Approach to management ISCHEAMIC STROKE 2023.pptx

Ischemic stroke

1. I schemic Stroke Moderator : Dr. Medina ( MD, consultant neurologist) Presenter : Dr. Jama Abdi ( I MR1 ) 09.11.2023

2. Outline Introduction Epidemiology Pathophysiology Stroke syndromes Clinical approach Management References ISCHEMIC STROKE 2023

3. Brain storming 65-yrs-old right handed female developed a sudden inability to speak properly while she was at home . Her husband brought her to hospital immediately and described the problem as if she were talking “double Dutch”. PMH has HTN and OA. She was taking bendroflumethiazide 2.5mg od and prn codeine. Urgent imaging confirmed an infarct in the left MCA territory and she was admitted to the Acute Stroke Unit. 12-lead ECG, and her glucose, CRP and cholesterol results were normal. Bilateral carotid Doppler studies revealed a 70%+ stenosis on the right side, with 30% stenosis on the left. What is the next best step in management? A. Ambulatory 24 hour ECG to look for paroxysmal AFIB B. Clopidogrel 75 mg orally C. Echocardiogram D. Medical management of vascular risk factors E. Referral for urgent carotid endarterectomy ISCHEMIC STROKE 2023

4. Introduction Stroke or cerebrovascular accident, is an abrupt onset of a neurologic deficit that is attributable to a focal vascular cause. Worldwide, stroke is the 2 nd most common cause of both mortality and disability Decreasing incidence of stroke is in high-income countries, increasing in low-income countries ISCHEMIC STROKE 2023

5. cont.. Cerebral ischemia is caused by a reduction in blood flow that lasts longer than several seconds. If the cessation of flow lasts for more than a few minutes, infarction or death of brain tissue results. When blood flow is quickly restored, brain tissue can recover fully and the patient's symptoms are only transient: This is called a transient ischemic attack (TIA). ISCHEMIC STROKE 2023

6. Epidemiology Global prevalence of stroke in 2019 was 101.5 million people: Ischemic stroke was 77.2 million, ICH was 20.7 million, and that of SAH was 8.4 million 6.5million people die from stroke annually A higher incidence of hemorrhagic stroke in low- and middle-income countries M>F Increased risk of stroke in Blacks and Hispanics > white ISCHEMIC STROKE 2023

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8. Results A total of 163 stroke patients were recruited during the study period, of which 82 (50.3%) patients had ischemic stroke while 81 (49.7%) had hemorrhagic stroke . Stroke risk factors included hypertension (50.9%), cardiac diseases (16.6%), diabetes mellitus (7.4%), alcohol (10.4%), cigarette smoking (4.9%) and tuberculous meningitis (3.1%). In-hospital stroke mortality was 14.7%. Conclusion T he proportion of hemorrhagic stroke is higher than in Western countries. Hypertension is the most common risk factor for stroke. More than half of the patients were discharged with severe disability. ISCHEMIC STROKE 2023

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10. Risk factors ISCHEMIC STROKE 2023

11. Risk factors ISCHEMIC STROKE 2023

12. Risk factors Slide , MD ISCHEMIC STROKE 2023

13. Etiology Establishing a cause is essential in reducing the risk of recurrence. Particular focus should be on atrial fibrillation and carotid atherosclerosis, as these etiologies have proven secondary prevention strategies The clinical presentation and examination findings often establish the cause of stroke or narrow the possibilities to a few ISCHEMIC STROKE 2023

14. Etiology Thrombosis Lacunar stroke (small vessel) Large vessel thrombosis Dehydration Embolic occlusion Artery-to-artery Carotid bifurcation Aortic arch Arterial dissection Cardioembolic Atrial fibrillation Mural thrombus Myocardial infarction Dilated cardiomyopathy Valvular lesions Paradoxical embolus ISCHEMIC STROKE 2023

15. Etiology Hypercoagulable states Venous sinus thrombosis Fibromuscular dysplasia Vasculitis Systemic vasculitis [PAN, granulomatosis with polyangiitis (Wegener's), Takayasu's , giant cell arteritis] Primary CNS vasculitis Meningitis (syphilis, tuberculosis, fungal, bacterial, zoster) Subarachnoid hemorrhage vasospasm Drugs: cocaine, amphetamine Moyamoya disease Eclampsia ISCHEMIC STROKE 2023

16. Cardioembolic Stroke The most significant cause of cardioembolic stroke in most of the world is patients with atrial fibrillation R esponsible for 20% of all ischemic strokes High embolic potential Cardioembolic cerebral infarcts are often large, multiple, bilateral, and wedge shaped ISCHEMIC STROKE 2023

17. Atrial fibrillation Accounts for ½ to 2/3 of emboli of cardiac origin Incidence of thromboembolism 4% to 7.5% per year . NVAF is the leading source of cardioembolic infarctions in older adults 5-6 fold increase in stroke incidence with cumulative risk of 35% over a lifetime . Patients with rheumatic atrial fibrillation have a 17-fold increase in stroke incidence ISCHEMIC STROKE 2023

18. Artery to artery thrombosis Thrombus formation on atherosclerotic plaques may embolize to intracranial arteries producing an artery-to-artery embolic stroke. Unlike the myocardial vessels, artery-to-artery embolism, rather than local thrombosis, appears to be the dominant vascular mechanism causing brain ischemia ISCHEMIC STROKE 2023

19. Artery to artery thrombosis Any diseased vessel may be an embolic source, including the aortic arch, common carotid, internal carotid, vertebral, and basilar arteries . Carotid Atherosclerosis Carotid atherosclerosis produces an estimated 10% of ischemic stroke Atherosclerosis within the carotid artery occurs most frequently within the common carotid bifurcation and proximal internal carotid artery , carotid siphon (portion within the cavernous sinus) is also vulnerable ISCHEMIC STROKE 2023

20. Hypercoagulable Disorders These disorders account for 1% of all strokes and 2% to 7% of ischemic strokes in young patients ISCHEMIC STROKE 2023

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22. Pathophysiology ISCHEMIC STROKE 2023

23. Pathophysiology ISCHEMIC STROKE 2023

24. 1 . Ischemic Penumbra Ischemic zone that surrounds a central core of infarction with CBF of 25% - 50% of normal and Loss of auto regulation ISCHEMIC STROKE 2023

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26. Transient Ischemic Attacks TIA is now defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction The onset of TIA symptoms is sudden, reaching maximum intensity almost immediately. To qualify as a TIA, therefore, an episode should also be followed by complete clinical recovery. ISCHEMIC STROKE 2023

27. Transient Ischemic Attacks The risk of stroke after a TIA is ~10–15% in the first 3 months, with most events occurring in the first 2 days The interval from the last TIA is an important predictor of stroke risk; 21% experience stroke within 1 month and 51% within 1 year of the last TIA This risk can be directly estimated using the well-validated ABCD2 score ISCHEMIC STROKE 2023

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29. TIA ISCHEMIC STROKE 2023

30. Stroke syndromes Anterior Posterior ISCHEMIC STROKE 2023

31. Clinical Syndromes of Cerebral Ischemia 3 main type of stroke syndromes Large vessel stroke within the anterior circulation ( ACA,MCA) Large vessel stroke within the posterior circulation ( VA,BA,PCA) Small vessel disease of either of vascular beds ISCHEMIC STROKE 2023

32. Large Vessel Stroke Syndromes ISCHEMIC STROKE 2023

33. Lacunar (small vessel) syndromes Small ischemic infarctions in the deep regions of the brain that range in diameter from 0.5 to 15 mm These infarctions result from occlusion of the penetrating arteries, chiefly the anterior choroidal, middle cerebral, posterior cerebral, and basilar arteries ISCHEMIC STROKE 2023

34. Young stroke “<45 years” Incidence is increasing since 1980s Men > Women in the 35 - 44 yr old age group Ischemic > Hemorrhagic ~35 %, etiology is unknown Cardioembolic stroke is more common ( 15–35% ) Uncommon and often a diagnostic challenge ISCHEMIC STROKE 2023

35. Approach to diagnosis of Stroke Clinicians should first ask whether the findings could be caused by a non-vascular process Is it stroke or not?? Two diagnostic questions What is the disease mechanism – the pathology and pathophysiology? And Where is the lesion(s) – the anatomy of the disorder? ISCHEMIC STROKE 2023

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37. Diagnosis-Localization Analysis of the neurological symptoms and their distribution Findings on neurological examination Findings from brain and vascular imaging To assess for any complications To detect vascular and cardiac abnormalities To localize the process within the CNS ISCHEMIC STROKE 2023

38. General physical examination General appearance ABC of life Vital signs Examine the Eyes Examine the Vascular system Examine the Heart Other systems ISCHEMIC STROKE 2023

39. Localization-Neurological examination Level of alertness High level cortical function Cranial nerves Motor function Somatosensory function Gait Coordination ISCHEMIC STROKE 2023

40. The Gugging Swallowing Screen (GUSS) Assess mentation The patient should sit in bed in at least a 60° upright position Deglutition, involuntary cough, drooling, and voice change are checked in each subtest GUSS Part 1: Preliminary Assessment: Indirect Swallowing Test GUSS Part 2: Direct Swallowing Test Semisolid Swallowing Trial- 1/3 to 1/2 teaspoon then 5 half-teaspoons Liquid Swallowing Trial- 3, 5, 10, 20, 50ml Solid Swallowing Trial- A small piece of dry bread ISCHEMIC STROKE 2023

41. NIHSS A highly reliable and valid screening assessment for the rapid evaluation of a patient with acute stroke 11-item scale The maximum possible score is 42 and the lowest is 0 Should be completed at baseline prior to treatment, at 2 hours post-treatment, at 24 hours, at 7-10 days, and at 3 months ISCHEMIC STROKE 2023

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43. Imaging and Laboratory Is the brain lesion(s) caused by ischemia or hemorrhage, or is it related to a non-vascular stroke mimic? Where is the brain lesion(s)? What is its size, shape, and extent? What are the nature, site, and severity of the vascular lesion(s), and how do the vascular lesion(s) and brain perfusion abnormalities relate to the brain lesion(s)? Are abnormalities of blood constituents causing or contributing to brain ischemia or hemorrhage? Is the patient with stroke or transient neurological deficits having seizures? ISCHEMIC STROKE 2023

44. Imaging and Laboratory Urgent studies Finger stick blood glucose Non-contrast brain CT or brain MRI Immediate tests ECG CBC Coagulation profiles Serum electrolytes OFT Toxicology screen Pregnancy test CXR LP if SAH is suspected and head CT scan is negative for blood EEG if seizures are suspected VDRL ISCHEMIC STROKE 2023

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46. Neuroimaging of acute stroke CTA with CTP or MRA with DW-MRI with or without MRP is useful for selecting candidates for mechanical thrombectomy between 6 and 24 hours after last known well MRI to identify diffusion-positive fluid-attenuated inversion recovery (FLAIR)–negative lesions can be useful for selecting those who can benefit from IV alteplase among awake with stroke ISCHEMIC STROKE 2023

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48. Early signs brain ct Hyperdense MCA sign Cortical ribbon sign Hypoattenuation and obscuration of the lentiform nucleus . ISCHEMIC STROKE 2023

49. Early sign of stroke ISCHEMIC STROKE 2023

50. Intracranial vascular imaging NON INVASIVE CTA MRA Perfusion-diffusion CT/MRI ( IMAGES penumbra) Trans cranial doppleer ( TCD) INVASIVE Conventional angiography Extracranial vascular imaging Carotid doppler u/s : safe and inexpensive Sensitivity & spe . To peak stenosis > 70% is 83-86% and 87-99% respectively

51. Treatment of Ischemic stroke The three main principles of acute ischemic stroke care are: Achieve timely recanalization of the occluded artery and reperfusion of the ischemic tissue Optimize collateral flow, and Avoid secondary brain injury ISCHEMIC STROKE 2023

52. Maximizing blood flow Position and activity Managing blood pressure, blood volume, and cardiac output ISCHEMIC STROKE 2023

53. Acute Reperfusion treatments Following intracranial large vessel occlusion- 3 zones of injury the ischemic core zone the ischemic penumbra and the zone of benign oligemia ISCHEMIC STROKE 2023

54. Acute Reperfusion Treatments IV thrombolysis with rtPA and endovascular thrombectomy with a retrievable stent are both solidly established treatments for appropriate candidates with AIS. Should be administered as quickly as possible after stroke onset, can be combined, and are safe in appropriately selected candidates ISCHEMIC STROKE 2023

55. IV thrombolysis Proven to be effective in improving functional outcomes after an ischemic stroke up to 4.5 hours after symptom onset Necessary information The time the patient was last known to be well Any contraindication NIHSS RBS BP Non-contrast Brain CT ISCHEMIC STROKE 2023

56. Indications ISCHEMIC STROKE 2023

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58. IV rtPA Alteplase- approved Tenecteplase-may be preferred in the future The standard dose of IV rtPA for acute ischemic stroke is 0.9 mg/kg, with 10% administered as a bolus and the remainder infused over 1 hour The total dose should not exceed 90 mg ISCHEMIC STROKE 2023

59. Treatment of AIS: IV Administration of Alteplase ISCHEMIC STROKE 2023

60. IV Alteplase ISCHEMIC STROKE 2023

61. Possible complication Hemorrhagic transformation ( 5 to 7%) Alteplase  increased the risk of symptomatic ICH Anaphylaxis reaction Orolingual angioedema (1 to 8%) Systemic bleeding Mild mucocutaneous No need d/c serious bleeding Stop ISCHEMIC STROKE 2023

62. Mechanical thrombectomy rtPA often fails to recanalize proximal artery occlusions caused by large clots  An intracranial large artery occlusion in the proximal anterior circulation using second-generation stent retriever devices within 6 hours of symptom onset regardless of whether they receive intravenous alteplase ISCHEMIC STROKE 2023

63. Mechanical Thrombectomy Indications Prestroke mRS score of 0 to 1 Causative occlusion of the internal carotid artery or MCA segment 1 (M1) Age ≥18 years; NIHSS score of ≥6; ASPECTS of ≥6; and Treatment can be initiated (groin puncture) within 6 hours of symptom onset. Direct aspiration thrombectomy is noninferior to stent retriever ISCHEMIC STROKE 2023

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65. Medical Management for Secondary Stroke Prevention The high risk of recurrent stroke after an ischemic stroke or TIA justifies an early and aggressive approach to secondary stroke prevention A certain sense of urgency and opportunity is needed to ensure that patients with stroke are rapidly evaluated so that properly targeted and optimized secondary prevention measures can be applied ISCHEMIC STROKE 2023

66. Antihypertensive therapy As a primary prevention , meta-analysis showed that a reduction in diastolic blood pressure of just 5 mm Hg , achieved primarily with diuretics or beta-blockers, led to a 42% reduction in stroke risk. For secondary stroke prevention specifically, a meta-analysis of nearly 39,000 patients from 11 trials estimated that antihypertensive therapy in patients with prior stroke or TIA led to a 19% reduction in stroke risk (95% CI, 7% to 30% reduction) ISCHEMIC STROKE 2023

67. Timing of antihypertensive BP lowering in the acute phase has the potential to extend infarcts and worsen stroke symptoms in some patients and should be approached with caution Acute antihypertensive therapy is typically indicated when blood pressure is >220/120 mm Hg , but more stringent goals can be justified when other conditions such as end organ damage, aortic dissection, or preeclampsia/eclampsia are apparent. ISCHEMIC STROKE 2023

68. Timing of antihypertensive Most patients with TIA can be safely restarted or initiated on antihypertensive therapy right away, especially since the acute observation period may be brief. For patients with acute stroke, waiting 24 to 72 hours to initiate or reintroduce an antihypertensive regimen is reasonable, and for those deemed at high risk of neurologic deterioration or those who are neurologically unstable, a longer waiting period can be justified. ISCHEMIC STROKE 2023

69. Class of antihypertensive ACE-I Calcium channel blockers Diuretic (Indapamide, Thiazide) Beta-blockers and Angiotensin II receptor antagonists The choice of antihypertensive agents used should be individualized with a focus on the degree of blood pressure reduction achieved ISCHEMIC STROKE 2023

70. The use of CCBs therapy, compared with placebo (OR, 0.68), β-blockers (OR, 0.79), diuretics combined with β-blockers (OR, 0.89), ACE-inhibitors (OR, 0.92), and diuretics (OR, 0.95), was associated with a lower incidence of stroke events in the patients with hypertension. ISCHEMIC STROKE 2023

71. Long term BP goals Initiate or restart antihypertensive treatment for patients with a history of stroke and an established blood pressure of >140/90 mm Hg For secondary stroke prevention, a BP target of <140/90 mm Hg is justified, and a more stringent goal of <130/80 mm Hg is reasonable for selected patients Current guidelines indicate that a SBP goal of <130mmHg for lacunar stroke and a more broadly applied goal of <130/80 mm Hg may still be reasonable to consider. ISCHEMIC STROKE 2023

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73. Antiplatelet therapy For most stroke subtypes including lacunar stroke, aortic arch atheroma, cervical artery dissection and intracranial atherosclerosis with the notable exception of cardioembolic stroke including AF and VHD Aspirin Clopidogrel Dipyredimole Cilostazol Ticagrelor ISCHEMIC STROKE 2023

74. Aspirin Aspirin (at least 162 mg) is indicated within the first 48 hours of ischemic stroke to prevent early recurrent stroke--in practice most patients receive a 325-mg dose of aspirin Most patients with ischemic stroke should be continued on aspirin therapy long term Aspirin confers an approximately 13% reduction in the relative risk for recurrent stroke Most patients taking aspirin for secondary stroke prevention chronically should be maintained on the lower dose of 81 mg/d ISCHEMIC STROKE 2023

75. Antiplatelet Treatment Administration of aspirin is recommended in patients with AIS within 24 to 48 hours after onset. Any Role for Dual antiplatelet therapy? CHANCE and POINT trials ISCHEMIC STROKE 2023

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78. Anticoagulation therapy The most important indication for anticoagulation therapy for secondary stroke prevention is atrial fibrillation ISCHEMIC STROKE 2023

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80. Anticoagulation therapy Warfarin T he relative risk for stroke is reduced by 68% with the use of warfarin. The RRR with aspirin therapy was 21% Target INR:2.0-3.0 ISCHEMIC STROKE 2023

81. Anticoagulation therapy DOAs Dabigatran, Rivaroxaban, Apixaban, and Edoxaban All of these direct oral anticoagulants appear to have similar efficacy for preventing thromboembolic events and lower ICH risks compared with warfarin ISCHEMIC STROKE 2023

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84. Cholesterol lowering therapy Works, at least in part, by targeting pathways that are involved in development and progression of atherosclerosis Statins Ezetimibe PCSK9 inhibitors ISCHEMIC STROKE 2023

85. Statins Reduction in serum lipid levels Normalization of the vascular endothelium Anti-inflammatory effects Depletion and stabilization of the lipid core content of plaques S trengthening of the fibrous cap of plaques D ecrease in formation of platelet–fibrin thrombi and decreased deposition of white clots on endothelial surfaces R eduction in the thrombogenicity of plaque elements; and Increase in cerebrovascular reactivity ISCHEMIC STROKE 2023

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88. CAROTID REVASCULARIZATION ISCHEMIC STROKE 2023

89. Carotid revascularization Patients likely to benefit Stenosis 70 to 99 percent – life expectancy of at least two years, Revascularizations should occur within two weeks of symptom onset Stenosis 50 to 69 percent – life expectancy of at least three years, Patients unlikely to benefit Stenosis less than 50 percent. Severe comorbidity Stroke associated with persistent, severe neurologic deficits Near occlusion of the symptomatic ipsilateral internal carotid artery ISCHEMIC STROKE 2023

90. Choice of the procedure Patients appropriate for CEA An ipsilateral transient ischemic attack (TIA) or nondisabling ischemic stroke as the symptomatic event A surgically accessible carotid artery lesion No prior ipsilateral endarterectomy No contraindications to revascularization Patients appropriate for CAS A carotid lesion that is not suitable for surgical access Radiation-induced stenosis Carotid restenosis after endarterectomy Clinically significant cardiac, pulmonary, or other disease that greatly increases the risk of anesthesia and surgery Unfavorable neck anatomy ISCHEMIC STROKE 2023

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92. Glycemic control In acute setting Intensive glycemic control may have benefits for microvascular disease, but intensive management of glucose levels after acute stroke or for chronic secondary stroke prevention may have limited benefits over standard therapy. ISCHEMIC STROKE 2023

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95. VTE prophylaxis in AIS ISCHEMIC STROKE 2023

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98. Lifestyle ISCHEMIC STROKE 2023

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101. Treatment of acute complications- Cerebral Edema the most lethal complication of stroke that develops after large ischemic and hemorrhagic strokes Cytotoxic edema, Vasogenic edema Global cerebral edema primarily results in a global rise in ICP, while focal cerebral edema can result in cerebral herniation syndromes with or without ICP elevation Brain edema may begin within hours but usually does not become clinically obvious until 1–4 days after the stroke Deterioration in mentation Pupillary asymmetry or lack of pupillary response to light Periodic breathing patterns VIth nerve paresis. Extensor plantar responses on the previously spared side Papilledema Headache or vomiting Bilateral spontaneous extensor posturing ISCHEMIC STROKE 2023

102. Cerebral edema Avoid factors that can further increase ICP and promote fluid retention Specific measures can be attempted to decrease pressure Hyperventilation with reduction of the PaCO 2 to 20 and 34 mmHg Mannitol , or hypertonic saline In cytotoxic edema, while osmotic agents have been used as a temporizing measure, the evidence for efficacy is poor, and surgical decompression may be considered in the appropriate clinical context. ISCHEMIC STROKE 2023

103. Increased ICP ISCHEMIC STROKE 2023

104. References ISCHEMIC STROKE 2023

105. Thank You! Any Questions or Comments? ISCHEMIC STROKE 2023