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      Severe carotid stenosis and delay of reperfusion in endovascular stroke treatment: an Interventional Management of Stroke-III study

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          Abstract

          OBJECTIVE

          The impact of extracranial carotid stenosis on interventional revascularization of acute anterior circulation stroke is unknown. The authors examined the effects of high-grade carotid stenosis on the results of endovascular treatment of patients in the Interventional Management of Stroke (IMS)-III trial.

          METHODS

          The 278 patients in the endovascular arm of the IMS-III trial were categorized according to the degree of carotid stenosis as determined by angiography. In comparing patients with severe stenosis or occlusion (≥ 70%) to those without severe stenosis (< 70%), the authors evaluated the time to endovascular reperfusion, modified Thrombolysis in Cerebrovascular Infarction (mTICI) scores, 24-hour mean infarct volumes, symptomatic intracerebral hemorrhage rates, and modified Rankin Scale (mRS) scores at 90 days.

          RESULTS

          Compared with the 249 patients with less than 70% stenosis, patients with severe stenosis (n = 29) were found to have a significantly longer mean time to reperfusion (105.7 vs 77.7 minutes, p = 0.004); differences in mTICI scores, infarct volumes, hemorrhage rates, and mRS scores at 90 days did not reach statistical significance. Multiple regression analysis revealed that severe carotid stenosis (p < 0.0001) and higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (p = 0.004) were associated with an increase in time to reperfusion. Older age (p < 0.0001), higher NIHSS score (p < 0.0001), and the absence of reperfusion (p = 0.001) were associated with worse clinical outcomes.

          CONCLUSIONS

          Severe ipsilateral ICA stenosis was associated with a significantly longer time to reperfusion in the IMS-III trial. Although these findings may not translate directly to modern devices, this 28-minute delay in reperfusion has significant implications, raising concern over the treatment of tandem ICA stenosis and downstream large-vessel occlusion.

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          Most cited references17

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          Good clinical outcome after ischemic stroke with successful revascularization is time-dependent.

          Trials of IV recombinant tissue plasminogen activator (rt-PA) have demonstrated that longer times from ischemic stroke symptom onset to initiation of treatment are associated with progressively lower likelihoods of clinical benefit, and likely no benefit beyond 4.5 hours. How the timing of IV rt-PA initiation relates to timing of restoration of blood flow has been unclear. An understanding of the relationship between timing of angiographic reperfusion and clinical outcome is needed to establish time parameters for intraarterial (IA) therapies. The Interventional Management of Stroke pilot trials tested combined IV/IA therapy for moderate-to-severe ischemic strokes within 3 hours from symptom onset. To isolate the effect of time to angiographic reperfusion on clinical outcome, we analyzed only middle cerebral artery and distal internal carotid artery occlusions with successful reperfusion (Thrombolysis in Cerebral Infarction 2-3) during the interventional procedure (<7 hours). Time to angiographic reperfusion was defined as time from stroke onset to procedure termination. Good clinical outcome was defined as modified Rankin Score 0-2 at 3 months. Among the 54 cases, only time to angiographic reperfusion and age independently predicted good clinical outcome after angiographic reperfusion. The probability of good clinical outcome decreased as time to angiographic reperfusion increased (unadjusted p = 0.02, adjusted p = 0.01) and approached that of cases without angiographic reperfusion within 7 hours. We provide evidence that good clinical outcome following angiographically successful reperfusion is significantly time-dependent. At later times, angiographic reperfusion may be associated with a poor risk-benefit ratio in unselected patients.
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            Revascularization results in the Interventional Management of Stroke II trial.

            Our aim was to detail revascularization results, including impact on outcome and mortality, in the Interventional Management of Stroke (IMS) II trial. IMS II was designed to obtain estimates of the efficacy and safety of reduced-dose intravenous recombinant tissue plasminogen activator (rtPA) followed by additional intra-arterial rtPA and low-energy sonography via the EKOS Primo Micro-Infusion Catheter at the occlusion in selected patients with ischemic stroke treated within 3 hours of onset. Revascularization outcomes were detailed and compared with modified Rankin Scale scores 0-2, mortality outcomes, and results from IMS I. Complete recanalization at 60 minutes occurred in 12 of 29 (41.4%) sonography microcatheter-treated occlusions. Complete recanalization was achieved at 2 hours or procedure end in 20/29 (68.9%) in the ultrasound catheter-treated group, and final thrombolysis in cerebral infarction (TICI) 2/3 reperfusion was achieved in 18/29 (62.0%) ultrasound-treated subjects. Fifteen-minute angiograms demonstrated some recanalization in 69/145 (46.7%) sonography microcatheter treatment intervals, compared with 39/111 (35.1%) in IMS I treatments in 23 subjects with reliable 15-minute angiograms (P = .046). Pooled IMS I-II data demonstrated that partial or complete recanalization occurred in 56/75 (74.6%) and good reperfusion (TICI 2/3) occurred in 46/75 (61.3%) of internal carotid artery T and M1 occlusions. Revascularization correlated with good outcome for TICI 2/3 reperfusion (P = .0004), TICI 2B/3 reperfusion (P = .0002), and arterial occlusive lesion 2/3 recanalization (P = .03). IMS II provides evidence that the EKOS Primo sonography microcatheter exhibits a trend toward improved recanalization of the occlusion compared with a standard microcatheter and again confirms the correlation between recanalization and reperfusion with good clinical outcome and reduced mortality.
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              The Interventional Management of Stroke (IMS) II Study.

              (2007)
              The purpose of this study was to further investigate the feasibility and safety of a combined intravenous and intra-arterial approach to recanalization for ischemic stroke. Subjects, ages 18 to 80, with a baseline NIHSS > or =10 had intravenous recombinant tissue plasminogen activator (rt-PA) started (0.6 mg/kg over 30 minutes) within 3 hours of onset. For subjects with an arterial occlusion at angiography, additional rt-PA was administered via the EKOS micro-infusion catheter or a standard microcatheter at the site of the thrombus up to a total dose of 22 mg over 2 hours of infusion or until thrombolysis. The 81 subjects had a median baseline NIHSS score of 19. The median time to initiation of intravenous rt-PA was 142 minutes as compared with 108 minutes for placebo and 90 minutes for rt-PA-treated subjects in the NINDS rt-PA Stroke Trial (P or =2.7) and better outcomes than NINDS rt-PA-treated subjects as measured by the Barthel Index and Global Test Statistic. A randomized trial of standard intravenous rt-PA as compared with a combined intravenous and intra-arterial approach is warranted and has begun.
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                Author and article information

                Journal
                Journal of Neurosurgery
                Journal of Neurosurgery Publishing Group (JNSPG)
                0022-3085
                1933-0693
                January 2018
                January 2018
                : 94-99
                Article
                10.3171/2016.9.JNS161044
                28156253
                f28a4f46-42e9-4571-aa22-91257dc84276
                © 2018
                History

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