Recent Management of Acute ischaemic Stroke – An Update

Sudden onset Neurological deficit (Focal/ Global) of vascular etiology motor weakness, sensory disturbance,visual disturbance, speech disturbance and Imbalance.
Every year 15 million people worldwide suffer a stroke
Stroke is second leading cause of death over the age of 60
Stroke is the second leading cause of disability, after dementia
15% - 30% of stroke survivors are permanently disabled.

1. Recent Management of Acute ischaemic Stroke – An Update Dr. Aminur Rahman FCPS (Med), MD( Neuro ) ,FINR (Switzerland), Member ACP (USA), Member AAN(USA), Fellow Interventional Neuroradiology (Thailand) Assistant Professor Department of Neurology Sir Salimullah Medical College

2. Objectives Overview of stroke Emergency Stroke Evaluation Role of Neuroimaging in Diagnosis of AIS Management of Acute Ischaemic stroke Prevention of Ischemic Stroke Pitfalls of treatment in AIS

3. Overview of stroke

4. What is Stroke? Sudden onset Neurological deficit ( Focal / Global ) of vascular etiology Motor weakness Sensory disturbance Visual disturbance Speech Disturbance Imbalance

5. Types of Stroke

6. Stroke: Globally By The Numbers Every year 15 million people worldwide suffer a stroke Stroke is second leading cause of death over the age of 60 Stroke is the second leading cause of disability, after dementia 15% - 30% of stroke survivors are permanently disabled . * Lancet 2012; 380:2095

7. Emergency Stroke Evaluation

8. http://www.phillystroke.org/content/learn_about_stroke/act_fast.asp

9. ROSIER Scale (Recognition of Stroke in the Emergency Room) Unilateral facial weakness +1 Unilateral grip weakness +1 Unilateral arm weakness +1 Unilateral leg weakness +1 Speech loss +1 Visual field defect +1 Loss of consciousness −1 Seizure −1 Total (−2 to +6) ; score of > 0 indicates stroke is possible cause Exclude hypoglycaemia Bedside blood glucose testing

10. Ischemic Stroke What happens in Ischemic Stroke?

11. Vascular occlusion causes Ischaemic stroke 50-70% of all stroke is due to embolism ( cardiogenic and artery-to-artery) 80 % of acute strokes are due to MCA territory ischemia

12. Role of Neuroimaging in Diagnosis of AIS

13. Role of CT in Diagnosis of Acute Ischemic Stroke (AIS) To Rule out bleed Can detect early stage acute ischemia : by depicting features such as the  1) Hyper dense MCA sign, 2) Insular ribbon sign and 3) Reduced parenchymal attenuation with effacement of cortical sulci.

14. Hyper acute ischemic stroke in CT Hyper dense MCA sign Hyper dense MCA sign

15. Loss of gray-white matter differentiation” Diffuse cerebral swelling with loss of cortical sulci Hyper acute ischemic stroke in CT

16. Insular ribbon sign Insular ribbon sign Hyper acute ischemic stroke in CT

17. 1. No bleed. 2. Faint low attenuation involving right insular cortex and adjacent basal ganglia - 'insular ribbon' sign. 3. Effacement of right hemispheric cortical sulci .  1 2 3 Hyper acute ischemic stroke in CT

18. CT perfusion maps TTP Red means longer TTP (bad) Blue means shorter TTP (good). CBF Red means faster flow (good), Blue means less flow (bad). CBV Red means more volume ( good) Blue means less volume ( bad) Bad- infract core Good- Pneumbra

19. Alberta stroke program early CT score (ASPECTS)

20. MCA-ASPECTS: 1 point is deducted from the initial score of 10 for every region involved Divide of MCA territory- M1-6 CN - Caudate LN - Lentiform neucleus IC - Internal capsule I - Insular cortex Dr Daniel J Bell  et al.

21. Posterior circulation ASPECTS (pc-ASPECTS) 1 point is deducted from the initial score of 10 for every region involved Thalami (1 point each) Occipital lobes (1 point each) Midbrain (2 points) Pons (2 points) Cerebellar hemispheres (1 point each)  Dr Daniel J Bell  et al.

22. Clinical use of ASPECTS An ASPECTS ≤ 7 predicts a worse functional outcome at 3 months as well as symptomatic haemorrhage. According to the study performed by R. I. Aviv et al., patients with ASPECTS less than 8 treated with thrombolysis did not have a good clinical outcome.

23. Role MRI in Diagnosis of AIS MRI is more sensitive in early detection of acute ischaemic stroke . Can detect acute infarct within mints CT Scan: Sensitivity and specificity < 50% MRI in DWI: Sensitivity 88-100% Specificity 86-100%

24. Role MRI in Diagnosis of AIS Within minutes of arterial occlusion demonstrates Increased DWI signal (hyper intense) and Reduced ADC values (hypo intense).   If an infarct seen on  diffusion and not seen FLAIR called  FLAIR / Diffusion Mismatch  indicate hyper acute infarct. If changes are marked on FLAIR indicate already infracted and non salvageable tissue.

25. Early hyper acute ( < 4.5 hours)   DWI= Hyperintense ADC= Hypointense FLAIR= Isointense

26. DWI= Hyperintense ADC= Hypointense FLAIR= Isointense

27. Positive DWI, Negative FLAIR may identify Hyperacute Stroke < 4.5 hours 90 min 125 min 130 min 282 min DWI FLAIR Thomalla et al. Ann Neurol. 2009.

28. Management of Acute Ischaemic stroke

29. Goal of Acute Management: Minimizing brain injury

30. Time is Brain: Prompt initiation is the key Why ??

31. Why are we so aggressive with stroke? 1.9 million neurons are damaged in each minute if stroke treatment is delayed Saver Stroke 2009

32. Penumbra is zone of reversible ischemia around core of irreversible infarction—salvageable in first few hours after ischemic stroke onset. Concepts for RX in the First Few Hours ??? Penumbra Core Clot in Artery “TIME IS BRAIN: SAVE THE PENUMBRA”

33. Vessel Recanalization is Important Ischemic penumbra can be salvaged if vessel is rapidly recanalized Meta-analysis shows strong correlation between recanalization and good outcome . Successful recanalization is associated with: 4-5 fold increase in the good functional outcome 4-5 fold decrease in the mortality

34. Treatment Options of AIS Mechanical thrombectomy Mechanical disruption or removal of the clot using standard endovascular approaches IV tPA Gold-standard in ischemic stroke care. Drug is designed to break apart the clot. Medical Management Monitor vitals and provide secondary stroke prevention. Patient is send to rehab or a nursing facility when stable. Bridging Therapy

35. Medical Management Supportive management- airway, temperature, blood pressure, blood glucose, cardiac assessment. Thrombolysis – intravenous / intra arterial Antiplatelet drugs Anticoagulant drugs Hemodilution, vasodilators and induced hypertension Neuroprotective agents

36. Options for revascularizations Intravenous thrombolysis (IVT) with rt -PA ( alteplase )    is approved for use within 3 hours (NINDS) and 4.5 hours (ECASS 3). Intra-arterial therapy (IAT) with rt -PA ( alteplase )  has proven to be safe and effective within 6 hours (PROACT II) within 6 hours (PROACT II). Combined IV/IA may be more effective than IV t-PA (Interventional Management of Stroke -IMS). Endovascular mechanical thrombectomy can restore vascular patency of these vessels between 41% and 54% of the time.

37. Trends in Revascularization IV Streptokinase was started in 1965 IV Urokinase was started in 1975 IV rt -PA with dose 1.1 mg/kg was before NINDS NINDS result was published in 1995 Approval by US FDA -1997 Canada 1999 Germany 2000

38. Intravenous Thrombolysis Results from the NINDS trial showed that intravenous rtPA ( alteplase ) improves functional outcome at three months, if given within 3 hours of symptom onset. The ECASS 3 clinical trial found that intravenous alteplase is beneficial when given up to 4.5 hours after stroke onset.

39. Principle of I.V Thrombolysis Principle behind the time dependency of thrombolysis is that to save penumbra which decreases every minute after stroke.

40. Inj ACTILYSE 50MG - I.V rtPA ( alteplase ) Dose: 0.9 mg/kg IV; not to exceed 90 mg total dose; administer 10% of the total dose as an initial IV bolus over 1 minute and the remainder infused over 60 minutes 

41. Updated Criteria for IV tPA Inclusions: Measurable neurological deficit Onset of symptoms < 4.5 hours Age > 18 AHA Guidelines 2015

42. Exclusions Head Trauma or Stroke in previous 3 mo SAH Arterial puncture at noncompressible site in previous 7 Day History of ICH Intracranial neoplasm, AVM, or aneurysm ↑ BP (SBP > 185 or SBP > 110) Active internal bleeding Platelet count < 100K Heparin within 48 hours with ↑PTT INR > 1.7 or PT > 15s Direct thrombin or direct Factor Xa inhibitors Blood glucose < 50 CT showed hypodensity> 1/3 hemisphere AHA Guidelines 2015

43. Relative exclusions Only minor or rapidly improving symptoms . Pregnancy Seizure at onset Major surgery or serious trauma in 14 d Recent GI or urinary tract hemorrhage in 21 d Recent acute MI with last 3 mo AHA Guidelines 2015

44. Result of iv rtPA therapy in AIS As compared with patients given placebo, patients treated with t-PA were at least 30 percent more likely to have minimal or no disability at three months on the assessment scales. Symptomatic intracerebral hemorrhage within 36 hours after the onset of stroke occurred in 6.4 percent of patients given t-PA. AHA Guidelines 2015

45. Intra Arterial thrombolysis In large vessel occlusions(LVO) , early recanalization rates with IV rtPA are low, approximately 10% in internal carotid artery (ICA) occlusion and 30% in proximal middle cerebral artery (MCA) occlusion.   PROACT II study suggests that intra-arterial thembolysis (IAT) can be given up to six hour window period in patients with middle cerebral artery occlusion and is an effective treatment.

46. Intra Arterial thrombolysis

47. Intra- Arterial Thrombolysis MCA

48. Before After IA Intra- Arterial Thrombolysis

49. I/A Alteplase

50. 35-40% of Ischemic Strokes are Considered “Large Vessel” This subset of ischemic stroke comprises blockages in the: Internal Carotid Artery (ICA) Middle Cerebral Artery (MCA) Vertebral / Basilar Artery If left untreated, patient prognosis with these types of stroke is poor . 1 . Jansen O, et al. 2. Furlan A et al. PROACT II Trial 3. Brückmann H et al. Vessel Mortality Rate ICA 53% 1 MCA 27% 2 Basilar Artery 89-90% 3

51. Endovascular devices are approved by the FDA Mechanical Embolus Removal in Cerebral Ischemia (MERCI) Retriever : Corkscrew-shaped device that captures and engages clots . Solitaire FR Revascularization Device: Stent-retriever system; combines the ability to restore blood flow and retrieve clot . Penumbra System : Employs both aspiration and Trevo: Stent-retriever system .

52. Laurent Pierot . Stroke. Techniques for Endovascular Treatment of Acute Ischemic Stroke, Volume: 46, Issue: 3, Pages: 909-914, DOI: (10.1161/STROKEAHA.114.007935) © 2015 American Heart Association, Inc.

53. Mechanical Thrombectomy Merci Device

54. Occluded right carotid terminus (black arrows A, B)- Mechanical Thrombectomy L6 Merci device (black arrow F)

55. Received tPA and taken for a Mechanical thrombectomy •Left hospital with NIHSS 2 (1 RUE, 1 RLE)

56. Mechanical Thrombectomy by Navien 5 catheter & Solitaire 4x40mm   Courtesy: Sirajee Shafiqul Islam

57. Suction Thrombectomy Penumbra aspiration Device

58. Prevention of Ischemic Stroke

59. Prevention of Ischemic Stroke Optimal Medical management Angioplasty and Stenting (Interventional) Carotid End Arterectomy (CEA)

60. Prevention of Ischemic Stroke Carotid End Arterectomy (CEA). Revascularization is beneficial for Carotid Stenosis. Effective for reducing the risk of stroke. Timing: Within 2 weeks of non disabling stroke or TIA (but not the first 2 days).

61. Carotid Angioplasty and Stenting Indication: Symptomatic : > 50% stenosis Asymptomatic: > 70% stenosis Carotid Angioplasty and Stenting DSA Carotid stenosis

62. Ulcerated Plaque Carotid Angioplasty and Stenting

63. Carotid Stenting

64. Patient presented with transient ischemic attack (TIA). CT Angiogram (CTA) of neck vessels may miss near total occlusion. 1% flow could be excluded by Digital Subtraction Angiogram (DSA). Endovascular Stent angioplasty was done  Courtesy: Sirajee Shafiqul Islam

65. Surgical interventions Indications — Carotid endarterectomy (CEA) is most commonly performed for symptomatic or asymptomatic high-grade (>50 or >70% ) internal carotid artery stenosis HOWEVER , emergency carotid endartectomy efficacy is not established.

66. Pitfalls of treatment in AIS

67. Pitfalls of treatment in AIS: Patient’s inability to recognize stroke symptoms 40% of stroke patients can’t name a single sign or symptom of stroke or stroke risk factor. 75% of stroke patients misinterpret their symptoms 86% of patients believe that their symptoms aren’t serious enough to seek urgent care serious enough to seek urgent care Physician’s lack of experience with stroke treatment and therefore reluctance to “risk” treatment Lack of organized delivery of care in many medical centers throughout the country.

68. In Ischemic Stroke: Vascular imaging should be done and interpret properly In Acute Ischemic Stroke, revascularization is our main target. And intervention has a role For prevention of ischemic stroke, Carotid Angioplasty and Stenting (CAS) can be done in selected patients. Take Home Message

69. Acknowledgements Department of Neurology ,SSMC Society of Neurologist of Bangladesh(SNB) Bangladesh Society of Neurointervention (BSNI) Dr Subash kanti Dey , Associate Professor, Dept of Neurology ,BSMMU. Dr. Sirajee Shafiqul Islam, Associate Professor, Dept of Interventional Neurology , NINS Dr. Md. Shahidullah , Associate Professor, Dept of Neurology ,BSMMU.

70. Thank you