Mikael Mazighi

Bio: Mikael Mazighi is an academic researcher from University of Paris. The author has contributed to research in topics: Stroke & Modified Rankin Scale. The author has an hindex of 48, co-authored 249 publications receiving 9611 citations. Previous affiliations of Mikael Mazighi include Cleveland Clinic & University of Toronto.

Endovascular Therapy after Intravenous t-PA versus t-PA Alone for Stroke

Abstract: BACKGROUND Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic stroke, but whether a combined approach is more effective than intravenous t-PA alone is uncertain. METHODS We randomly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone, in a 2:1 ratio. The primary outcome measure was a modified Rankin scale score of 2 or less (indicating functional independence) at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). RESULTS The study was stopped early because of futility after 656 participants had undergone randomization (434 patients to endovascular therapy and 222 to intravenous t-PA alone). The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment (40.8% with endovascular therapy and 38.7% with intravenous t-PA; absolute adjusted difference, 1.5 percentage points; 95% confidence interval [CI], −6.1 to 9.1, with adjustment for the National Institutes of Health Stroke Scale [NIHSS] score [8–19, indicating moderately severe stroke, or ≥20, indicating severe stroke]), nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher (6.8 percentage points; 95% CI, −4.4 to 18.1) and those with a score of 19 or lower (−1.0 percentage point; 95% CI, −10.8 to 8.8). Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days (19.1% and 21.6%, respectively; P = 0.52) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P = 0.83). CONCLUSIONS The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA, as compared with intravenous t-PA alone. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00359424.)

A transient ischaemic attack clinic with round-the-clock access (SOS-TIA): feasibility and effects.

Abstract: Summary Background Diagnosis and treatment of cerebral and retinal transient ischaemic attacks (TIAs) are often delayed by the lack of immediate access to a dedicated TIA clinic. We evaluated the effects of rapid assessment of patients with TIA on clinical decision making, length of hospital stay, and subsequent stroke rates. Methods We set up SOS-TIA, a hospital clinic with 24-h access. Patients were admitted if they had sudden retinal or cerebral focal symptoms judged to relate to ischaemia and if they made a total recovery. Assessment, which included neurological, arterial, and cardiac imaging, was within 4 h of admission. A leaflet about TIA with a toll-free telephone number for SOS-TIA was sent to 15 000 family doctors, cardiologists, neurologists, and ophthalmologists in Paris and its administrative region. Endpoints were stroke within 90 days, and stroke, myocardial infarction, and vascular death within 1 year. Findings Between January, 2003, and December, 2005, we admitted 1085 patients with suspected TIA; 574 (53%) were seen within 24 h of symptom onset. 701 (65%) patients had confirmed TIA or minor stroke, and 144 (13%) had possible TIA. 108 (17%) of the 643 patients with confirmed TIA had brain tissue damage. Median duration of symptoms was 15 min (IQR 5–75 min). Of the patients with confirmed or possible TIA, all started a stroke prevention programme, 43 (5%) had urgent carotid revascularisation, and 44 (5%) were treated for atrial fibrillation with anticoagulants. 808 (74%) of all patients seen were sent home on the same day. The 90-day stroke rate was 1·24% (95% CI 0·72–2·12), whereas the rate predicted from ABCD 2 scores was 5·96%. Interpretation Use of TIA clinics with 24-h access and immediate initiation of preventive treatment might greatly reduce length of hospital stay and risk of stroke compared with expected risk.

Effect of Endovascular Contact Aspiration vs Stent Retriever on Revascularization in Patients With Acute Ischemic Stroke and Large Vessel Occlusion: The ASTER Randomized Clinical Trial.

Abstract: Importance The benefits of endovascular revascularization using the contact aspiration technique vs the stent retriever technique in patients with acute ischemic stroke remain uncertain because of lack of evidence from randomized trials. Objective To compare efficacy and adverse events using the contact aspiration technique vs the standard stent retriever technique as a first-line endovascular treatment for successful revascularization among patients with acute ischemic stroke and large vessel occlusion. Design, Setting, and Participants The Contact Aspiration vs Stent Retriever for Successful Revascularization (ASTER) study was a randomized, open-label, blinded end-point clinical trial conducted in 8 comprehensive stroke centers in France (October 2015-October 2016). Patients who presented with acute ischemic stroke and a large vessel occlusion in the anterior circulation within 6 hours of symptom onset were included. Interventions Patients were randomly assigned to first-line contact aspiration (n = 192) or first-line stent retriever (n = 189) immediately prior to mechanical thrombectomy. Main Outcomes and Measures The primary outcome was the proportion of patients with successful revascularization defined as a modified Thrombolysis in Cerebral Infarction score of 2b or 3 at the end of all endovascular procedures. Secondary outcomes included degree of disability assessed by overall distribution of the modified Rankin Scale (mRS) score at 90 days, change in National Institutes of Health Stroke Scale (NIHSS) score at 24 hours, all-cause mortality at 90 days, and procedure-related serious adverse events. Results Among 381 patients randomized (mean age, 69.9 years; 174 women [45.7%]), 363 (95.3%) completed the trial. Median time from symptom onset to arterial puncture was 227 minutes (interquartile range, 180-280 minutes). For the primary outcome, the proportion of patients with successful revascularization was 85.4% (n = 164) in the contact aspiration group vs 83.1% (n = 157) in the stent retriever group (odds ratio, 1.20 [95% CI, 0.68-2.10]; P = .53; difference, 2.4% [95% CI, −5.4% to 9.7%]). For the clinical efficacy outcomes (change in NIHSS score at 24 hours, mRS score at 90 days) and adverse events, there were no significant differences between groups. Conclusions and Relevance Among patients with ischemic stroke in the anterior circulation undergoing thrombectomy, first-line thrombectomy with contact aspiration compared with stent retriever did not result in an increased successful revascularization rate at the end of the procedure. Trial Registration clinicaltrials.gov Identifier:NCT02523261

Time to angiographic reperfusion and clinical outcome after acute ischaemic stroke: an analysis of data from the Interventional Management of Stroke (IMS III) phase 3 trial

Abstract: Summary Background The IMS III trial did not show a clinical benefit of endovascular treatment compared with intravenous alteplase (recombinant tissue plasminogen activator) alone for moderate or severe ischaemic strokes. Late reperfusion of tissue that was no longer salvageable could be one explanation, as suggested by previous exploratory studies that showed an association between time to reperfusion and good clinical outcome. We sought to validate this association in a preplanned analysis of data from the IMS III trial. Methods We used data for patients with complete proximal arterial occlusions in the anterior circulation who received endovascular treatment and achieved angiographic reperfusion (score on Thrombolysis in Cerebral Infarction scale of grade 2–3) during the endovascular procedure (within 7 h of symptom onset). We used logistic regression to model good clinical outcome (defined as a modified Rankin Scale score of 0–2 at 3 months) as a function of the time to reperfusion. We prespecified variables to be considered for adjustment, including age, baseline National Institutes of Health Stroke Scale score, sex, and baseline blood glucose concentration. Findings Of 240 patients who were otherwise eligible for inclusion in our analysis, 182 (76%) achieved angiographic reperfusion. Mean time from symptom onset to reperfusion (ie, procedure end) was 325 min (SD 52). Increased time to reperfusion was associated with a decreased likelihood of good clinical outcome (unadjusted relative risk for every 30-min delay 0·85 [95% CI 0·77–0·94]; adjusted relative risk 0·88 [0·80–0·98]). Interpretation Delays in time to angiographic reperfusion lead to a decreased likelihood of good clinical outcome in patients after moderate to severe stroke. Rapid reperfusion could be crucial for the success of future acute endovascular trials. Funding US National Institutes of Health and National Institute of Neurological Disorders and Stroke.

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

Abstract: 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).

Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Abstract: Background and Purpose—The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audienc...

A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke

Abstract: Methods We randomly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone. Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset. The primary outcome was the modified Rankin scale score at 90 days; this categorical scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death). The treatment effect was estimated with ordinal logistic regression as a common odds ratio, adjusted for prespecified prognostic factors. The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores, as compared with usual care alone (shift analysis). Results We enrolled 500 patients at 16 medical centers in the Netherlands (233 assigned to intraarterial treatment and 267 to usual care alone). The mean age was 65 years (range, 23 to 96), and 445 patients (89.0%) were treated with intravenous alteplase before randomization. Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to intraarterial treatment. The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.30). There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs. 19.1%). There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage. Conclusions In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe. (Funded by the Dutch Heart Foundation and others; MR CLEAN Netherlands Trial Registry number, NTR1804, and Current Controlled Trials number, ISRCTN10888758.)

Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke

Abstract: Among patients with a proximal vessel occlusion in the anterior circulation, 60 to 80% of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment. We evaluated rapid endovascular treatment in addition to standard care in patients with acute ischemic stroke with a small infarct core, a proximal intracranial arterial occlusion, and moderate-to-good collateral circulation. Methods We randomly assigned participants to receive standard care (control group) or standard care plus endovascular treatment with the use of available thrombectomy devices (intervention group). Patients with a proximal intracranial occlusion in the anterior circulation were included up to 12 hours after symptom onset. Patients with a large infarct core or poor collateral circulation on computed tomography (CT) and CT angiography were excluded. Workflow times were measured against predetermined targets. The primary outcome was the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention would lead to lower scores on the modified Rankin scale than would control care (shift analysis). Results The trial was stopped early because of efficacy. At 22 centers worldwide, 316 participants were enrolled, of whom 238 received intravenous alteplase (120 in the intervention group and 118 in the control group). In the intervention group, the median time from study CT of the head to first reperfusion was 84 minutes. The rate of functional independence (90-day modified Rankin score of 0 to 2) was increased with the intervention (53.0%, vs. 29.3% in the control group; P<0.001). The primary outcome favored the intervention (common odds ratio, 2.6; 95% confidence interval, 1.7 to 3.8; P<0.001), and the intervention was associated with reduced mortality (10.4%, vs. 19.0% in the control group; P = 0.04). Symptomatic intracerebral hemorrhage occurred in 3.6% of participants in intervention group and 2.7% of participants in control group (P = 0.75). Conclusions Among patients with acute ischemic stroke with a proximal vessel occlusion, a small infarct core, and moderate-to-good collateral circulation, rapid endovascular treatment improved functional outcomes and reduced mortality. (Funded by Covidien and others; ESCAPE ClinicalTrials.gov number, NCT01778335.)

Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection

Abstract: Background Trials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently developed devices, and earlier intervention improve outcomes. Methods We randomly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever or to continue receiving alteplase alone. All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The coprimary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3). Secondary outcomes included the functional score on the modified Rankin scale at 90 days. Results The trial was stopped early because of efficacy after 70 patients had undergone randomization (35 patients in each group). The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group (median, 100% vs. 37%; P<0.001). Endovascular therapy, initiated at a median of 210 minutes after the onset of stroke, increased early neurologic improvement at 3 days (80% vs. 37%, P = 0.002) and improved the functional outcome at 90 days, with more patients achieving functional independence (score of 0 to 2 on the modified Rankin scale, 71% vs. 40%; P = 0.01). There were no significant differences in rates of death or symptomatic intracerebral hemorrhage. Conclusions In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome. (Funded by the Australian National Health and Medical Research Council and others; EXTEND-IA ClinicalTrials.gov number, NCT01492725, and Australian New Zealand Clinical Trials Registry number, ACTRN12611000969965.)