1. A multimodal step-up approach as rescue therapy of ischemic stroke L. Verganti, S. Vallone, C. Moratti, M. Malagoli, P. Carpeggiani Department of Neuroscience, Neuroradiology division, NOCSAE Modena

2. Epidemiology of ischemic stroke in NOCSAE neurology departement Between 2006 and 2009: 1157 patients (909 in stroke unit) Mean age: 68 years old (21-98) 60.16% male and 38.84% female NIH score at admission: 0-5 (47.1%) 6-22 (45.2%) >22 (7.7%)

3. Patients selection CT, CTA and CT perfusion on admittance: performed within 4.5 hours after the onset of symptoms allow to identify eligible patients for IV thrombolisis Not eligible patients with a large ischemic core undergo an early (within 12 hours after the onset of symptoms) decompressive craniectomy

4. Patients selection for rescue therapy During IV rt-PA patients are monitored with transcranial US and clinical neurological examination. Patients with inadequate recanalization and clinical worsening undergo DWI MRI in order to evaluate the ischemic core and decide whether they are still eligible for an endovascular IA treatment (clinical-DWI mismatch).

5. I.V. thrombolisis has shown its efficacy in treating patients with relatively low NIH score, between 6 and 10, which are usually related to small vessels occlusions In the last few years many endovascular devices have been developed for mechanical endovascular thrombectomy and clot retrieval (MERCI, CTA, Solitarie, Microcatheter) Increased possible combinations of IV and IA therapy in acute ischemic stroke enlarge the basic concept of bridging therapy, which can now be better defined as a multimodal approach T.C. Burns, G.J. Rodriguez, S. Patel, H.M. Hussein, A.L. Georgiadis, K. Lakshminarayan, and A.I. Qureshi Endovascular Interventions following Intravenous Thrombolysis May Improve Survival and Recovery in Patients with Acute Ischemic Stroke: A Case-Control Study. AJNR Am. J. Neuroradiol., November 1, 2008; 29(10): 1918 - 1924. T.C. Burns, G.J. Rodriguez, S. Patel, H.M. Hussein, A.L. Georgiadis, K. Lakshminarayan, and A.I. Qureshi Endovascular Interventions following Intravenous Thrombolysis May Improve Survival and Recovery in Patients with Acute Ischemic Stroke: A Case-Control Study. AJNR Am. J. Neuroradiol., November 1, 2008; 29(10): 1918 - 1924. S. Sugiuara, K. Iwaisako, S. Toyota and H. Takimoto Simultaneous treatement with Intravenous Recombinant Tissue Plasmiminogen Activator and Endovascular Therapy for Acute Ischemic Stroke Within 3 Hours of Onset. AJNR Am J Neuroradiol, June 1,2008;29(6):1061-1066 S. Sugiuara, K. Iwaisako, S. Toyota and H. Takimoto Simultaneous treatement with Intravenous Recombinant Tissue Plasmiminogen Activator and Endovascular Therapy for Acute Ischemic Stroke Within 3 Hours of Onset. AJNR Am J Neuroradiol, June 1,2008;29(6):1061-1066 Multimodal approach

6. Bridging therapy Combined intravenous and intra-arterial r-TPA versus intra-arterial therapy of acute ischemic stroke: Emergency Management of Stroke (EMS) Bridging Trial. Stroke 1999; 30:2598-2605 Combined intravenous and intra-arterial r-TPA versus intra-arterial therapy of acute ischemic stroke: Emergency Management of Stroke (EMS) Bridging Trial. Stroke 1999; 30:2598-2605 Combined intravenous and intra-arterial recanalization for acute ischemic stroke: the Interventional Management of Stroke Study. Stroke. 2004; 35: 904–91 1 Combined intravenous and intra-arterial recanalization for acute ischemic stroke: the Interventional Management of Stroke Study. Stroke. 2004; 35: 904–91 1

7. Why a multimodal step-up approach? IV rt-PA is the first choice because it remains the only approved treatement for acute ischemic stroke I.V. rt-PA has shown to have limited benefit in patients with proximal occlusion and / or a NIH scores >10 Step 1: IV thrombolisis

8. Step 11: Endovascular mechanical thrombectomy It offers a better chance of recanalization without the administration of further fibrinolytic agents Case 1: M.O. female, 79 years old. Sudden onset of aphasia and right emiparesis CT on admission

9. Angio-CT Bilateral occlusion of MCA; NIHSS 24

10. No clinical improvement after IV rt-PA Angiography Left MCA

11. Right MCA Occlusion at the bifurcation of right MCA

12. Thrombus disruption with microcatheter Right MCA almost completely recanalized

13. NIHSS at the time of neurology department discharge: 3

14. Other endovascular devices for mechanical thrombectomy Right MCA occlusion Thrombus disruption with MERCI MCA ricanalization

15. Step 111: Ballon angioplasty and/or stenting They can improve backward and collateral circulation on the ischemic area (when the clot cannot be removed or in case of atherosclerotic plaques) Case 11: G.S., male, 56 y/o, floating right hemiparesis and aphasia CT on admission

16. No clinical improvement after IV rt-PA: DWI MRI and MRA Clinical/DWI mismatch Occlusion of the ICA and ricanalization from the ophtalimc artery

17. Angiography Occlusion of the intra-cranial ICA, before the biforcation treated with Solitaire and baloon angioplasty

18. CT perfusion after 7 days No significant alteration of CBF and CBV

19. Step 1V Administration of IA fibrinolytic drugs (urokinase IA) when an adequate recanalization is not achieved with the previuos approaches Case 111: male 51 y/o, diplopia, vertigo and left hemiparesis CT on admission: negative

20. Clinical worsening after IV thrombolisis, onset of drowsiness DWI MRI: clinical/DWI mismatchMRA: occlusion of SCA and PCA

21. Angiography Left SCA and PCA occlusion and clots in BA Ricanalization after thrombus disruption and IA urokinasi PCA 300.000 units Urokinasi

22. Our experience 22 patients with severe ischemic stroke eligible for IV therapy (between 2008 and 2009) NIHSS > 10 (median 18; range 11-32) After IV thrombolisis: 17 clinical unchanged without adequate ricanalization 5 worsening of clinical setting without adequte ricanalization 2 patients not eligible for IA treatment after DWI MRI 20 treated with an IA multimodal rescue therapy

23. Recanalization rate Recanalization rate has been evaluated with TIMI score 4 TIMI 0 3 TIMI 1 7 TIMI 2 8 TIMI 3

24. Clinical outcome (3 months) NIHSS between 0 and 5 in TIMI 2 and 3 NIHSS between 12 and 22 in TIMI 1 1 death and 1 NIHSS 32 in TIMI 0 0 hemorrage

25. Conclusions IA multimodal step up approach has enabled good results in terms of ricanalization and clinical outcome in patients with severe ischemic stroke and failure of IV rt-PA thrombolisis In our experience there is correspondence between the degree of ricanalization and clinical outcome

26. Thank you