseintheclassicneurovascu- trating arteriesthat,whenstenoticoroccluded,carrythe of “largevesselocclusions.” Belowarethenarrowpene- intracranial arteriesthat,whenobstructed,carrythelabel are the wideproximal the neurovascularliterature.Above by 2vesselsizerangeswithwell-establishedrubricsin The intermediate-sizecerebralarterialtreeisbounded Vessel Size separated fromitsmanipulableendbymultipleturns. strains thephysicalforcesdeliverablebyaretrievaldevice of successfulnavigationtotargetocclusionsand con- occipital lobe(PCA). This tortuosityincreasesthedifficulty (ACA), insula and temporal and lobe temporal (MCA), and neuroanatomic structuressuch asthecorpuscallosum branch stepsthanproximal arteriesandalsolooparound the arterialpuncturesite.Distalarterieshave≥ tances and more tortuous cumulative travel pathways from The distalcerebralarteriesaredistinguishedbylongerdis- Vessel Distance/Tortuosity distance/tortuosity and(2)vesselsize. dure conductandendovasculardevicedesign:(1)vessel cerebral arteriesprofoundlyaffect endovascularproce- Two keydistinctiveanatomicfeatures ofdistal,medium GENERAL TERMINOLOGY AND FEATURES DISTINCTIVE KEY are delineated. systematicinvestigation steps topromotecollaborative, Promisingof EVTforDMVOs. research directionsand rent understandingoftheopportunitiesandlimitations its ischemic syndromes,toprovideastatementofcur- sic understanding of the distal cerebral vasculature and endovascular therapy, andclinicaltrialdesignwithclas- strokeepidemiology,on DMVO imaging,medicaland lation isdesirable. arisingfrominitialthrombusmanipu- therapy forDMVOs Saver etal diameter, 0.5mm),longpial penetratorarteries,and deep penetratorarteries(typical lenticulostriateartery 0.75-mm threshold placesintothesmallvesselcategory This consensusstatementintegratesrecentresearch September 2020 3–5 1 additional 1 additional The lower 1,2 small arteriesinsize. dominant segmentsthataresimilartoM3andothermuch still moredistalandbranched/tortuous toreach) orinnon- dominant segmentsthataresimilartoM1insize(though labra include bifurcation,trifurcation,tetrafurcation,andcande- branchheterogenous acrosspatients.M2MCA patterns larly challenging, angioarchitecture asM2MCA ishighly of the M2 within MCA any classification system is particu- decision-making. In addition, the Consensus Group felt differences inthevasculaturethatarerelevant toclinical that such anapproach wouldelideimportant anatomic mm), M4 MCA, A2toA5ACA,mm), M4MCA, andP2toP5PCA. M3 arteries MCA (typical diameters at origin, 1.1–1.5 of M2 MCA, A1ACA,of M2MCA, andP1PCA hasvaried. However, andSCAs. AICA, ments, andPICA, categorization segments, A2toA5ACA segments,P2toP5PCA seg- middle arterycategoryasincludingtheM3andM4MCA artery. Similarly, a general consensus recognizes the distal, segment,intracranialvertebralarteries,andbasilar MCA M1 mal, largearterycategoryincludestheintracranialICA, ing 2mmdiameter, wouldbeaDLVO. an occlusionintheinitialsegmentofartery, exceed- Similarly, division, inapatientwithdominant M2MCA sion wouldbeadistal,largevesselocclusion[DLVO]). ment maybedistalbutlargeindiameter(andanocclu- Conversely, inapatientwithanazygous ACA, theA2seg- would beaproximal, medium vesselocclusion [PMVO]). be proximal butmediumindiameter(andanocclusion with a duplicate stem, MCA the M1 segment MCA may occur in a dissociated manner. For example, in a patient large vesselocclusions[LVOs], respectively ). (contrasted withproximal vesselocclusions[PVOs] or occlusions (DVOs) ormediumvesselocclusions(MVOs) anatomic features alonewasalsoendorsed:distalvessel priate, the use oflabels using either of the distinctive Wheregeneral labelthatcapturesboth—DMVOs. appro- aspects, theSummitgrouprecommendedadoptinga to 2.1mmindiameter mm). surface pialarteries(typicalarterydiameter, 0.2–0.7 vessel. defining anyendovascularly accessiblearteryasalarge vessels byconflatingthe two intoasinglecategory, demarcating proximal largevesselsversus distalmedium approach differences betweeninvestigativegroupswhen that istheapproach hereproposed. sification inanevidence-based,case-specificmanner, and talness segment of theinvolvedM2 to drive MCA clas- category. Itispreferable touse theparticularsizeanddis- inallpatientsoneoranother segments ofallM2MCAs advance a fixed, inflexible naming system that places all 2020;51:00–00. DOI: 10.1161/STROKEAHA.120.028956 Stroke. 2020;51:00–00. DOI: There iswideagreementintheliteraturethatproxi - It isimportanttonotethese2anatomicfeatures may Since distancetortuosityandsizeareeach important A proposalhasbeenadvancedtoresolvethemild 8,10 6,7 13 Squarelyinthemediumvesselcategoryare ; M2 MCA vessel segments range in size from 1.1 vesselsegmentsrangeinsizefrom1.1 ; M2MCA However, the ConsensusGroup was concerned 12 11 Accordingly, itseemsilladvisedto ; M2 MCA occlusions may occur in occlusionsmayoccurin ; M2MCA Distal, MediumVessel Occlusions 9 Positioning 2,8 Special Report

2 9 3 The exact fre- exact The September 2020 20–24 8 The remainder, it can be remainder, The Distal, Medium Vessel Occlusions Vessel Medium Distal, 9,16–19 The outcome of DMVO-AISThe under medical therapy Using angiography-based terminology, M1, M2, M3, terminology, Using angiography-based - the MCA stem bifurcates, the superior and infe When is characterized by frequent disability and, among M2 among and, disability frequent by characterized is In the but not other occlusion locations, high mortality. - Stroke study (Screening Technol multicenter STOP at 6 m, M2 occlusions were ogy and Outcome Project), EPIDEMIOLOGY, OUTCOMES, AND CLINICAL FEATURES OF SPONTANEOUS DMVOS and large clinical registry data population-based Available DMVOsindicate spontaneous (not procedure-related) are a common cause of AIS and the source of substantial patient precise frequency of DMVOs has been The morbidity. studiesincompletely delineated, as many epidemiologic vessel imag- have not systematically performed intracranial useful ranging estimates can be obtained by ing. However, population- Broadly, considerations. elimination of process based and large clinical registry studies suggest that AIS in 35% to 40%, presentations are due to acute PLVOs acute small vessel (deep and long pial penetrator) occlusions in 20% to 25%, hemodynamic watershed ischemia in 2% to 5%, and unusual and disseminated conditions (eg, reversible vasoconstriction syndrome, hyperviscocity, moyamoya) in 1% to 5%. divisions give off 12 distal arterial branches: orbitofrontal, orbitofrontal, branches: off 12 distal arterial divisions give posterior anterior parietal, precentral, central, prefrontal, temporal, posterior temporo-occipital, parietal, angular, and temporopolar. anterior temporal, middle temporal, the MCA based on are distinguished and M4 segments sphe- or M1 The triangle. Sylvian the through trajectory horizontally from the artery origin noidal segment runs encompasses M1 typically The to the limen insulae. the entire MCA short segments of the stem and initial MCA the MCA divisions, although sometimes stem can the MCA the insula, turns vertically into M2. At extend most MCA segment, from which as the M2 or insular M3 or opercular segment arise. The cortical branches the of surface lateral the to inferolaterally courses then begins as The M4 or cortical segment Sylvian fissure. fissure and fan over the convex the Sylvian vessels exit surface of the cerebral hemispheres. in diameter, average 2.4 mm at their origin rior divisions in the large ves- placing a majority of initial M2 segments with trifur- size is smaller but division vessel sel category, to range from 1.1 arteries branch 12 cortical The cations. 1.5 mm in diameter at their origin. quencies of individual DMVO occlusion sites have varied with population studied, method of vessel imaging per- 1). used (Table versus MVO LVO formed, and definition of inferred, are preponderantly due to acute DMVOs, which are preponderantly due to acute DMVOs, which inferred, 40%to 25% for account then must AIS—anof estimate that accords with available series data. Altogether, Altogether, 15 . Verbal descriptions of descriptions Verbal 1. 4 trunks (10%). The MCA The (10%). trunks ≥4 There are differences in the are differences There 14 Figure for the ACA, PCA, PICA, PCA, AICA, ACA, the for Supplement Data - advance is that, sub that we the approach Supporting these vessels typically have 25 anatomic segments and anatomic arteries. Their give rise to 34 distinct branch courses, distal territories supplied, and symptoms when in shown are occluded segments, course, and branches are provided in Text I are provided in Text segments, course, and branches the in for the largest, most paragraphs and SCA and in the next vascular arbor—thefrequently affected MCA. Two MCA anatomy classification schemes are widely MCA anatomy classification schemes Two used. Under arboreal. terminology trunk-division-branch and then the MCA arises from the ICA, courses laterally, divides generally according to 1 of 3 patterns: (1) bifurca- trifurcation divisions (78%), tion into superior and inferior divisions (12%), and a middle, and inferior into superior, off directly giving candelabra Middle Cerebral Artery Middle Cerebral The distal, medium-size cerebral arterial vasculature distal, medium-size The arbors:encompasses all or portions of 6 arterial the PICA, MCA, PCA, AICA, and SCA. ACA, SELECTED ASPECTS THE OF ANATOMY OF THE MEDIUM-SIZE DISTAL, CEREBRAL ARTERIAL TREE that definitions of anatomic terms (eg, large) should rest terms (eg, large) should of anatomic that definitions rather time, over stable be and properties anatomic upon and properties technology catheter evolving on rest than over time. fluctuate the and conference our international consensus sequent to and subsequent to the first sub- framing of our proposals groupsingle-center a manuscript, current the of mission article similarly supporting for- published a perspective vessels frommedium-size distal, more distinguishing mally than conflating larger size vessels, rather more proximal, the two in a single category. new approaches recommended. Our international Consen- recommended. Our international new approaches the the terms DMVOsus Group has proposed and PLVO; (medium proposed the terms MeVO single-center group As noted above,pur- we and LVO. vessel occlusion) incorporates both,posely selected a naming system that not just one, of the two most salient biopathophysiologic (1) dimensions for EVT of the cerebral angioarchitecture: these target ves- distance-tortuosity and (2) size. Both of for EVT devicesel properties have important implications EVT procedure conduct. Also, as design and technology appropriate, thenoted, we do additionally support, when only on size (MVO use of single dimension terms, focused PVO). and or only on distance tortuosity (DVO and LVO) more com- our proposed nomenclature is the Accordingly, while bothprehensive and subsumes the other proposal, the time is right todemonstrate that the field recognizes articulate an improved naming system. Stroke. 2020;51:00–00. DOI: 10.1161/STROKEAHA.120.028956 Saver et al et Saver

Downloaded from http://ahajournals.org by on August 7, 2020 Downloaded from http://ahajournals.org by on August 7, 2020 7, August on by http://ahajournals.org from Downloaded Special Report 4 A, Anteriorcerebral artery(ACA),C), posteriorcerebral (artery(PCA), (B ), middlecerebral artery (MCA), and( D), cerebellararteries.Continued ) ( Figure 1.Courseandterritoriesofthecomponent branch arteries ofthedistal,middle-sizecerebralvasculature. mortality in24%. ofpatientsand score,3–6)in60% Rankin Scale[mRS] associated with functional dependency/death (modified Saver etal DMVOs canbesubtle,moreproximalmore distal DMVOs DMVOs sual fielddefects (Figure 1).While presentingdeficitsof or hemianesthesia,aswellpartialcompletehemivi- aphasia, fractionatedratherthancompletehemiparesis cial whitematter. Commonarepartialratherthanglobal and visualfunctionsubservedbythecortex andsuperfi- highly focalcompromiseofcognitive,motor, sensory, score,3–6)in77%(mRS andmortalityin8%. were associatedwithfunctionaldependency/death The reflect clinicalsyndromesofhemisphericDMVOs September 2020 21 Proximal ACA andPCA occlusions distal embolization oftargetthrombimayoccurduring distal embolization During EVTproceduresforPLVOs, fragmentationand EVT COMPLICATING TERRITORIES DISTAL IN EMBOLI AND TERRITORIES NEW IN OFEMBOLI FEATURES CLINICAL AND OUTCOMES, EPIDEMIOLOGY, A2–12.4, P1–16.3,andP2–10.4. of HealthStrokeScalescoreswere:M2–11.5,A1–8.5, center STOP Strokestudy, initialmeanNationalInstitutes generally produce severe initial symptoms. In the multi- 2020;51:00–00. DOI: 10.1161/STROKEAHA.120.028956 Stroke. 2020;51:00–00. DOI: Distal, MediumVessel Occlusions 21 Special Report 5 September 2020 Distal, Medium Vessel Occlusions Vessel Medium Distal, Typical clinical manifestations additionally shown for MCA (frequently disabling) and cerebellar branches (uncommonly additionally shown for MCA (frequently disabling) and cerebellar branches clinical manifestations Figure 1 Continued. Typical have been less well delineated but can include disinhibition; apathy/abulia; contralateral leg branches disabling). Syndromes of individual ACA transcortical motor aphasia. Syndromes of predominant weakness; urinary incontinence; callosal disconnection syndromes, alien hand; and without agraphia, alexia less well delineated but can include quadrantanopia/hemianopia, hemiachromatopsia, have been branches individual PCA acute confusional state, verbal memory impairment, and visual memory impairment. UE indicates upper extremity. Stroke. 2020;51:00–00. DOI: 10.1161/STROKEAHA.120.028956 Saver et al et Saver

Downloaded from http://ahajournals.org by on August 7, 2020 Downloaded from http://ahajournals.org by on August 7, 2020 7, August on by http://ahajournals.org from Downloaded Special Report clinical outcome. resonance imaging)andwas associatedwithworse of patientsevaluatedwith postproceduremagnetic was observedin5.0%of EVTpatients(and12% CT toRecanalizationTimes), infarctinnewterritory tion Proximal OcclusionWith EmphasisonMinimizing lar Treatment forSmallCoreandAnteriorCircula- 6 orACAMCA target segments beyondaninitialICA 20%). andhigher mortality(35%versusversus 48%), functional independence(25%37%), less90-day and had more radiologic hemorrhage (65% versus thrombectomy, 9.4%experienced ACA embolism toms. Among650patientsundergoingmechanical symp- abulia, addedtopreproceduralMCA-typical dyscontrol, transcorticalmotoraphasia,apraxia,and contralateral legweaknessandsensoryloss,bladder present asnewACA-typical symptoms,including occlusion.Clinically,for a targetMCA may ACA ENT a previouslyunaffected ipsilateralACA duringEVT devices used. andtypesofthrombectomy intravenous thrombolysis, locations, thrombuscomposition,frequencyofpre-EVT different series,reflectingvariationsintargetocclusion rateshavevariedin andEDT the retrievaldevice.ENT control ofthrombusduringtheinitialengagementwith EDTs are typically due to fragmentation and loss of tation andlossofcontrolthrombusduringpullback. ENTstial ischemic field. aretypicallyduetofragmen- compromised byischemia, and(2)EDTs withintheini- distinguished: (1)ENTs affecting fieldsnotpreviously eral typesofprocedure-relateddistalocclusionsmaybe 3), largerinfarcts,andworseclinicaloutcome.Two gen- 2a–2cratherthan TICI sis incerebralinfarction[TICI] end can cause thrombus manipulation. Distal occlusions at procedure Saver etal hard, fibrin-andplatelet-rich whiteclots. than more vulnerable to fragmentation and embolization in detectingDMVOs. VA, vertebralartery. posteriorinferior notreported; PCA, superiorcerebellarartery;and cerebellarartery;SCA, posteriorcerebralartery;PICA, middlecerebralartery;NR, occlusion; MCA, Table 1. Among allAIS

Among AntCircAIS

*Observed frequencieslikelyunderestimateactualincidenceduetoonlymoderatesensitivityofcomputedtomographyangiography/magneticresonance ACA acuteischemic anteriorinferior indicates anterior cerebralartery;AICA, distalmediumvessel stroke;AntCirc,anteriorcirculation; DMVO, cerebellarartery;AIS, Stop Stroke Zhao etal Heldner etal Rai etal The most common types of EDT are emboli toThe are emboli mostcommontypesofEDT to isembolism The mostcommontypeofENT September 2020 28 In the ESCAPE multicentertrial (Endovascu- IntheESCAPE 23 DMVO Frequency inAIS* DMVO 22 21 24 25–30 - incomplete final reperfusion(thromboly 31 Soft, erythrocyte-rich redclotsare Soft, ACA/M3/M4, 16% 0.3% A1 0.7% 1% ACA 1% A2 A3–5 NR NR NR NR 27 20% 15% 20% 4% M2 MCA See left M3/4 8% NR NR fusion, eTICI 3(100%),occurredinonly9%. fusion, eTICI in 23%; completereper- 2C(90%–99%) and eTICI 2b67 reperfusion) in30%, (67%–89% in 14%,eTICI reperfusion) 2b50(50%–66% fusion) in14%,eTICI reper- 2a(1%–49% (eTICI) including expanded TICI ofpatients, reperfusion wasfrequent,presentin80% EVTpatients,partial ized clinicaltrialdata,among801 Multiple EndovascularStroketrials) pooledrandom- (Highly Effective ReperfusionEvaluatedin HERMES reperfusion oftheinitialPLVO targetocclusion.In isacauseofincompletean initialM1target.EDT toM2M4segmentsbeyond occlusion oremboli to characterize PLVOs, areofsomevalue butrequire Current imagingtechniques andratingscales,developed OFDMVOS ASPECTS IMAGING presenting deficits. lar fielddespiteresolution/improvement ofotherinitially as persistentdeficitsrelatedtotheaffected distalvascu- reperfusion. When clinicallymanifest, EDTs maypresent evolves fromtheinitialproximal vesselocclusiondespite occurring in22%to23%ofpatients. resonance-imaged patients,EDTs werecommon, beyond thetargetocclusion.In2seriesofmagnetic weighted imagingorbycathetercontrastinjection start, bymagneticresonanceimagingsusceptibility- distal vasculatureisimagedbefore/duringprocedure these mechanisms canbedistinguishedwhenthe event oraroseasprocedure-relatedEDTs. However, ized distalocclusionswerepartoftheinitialocclusive occlusion, precludingdeterminationofwhethervisual- imaged only after reperfusion of the proximal target versus 12.6%). andincreasedmortality(8.3%versus9.2% 46.6%) versus 52.3% versusfunctional independence (60.1% associated withworseoutcomes,includingreduced 2b,was 2ctoTICI 3toTICI reperfusion, from TICI 2020;51:00–00. DOI: 10.1161/STROKEAHA.120.028956 Stroke. 2020;51:00–00. DOI: EDTs maybeclinicallycovertwhenalargeinfarct In manyEVT cases, thedistal vascular tree is first See right 1.2% 2% P1

PCA 1.3% P2

P3–5 NR NR NR

Distal, MediumVessel Occlusions VA/P1/P2/PICA/AICA/SCA, 17% 0.5% PICA NR

Cerebellar 30,33 0.1% AICA NR

32 0.2% SCA Less Less NR

Special Report 7 September 2020 Distal, Medium Vessel Occlusions Vessel Medium Distal, Selected Promising Imaging Research Directions Imaging Research Selected Promising Select DMVO imaging aspects meriting additional CT hyperdense vessel signs: human and AI approaches to systematic CT hyperdense vessel signs: human and AI approaches identification to systematic MR susceptibility vessel signs: human and AI approaches identification Human and AI approaches to systematic identification Multiphase CTA Time-resolved MRA AI classification on perfusion CT/MRI Ultra-high-resolution CTA Dual-energy CTA Ultra-high high-field (7T–11.7T) MRA Vessel segmentation algorithms: multiscale vesselness, diffusion-based filters Perfusion-core/collateral-core/FLAIR-diffusion/clinical-core mismatch computed tomography; CTA, computed computed tomography; CTA, CT, AI indicates artificial intelligence; Parenchymal imaging Standard CTA/MRA Longer acquisition CTA/MRA High spatial resolution MR vessel wall imaging Distal territory hypoperfusion patterns Novel CTA techniques for DMVO visualization WaveletCTA Novel MRA techniques for DMVO visualization Salvageable tissue identification tomography angiography; DMVO, distal medium vessel occlusion; FLAIR, fluid attenuation inversion recovery; MR, magnetic resonance; MRA, magnetic resonance angiography; and MRI, magnetic resonance imaging. Table 2. Table in DMVOs Catheter Angiography arteries superior visualization of medium-size Providing catheter angiography remains and their sudden cutoff, DMVOs. for detecting - How the most sensitive technique with the American collateral flow characterizing ever, Society- Neuroradiol of Interventional and Therapeutic ogy/Society of Interventional Radiology grading system of the territory with can be difficult, as the proportion challenging to quantify, reduced collateral flow may be collateral flow. due to smaller field size and often faster Fine-grained TICI reperfusion grades can similarly be more difficult to assign. 2. Table are shown in research regions to individual arterial branches. Blood flow delays Blood flow branches. individual arterial regions to due occlusions proximal beyond distal than may be less convexity; over the cerebral routes collateral to shorter may not penumbral threshold >6-s a Tmax accordingly, - occlu distal as proximal same meaning for have the penumbral imaging via perfusion- sions. Nonetheless, can be informative in distal occlusions, core mismatch thresholds for decision-making after adjusting lesion size at risk. to the smaller fields However, systematic search for search systematic However, 34 36,37 Hypoperfusion in a wedge-shaped 38 However, erythrocyte-poor, isointense erythrocyte-poor, However, 30,33,35 occlusions will not be directly visualized, though local occlusions will not be directly visualized, inversion recov- slow flow evidenced by fluid attenuation ery vascular hyperintensity may be suggestive. computed tomography dot signs is often not performed dot signs is often not performed computed tomography PCA, ACA, similar findings in in clinical interpretations; arteries have not been extensively and cerebellar branch will isodense occlusions described; and erythrocyte-poor, resonance magnetic routine on Similarly, seen. be not distal occlusive thrombi will pro- imaging, erythrocyte-rich as intravascular, duce susceptibility vessel signs, evident on susceptibility-weighted signals low-intensity tubular sequences. - imaging is helpful in indicating indirectly pres Perfusion ence of DMVOs. Computed Tomography Perfusion/Perfusion Computed Tomography Resonance Imaging Magnetic Weighted On computed tomography angiography (CTA) and mag- (CTA) On computed tomography angiography netic resonance angiography (MRA), distal occlusions are and MRA detect evident as sudden vessel cutoffs. CTA cerebellar artery and proximal PCA, P1 M2 MCA, A1 ACA, they are less reli- However, occlusions with high accuracy. occlusions, as reduced artery able for more distal branch anatomy variability can make it diffi- caliber and branch vessel signal iscult to determine whether loss of distal Detection ofdue to an occlusion or anatomic variation. acquisitions that distal occlusions is aided by CTA/MRA continue late into the passage of contrast through the cerebral vasculature, including multiphase, rather than and time-resolved MRA. Spatial resolu- single-phase, CTA, tion and delineation of smaller vessels is improved by aug- analysismented signal-to-noise computed tomography and higher magnetic resonance field strength; waveletCTA MRA7T and arebut clearly occlusions vessel distal show not widely available. Computed Tomography Angiography/Magnetic Computed Tomography Resonance Angiography Computed Tomography/Magnetic Resonance Resonance Tomography/Magnetic Computed Imaging erythrocyte-rich tomography, On noncontrast computed will produce hyperdense vessel distal occlusive thrombi - to M4 occlusions, these appear as circu M3 signs. With in the Sylvian triangle—the computed lar hyperdensities tomography dot sign. refinement and further development to optimally delin- optimally to development further and refinement eate DMVOs. region matching the typical territory of an ACA, MCA, the typical territory of an ACA, region matching sug- strongly artery branch distal cerebellar or PCA, vessel. Artificial intel- gests occlusion of the feeding hypoperfusion map focal help may algorithms ligence Stroke. 2020;51:00–00. DOI: 10.1161/STROKEAHA.120.028956 Saver et al et Saver

Downloaded from http://ahajournals.org by on August 7, 2020 Downloaded from http://ahajournals.org by on August 7, 2020 7, August on by http://ahajournals.org from Downloaded Special Report come (52%versus29%). versus 17%)andtendedtoincreaseindependentout- increased partial or complete reperfusion rates (54% with isolatedM2occlusions,intra-arterialprourokinase 2),among44patients Cerebral Thromboembolism InthePROACT-2DMVOs. trial (Prourokinase inAcute evaluated intra-arteriallysisasaprimarytherapyfor reduced systemiclyticexposure. Severalstudieshave of higherdrugconcentrationtothetargetthrombusand recanalizing onlyone-thirdtoone-halfofvisualizedthrombi. aloneisimperfect forDMVOs, intravenous thrombolysis with 35% for M1 MCA, 13% for ICA, and13%forbasilar. 13%forICA, with 35%forM1MCA, occlusions,compared MCA achieved in52%ofM2/M3 plete recanalizationwithintravenousalteplasealonewas patients across 26 studies, partial or com- ysis of 2063 increased riskofhemorrhagictransformation. arterial fibrinolysiscanincreasereperfusionwithminimal endovascular mechanical thrombectomy, judicious intra- 8 smaller devices haverecentlybeenreleased, including3 tial stentretrievershadradial diametersof6and4mm, haveiterativelyadvanced.Whileapplied toDMVOs ini- vascular devicessufficiently smallandnavigabletobe rial tree.Ascathetertechnology has improved, endo- extending EVTtherapyfurtherupthe cerebralarte- seems likely well-selected patients could behelped by ing andEVTforPLVOs isoverwhelminglybeneficial, it ever, as in DMVOs strategic locations can be debilitat- volumes constrainpotentialreperfusionbenefit.How- foration, andvasospasm;thesmallerat-risktissue arterial wallspotentiallyincreaseriskofdissection,per- Their longer, more tortuous access route and thinner endovascular mechanical thrombectomy procedures. Distal, mediumvesselswerenotaninitialtargetfor FORDMVOS THROMBECTOMY MECHANICAL ENDOVASCULAR sions. plete recanalizationin76% ofM2and33%M3occlu- study, intra-arterialurokinaseachieved partialorcom- PLVOs. thanthelargerclotburdensof clot burdensofDMVOs Pharmacologic fibrinolysisismoreeffective forthesmaller FORDMVOS TREATMENT FIBRINOLYTIC INTRA-ARTERIAL AND INTRAVENOUS Saver etal and 11%forICA. comparedwith22%forM1MCA and 37%ofM2MCA, ACA,tion recanalized43%ofM3MCA, orPCA occlusions phy), intravenousalteplasebeforeendovascularinterven- Alteplase and Other Treatments Using Serial CT Angiogra- Predicting EarlyRecanalizationandReperfusionWith IV Approaches toOptimizeThrombus Characterization for study (IdentifyingNew In theEVTera,inINTERRSeCT Intra-arterial infusionoffibrinolyticspermitsdelivery September 2020 44 39,40 Asrescuetherapyafterincompletelysuccessful For intravenousfibrinolysis,inameta-anal- 42 Nonetheless, as these data attest, Nonetheless,asthesedataattest, 43 Inalargesingle-center 45,46 41

in 5%. andnondominant nant divisionin56%,codominant38%, anddistalM2in11%adomi - proximal M2in89% in 7randomizedclinicaltrials,thetargetocclusionwas occlusions patientswithM2MCA pooled analysisof130 HERMES tial benefitofEVTinthedistalarterialtree.Ina evidence providesimportantinitialperspectiveonpoten- randomizedclinicaltrial sions). Nonetheless,theM2MCA occlusions(M1-likeM2occlu - sibility similartoM1MCA in proximal, divisionswithsizeandacces- largeM2MCA ther, occlusionshavelargelybeen theenrolledM2MCA ratherthanmoredistal,smallerarteries.Furof M2MCA - patientsandpreponderantlyocclusions number ofDMVO lower bloodpressure,impairingcollaterals. tial forgeneralanesthesiatodelayprocedurestartand arteries; however, concernsremainregardingthepoten- catheter navigationtothemoredistalandfragiletarget asreducedpatientmovementfacilitates for DMVOs, advantage compared with procedural sedation for EVT ure 3). less traumatictips,andappropriatesuctionforce(Fig- for the distal vasculature, including increased flexibility, devices have increased suitability thromboaspiration sions. versus stentretrievers,79 enrolledpatientshadM2occlu- Revascularization) comparing EVT with contact aspiration (Contact AspirationVersus StentRetrieverforSuccessful patients comparedwith7.9% trial incontrols.IntheASTER intracranial hemorrhage(0%)wasobservedinEVT-treated segmentocclusions.Intriguingly,MCA nosymptomatic EVT benefitwasgreatestwithproximal anddominantM2 P 3-m functionalindependence(58%versus40%; and EVTcomparedwithmedicaltherapyaloneincreased 2b–3)wasachieved in59%, Cerebral Infarction[mTICI] triever 13), ture LP, Trevo ProVue) XP and2.5mm(eg,theTiger- LITE, MindframeCap- mm (eg,theCatch Mini,pREset thromboaspiration in 45%. Outcomes included substantial in45%.Outcomesincluded substantial thromboaspiration stent retrieversin54%,intra-arterial alteplasein52%,and occlusions presentafterPLVO EVT. including 62%primarydistal occlusionsand33%distal ACA (54%), or (43%), M3MCA PCA (10%) occlusions, patients with center series,EVTwasperformed in69 series rather than randomized trials. In a large single- was noted(20%versus3%). a trendtowardincreasedmortalitywithcontactaspiration aspiration and stent retriever (54% versus 50%), though days was similar between contact independence at 90 3:35%versus42%.Functional versus84%;TICI 3, 90% 2bto afteruse ofrescuedevices:TICI 29% versus39%; 3, TICI 2b/3,65%versus68%; versus stentretriever:TICI reach statistical significance:afterinitialcontactaspiration able slider(Figure 2). control overamountofradialopeningusinganadjust- 2020;51:00–00. DOI: 10.1161/STROKEAHA.120.028956 Stroke. 2020;51:00–00. DOI: Randomized trials of EVT have enrolled only a limited Randomized trialsofEVThaveenrolledonlyalimited For evidenceisprimarilyfromcase otherDMVOs, 54 12 52,53 Nominaldifferences inreperfusion ratesdidnot Substantial reperfusion (modified Thrombolysis in in Substantialreperfusion(modified Thrombolysis Generalanesthesiamayhavegreaterrelative 47–50 aswelldevicesthataffordoperator 51 Similarly, technical advancesin Distal, MediumVessel Occlusions 55 Modalities were Modalitieswere =0.03). =0.03). Special Report 9 Lower left, September 2020 Distal, Medium Vessel Occlusions Vessel Medium Distal, Given this clinical heterogeneity, one approach would approach one heterogeneity, clinical this Given heterogeneity in potential study populations. In primary dis- heterogeneity in potential study populations. tal occlusions, DMVO-relateddeficits appear in isolation; in and added to those of the initial presenting occlusion; ENT, blended into those of the initial presenting occlu- in EDT, yield fairly while anterior circulation PLVOs sion. Further, homogenous clinical deficits, defi- disparate yield DMVOs cits varying with the fractionated arterial territory compro- with alexia ACA, isolated abulia due to with Patients mised. and agraphia due to MCA, quadrantanopia due to PCA, radi- unilateral ataxia due to PICA infarction differ branch their impair- Moreover, cally in symptomatic manifestations. ments are often not well captured by the National Institutes of Health Stroke Scale and the mRS—the standard acute stroke trial entry and outcome assessment scales. be to adopt as the primary efficacy end point the more status/reper- vessel of outcome technical homogenous be not might controls randomized to Comparison fusion. required in an objective performance criterion trial, as immediate spontaneous reperfusion in distal occlusions DMVOs pose several challenges, none insuperable, to DMVOs pose several challenges, of DMVOs create 3 mechanisms clinical trial design. The DESIGNING CLINICAL TRIALS FOR ISCHEMIC STROKES DUE DMVOS TO reperfusion (mTICI hematoma 2b–3) in 83%, parenchymal in the distal arterial field in 4%, 90-day functional independence in 30%, the Distal Sum- and mortality in 20%. At mit, preliminary results were presented from Essen of EVT EDT after intracranial occlusion patients, 77% in 44 ACA 20% primary occlusions, and 2% ENT ICA thrombectomy, after MCA thrombectomy (Chapot, personal communi- Substantial reperfusion (TICIcation, 2019). 2b–3) was in 93% with complications of bleeding in 2% and achieved ENT EVT is now able findings demonstrate in 2%. These high reperfusion rates in at least some DMVO to achieve complications, indicating more targets with relatively few formal, multicenter testing is warranted. Tiger 13 stentriever advanced through Headway27 microcatheter into target branch artery. Lower right, Retrieved thrombus. Image courtesy of artery. 13 stentriever advanced through Headway27 microcatheter into target branch Tiger Rene Chapot, MD. reperfusion by stent retriever. Figure 2. Distal medium vessel occlusion endovascular thrombectomy for an M1 middle cerebral artery (MCA) or new occlusion, angiography showed a residual Upper left, Following procedure (yellow circle). occlusion (yellow circle). Upper right, Reperfusion of M4 after distal thrombectomy distal M4 MCA branch Stroke. 2020;51:00–00. DOI: 10.1161/STROKEAHA.120.028956 Saver et al et Saver

Downloaded from http://ahajournals.org by on August 7, 2020 Downloaded from http://ahajournals.org by on August 7, 2020 7, August on by http://ahajournals.org from Downloaded Special Report ing, toileting,hygiene,andeating)orreturningtowork. forming basic activitiesofdailyliving (bathing, ambulat- that, if unchanged, would prevent the patient from per- rtPA forIschemic StrokesWith MildSymptoms):adeficit mildstroketrial (Potential of developed forthePRISMS a disablingdeficit,usingtheoperationalizeddefinition criteria couldalsooralternativelyrequirepresenceof ing motor, visual,language,ormemoryfunction).Entry artery supplyaneloquentterritory(eg,aregionsubserv- benefit, entrycriteriacouldrequirethecompromised 10 points areanother potentialapproach. This strategyhas biomarker secondaryoutcomes. volume andpenumbrasalvagecouldbeusefuladditional would besecondaryendpoints.Branch-territory infarct global disability,Clinical outcomes, including 3-m mRS is rare. artery. Lowerright,Retrievedthrombus.ImagecourtesyofDanMeila,MD. Reperfusion attheendofdistalthrombectomyprocedure(yellowcircle).Lowerleft,Headway27microcatheteradvancedintotargetbranch M3middlecerebralarterybranch occlusion(yellowcircle).Upperright, Upper left,Initialangiographyshowedaprimarycardioembolic Figure 3.Distalmediumvesselocclusionreperfusionbyendovascularthromboaspiration. Saver etal nical, benefit. onstrating forpayorsdefinite clinical,inadditiontotech- PLVO retrievaldevice butalsoitsdrawback ofnotdem- the DMVOs rapid regulatory clearance path of the first sel outcomesasprimaryend pointswouldreplicatefor Modality-specific functional measuresasprimaryend September 2020 56 To ensurereperfusionhadpotentialclinical 58 50 Usingtechnical ves- 57

aphasia orvisualstimulationforvisual-fielddefects. target specificdeficits,such aslanguagetherapyfor been usedinstrokerecoverytrialswhich treatments patients occurred frequently:50%to87% ofA1,A2,M2, score,3–6)inmedicallytreatedDMVO or death(mRS branch infarcts. In the STOP Stroke study, dependency MCA, andhemianopiafromPCAreading difficultyfrom level2)issensitivetowalkingdifficultyfrom ACA,(mRS different neurologicdeficits.Inability to returnwork ability, itcancapturefunctionallimitationsarising from assessesglobal,all-causedis- duce. BecausethemRS despitetheheterogenousdeficitstheypro- DMVOs mayproveresponsivefor measure, such asthemRS, ACA infarcts. measure reflectinglower extremity motorfunctionin is gaitspeed(10-mwalktest)asafunctionaloutcome Memory Test), andvision(visualfields).Ofparticularnote Quality ofLife Scale),memory(RivermeadBehavioural Research Arm Test), language (Stroke and Aphasia able, includingforarmmotorfunction(eg,theAction variety ofmodality-specificoutcomemeasuresareavail- 2020;51:00–00. DOI: 10.1161/STROKEAHA.120.028956 Stroke. 2020;51:00–00. DOI: But if appropriately analyzed, a global disability Distal, MediumVessel Occlusions 59 A Special Report

11 D, Cetković I, Djordjević September 2020 Distal, Medium Vessel Occlusions Vessel Medium Distal, A, Jovanović 2017;27:671–681. doi: 2017;27:671–681. Neurosurg. Turk M.of supply region Morphometric analysis, S, Maliković V, Milisavljević V, J Neurointerv Surg. 2019;11:1065–1069. doi: 10.1136/ J Clin Neurosci. 2012;19:1416–1421. doi: 10.1016/j.jocn. V, Marinković V, Schwaiger BJ, Gersing AS, Zimmer C, Prothmann S. The curved MCA: The S. Zimmer C, Prothmann BJ, Gersing AS, Schwaiger - results of mechani influence of vessel anatomy on recanalization stroke. AJNR Am J Neuroradiol. cal thrombectomy after acute ischemic doi: 10.3174/ajnr.A4222 2015;36:971–976. Cline B, Hobbs G. Cerebrovascular geometry in the ante- Hogg JP, Rai AT, J Neu- length and the vessel taper. rior circulation: an analysis of diameter, doi: 10.1136/neurintsurg-2012-010314 rointerv Surg. 2013;5:371–375. El-Barhoun EN, Gledhill SR, Circle of willis artery diameters on Pitman AG. Radiat Imaging Med database. J mr angiography: an Australian reference Oncol. 2009;53:248–260. doi: 10.1111/j.1754-9485.2009.02056.x I, Zhjeqi S, Ahmetgjekaj S, Krasniqi S, Kabashi D, Bexheti Shatri J, Bexheti Influence of gender and age on average dimensions of arteries form- V. - on Koso ing the circle of willis study by magnetic resonance angiography doi: vo’s population. Open Access Maced J Med Sci. 2017;5:714–719. 10.3889/oamjms.2017.160 Cerebral vascular FL, Severino AG. Stefani MA, Schneider AC, Marrone - examina angiographic resonance magnetic the during observed diameters . 2013;56:45–52. tion of willis circle. Brazi Arch Biol Technol ć M, Todorovi sig- their clinical arteries and lenticulostriate of the and microanatomy nificance. 2011.10.025 CL, Bevan PL, Walters Penar N, Hyman T, Bartolotta N, Thorin-Trescases RD,arter- pial human of tone myogenic of dependence Diameter JA. Bevan Stroke. 1997;28:2486–2492. doi: relation to distensibility. ies. Possible 10.1161/01.str.28.12.2486 branches, cortical artery: cerebral middle the of Anatomy BJ. Page K, Cilliers anomalies. and pattern branching 10.5137/1019-5149.JTN.18127-16.1 of definition and Siddiqui AH. Effect K, Chin F, Vakharia M, Rai AT, Waqas methods on estimates of prevalence of large vessel occlusion in acute stroke: a systematic review and meta-analysis. J Neurointerv Surg. ischemic 2020;12:260–265. doi: 10.1136/neurintsurg-2019-015172 In: Bogousslavsky J, Saver JL, Biller J. Superficial middle cerebral artery. NY: Cambridge University eds. Stroke syndromes. New York, Caplan LR, 1996:247–258. Press; S, Ascoli GA, Cebral JR. Morphometric, geographic, and ter- Wright Mut F, of brain arterial trees. Int J Numer Method Biomed ritorial characterization 10.1002/cnm.2627 doi: Eng. 2014;30:755–766. Menon BK, Hill MD, Dippel Davalos A, Roos YBWEM, Campbell BCV, Saver JL, AM, et al. Effi- A, Demchuk Lugt van der Guillemin F, DWJ, cacy of endovascular thrombectomy in patients with M2 segment middle cerebral artery occlusions: meta-analysis of data from the HERMES Col- laboration. neurintsurg-2018-014678 Hussain MS,Arthur AS, Singh Baxter BW, Chandra RV, T, Leslie-Mazwi Society JA; of NeuroIn- Albuquerque FC, Hirsch Klucznik RP, DF, Frei IP, an operational definition. J Neurointerv Surg. ELVO: terventional Surgery. doi: 10.1136/neurintsurg-2018-013792 2018;10:507–509. Goyal M, Ospel JM, Menon BK, Hill MD. frontier? J Neuro- the next MeVO: 10.1136/neurintsurg-2020-015807 doi: interv Surg. 2020;12:545–547. Kim DE, JH, SK, Park D, Ryu WS, Lee Jang MU, Schellingerhout Jeong SW, JE, Park EJ, et al. Mapping the supratentorial cerebral arterial Lee Na JY, 7. 1. 2. 3. 4. 5. 8. 9. 6. Djulejić 10. 11. 12. 13. 14. 15. Disclosures Medical/Medtronic/Stryker/Cerenovus/BoehringerDr Saver: Rapid Ingelheim/ Chapot/Agid/Lobotesis/Meila/Meyer/Raphaeli:BrainsGate; Dr Medical; Rapid Rapid Medical/Medtronic/Stryker/Penumbra/Balt/Microvention/Dr Hassan: GE Rapid Medical/Cerenovus/Genentech/ Dr Liebeskind: Healthcare/Vizai; Dr Gupta: Rapid Medical/Penumbra/Stryker/Cerenovus/Medtronic/Stryker; . author reports no conflicts other Zoll. The APPENDIX Gunnar Andsberg, Summit collaborators:Distal Thrombectomy Pietro Amista’, Salva- Kiriaki Kollia, Sanja Karabegovic, Cagnazzo, Maurizio Isalberti, Federico Erez Weitzel Mudersbach, Paul von Antonio Moreno, tore Mangiafico, Marcin Mis, Rudnicka, Raz, Joao Reis, Svetlana Eytan Piasecki, Piotr Guglielmo Pero, Nossek, Zamaro. Undren, Joaquin Stavngaard, Per Trine Matias Sinisalo, Marco Spinetta, REFERENCES

The mRS The to can be optimized 21 be informative in milder stroke patients by use of shift patients by use in milder stroke be informative (eg, of good outcomes granular sampling analysis with at mRStrichotomized at 0, 1, 2, 3–6 or tetrachotomized using prog- analysis or of sliding dichotomy 0–1, 2, 3–6) randomization stratified With nosis-adjusted modeling. balance in treatment arms, global by location to ensure used be potentially could measures outcome functional in DMVO trials. We are grateful to Bat-Orgil scientific figure preparation. Bat-Erdene for expert We Funding of Sources Summit was provided by Rapid Medi- support for the Distal Thrombectomy Travel work was supported, in part, by NIH-NINDScal. This U10NS086497 (Dr Saver). Acknowledgments Affiliations of Medicine at UCLA, School An- David Geffen Los Department of Neurology, Endo- Intracranial and Neuroradiology D.S.L.). Department of (J.L.S., CA geles, Essen, Germany (R.C.). Division of Krankenhaus, Krupp Alfried vascular Therapy, Hospital, JDMI, Western UHN, Toronto Canada (R.A.). Depart- Neuroradiology, Baptist Medical Valley Rio Grande Valley, University of Texas ment of Neurology, University Neurosurgery, and Neurology of Departments (A.H.). Harlingen Center, Imperial Department of Neuroradiology, (A.P.J.). PA of Pittsburgh Medical Center, United Kingdom (K.L.). Department of London, College Healthcare NHS Trust, Johanna-Étienne-Hospital, Neuss, Germany (D.M.). Interventional Neuroradiology, University Medical Department of Diagnostic and Interventional Neuroradiology, Center Hamburg-Eppendorf, Hamburg, Germany (L.M.). Departments of Neurol- Tel ogy (G.R.) and Interventional Neuroradiology (G.R.), Rabin Medical Center, Israel. Departments of Neurology (R.G.) and Neuroradiology (R.G.), WellStar Aviv, GA. Health System, Atlanta, ARTICLE INFORMATIONARTICLE CONCLUSIONS DMVOs produce 24% to 40% of AIS,- arising as sponta thromboembolineous consequences unintended as and arterial arbors 6 distal medium The of EVT for PLVOs. PICA, M2–M4 MCA, PCA, AICA, and SCA) have (ACA, 34 arte- 25 distinct anatomic segments and encompass largely highly differentiated, that supply rial branches regions. superficial cerebral neuroanatomical DMVOs are heterogenous engender clinical syndromes that more Though and fractionated but frequently disabling. occlusions, intravenous proximal for distal than effective one-half to fibrinolytics nonetheless fail to recanalize is an unmet there two-thirds of occlusions. Accordingly, a are territories these DMVOs, and of treatment for need for endovascular intervention. Ini- frontier promising next stent navigable more smaller, of studies cohort clinical tial retriever and thromboaspiration devices suggest EVT for col- Sustained, effective. technically and safe DMVOsis laborativeimag- advance to desirable are investigations designs device iterate DMVOs,further of recognition ing large reg- and conduct efficacy, and improve reperfusion harmonized, trials using formal clinical istry studies and this of treatment improve to elements data common common stroke subtype. P1, and P2 occlusions. P1, and P2 Stroke. 2020;51:00–00. DOI: 10.1161/STROKEAHA.120.028956 Saver et al et Saver

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