Jan Gralla

Prospective, Multicenter, Single-Arm Study of Mechanical Thrombectomy Using Solitaire Flow Restoration in Acute Ischemic Stroke

Background and Purpose— Mechanical thrombectomy using stent retriever devices have been advocated to increase revascularization in intracranial vessel occlusion. We present the results of a large prospective study on the use of the Solitaire Flow Restoration in patients with acute ischemic stroke. Methods— Solitaire Flow Restoration Thrombectomy for Acute Revascularization was an international, multicenter, prospective, single-arm study of Solitaire Flow Restoration thrombectomy in patients with large vessel anterior circulation strokes treated within 8 hours of symptom onset. Strict criteria for site selection were applied. The primary end point was the revascularization rate (thrombolysis in cerebral infarction ≥2b) of the occluded vessel as determined by an independent core laboratory. The secondary end point was the rate of good functional outcome (defined as 90-day modified Rankin scale, 0–2). Results— A total of 202 patients were enrolled across 14 comprehensive stroke centers in Europe, Canada, and Australia. The median age was 72 years, 60% were female patients. The median National Institute of Health Stroke Scale was 17. Most proximal intracranial occlusion was the internal carotid artery in 18%, and the middle cerebral artery in 82%. Successful revascularization was achieved in 79.2% of patients. Device and procedure-related severe adverse events were found in 7.4%. Favorable neurological outcome was found in 57.9%. The mortality rate was 6.9%. Any intracranial hemorrhagic transformation was found in 18.8% of patients, 1.5% were symptomatic. Conclusions— In this single-arm study, treatment with the Solitaire Flow Restoration device in intracranial anterior circulation occlusions results in high rates of revascularization, low risk of clinically relevant procedural complications, and good clinical outcomes in combination with low mortality at 90 days. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01327989.

Mechanical thrombectomy in acute ischemic stroke: Consensus statement by ESO-Karolinska Stroke Update 2014/2015, supported by ESO, ESMINT, ESNR and EAN

The original version of this consensus statement on mechanical thrombectomy was approved at the European Stroke Organisation (ESO)-Karolinska Stroke Update conference in Stockholm, 16–18 November 2014. The statement has later, during 2015, been updated with new clinical trials data in accordance with a decision made at the conference. Revisions have been made at a face-to-face meeting during the ESO Winter School in Berne in February, through email exchanges and the final version has then been approved by each society. The recommendations are identical to the original version with evidence level upgraded by 20 February 2015 and confirmed by 15 May 2015. The purpose of the ESO-Karolinska Stroke Update meetings is to provide updates on recent stroke therapy research and to discuss how the results may be implemented into clinical routine. Selected topics are discussed at consensus sessions, for which a consensus statement is prepared and discussed by the participants at the meeting. The statements are advisory to the ESO guidelines committee. This consensus statement includes recommendations on mechanical thrombectomy after acute stroke. The statement is supported by ESO, European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), and European Academy of Neurology (EAN).

Stent Placement in Acute Cerebral Artery Occlusion Use of a Self-Expandable Intracranial Stent for Acute Stroke Treatment

Background and Purpose— Stent placement has been applied in small case series as a rescue therapy in combination with different thrombolytic agents, percutaneous balloon angioplasty (PTA), and mechanical thromboembolectomy (MT) in acute stroke treatment. These studies report a considerable mortality and a high rate of intracranial hemorrhages when balloon-mounted stents were used. This study was performed to evaluate feasibility, efficacy, and safety of intracranial artery recanalization for acute ischemic stroke using a self-expandable stent. Methods— All patients treated with an intracranial stent for acute cerebral artery occlusion were included. Treatment comprised intraarterial thrombolysis, thromboaspiration, MT, PTA, and stent placement. Recanalization result was assessed by follow-up angiography immediately after stent placement. Complications related to the procedure and outcome at 3 months were assessed. Results— Twelve patients (median NIHSS 14, mean age 63 years) were treated with intracranial stents for acute ischemic stroke. Occlusions were located in the posterior vertebrobasilar circulation (n=6) and in the anterior circulation (n=6). Stent placement was feasible in all procedures and resulted in partial or complete recanalization (TIMI 2/3) in 92%. No vessel perforations, subarachnoid, or symptomatic intracerebral hemorrhages occurred. One dissection was found after thromboaspiration and PTA. Three patients (25%) had a good outcome (mRS 0 to 2), 3 (25%) a moderate outcome (mRS 3), and 6 (50%) a poor outcome (mRS 4 to 6). Mortality was 33.3%. Conclusions— Intracranial placement of a self-expandable stent for acute ischemic stroke is feasible and seems to be safe to achieve sufficient recanalization.

Outcome of Stroke With Mild or Rapidly Improving Symptoms

Background and Purpose— Acute ischemic stroke with mild or rapidly improving symptoms is expected to result in good functional outcome, whether treated or not. Therefore, thrombolysis with its potential risks does not seem to be justified in such patients. However, recent studies indicate that the outcome is not invariably benign. Methods— We analyzed clinical and radiological data of patients with stroke who presented within 6 hours of stroke onset and did not receive thrombolysis because of mild or rapidly improving symptoms. Univariate and logistic regression analyses were performed to define predictors of clinical outcome. Results— One hundred sixty-two consecutive patients (110 men and 52 women) aged 63±13 years were included. The median National Institutes of Health Stroke Scale score on admission was 2 (range, 1 to 14). All patients presented within 6 hours of symptom onset. After 3 months, modified Rankin Scale score was ≤1 in 122 patients (75%), indicating a favorable outcome. Thirty-eight patients (23.5%) had an unfavorable outcome (modified Rankin Scale 2 to 5) and 2 patients (1.3%) had died. Baseline National Institutes of Health Stroke Scale score ≥10 points increased the odds of unfavorable outcome or death 16.9-fold (95% CI: 1.8 to 159.5; P<0.013), and proximal vessel occlusion increased the odds 7.13-fold (95% CI: 1.1 to 45.5; P<0.038). Conclusions— Seventy-five percent of patients with mild or rapidly improving symptoms will have a favorable outcome after 3 months. Therefore, a decision against thrombolysis seems to be justified in the majority of patients. However, selected patients, especially those with proximal vessel occlusions and baseline National Institutes of Health Stroke Scale scores ≥10 points, might derive a benefit from thrombolysis.

Retrospective Multicenter Study of Solitaire FR for Revascularization in the Treatment of Acute Ischemic Stroke

Background and Purpose— The purpose of this study was to evaluate safety and efficacy of the Solitaire FR device in the treatment of patients with acute ischemic stroke secondary to large artery occlusion. Methods— We conducted a retrospective study of consecutive patients presenting with acute ischemic stroke treated with Solitaire FR as the first-line device to restore blood flow in 6 experienced European centers. This study was entirely funded and supported by Coviden Neurovascular. An independent Corelab determined modified Thrombolysis in Cerebral Infarction scores on the preprocedure and postprocedure angiograms. Complete revascularization was defined as modified Thrombolysis in Cerebral Infarction 2b or 3 post-Solitaire FR device use. Symptomatic intracranial hemorrhage was defined as parenchymal hemorrhage Type 2 associated with a decline of ≥4 points in the National Institutes of Health Stroke Scale score within 24 hours or causing death. Favorable functional outcome was considered as modified Rankin Scale score ⩽2 at Day 90. Results— We studied 141 patients (mean age, 66 years; median National Institutes of Health Stroke Scale, 18); 74 patients received intravenous tissue-type plasminogen activator before endovascular treatment. Complete revascularization was achieved in 120 of 142 occlusion sites (85%) and good outcome in 77 of 141 (55%) patients. Good outcome was more frequent in patients treated with intravenous tissue-type plasminogen activator than in those without (66% versus 42%; P<0.01). Symptomatic intracranial hemorrhage was reported in 5 patients (4%) and 29 of 141 (20%) patients died or were lost during follow-up (3 cases). Conclusions— This retrospective study with centralized evaluation shows that the use of Solitaire FR is safe and achieves good revascularization rates and functional outcomes in patients with acute ischemic stroke and large artery occlusion.

National Institutes of Health Stroke Scale Score and Vessel Occlusion in 2152 Patients With Acute Ischemic Stroke

Background and Purpose— There is some controversy on the association of the National Institutes of Health Stroke Scale (NIHSS) score to predict arterial occlusion on MR arteriography and CT arteriography in acute stroke. Methods— We analyzed NIHSS scores and arteriographic findings in 2152 patients (35.4% women, mean age 66±14 years) with acute anterior or posterior circulation strokes. Results— The study included 1603 patients examined with MR arteriography and 549 with CT arteriography. Of those, 1043 patients (48.5%; median NIHSS score 5, median time to clinical assessment 179 minutes) showed an occlusion, 887 in the anterior (median NIHSS score 7/0–31), and 156 in the posterior circulation (median NIHSS score 3/0–32). Eight hundred sixty visualized occlusions (82.5%) were located centrally (ie, in the basilar, intracranial vertebral, internal carotid artery, or M1/M2 segment of the middle cerebral artery). NIHSS scores turned out to be predictive for any vessel occlusions in the anterior circulation. Best cut-off values within 3 hours after symptom onset were NIHSS scores ≥9 (positive predictive value 86.4%) and NIHSS scores ≥7 within >3 to 6 hours (positive predictive value 84.4%). Patients with central occlusions presenting within 3 hours had NIHSS scores <4 in only 5%. In the posterior circulation and in patients presenting after 6 hours, the predictive value of the NIHSS score for vessel occlusion was poor. Conclusions— There is a significant association of NIHSS scores and vessel occlusions in patients with anterior circulation strokes. This association is best within the first hours after symptom onset. Thereafter and in the posterior circulation the association is poor.

What Is a Minor Stroke

Background and Purpose— The term “minor stroke” is often used; however a consensus definition is lacking. We explored the relationship of 6 “minor stroke” definitions and outcome and tested their validity in subgroups of patients. Methods— A total of 760 consecutive patients with acute ischemic strokes were classified according to the following definitions: A, score ≤1 on every National Institutes of Health Stroke Scale (NIHSS) item and normal consciousness; B, lacunar-like syndrome; C, motor deficits with or without sensory deficits; D, NIHSS ≤9 excluding those with aphasia, neglect, or decreased consciousness; E, NIHSS ≤9; and F, NIHSS ≤3. Short-term outcome was considered favorable when patients were discharged home, and favorable medium-term outcome was defined as a modified Rankin Scale score of ≤2 at 3 months. The following subgroup analyses were performed by definition: sex, age, anterior versus posterior and right versus left hemispheric stroke, and early (0 to 6 hours) versus late admission (6 to 24 hours) to the hospital. Results— Short-term and medium-term outcomes were most favorable in patients with definition A (74% and 90%, respectively) and F (71% and 90%, respectively). Patients with definition C and anterior circulation strokes were more likely to be discharged home than patients with posterior circulation strokes (P=0.021). The medium-term outcome of older patients with definition E was less favorable compared with the outcome of younger ones (P=0.001), whereas patients with definition A, D, and F did not show different outcomes in any subgroup. Conclusions— Patients fulfilling definition A and F had best short-term and medium-term outcomes. They would be best suited to the definition of “minor stroke.”

Factors that determine penumbral tissue loss in acute ischaemic stroke

The goal of acute stroke treatment with intravenous thrombolysis or endovascular recanalization techniques is to rescue the penumbral tissue. Therefore, knowing the factors that influence the loss of penumbral tissue is of major interest. In this study we aimed to identify factors that determine the evolution of the penumbra in patients with proximal (M1 or M2) middle cerebral artery occlusion. Among these factors collaterals as seen on angiography were of special interest. Forty-four patients were included in this analysis. They had all received endovascular therapy and at least minimal reperfusion was achieved. Their penumbra was assessed with perfusion- and diffusion-weighted imaging. Perfusion-weighted imaging volumes were defined by circular singular value decomposition deconvolution maps (Tmax > 6 s) and results were compared with volumes obtained with non-deconvolved maps (time to peak > 4 s). Loss of penumbral volume was defined as difference of post- minus pretreatment diffusion-weighted imaging volumes and calculated in per cent of pretreatment penumbral volume. Correlations between baseline characteristics, reperfusion, collaterals, time to reperfusion and penumbral volume loss were assessed using analysis of covariance. Collaterals (P = 0.021), reperfusion (P = 0.003) and their interaction (P = 0.031) independently influenced penumbral tissue loss, but not time from magnetic resonance (P = 0.254) or from symptom onset (P = 0.360) to reperfusion. Good collaterals markedly slowed down and reduced the penumbra loss: in patients with thrombolysis in cerebral infarction 2 b-3 reperfusion and without any haemorrhage, 27% of the penumbra was lost with 8.9 ml/h with grade 0 collaterals, whereas 11% with 3.4 ml/h were lost with grade 1 collaterals. With grade 2 collaterals the penumbral volume change was -2% with -1.5 ml/h, indicating an overall diffusion-weighted imaging lesion reversal. We conclude that collaterals and reperfusion are the main factors determining loss of penumbral tissue in patients with middle cerebral artery occlusions. Collaterals markedly reduce and slow down penumbra loss. In patients with good collaterals, time to successful reperfusion accounts only for a minor fraction of penumbra loss. These results support the hypothesis that good collaterals extend the time window for acute stroke treatment.

Endovascular Therapy of 623 Patients With Anterior Circulation Stroke

Background and Purpose— Endovascular therapy of acute ischemic stroke has been shown to be beneficial for selected patients. The purpose of this study is to determine predictors of outcome in a large cohort of patients treated with intra-arterial thrombolysis, mechanical revascularization techniques, or both. Methods— We prospectively acquired data for 623 patients with acute cerebral infarcts in the carotid artery territory who received endovascular treatment at a single center. Logistic regression analysis was performed to determine predictors of outcome. Results— Median National Institutes of Health Stroke Scale (NIHSS) at admission was 15. Partial or complete recanalization was achieved in 70.3% of patients; it was independently associated with hypercholesterolemia (P=0.02), absence of coronary artery disease (P=0.023), and more proximal occlusion site (P<0.0001). After 3 months, 80.5% of patients had survived, and 48.9% of patients reached favorable outcome (modified Rankin scale score 0–2). Good collaterals (P<0.0001), recanalization (P=0.023), hypercholesterolemia (P=0.03), lower NIHSS at admission (P=0.001), and younger age (P<0.0001) were independent predictors for survival. More peripheral occlusion site (P<0.0001), recanalization (P<0.0001), hypercholesterolemia (P=0.002), good collaterals (P=0.002), lower NIHSS (P<0.0001), younger age (P<0.0001), absence of diabetes (P=0.002), and no previous antithrombotic therapy (P=0.036) predicted favorable outcome. Time to treatment was only a predictor of outcome, when collaterals were excluded from the model. Symptomatic intracerebral hemorrhage occurred in 5.5% and was independently predicted by poor collaterals (P=0.004). Conclusions— Several independent predictors for outcome and complications were identified. Unlike in intravenous thrombolysis trials, time to treatment was a predictor of outcome only when collaterals were excluded from the model, indicating the important role of collaterals for the time window.

Optimal Workflow and Process-Based Performance Measures for Endovascular Therapy in Acute Ischemic Stroke Analysis of the Solitaire FR Thrombectomy for Acute Revascularization Study

Background and Purpose— We report on workflow and process-based performance measures and their effect on clinical outcome in Solitaire FR Thrombectomy for Acute Revascularization (STAR), a multicenter, prospective, single-arm study of Solitaire FR thrombectomy in large vessel anterior circulation stroke patients. Methods— Two hundred two patients were enrolled across 14 centers in Europe, Canada, and Australia. The following time intervals were measured: stroke onset to hospital arrival, hospital arrival to baseline imaging, baseline imaging to groin puncture, groin puncture to first stent deployment, and first stent deployment to reperfusion. Effects of time of day, general anesthesia use, and multimodal imaging on workflow were evaluated. Patient characteristics and workflow processes associated with prolonged interval times and good clinical outcome (90-day modified Rankin score, 0–2) were analyzed. Results— Median times were onset of stroke to hospital arrival, 123 minutes (interquartile range, 163 minutes); hospital arrival to thrombolysis in cerebral infarction (TICI) 2b/3 or final digital subtraction angiography, 133 minutes (interquartile range, 99 minutes); and baseline imaging to groin puncture, 86 minutes (interquartile range, 24 minutes). Time from baseline imaging to puncture was prolonged in patients receiving intravenous tissue-type plasminogen activator (32-minute mean delay) and when magnetic resonance–based imaging at baseline was used (18-minute mean delay). Extracranial carotid disease delayed puncture to first stent deployment time on average by 25 minutes. For each 1-hour increase in stroke onset to final digital subtraction angiography (or TICI 2b/3) time, odds of good clinical outcome decreased by 38%. Conclusions— Interval times in the STAR study reflect current intra-arterial therapy for patients with acute ischemic stroke. Improving workflow metrics can further improve clinical outcome. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01327989.