Intravenous acute ischemic stroke including thrombectomy

For radiology pgt

1. Interventions in Acute Ischemic Stroke including Thrombectomy Moderators Dr. P. Borah( HoD ) Dr. M H Bhuyan Dr. D J Borpatrogohain Dr. L Nath Dr. P N Taye Dr. S S Biswas Presenter: Dr. Beulah L Khoum

2. Introduction Stroke is characterized as an acute, abrupt onset, central nervous system injury of vascular origin. “stroke” encompasses cerebral ischemia/infarcts, intracerebral hemorrhage and subarachnoid hemorrhage . Acute ischemia constitutes approximately 80% of all strokes and is an important cause of morbidity and mortality.

3. Pathophysiology Cerebral blood flow is maintained by cerebral auto-regulation at a stable level. Auto regulation functions between 60–150 mm Hg mean arterial pressure. The brain is unable to compensate for changes in pressure either below or above this, leading to cerebral injury. When a major cerebral vessel undergoes acute occlusion, there is reduction of cerebral blood flow in the distribution of that particular vascular territory. This leads to a complex sequence of biochemical events that end with death of the involved neural tissue. Normal CBF 50–60 mL/100 g/min Oligemic State CBF 35 mL/100 g/min Ischemic State CBF 20 mL/100 g/min Infarction CBF <10 mL/100 g/min

4. If the duration of ischemia lasts for >30 mins, cytotoxic edema sets in. The ion gradient across cell membranes is lost leading to cytotoxic edema. Cytotoxic edema manifests as focal swelling of the brain parenchyma with effacement of sulci and loss of gray white matter differentiation. 5–10 minutes of complete occlusion may lead to an infarct. Release of excitatory neurotransmitters, oxygen free radicles and apoptosis occur.

5. Vasogenic edema, that occurs due to extravasation of water through damaged endothelial cells, develops in 3–6 hours and may extend into the white matter. Within 24–48 hours of infarction, in growth of phagocytic microglial cells occurs with proliferation of new capillaries. These capillaries lack tight junction and are permeable to both large molecules and water. This process begins at the periphery of the infarct and proceeds centrally. Slowly, the necrotic tissue is removed by the macrophages and the remnant cavities and cysts occupy the infarcted area with glial scar tissue. Over subsequent weeks, complete resorption of necrotic tissue takes place with resultant encephalomalacia and loss of volume .

6. Significance of a Penumbra In presence of complete occlusion of a major artery, neuron can remain viable for approximately 2–3 minutes. It is estimated that about 1.9 million neurons die every minute. When the ischemia is incomplete, the injured brain continues blood supply from patent arteries and leptomeningeal collaterals. Therefore, acute cerebral ischemia may result in a central irreversibly infarcted tissue core surrounded by a peripheral zone of potentially salvageable(reversible ischemia) called a “Penumbra”.

7. Etiology Four subtypes Atherosclerotic Small vessel disease Cardioembolic Others. Atherosclerotic strokes: most common Emboli arise from thrombi that develop at the site of an "at risk" plaque. Atherosclerotic plaques are most commonly found at the level of the carotid bifurcation followed by the cavernous internal carotid artery Middle cerebral artery is the most frequently occluded intracranial vessel

8. Small vessel disease : 15–30% Small artery occlusions or lacunar infarcts: lesions <15 mm in diameter. Lacunar infarcts can be embolic, atheromatous, or thrombotic in nature. Penetrating arteries in the basal ganglia/thalami, pons, internal capsule and deep cerebral white matter. Cardioembolic disease: 15–25% Myocardial infarction, arrhythmia (most often atrial fibrillation), and valvular heart disease may lead to release of emboli from the heart. Other: heterogeneous group with miscellaneous but known etiologies together with strokes of undetermined etiology (cryptogenic stroke)

9. Imaging in Ischemic Stroke P rimary goals D istinguish ischemic stroke from intracranial haemorrhage S elect/triage patients for possible reperfusion therapies.

10. Computed Tomography I nitial imaging modality used R ole of CT is to identify intracranial hemorrhage and to rule out other pathologies like neoplasms, that may mimic stroke. R ecent studies have pointed out that CT, in the context of use of thrombolytic therapy, has significant prognostic value in the evaluation of acute stroke patients

11. Early signs of ischaemia : result of cytotoxic edema R eduction in the density of gray matter in the ischemic tissue and obliteration of sulci and gray -white matter differentiation. In MCA territory infarction these changes lead to loss of the insular cortex ( insular ribbon sign ) obscuration of lentiform nuclei ( disappearing basal ganglia sign ) due to acute ischemia of lenticulostriate territory Wedge-shaped parenchymal hypodensity with indistinct GM-WM borders and cortical sulcal effacement develops in large territorial occlusions. A C B

12. Most specific but least sensitive sign: hyperattenuating vessel filled with acute thrombus. ” D ense MCA" sign is seen in 30% of cases with documented M1 occlusion. Less common sites: intracranial internal carotid artery, basilar artery, and MCA branches in the sylvian fissure ("dot sign”) Uncommon: calcified embolus most likely from an "at-risk" ulcerated atherosclerotic plaque in the cervical or cavernous ICA. near 50% risk of repeat ischemic stroke.

13. ASPECTS Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) M easure of early ischemic change C alculated by subtracting one point for each of 10 regions affected. The MCA cortex and insular ribbon are allotted seven points, and subcortical structures are allotted three points. Score ≤ 6 equates to more than one-third of the MCA territory and is associated with increased risk of haemorrhage and poor outcome.

14. CECT • ± Enhancing vessels (slow flow, collaterals) Cortical gyriform enhancement CTA • Shows site, length of major vessel thrombus • ASVD ○ Extracranial: aorta, carotid bifurcation ○ Intracranial: cavernous ICA, circle of Willis + branches

15. pCT Colour coded perfusion map Well-perfused gray matter appears red/yellow, white matter appears blue ischemic brain is blue/purple. Infarct core (irreversibly damaged brain) Matched perfusion (CBV, CBF both ↓) ↑ MTT

16. Ischemic penumbra ○ Perfusion "mismatch" (↓ CBF but normal CBV)

17. MRI T1WI normal in first 4-6 hours Subtle gyral swelling and hypointensity within 12-24 hours; seen as blurring of the GM-WM interfaces Loss of "flow void” in occluded large vessel T1 C+ I ntravascular enhancement. Parenchymal enhancement is uncommon in acute/hyperacute ischemia

18. T2WI/FLAIR • T2: normal in first 4-6 hours; positive within 12-24 hours • FLAIR: first 4-6 hours ○ Cortical swelling, gyral hyperintensity ○ Intraarterial hyperintensity (usually slow flow, not thrombus)

19. T2* (GRE, SWI) • Thrombus may "bloom" • Large infarcts may show prominent hypointense medullary veins • Microbleeds (chronic hypertension, amyloid)

20. DWI and DTI • Most sensitive sequence > 95% restriction within minutes cytotoxic edema reduced water diffusibility caused by decreased levels of astrocytic aquaporin-4 (AQP4). Hyperintense on DWI Hypointense on ADC map • "Diffusion-negative" acute strokes Small (lacunar) infarcts Brainstem lesions: DTI is even more sensitive than DWI Rapid clot lysis/recanalization Transient/fluctuating hypoperfusion

21. pMR • DWI-PWI "mismatch" estimates penumbra • CBV-CBF, DWI-FLAIR mismatches estimate penumbra

22. Angiography DSA obtained only as a prelude to intraarterial thrombolysis or mechanical thrombectomy. Clot location and length can be precisely determined Collateral circulation delineated. Vessel "cut-off," "meniscus" sign, tapered/"rat-tail" narrowing

23. "Bare" area of unperfused brain Slow antegrade or retrograde filling

24. DSA • Delayed intraarterial contrast washout • Luxury perfusion ○ "Blush" around "bare area" ○ "Early draining" veins

25. Differential Diagnosis "hyperdense vessel" sign elevated hematocrit (all the vessels appear dense, not just the arteries) arterial wall microcalcifications hypodense brain parenchyma (e.g., diffuse cerebral edema) Stroke "mimics" with restricted DWI include infection status epilepticus (affects cortex in a nonvascular distribution; spares underlying subcortical WM) acute hypoglycemia

26. Treatment

27. R ecanalization strategies Intravenous Thrombolysis Endovascular/intra-arterial Therapy Mechanical thrombectomy stent retrievers Penumbra aspiration thrombectomy Intra-arterial fibrinolysis

28. Intravenous Thrombolysis Recombinant Tissue Plasminogen Activator ( rtPA ) S elected patients up to 4.5 hours after symptom onset. 0.9 mg/kg IV (maximum 90 mg) IV as 10% of total dose by bolus, followed by remainder of total dose over 1 h.

29. Indication for IV tPA Clinical diagnosis of stroke Onset of symptoms to time of drug administration ≤4.5 hrs CT scan showing no haemorrhage or edema of >1/3 of the MCA territory Age ≥18 years Contraindication Sustained BP >185/110 mmHg despite treatment Bleeding diathesis Recent head injury or intracerebral hemorrhage Major surgery in preceding 14 days Gastrointestinal bleeding in preceding 21 days Recent myocardial infarction

30. Unfortunately, IV tPA is often ineffective in large vessel occlusion (LVO) stroke that carries a high morbidity and mortality. Multiple prospective randomized controlled trials have demonstrated that endovascular thrombectomy is highly effective in reducing disability in selected patients with acute LVO anterior circulation stroke. An estimated 1.9 million neurons are lost per minute in untreated acute LVO strokes. Every 30-minute delay is associated with a 10% decrease in function outcome at 90 days. Time can be saved across every level of stroke care from prehospital care to intraprocedural technique.

31. Intraarterial Therapy As per the 2018 AHA guidelines for acute stroke Patients should receive mechanical thrombectomy if they meet all the following criteria: Prestroke mRS score should be between 0 to 1 The occluding thrombus causing symptoms should involve the internal carotid artery or MCA (M1 segment) Age ≥18 years NIHSS score greater than or equal to 6 ASPECTS greater than or equal to 6 Groin puncture for endovascular thrombectomy can be performed within 6 hours of stroke onset.

32. No clear guidelines for endovascular management in posterior circulation stroke. Mechanical thrombectomy may be performed for basilar artery occlusion up to 12–24 hours after symptom onset . R ecent analysis of Basilar Artery International Cooperation Study registry: severe strokes at presentation treated beyond 9 hours after onset had poor clinical outcome.

33. Absolute Contraindication 1. Anaphylactic reaction to contrast 2. Haemorrhagic conversion of stroke or midline shift 3. Large core infarct with expected futile revascularization a. MRI diffusion-weighted imaging (DWI) core infarct >70 mL b. Hypodensity >1/3 middle cerebral artery (MCA) territory or Alberta Stroke Program Early Computed Tomography Scan (ASPECTS) <6 on non-contrast CT c. Matched defect or <20% penumbra with perfusion imaging d. <50% filling of MCA collaterals on multiphase computed tomographic angiography (CTA) (correlates well with ASPECTS ≤5)

34. Relative Contraindication Lack of appropriate vascular access C arotid and upper extremity access limits safe and timely therapy for operators not skilled with more advanced techniques. Poor baseline functional status Limited life expectancy or other severe medical comorbidities Medical factors that increase bleeding risks

35. Pre-procedure Preparation 1. History, physical examination, National Institutes of Health stroke scale (NIHSS), and consultation with a neurologist P rimary objective is to establish a correct diagnosis of acute ischemic stroke. Large vessel anterior or posterior stroke syndromes should be differentiated from lacunar stroke syndromes

36. c. Establishing the correct time of onset of symptoms; acceptable time window d. Review of medications, allergies, and comorbidities e. Pulse exam; stroke interventions are performed from a femoral approach. 2. Laboratory evaluation C omplete blood count; international normalized ratio (INR); and serum electrolytes including creatinine, glucose, and troponin. Electrocardiogram

37. 3. Imaging evaluation Urgent imaging Radiologic imaging should begin within 25 minutes I nterpreted within 45 minutes of arrival in at least 80% of cases i . Noncontrast computed tomography (NCCT) exclusion of hemorrhage ASPECTS: score <6 should be excluded from endovascular therapy ii. Computed tomographic angiography (CTA) identification of vascular occlusion and information obtained about the aortic arch and neck vasculature is useful for planning endovascular interventions iii. Multiphase CTA ( mCTA ) utilizes additional venous phases to assess collaterals and exclude patients with a large core infarct

38. iv . CT perfusion (CTP) CTP involves an additional contrast bolus with continuous scanning of either a segment of brain or more recently whole brain imaging where software can then be used to calculate various parameters such as time to start (TTS), time to peak (TTP), mean transit time (MTT), cerebral blood volume (CBV), and cerebral blood flow (CBF). Color-coded maps are generated. Brain at risk is best quantified by areas where TTP is >6 seconds although areas of increased MTT and TTS roughly approximate penumbra as well. Areas where CBV or CBF falls below specified thresholds are used to estimate the core infarct. v . Magnetic resonance imaging (MRI) Diffusion-weighted restriction on MRI is the most sensitive modality for early detection of irreversibly injured brain. MR perfusion-weighted images can be used to determine the ischemic penumbra of brain at risk similar to CTP.

39. 4. All patients who are eligible should receive full-dose (0.9 mg per kg) IV tPA. Bridging strategies are no longer recommended. 5. In acute stroke intervention, consent is not practically obtained from the patient. Consent should be expeditiously obtained from family when practical. Emergency consent may be required and should be a consensus decision with the consulting neurologist. Institutional preprinted consents are recommended to save time and standardize risk and benefit discussion. 6. IV access is critical for administration of IV fibrinolytics and medications for blood pressure control. At least two large-bore IVs should be placed. IV fluids can be administered to decrease risks of contrast. 7. Invasive pressure monitoring 8 . Groin preparation

40. Procedure General considerations Airway protection and anaesthesia considerations: Conscious sedation with anaesthesia present to provide airway support and blood pressure control. Conversion to general anaesthetic can be performed for airway protection or with an uncooperative patient. Angiographic equipment: Biplane angiography (simultaneously x-ray images from two angles: from front to back and from side to side) ; E asier identification of emboli, increased safety navigating intracranial anatomy, and lower contrast use. Ultrasound-guided micro-puncture access can mitigate vascular complications

41. Mechanical thrombectomy M ain advantage: ability to remove large clots rapidly & avoid use of fibrinolytics. Stent retrievers Penumbra aspiration catheter

42. a. Stent retrievers Solitaire stent retriever is available in 4 mm and 6 mm diameters in varying lengths. The 4-mm device is delivered through a 0.021-in. internal diameter (ID) microcatheter, whereas the 6-mm device is delivered through a 0.027-in. ID microcatheter. The Solitaire stent has an overlapping stent design, is not packaged with a microcatheter, and only has radiopaque markers at the ends of the stent.

43. Trevo ProVue stent retriever comes in 4-mm and 6-mm diameters and is packaged with its own delivery catheter. It is composed of a single circular stent and is radiopaque.

44. Technique Access is made through a 6-F/8-F sheath. Initial angiogram is performed to assess exact location of occlusion and to assess hemodynamics of cerebral perfusion. Heparin is given in a bolus dose of 5,000 U followed by 1,000 U/ hr for 2 hours or until the end of the procedure. A guide catheter is introduced through the femoral artery. Subsequently, a microcather is advanced into the occluded middle cerebral artery over a 0.14 microguide wire. Both microcatheter and microwire must be navigated across the site of occlusion.

45. A stent retriever is then deployed at the site of the thrombus via the microcatheter. Once the stent is delivered into the vessel it self-expands within the thrombus pushing the clot against the wall of the artery, reestablishing blood flow to the brain. The stent is kept deployed for a few minutes, thus allowing it to ensnare the thrombus within its tines. The stent, microcatheter and the ensnared thrombus are then pulled out of the vessel while simultaneously aspirating with a 50-cc syringe through the guide catheter. Aspiration of the clot may also be performed using the penumbra device. This is a trackable reperfusion catheter with a large inner lumen that is deployed at the surface of the thrombus. A suction pump is used to generate negative pressure that allows the thrombus to be digested.

46. b. Penumbra aspiration catheter The Penumbra Aspiration System (Penumbra, Inc, Alameda, CA) is composed of a reperfusion catheter, a suction pump, suction tubing, and a diamond-tipped separator. A suction pump is used to generate negative pressure that allows the thrombus to be digested.

47. Intra-arterial fibrinolysis Endovascular therapy delivers lytic agent at high concentration directly to the clot, increasing lysis rates compared with intravenous therapy, while minimizing systemic exposure and extracerebral bleeding complications. B oth tPA and glycoprotein IIb/ IIa inhibitors such as abciximab Indications M ost commonly used when mechanical methods fail smaller distal vessels where mechanical devices cannot be safely delivered To treat distal embolic complications of mechanical embolectomy.

48. Post procedure Management 1. Patients are managed in the intensive care unit (ICU) 2. Frequent reassessment of the patient should occur after ischemic stroke to evaluate for clinical worsening, which may be a sign of symptomatic intracranial hemorrhage (SICH). 3. The femoral artery puncture site and distal pulses should be monitored. Groin hematoma is the most common complication at the puncture site. 4. Maintaining systolic blood pressure less than 140 to 160 mm Hg is prudent to reduce the risk of reperfusion hemorrhage. 5. An NCCT is typically obtained within the first 24 hours to evaluate for hemorrhage and swelling. 6. Workup for etiology may include carotid ultrasound, cardiac echocardiography and hemoglobin A1C.

49. Complications 1. Symptomatic intracranial haemorrhage (SICH): P arenchymal hematoma or subarachnoid haemorrhage 2. Vessel perforation 3. Groin complications: Most common is groin hematoma exacerbated by concurrent IV tPA administration Pseudoaneurysm R etroperitoneal haemorrhage A rteriovenous (AV) fistula Thrombosis I nfection 4. Embolization: dislodging clots may cause embolic occlusion in new territories.

50. Conclusion Both CT and MR imaging are useful for the comprehensive evaluation of acute stroke and can provide important and necessary information for therapy planning. Interprofessional communication and concurrent workflows are essential components of stroke management and the safe, prompt application of mechanical thrombectomy in stroke treatment. The duration of effective revascularization is a critical parameter in assessing patient outcomes. The ESCAPE clinical trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimising CT to Recanalisation Times) established that enhanced workflow could positively influence both functional outcomes and death rates.

51. Thank You