Consensus statement on mechanical thrombectomy in acute ischemic stroke

Consensus statement on mechanical thrombectomy in acute ischemic stroke – ESO-Karolinska Stroke Update 2014 in collaboration with ESMINT and ESNR

New evidence since KSU 2012

Since the previous Karolinska Stroke Update consensus statement on mechanical thrombectomy 2012, results from randomized clinical trials and other retrospective cohort studies were made available as follows:

A. Large metaanalysis from randomized clinical trials of intravenous thrombolysis (IVT)

A recently published meta-analysis of individual patient data from 6756 patients in nine randomized trials comparing IVT with alteplase versus placebo or open control showed that alteplase signiﬁcantly improves functional outcomes when delivered within 4,5 h of stroke onset, with earlier treatment associated with bigger proportional beneﬁts (OR 1·75, 95% CI 1·35–2·27), thus emphasizing the need for preventing delays in acute stroke treatment.1

B. Randomized clinical trials on mechanical thrombectomy

a) Older generation devices and first use of stent retrievers

Three trials evaluating endovascular therapy, published in 2013, IMS III, MR RESCUE and SYNTHESIS, reported neutral results on clinical outcome. Possible explanations for failure to demonstrate superiority of endovascular therapy were long delay between symptom onset and treatment, inadequate patient selection, less than desired recanalization rates and use of older generation devices. IMS III showed no difference in safety and clinical outcomes compared to IVT but used 6 different procedural techniques with only 4 patients being treated with the new generation stent retrievers.2 A subgroup analysis of IMS III showed 48.2% modified Rankin score (mRS) 0-2 when recanalization mTICI 2b/3 was achieved (for ICA (37-42%) and M1 occlusions (44%))3, emphasizing the importance of recanalization of proximal occlusion. Importantly, IMS III demonstrated that a delay in time to reperfusion was associated with lower likelihood of good clinical outcome.4 MR RESCUE allowed procedures up to 8 h based on penumbral imaging but used previous generation MERCI or Penumbra devices achieving mTICI 2b/3 recanalization rates of 67%.5 The SYNTHESIS EXPANSION trial also used very few stent retrievers.6 However, regarding safety, these trials showed similar rates of symptomatic intracranial hemorrhage (SICH) compared to IVT and even equivalence/superiority of IVT for minor stroke and stroke without large vessel occlusion on imaging.7

b) Stent retrievers in recent randomized controlled trials

Two smaller phase IIb randomized controlled studies compared stent retrievers with the original MERCI™ device (see also thrombectomy consensus statement from the 2012 KSU meeting).

The SWIFT study (Solitaire™ With the Intention For Thrombectomy) compared thrombectomy with the Solitaire™ and with the MERCI™ devices and was prematurely stopped after 113 patients because of efficacy. The primary outcome, recanalisation defined as Thrombolysis In Myocardial Ischemia (TIMI) scale 2 or 3, was more frequent with the Solitaire ™ device with an odds ratio (OR) of 4.9 (95% CI 2.1–11.1). Also, 3 months mRS ≤ 2 was more frequent with the Solitaire™ with an OR of 2.8 [1.2–6.2].8

The TREVO-2 trial (Trevo versus Merci retrievers for thrombectomy REvascularisation of large Vessel Occlusions) compared thrombectomy with the TREVO Retriever™ and with the MERCI™ device in 178 patients. Reperfusion measured by Thrombolysis In Cerebral Infarction (TICI) scores of ≥ 2 was more frequent with the TREVO Retriever™ with an OR of 4.2 (95% CI 1.9–9.7). 3 months mRS ≤ 2 was more frequent with Trevo™: 40.0% vs. 21.8%, but there was a trend towards higher mortality.9

The MR CLEAN trial (Multicenter Randomized Clinical trial of Endovascular Treatment in the Netherlands)10, using stent retrievers in 97% of the cases, showed benefit of endovascular therapy up to 6 h after stroke onset in the proximal anterior circulation in addition to best medical therapy (IVT up to 4.5 h in most patients). Onset to IVT was 85-87 min in both intervention and control groups and onset time to arterial puncture was 260 min. The endovascular procedure was associated with a shift to improved function at 90 days, as reflected in more patients in the lower mRS categories, with an adjusted common odds ratio (acOR) of 1.67 (95% confidence interval [CI], 1.21 - 2.30).

Secondary outcome parameters (NIHSS at 24h and 1wk, recanalization at 24h and final infarct at 1wk) were all statistical significantly favoring the intervention group. Treatment effect was consistent in all pre-defined subgroups.

The ESCAPE trial (Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing CT to recanalization times) was prematurely halted after randomization of 316 patients due to a positive interim analysis. To be randomized, patients needed to have a NIHSS > 5, a CTA confirmed occlusion of the carotid T or the middle cerebral artery (MCA, M1 or large M2 segment), good collaterals on multiphase CTA, a CT-ASPECTS > 5, and had to be enrolled < 12 hours. rtPA before randomization was given if patients were eligible. Results: The adjusted risk ratio for a mRS shift with thrombectomy at 90 days was 3.1 (CI : 2.0 – 4.7). A favourable modified Rankin score (mRS) of 0-2 at 90 days was seen in 53.0% in thrombectomy vs. 29.3% in controls (NNT=4), and reduction of mortality was significant. All subgroups of patients had similar benefit, including the elderly and patients treatable after 6 hours from onset time. About 75% of patients received IVT and stent retrievers were used in 86.1%.11

The SWIFT PRIME trial (Solitaire™ With the Intention For Thrombectomy as PRIMary treatment for acute ischemic strokE) was prematurely stopped after a positive interim analysis of the first 196 patients. To be randomized, all patients needed to have received IVT < 4.5 hours, a NIHSS between 8 and 29, a CTA or MRA showing an occlusion of the intracranial carotid or M1 segment of the MCA without extracranial carotid occlusion, an ASPECTS > 6 and CT hypodensity (or MRI hyperintensity) < 1/3 of the MCA territory, and treatable < 6 hours. Results (two co-primary endpoints): The OR for a mRS shift at 90 days with thrombectomy using the Solitaire™ FR stent retriever was highly significant (p< 0.001), and mRS 0-2 at 90 days was 60.2% in thrombectomy patients vs. 35.5% in controls (p < 0.001, NNT=4). There was a trend for reduced mortality. The onset-to-arterial-puncture delay was 252 min. All subgroups of patients had similar benefit.12

The EXTEND-IA trial (EXtending the time for Thrombolysis in Emergency Neurological Deficits with Intra-Arterial therapy), a phase II trial looking at early reperfusion and neurological improvement on day 3, was prematurely stopped because of a positive interim analysis of the first 70 randomized patients. To be randomized, all patients needed to have received IVT < 4.5 hours, a CT or MR angiography showing an occlusion of the intracranial carotid, M1 or M2 segment of the MCA, significant mismatch and limited core on MR- or CT perfusion (using the RAPID® software), and had to be treatable <6 hours. Results (two co-primary endpoints): Early reperfusion of the ischemic tissue at 24h hours with thrombectomy with the Solitaire™ FR stent retriever was 100% vs. 37% in the control group (p<0.001), a NIHSS reduction ≥ 8 points or NIHSS 0-1 at 3 days with thrombectomy was 80% vs 37% in the control group (p<0.001). mRS 0-2 at 90 days was 71% in thrombectomy patients and 40% in controls (p<0.01, NNT =3). There was a trend towards reduction of mortality. The onset-to-arterial-puncture delay was 210 min.13

In summary, there is very good evidence for early thrombectomy with stentretrievers. There is good evidence to favour stentretrievers over the MERCITM device. At this moment only limited data on other types of recanalization devices such as the PenumbraTM system are available.14 Given the variable success rates and clinical outcomes with different recanalisation devices in randomized trials, generalizability of all transvascular approaches cannot be assumed.

C. Aspects to be considered in mechanical thrombectomy

a) Stent retrievers

The STAR (Solitaire Flow Restoration Thrombectomy for Acute Revascularization) study was an international, multicentre, prospective, single-arm study of the SolitaireTM device in 202 patients with large vessel occlusion of the anterior circulation within 8 h of onset. It reported a 79% rate of successful revascularization, 57.9% of mRS 0-2, 1.5% SICH and 6.9% mortality. Support for stent retrievers was further gathered in a 2013 pooled analysis of 19 studies using the TrevoTM (n=221) or SolitaireTM (n=355) devices, showing mTICI 2b-3 scores in 83 and 82%, hemorrhage in 8 and 6%, device complications in 5 and 6%, good functional outcomes in 51 and 47% of the patients with similar times to recanalization and with a mortality of 31 and 14%, respectively.15

b) Mechanical thrombectomy in single centre cohorts: outcomes and risk factors

A recently published single centre series of 240 patients treated 2005-2011 with mechanical thrombectomy alone or in addition to IVT (40%) (using initially MERCITM and later on stentretrievers) achieved 50% mRS 0-2 at 3 months and reported 4.6% of SICH.16

In a retrospective single centre cohort of 176 consecutive patients focusing on complications of mechanical thrombectomy it was shown that prolonged endovascular procedure beyond one hour was associated with higher complication rates (such as SICH, embolism to new territories, dissection, vasospasm, stent dislocation/occlusion, cumulative 11% rate) but that the overall rate of SICH (5%) was comparable to IVT.17 Postinterventional subarachnoid hyperdensities were not shown to influence outcomes.18

c) Mechanical thrombectomy in elderly patients

In MR CLEAN 16% of the patients were 80 years or older; there was a positive treatment effect in this subgroup. This effect was significant and its size not different from the main effect size (OR 3.24, 95% CI 1.21-8.62)10. Similarly, both randomized trials ESCAPE and SWIFT PRIME (in the latter with upper age limit of 80 years old) showed benefit for all subgroups including the elderly, who should thus be considered for thrombectomy.11, 12 Previously, mortality in patients undergoing thrombectomy over 80 years of age was reported to be double that for younger patients in a large multicentre retrospective analysis in the US (9300 patients, of which 18% were above 80). However, the analysis period was restricted to 2008-2010, the type of device used was not mentioned and treatment effect could not be asessed.19 Almekhlafi et al. used the SPAN-100 index (i.e. positive index if age+NIHSS score = 100 or more) and found lower proportions of favourable outcome in the patients with positive (61%) compared to negative SPAN index (27%, OR 0.3; 95% CI 0.1-0.9), with 60% of positive SPAN index being 80 years of age and older.20 For the vertebrobasilar circulation, a retrospective analysis from a US nationwide database from 2006-2010 showed that age had an impact on in-hospital mortality of patients undergoing mechanical thrombectomy (n=631) but not IVT (n=1554), in particular those 65 years of age or older (43 vs 23%). However, the types of devices used during that period were not reported.21

d) Time to treatment and reperfusion

The positive effect in the MR CLEAN trial was time-dependent, with acOR decreasing from 3.0 (95% CI: 1.6 – 5.6) at 3.5 hours onset to reperfusion time, to 1.5 (95% CI: 1.1 – 2.2) at 6 hours.22 Treatment effect was not statistically significant anymore when reperfusion was achieved after 6h19m.
Benefit of thrombectomy was also shown to be time-dependent in IMS III, where increased time to reperfusion was associated with a decreased probability of good functional outcome (adjusted relative risk for every 30-min delay 0·88, 95% CI 0·80-0·98).4 Based on IMS III results and literature review, a cutoff of 347 min (5h47m) for superiority of endovascular procedure over IVT alone was recently suggested.23 These findings underline the necessity to treat as early as possible, and justify the time window of treatment within 6 hours from symptom onset.

In the ESCAPE trial, however, 49 (15.5%) patients were included beyond 6 hours, treatment effect was not different. This leaves room to investigate the possibilities of expanding the treatment time window for a selected group based on advanced imaging.

e) Tandem pathology

In the MR CLEAN trial 146 (29%) patients had an additional extracranial ICA occlusion (tandem pathology), with treatment effect in favor of thrombectomy (OR 1.43, 95% CI 0.78-2.64).10

In a systematic review of 32 studies including 1107 patients with intra and/or extracranial ICA occlusions, intraarterial thrombolysis was compared with any kind of mechanical treatment and/or stent placement. Acute stenting of occlusions of the extracranial ICA resulted in a higher recanalization rate (87% vs 48%, p=0.001) and favorable outcomes (68% vs 15%, p<0.001) as well as lower mortality (18% vs 41%, p=0.048) when compared to intra-arterial thrombolysis24.

Recently published cohort studies indicate that tandem stenosis/occlusions of the ICA/MCA can be treated with acute stenting of the extracranial internal carotid and stent retriever mechanical thrombectomy in the MCA with a reasonable risk profile.25-29 However further evaluation of this treatment strategy is warranted.

f) Basilar artery occlusion

Despite high mortality and morbidity rates associated with basilar artery occlusion 30, evidence from RCT's is lacking. A recent meta-analysis of 45 studies (n=2056) of reperfusion of acute basilar occlusion showed numbers needed to treat (NNT) of 3 and 2.5 to decrease death or dependency and death alone, respectively.31

Single-centre studies with samples inferior to 100 patients have shown good functional outcomes following thrombectomy of the basilar artery ranging from 30% 32, 33 to 48%. 34-36 Experience at the Karolinska Hospital showed a 57% rate of good functional outcome (95% CI 37% to 75%), and of 73% (95% CI 50% to 89%) when there were no signs of acute infarction prior to treatment, with about 21% mortality.37

Recanalisation rates over 75% were reported with new generation devices 33, 38 as well as with older generation devices in the MERCI and multi-MERCI trials but with lower benefit.39

A previous prospective registry, the Basilar Artery International Cooperation Study (BASICS) could not demonstrate superiority of endovascular therapy against IVT, however, it employed mostly older-generation devices.40 The same investigators are now undertaking the BASICS treatment trial, comparing thrombectomy <6 hours in addition to IVT with IVT alone.

g) Anesthesia in mechanical thrombectomy

Conscious sedation has gained support from a retrospective analysis of patients receiving either general anesthesia or conscious sedation (n= 507 in both groups, 1:1 matching). Patients receiving general anesthesia had significantly more in-hospital mortality (25%) and pneumonia (17%) compared to patients receiving conscious sedation (12% and 9.3%, OR 2.37 and 2.0, respectively), but similar rates of SICH.41 A recent mini review from Takahashi et al also supports conscious sedation42. Previous single-centre cohort studies 43, 44 and a review of 5 such studies 45 have reported similar findings. The post-hoc analysis of the thromboectomy patients in MR CLEAN showed better functional 3 months outcome in the absence of general anesthesia, but patients were not randomized to the type of anesthesia.46

An expert consensus statement of the Society of Neurointerventional Surgery and the Neurocritical Care Society recommends the use of general anesthesia for patients with severe agitation, low level of consciousness (GCS <8), loss of airway protective reflexes, respiratory compromise and in selected posterior circulation stroke presenting with these features.47

h) Prehospital patient selection for immediate transfer to centres with multimodal imaging and availability of thrombectomy

A recently published SITS registry study found NIHSS scores of 11 and 12 points as predictors of baseline vessel occlusion and functional independence at 3 months in a cohort of 11,632 patients with available baseline imaging data and 3 month functional outcome.48 Moreover, if imaging was performed 3 h after stroke onset, NIHSS scores thresholds decreased to 9 and 10 points in predicting baseline vessel occlusion and functional outcome at 3 months, respectively. These results are in line with an initial single-centre retrospective study of 162 patients showing that a NIHSS score of 10 or more points up to 6 h after stroke onset increased by 16.9-fold the odds of unfavourable outcome or death (p = 0.013), and by 7.13-fold the odds of proximal vessel occlusion (p = 0.013 and p < 0.038, respectively; sensitivity, 83%; specificity, 78%).49

i) Imaging-guided patient selection

Acute non-invasive arterial imaging: All recent RCT trials of thrombectomy used non-invasive arterial imaging (CT-angiograhy or MR-angiography of cerebral and neck arteries) to select patients with an intracranial occlusion of the distal carotid and/or middle cerebral artery or M2 main stem. This may be a reason why such trials were positive, in contrast to the previous thrombectomy trials. If non-invasive arterial imaging cannot be performed, an elevated NIHSS ≥ 9 points within the first 3 hours, and ≥ 7 between 3 and 6 hours strongly suggests an occlusion of a major intracranial artery.48, 50 Still, acute non-invasive imaging of cervical and intracranial arteries is clearly superior to identify the appropriate patients for acute mechanical thrombectomy and should be performed for all patients who have clinical criteria for thrombectomy, and no contraindication to such added imaging.

ASPECTS (Alberta Score Program Early CT Score) on plain CT. The MR CLEAN trial subgroup analysis showed benefit of thrombectomy for patients with ASPECTS scores of 5 or more points (5-7 points, OR 1.97 and 8-10 points, OR 1.61, respectively) but probably not with ASPECTS scores 0-4 (OR 1.09, large 95% CI 0.14-8.46). Higher baseline ASPECTS also predicted favourable outcome in a cohort of 202 patients treated with Solitaire FR 20 and in a cohort 149 patients treated with Solitaire and Penumbra aspiration system51 The MR RESCUE study, in which the penumbra was identified with multimodal CT or MRI for patient randomization, showed neutral results for mechanical thrombectomy. In the ESCAPE and SWIFT-PRIME trials, a lower ASPECTS threshold of 5 and 6 were applied, respectively. Above these values, thrombectomy showed similar efficacy for different ASPECTS scores.11, 12

MRI-based imaging: DWI, PWI, mismatch: The single-centre RECOST study using MRI DWI-derived ASPECTS score on 165 patients showed benefit of thrombectomy when using this imaging technique for patient selection where the elderly could benefit from stent retriever thrombectomy if the ischemic core volume was low (with a clear cutoff at 70 years-old) whereas all patients below 70 years of age could benefit.52 A smaller study from the same centre on 31 consecutive patients, focusing on basilar artery occlusion treated with Solitaire FR device, found a good correlation between brainstem DWI score < 3 and favourable clinical outcome.36 The prospective, single-arm multicentric DEFUSE-2 trial showed favourable clinical outcomes in patients selected for endovascular treatment with MRI PWI mismatch in MCA or ICA occlusions (n=98, about half pretreated with IVT).53

Perfusion-CT based imaging: A multicentre analysis of 165 patients, the vast majority of whom underwent endovascular or intravenous recanalisation treatment, showed independent prognostic value of core and penumbra volumes on clinical outcome.54 The importance of recanalisation was particularly striking in patients with large penumbra volumes.55 In the positive EXTEND-IA trial, patients were selected based on a CTP showing a mismatch ratio >1.2, and absolute mismatch volume >10 ml, and an ischemic core lesion volume <70 ml, using RAPID™ software.13

D. Discussion regarding ongoing and future studies on mechanical thrombectomy

The recent results from several randomized controlled studies could potentially influence patient recruitment in ongoing RCT’s such as PISTE or BASICS. Until steering committees of the respective trials have halted the trial, randomization should be continue to help answer uncertainties of benefit and risk from thrombectomy in acute ischemic stroke.

Studies comparing active centres (IVT + possibility for thrombectomy) with control centres who do not yet have access to thrombectomy (IVT treatment alone), e.g. SITS-OPEN, should continue its recruitment to strengthen the level of evidence. There are many reasons to recommend this approach such as the need for confirmatory studies, the desirability of narrowing the confidence interval to get a tighter estimate of the effect size for health economic reasons and the necessity for a wide range of data allowing subgroup analysis with adequate power. This type of design will also test thrombectomy in standard clinical practice in experienced centres.

In addition, it is desirable that all patients undergoing some form of acute revascularization therapy (IVT, mechanical thrombectomy, etc.) are prospectively included in registries (e.g. SITS or SITS-TBY) to ensure further evidence from routine clinical practice data.

Consensus statements of the ESO-Karolinska Stroke Update,

in collaboration with ESMINT and ESNR

Prepared in December 2014, updated and released on February 20th 2015, after the International Stroke Conference

(Sources: Oxford Evidence-based level of evidence, Karolinska Stroke Update level of evidence for treatment recommendation)

Treatment recommendations

Mechanical thrombectomy, in addition to intravenous thrombolysis within 4.5 hours when eligible, is recommended to treat acute stroke patients with large artery occlusions in the anterior circulation up to 6 hours after symptom onset (Grade A, Level 1a, KSU Grade A). - new
Mechanical thrombectomy should not prevent the initiation of intravenous thrombolysis where this is indicated, and intravenous thrombolysis should not delay mechanical thrombectomy (Grade A, Level 1a, KSU Grade A). - changed

Mechanical thrombectomy should be performed as soon as possible after its indication (Grade A, Level 1a, KSU Grade A).
For mechanical thrombectomy, stent retrievers approved by local health authorities should be considered (Grade A, Level 1a, KSU Grade A). - new
Other thrombectomy or aspiration devices approved by local health authorities may be used upon the neurointerventionists discretion if rapid, complete and safe revascularisation of the target vessel can be achieved (Grade C, Level 2a, KSU Grade C) - new
If intravenous thrombolysis is contraindicated (e.g. Warfarin-treated with therapeutic INR) mechanical thrombectomy is recommended as first-line treatment in large vessel occlusions (Grade A, Level 1a, KSU Grade A) – changed and updated level of evidence.
Patients with acute basilar artery occlusion should be evaluated in centres with multimodal imaging and treated with mechanical thrombectomy in addition to intravenous thrombolysis when indicated (Grade B, Level 2a, KSU Grade C); alternatively they may be treated within a randomized controlled trial for thrombectomy approved by the local ethical committee - new
The decision to undertake mechanical thrombectomy should be made jointly by a multidisciplinary team comprising at least a stroke physician and a neurointerventionalist and performed in experienced centres providing comprehensive stroke care and expertise in neuroanesthesiology (Grade C, Level 5, GCP, KSU Grade C).
Mechanical thrombectomy should be performed by a trained and experienced neurointerventionalist who meets national and/or international requirements (Grade B, Level 2b, KSU Grade B) – changed in level of evidence.
The choice of anesthesia depends on the individual situation; independently of the method chosen, all efforts should be made to avoid thrombectomy delays (Grade C, Level 2b, KSU Grade C) – changed.

Patient selection

Intracranial vessel occlusion must be diagnosed with non-invasive imaging whenever possible before considering treatment with mechanical thrombectomy (Grade A, Level 1a, KSU Grade A) - new.
If vessel imaging is not available at baseline, a NIHSS score of ≥ 9 within three, and ≥ 7 points within six hours may indicate the presence of large vessel occlusion (Grade B, Level 2a, KSU Grade B) - new.
Patients with radiological signs of large infarcts (for ex. using the ASPECTS score) may be unsuitable for thrombectomy (Grade B, Level 2a, KSU Grade B) - new
Imaging techniques for determining infarct and penumbra sizes can be used for patient selection and correlate with functional outcome after mechanical thrombectomy (Grade B, Level 1b, KSU Grade B) - new.
High age alone is not a reason to withhold mechanical thrombectomy as an adjunctive treatment (Grade A, Level 1a, KSU Grade A) - new.

Recommendation for implementation, registries and further trials

Health authorities are strongly encouraged to implement access to thrombectomy within a reasonable time range in a network including stroke centres - new.
It is encouraged to perform and include patients in RCT addressing unresolved thrombectomy questions such as thrombectomy for basilar artery occlusion, treatment in a late und unknown time windows, treating patients with imaging findings not sufficiently covered in recent trials, comparing new devices with widely-used stent retrievers, thrombectomy with or without intravenous thrombolysis, and different types of anesthesia. - new.
Non-randomized trials comparing centres not yet having access to mechanical thrombectomy with others should continue (such as SITS OPEN) - new.
Ischemic stroke patients undergoing any type of acute revascularization treatment should be included systematically in national or international registries (such as SITS or SITS-TBY) - new.

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Appendix A:

Strength of evidence supporting recommendations as defined by the Karolinska Stroke Update consensus meeting (1998):

KSU GRADE A evidence: Strong support from randomized controlled trials and statistical reviews (at least one randomized controlled trial plus one statistical review)

KSU GRADE B evidence: Support from randomized controlled trials and statistical reviews (one randomized controlled trial or one statistical review)

KSU GRADE C evidence: No reasonable support from randomized controlled trials, recommendations based on small randomized and/or non-randomized controlled trials evidence.

Appendix B:

Levels and grades of evidence for therapy/prevention as defined by the Oxford centre for evidence-based medicine (2009), resumed:

Grade A: consistent Level 1 studies
Grade B: consistent level 2 or 3 studies or extrapolations from level 1 studies
Grade C: level 4 studies or extrapolations from level 2 or 3 studies
Level 1a: systematic review (homogeneity) of RCTs
Level 1b: individual RCT (with narrow confidence interval)
Level 2a: systematic review (homogeneity) of cohort studies
Level 2b: individual cohort study/low quality RCT e.g. with less than 80% follow-up
Level 3a: systematic review (homogeneity) of case-control studies
Level 3b: individual case-control study
Level 4: case-series
Level 5: expert opinion

Appendix C: Contributors to this Consensus Statement

ESO-Karolinska Stroke Update
Nils Wahlgren, Stockholm, SE (Organiser ESO-Karolinska Stroke Update)
Tiago Moreira, Stockholm, SE (Secretary of the ESO-Karolinska thrombectomy recommendations group)
Olaf Jansen, Kiel, DE (Chair of the interventional committee of the ESNR)
Christophe Cognard, Toulouse, FR (ESMINT and ESNR representative)
Heinrich Mattle, Berne, CH (ESO representative)
Wim H. van Zwam, Maastricht, NE
Staffan Holmin, Stockholm, SE
Turgut Tatlisumak, Helsinki, FI
Jesper Petersson, Malmö/Lund, SE

ESO representatives
Patrik Michel, Lausanne, CH (Secretary General of ESO)
Valeria Caso, Perugia, IT (President Elect of ESO)
Werner Hacke, Heidelberg, DE
Mikael Mazighi, Paris, FR
Marcel Arnold, Berne, CH
Urs Fischer, Berne, CH

ESMINT and ESNR representatives
Istvan Szikora, Budapest, HU (President of ESMINT)
Laurent Pierot, Reims, FR
Jens Fiehler, Hamburg, DE
Jan Gralla, Berne, CH