Neuro -Interventional Radiologic Procedures

1. Neuro-Interventional Radiologic Procedures Roberta (Robin) Novakovic, MD Assistant Professor Departments of Radiology and Neurology UT Southwestern Medical Center Dallas, TX

2. Incidence of Stroke • Stroke is the fourth leading cause of death in the United States • 795,000 new or recurrent events occur annually • 87% are ischemic, 10% ICH and 3% SAH • Leading cause of disability in the United States. Executive Summary: Heart Disease and Stroke Statistics-2014 Update. A Report From the American Heart Association. Circulation 2014, 129:399-410 Heart Disease and Stroke Statistics-2011 Update. A Report From the American Heart Association. Circulation 2011, 123:e18-2309

3. Outcomes • Patient variables associated with worse outcomes and increased health care burden from an ischemic stroke: • Occlusions of large intracranial vessels • High disease severity scores at presentation (NIHSS) • Older age at presentation • Successful recanalization of the occluded vessel during the acute ischemic stroke (AIS) is associated with: • Lower 3-month mortality • Improved functional outcomes

4. What Is an Ischemic Stroke? • A stroke is infarcted brain tissue that results from inadequate perfusion - blood flow. • That means permanent and irreversible damage to the brain tissue because of inadequate blood flow.

5. Brain Tissue Damage • Because that portion of the brain can not function properly the patient develops neurologic deficits: • Weakness • Sensory changes • Visual changes • Balance problems • Loss of speech • Somnolence

6. Patient JF • 72 year old man PMHX of A-fib, HLD, HTN and CABG 3 weeks prior. • He went to take a nap at 1400 and around 1515 his wife heard noises from the bedroom. • She found him having trouble getting out of bed and could not understand what he was saying. • She called 911, and when EMS arrived, he was not moving his right arm or leg at all. He was taken to Texas Health Presbyterian Plano.

7. Stroke Mechanisms • Embolic material • Cardioembolic • Artery-artery embolus • Thrombosis • Occlusive process initiated within vessel wall • Small vessel disease

8. Stroke Mechanisms • Narrowing of blood vessels cause stroke from hemodynamic failure – inadequate blood flow • Atherosclerotic stenosis • Dissection • Vasculitis • Vasospasm

9. Embolus Occlusion

10. Cerebral Blood Flow • Once an artery becomes occluded, the factors that determine if the brain tissue becomes permanently damaged include: • Regional cerebral blood flow (CBF) • Duration of the diminished perfusion • What does that mean?? • How much blood is actually getting there • And how long has the flow been suboptimal

11. Understanding the Physiology • CBF is the blood supply to the brain in a given time. • In an adult this is about 15% of the cardiac output. • Equates to 50-54 mL of blood/100 gram of brain tissue/minute. • Regional CBF is the blood supply to a specific area.

12. Primate Models • In primate models of focal acute ischemic stroke (AIS), the timing of opening the occluded middle cerebral artery (MCA) was strongly correlated with the amount brain tissue injury. • Reperfusion of the MCA is associated with minimal damage when it occurs within 20 minutes. • 50% of brain tissue is spared with reperfusion within 90 minutes. • No sparing of brain tissue when reperfusion occurs at 400 minutes (about 6 to 7 hours). Crowell R, Olsson Y, Klatzo I et al. Temporary occlusion of the middle cerebral artery in the monkey: clinical and pathological observations. Stroke. 1970;1:439-448. Zivin J. Factors determining the therapeutic window for stroke. Neurology. 1998;50:599-603. .

13. What is the Penumbra • Landmark study in 1977 changed the way we looked at stroke. • Astrup et al., showed that after the onset of focal ischemia, measurements of electrical activity of the brain tissue revealed regions that were dysfunctional but not yet dead. Astrup J, Symon L, Branston N.M. et al. Cortical evoked potential and extracellular K and H at critical levels of brain ischemia. Stroke 8, 51-57 (1977).

14. Summary Critical Factors • Critical factors that influence the fate of hypoperfused tissue – the ischemic penumbra: • Time elapsed since the onset of ischemia • The severity of CBF reduction • Presence of collateral blood flow to the brain tissue in jeopardy

15. Collateral Blood Flow

16. Understanding the Penumbra • The brain tissue supplied by an occluded artery is compartmentalized into areas of irreversibly damaged (infarct core) and areas of hypoperfused but viable tissue (ischemic penumbra) Astrup J, Symon L, Branston N.M. et al. Cortical evoked potential and extracellular K and H at critical levels of brain ischemia. Stroke 8, 51-57 (1977).

17. PET Studies • PET studies in humans suggest that the infarct core corresponds to CBF values of less 7 to 12 mL/100g/minute. • The ischemic penumbra corresponds to CBF of 17 to 20 mL/100g/minute. • Saving this tissue by restoring its flow to nonischemic levels is the aim of AIS therapy.

18. Imaging the Penumbra • Imaging modalities to define the penumbra can be qualitative or quantitative of CBF. • No method is clear cut in defining the penumbra region: • MRI DWI/PWI mismatch • PET scan • SPECT • Xenon-CT • CT perfusion

19. Imaging the Penumbra

20. Goal of AIS Therapy

21. AIS Therapy Goals • Numerous investigators have shown that the penumbra comprises about 40% of the total ischemic territory at the onset of the occlusion. • At times it can persist up to 24 hours from symptom onset. • In most cases, ischemic penumbra has a short lifespan, and rapidly converts into the infarct core within hours from onset.

22. Goal AIS Therapy • Main goal is to rapidly restore blood flow and improve perfusion to the affected brain region. • Cornerstone of current treatments include: • Dissolving the clot with a thrombolytic agent. • Or mechanical extraction of the clot.

23. Current AIS Treatment Options • Treatment options: • Intravenous (IV) thrombolytic therapy • Utilized up to 3 sometimes 4.5 hours from onset • Intra-arterial (IA) thrombolytic therapy • Up to 6 hours for anterior circulation • Up to 12 hours or beyond for basilar occlusions • Endovascular thrombectomy devices • Up to 8 hours

24. Reality of IV rt-PA • Unfortunately, IV rt-PA recanalization rates: • 9% for occluded extracranial ICA • 20-30% for occlusions of the M1 • Early re-occlusion occurs in 34% of patients treated with rt-PA who had any initial recanalization. Ribo M, Alvarez-Sabin J, Montaner J, Romero F, Delgado P, Rubiera M, Delgado-Mederos R, Molina CA. Temporal profile of recanalization after intravenous tissue plasminogen activator: selecting patients for rescue reperfusion techniques. Stroke. 2006;37:1000 –1004. Saqqur M, Uchino K, Demchuk AM, Molina CA, Garami Z, Calleja S, Akhtar N, Orouk FO, Salam A, Shuaib A, Alexandrov AV. Site of arterial occlusion identified by transcranial Doppler predicts the response to intravenous thrombolysis for stroke. Stroke. 2007;38:948 –954.

25. Recanalization Improves Outcome • Recanalization has been shown to be the most important predictor of good clinical outcome after thrombolysis in large vessel occlusive strokes. • Cornerstone of treatments include: • Dissolving the clot with a thrombolytic agent • Or mechanical extraction of the clot with or without IA thrombolytic.

26. Intra-Arterial Treatment • Endovascular treatment of AIS with IA thrombolytic agents or mechanical thrombectomy is a consideration in patients in whom: • IV rt-PA fails or considered likely to fail • Who are excluded from IV rt-PA treatment • Present with large vessel occlusion

27. Multisociety Consensus Quality Improvement Guideline: IA Treatment • IA Indications • Symptom onset up to 8 hours • NIHSS > 8 or severe aphasia • Patients not IV rt-PA candidates • No improvement after 60 minutes of IV rt-PA and large to medium vessel occlusion • Vertebrobasilar occlusion extended to 12 hours

28. IA Thrombolysis • IA thrombolysis up to 6 hours • Potential advantage: • Better rates of recanalization • High-concentration and direct drug delivery into the thrombus. • Reduced systemic effects and ICH, • Smaller dose of drug can reach a higher local concentration than with an IV infusion. • Can be alternative for some patients excluded from IV. • Patients with recent surgeries

29. IA Thrombolysis • IA thrombolysis gained validity on the basis of the results from two randomized trials and several case series. • The Prolyse in Acute Cerebral Thromboembolism II (PROACT II trial), was a prospective randomized trial to test efficacy and safety of IA prourokinase plus heparin versus heparin alone in patients with occlusion of the MCA who could have initiation of treatment within 6 hours of symptom onset.

30. PROACT II • Partial or complete recanalization was achieved in 67% of patient within the treatment group. • Within the treatment group 40% of patients had a mRS 0-2 at 90-days compared with 25% of control subjects (P=0.04). • Complete restoration of blood flow (Thromboliysis In Myocardial Infarction [TIMI] 3) was achieved in 20% and an additional 46% had partial recanalization (TIMI 2) in the treatment group versus only 20% TIMI 2-3 in the control group. • Symptomatic ICH occurred in 10% of patients within the treatment group compared to 2% of control patients (P=0.06).

31. IA Thrombolysis • The FDA required a confirmatory study prior to approval. • Currently not approved. • No placebo-controlled, randomized studies have tested the use of IA rt-PA therapy in AIS.

32. Patient JF • At presentation BP was 99/67 and NIHSS score 14. Right facial droop and 0/5 strength in his RUE and RLE, his speech was slurred and he had a hard time thinking of the words he wanted to say. • Labs unremarkable. • Head CT was negative for bleed and showed a hyperdense left MCA. • Not IV rt-PA candidate. • He was then transferred UT Southwestern Medical Center for further care.

33. Territory In Jeopardy

34. Endovascular Revacularization • The era of endovascular therapy for AIS started over 20 years ago.

35. Cerebral Arteriogram

37. Cerebral Circulation

38. Cerebral Anatomy ACA Right MCA Left MCA Right ICA Left ICA

39. Cerebral Anatomy

40. Earlier Past Approaches to ERT • Early IA treatments • IA thrombolysis • Endovascular thrombectomy (clot retrieval or suction aspiration devices) • Augmented fibrinolysis (catheter-tipped ultrasound and externally applied ultrasonography) • Mechanical clot disruption (ie, emergent angioplasty and stenting)

41. Endovascular Tools

42. IA Thrombolysis

43. Complications of Thrombolysis • IA thrombolysis is associated with: • Reduced and slower rates of recanalization • Potential higher risk of intracerebral hemorrhage

44. Mechanical Embolectomy • Mechanical thromboembolectomy techniques were at first used when there was: • Contraindications to thrombolytic therapy. • Failed recanalization after thrombolysis. • Outside the 6 hour IA thrombolysis window.

45. Mechanical Approaches • The theoretical advantages of mechanical approaches include: • Reduced need for thrombolytics • Faster rates of recanalization • Early studies utilizing endovascular thrombectomy or aspiration devices did not show the anticipated rates of clinical improvement despite achieving higher recanalization rates.

46. Mechanical Approaches • Three uncontrolled trials led to 2 early generation devices, the Merci Retriever (in 2004) and the Penumbra System (in 2008), to achieve FDA approval for the indication of intracranial clot retrieval in patients with AIS. • Merci Retriever (in 2004) • Penumbra System (in 2008)

47. Merci • The Mechanical Embolus Removal in Cerebral Ischemia (MERCI) system is an embolectomy device (Concentric Medical, Inc., Mountain View, California, USA) approved by the FDA in 2004.

48. Merci • The device has a flexible tapered wire with helical loops that can be embedded in the thrombus for retrieval of clot.

49. Penumbra Catheter • The Penumbra system (Penumbra, Inc., Alameda, California, USA) is another device approved by the FDA in 2008. • It was designed to mechanically disrupt thrombus and aspirate clot fragments through a catheter. Images courtesy of Penumbra, Inc.

50. Penumbra Device Images courtesy of Penumbra, Inc.