15/24 7/6/23, 11:55 AM Intracranial large artery atherosclerosis: Epidemiology, clinical manifestations, and diagnosis - UpToDate Mechanisms of stroke in patients with intracranial atherosclerotic disease Mechanisms of stroke in patients with ICAD. (A) Thrombotic occlusion is a rare phenotype of ICAD. MRA shows in situ thrombotic occlusion at the site of st plaque. DWI shows territorial infarcts by severe hemodynamic compromise and embolic infarcts on the corte High-resolution MRI can show vulnerable plaque on intracranial vessels. (B) Artery-to-artery embolism is one of common phenotypes of ICAD. Artery-to-artery embolism is usually associated with a severe degree of intracranial stenosis, and transcranial Doppler ultrasonography can detec symptomatic or asymptomatic embolism during microembolic signal monitoring. DWI shows small, scattered cortical embolic infarcts. (C) Hemodynamic impairment is another phenotype of ICAD. This phenotype is usually associated with a seve stenosis and a marked hemodynamic compromise, as seen on a PWI. DWI typically shows borderzone-type in and infarct growth is common with clinical deterioration. (D) Branch occlusive disease is a common phenotype of ICAD. This phenotype is often misclassified as small a disease due to a mild degree of stenosis on MRA, small deep infarcts on DWI, and relatively small perfusion d High-resolution MRI can reveal plaque without stenosis near the orifices of penetrating arteries. https://www.uptodate.com/contents/intracranial-large-artery-atherosclerosis-epidemiology-clinical-manifestations-and-diagnosis/print 16/24 7/6/23, 11:55 AM Intracranial large artery atherosclerosis: Epidemiology, clinical manifestations, and diagnosis - UpToDate ICAD: intracranial atherosclerotic disease; DWI: diffusion-weighted imaging; PWI: perfusion-weighted imagin MRA: time-of-flight magnetic resonance angiography. Reproduced with permission from: Bang OY. Intracranial atherosclerosis: current understanding and perspectives. J Stroke 2014; 16:27 Copyright 2014 Korean Stroke Academy. Graphic 105007 Version 1.0 https://www.uptodate.com/contents/intracranial-large-artery-atherosclerosis-epidemiology-clinical-manifestations-and-diagnosis/print 17/24 7/6/23, 11:55 AM Intracranial large artery atherosclerosis: Epidemiology, clinical manifestations, and diagnosis - UpToDate Eligibility criteria for the treatment of acute ischemic stroke with intravenous thrombolysis (recombinant tissue plasminogen activator or tPA) Inclusion criteria Clinical diagnosis of ischemic stroke causing measurable neurologic deficit Onset of symptoms <4.5 hours before beginning treatment; if the exact time of stroke onset is not known, it is defined as the last time the patient was known to be normal or at neurologic baseline Age 18 years Exclusion criteria Patient history Ischemic stroke or severe head trauma in the previous three months Previous intracranial hemorrhage Intra-axial intracranial neoplasm Gastrointestinal malignancy Gastrointestinal hemorrhage in the previous 21 days Intracranial or intraspinal surgery within the prior three months Clinical Symptoms suggestive of subarachnoid hemorrhage Persistent blood pressure elevation (systolic 185 mmHg or diastolic 110 mmHg) Active internal bleeding Presentation consistent with infective endocarditis Stroke known or suspected to be associated with aortic arch dissection Acute bleeding diathesis, including but not limited to conditions defined under 'Hematologic' Hematologic 3 Platelet count <100,000/mm * Current anticoagulant use with an INR >1.7 or PT >15 seconds or aPTT >40 seconds* Therapeutic doses of low molecular weight heparin received within 24 hours (eg, to treat VTE and ACS); this exclusion does not apply to prophylactic doses (eg, to prevent VTE) Current use (ie, last dose within 48 hours in a patient with normal renal function) of a direct thrombin inhibitor or direct factor Xa inhibitor with evidence of anticoagulant effect by laboratory tests such as aPTT, INR, ECT, TT, or appropriate factor Xa activity assays Head CT Evidence of hemorrhage https://www.uptodate.com/contents/intracranial-large-artery-atherosclerosis-epidemiology-clinical-manifestations-and-diagnosis/print 18/24 7/6/23, 11:55 AM Intracranial large artery atherosclerosis: Epidemiology, clinical manifestations, and diagnosis - UpToDate Extensive regions of obvious hypodensity consistent with irreversible injury Warnings Only minor and isolated neurologic signs or rapidly improving symptoms Serum glucose <50 mg/dL (<2.8 mmol/L) Serious trauma in the previous 14 days Major surgery in the previous 14 days History of gastrointestinal bleeding (remote) or genitourinary bleeding Seizure at the onset of stroke with postictal neurologic impairments Pregnancy** Arterial puncture at a noncompressible site in the previous seven days Large ( 10 mm), untreated, unruptured intracranial aneurysm Untreated intracranial vascular malformation Additional warnings for treatment from 3 to 4.5 hours from symptom onset Age >80 years Oral anticoagulant use regardless of INR Severe stroke (NIHSS score >25) Combination of both previous ischemic stroke and diabetes mellitus ACS: acute coronary syndrome; aPTT: activated partial thromboplastin time; ECT: ecarin clotting time; INR: international normalized ratio; PT: prothrombin time; NIHSS: National Institutes of Health Stroke Scale; tPA: intravenous alteplase; TT: thrombin time; VTE: venous thromboembolism. Although it is desirable to know the results of these tests, thrombolytic therapy should not be delayed while results are pending unless (1) there is clinical suspicion of a bleeding abnormality or thrombocytopenia, (2) the patient is currently on or has recently received anticoagulants (eg, heparin, warfarin, a direct thrombin inhibitor, or a direct factor Xa inhibitor), or (3) use of anticoagulants is not known. Otherwise, treatment with intravenous tPA can be started before availability of coagulation test results but should be discontinued if the INR, PT, or aPTT exceed the limits stated in the table, or 3 if platelet count is <100,000 mm . With careful consideration and weighting of risk-to-benefit, patients may receive intravenous alteplase despite one or more warnings. Patients who have a persistent neurologic deficit that is potentially disabling, despite improvement of any degree, should be treated with tPA in the absence of other contraindications. Any of the following should be considered disabling deficits: Complete hemianopia: 2 on NIHSS question 3, or Severe aphasia: 2 on NIHSS question 9, or Visual or sensory extinction: 1 on NIHSS question 11, or Any weakness limiting sustained effort against gravity: 2 on NIHSS question 5 or 6, or Any deficits that lead to a total NIHSS >5, or https://www.uptodate.com/contents/intracranial-large-artery-atherosclerosis-epidemiology-clinical-manifestations-and-diagnosis/print 19/24 7/6/23, 11:55 AM Intracranial large artery atherosclerosis: Epidemiology, clinical manifestations, and diagnosis - UpToDate Any remaining deficit considered potentially disabling in the view of the patient and the treating practitioner using clinical judgment Patients may be treated with intravenous alteplase if glucose level is subsequently normalized. The potential risks of bleeding with alteplase from injuries related to the trauma should be weighed against the anticipated benefits of reduced stroke-related neurologic deficits. The increased risk of surgical site bleeding with alteplase should be weighed against the anticipated benefits of reduced stroke-related neurologic deficits. There is a low increased risk of new bleeding with alteplase in the setting of past gastrointestinal or genitourinary bleeding. However, alteplase administration within 21 days of gastrointestinal bleeding is not recommended. Alteplase is reasonable in patients with a seizure at stroke onset if evidence suggests that residual impairments are secondary to acute ischemic stroke and not to a postictal phenomenon. * Alteplase can be given in pregnancy when the anticipated benefits of treating moderate or severe stroke outweigh the anticipated increased risks of uterine bleeding. The safety and efficacy of administering alteplase is uncertain for these relative exclusions. Although these were exclusions in the trial showing benefit in the 3 to 4.5 hour window, intravenous alteplase appears to be safe and may be beneficial for patients with these criteria, including patients taking oral anticoagulants with an INR <1.7. Adapted from: 1. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; 359:1317. 2. Del Zoppo GJ, Saver JL, Jauch EC, et al. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator. A science advisory from the American Heart Association/American Stroke Association. Stroke 2009; 40:2945. 3. Re-examining Acute Eligibility for Thrombolysis (TREAT) Task Force:, Levine SR, Khatri P, et al. Review, historical context, and clari cations of the NINDS rt-PA stroke trials exclusion criteria: Part 1: rapidly improving stroke symptoms. Stroke 2013; 44:2500. 4. Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scienti c rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2016; 47:581. 5. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2019; 50:e344. Graphic 71462 Version 26.0 https://www.uptodate.com/contents/intracranial-large-artery-atherosclerosis-epidemiology-clinical-manifestations-and-diagnosis/print 20/24 7/6/23, 11:55 AM Intracranial large artery atherosclerosis: Epidemiology, clinical manifestations, and diagnosis - UpToDate Indications for mechanical thrombectomy to treat patients with acute ischemic IV: intravenous; tPA: tissue plasminogen activator (alteplase or tenecteplase); CTA: computed tomography an artery occlusion; MT: mechanical thrombectomy; ASPECTS: Alberta Stroke Program Early CT Score; NIHSS: Na tomography; MRI: magnetic resonance imaging; mRS: modified Rankin Scale; MCA: middle cerebral artery; IC recovery. Patients are not ordinarily eligible for IV tPA unless the time last known to be well is <4.5 hours. However, im that is diffusion positive and FLAIR negative) is an option at expert stroke centers to select patients with wake associated UpToDate topics for details. Usually assessed with MRA or CTA, less often with digital subtraction angiography. There is intracranial arterial occlusion of the distal ICA, middle cerebral (M1/M2), or anterior cerebral (A1/A2 MT may be a treatment option for patients with acute ischemic stroke caused by occlusion of the basilar ar stroke centers, but benefit is uncertain. [1] Based upon data from the Aurora study . Reference: https://www.uptodate.com/contents/intracranial-large-artery-atherosclerosis-epidemiology-clinical-manifestations-and-diagnosis/print 21/24 7/6/23, 11:55 AM Intracranial large artery atherosclerosis: Epidemiology, clinical manifestations, and diagnosis - UpToDate 1. Albers GW, Lansberg MG, Brown S, et al. Assessment of Optimal Patient Selection for Endovascular Thrombectomy Beyond 6 Hou Neurol 2021; 78:1064. Graphic 117086 Version 3.0 https://www.uptodate.com/contents/intracranial-large-artery-atherosclerosis-epidemiology-clinical-manifestations-and-diagnosis/print 22/24 7/6/23, 11:55 AM Intracranial large artery atherosclerosis: Epidemiology, clinical manifestations, and diagnosis - UpToDate Acute ischemic stroke syndromes according to vascular territory Artery involved Syndrome Anterior cerebral artery Motor and/or sensory deficit (leg > face, arm) Grasp, sucking reflexes Abulia, paratonic rigidity, gait apraxia Middle cerebral artery Dominant hemisphere: aphasia, motor and sensory deficit (face, arm > leg > foot), may be complete hemiplegia if internal capsule involved, homonymous hemianopia Non-dominant hemisphere: neglect, anosognosia, motor and sensory deficit (face, arm > leg > foot), homonymous hemianopia Posterior cerebral artery Homonymous hemianopia; alexia without agraphia (dominant hemisphere); visual hallucinations, visual perseverations (calcarine cortex); sensory loss, choreoathetosis, spontaneous pain (thalamus); III nerve palsy, paresis of vertical eye movement, motor deficit (cerebral peduncle, midbrain) Penetrating vessels Pure motor hemiparesis (classic lacunar syndromes) Pure sensory deficit Pure sensory-motor deficit Hemiparesis, homolateral ataxia Dysarthria/clumsy hand Vertebrobasilar Cranial nerve palsies Crossed sensory deficits Diplopia, dizziness, nausea, vomiting, dysarthria, dysphagia, hiccup Limb and gait ataxia Motor deficit Coma Bilateral signs suggest basilar artery disease Internal carotid artery Progressive or stuttering onset of MCA syndrome, occasionally ACA syndrome as well if insufficient collateral flow Graphic 75487 Version 7.0 https://www.uptodate.com/contents/intracranial-large-artery-atherosclerosis-epidemiology-clinical-manifestations-and-diagnosis/print 23/24 7/6/23, 11:55 AM Intracranial large artery atherosclerosis: Epidemiology, clinical manifestations, and diagnosis - UpToDate Contributor Disclosures As'ad Ehtisham, MD, MBBS, FAHA No relevant financial relationship(s) with ineligible companies to disclose. Tanya N Turan, MD, MSCR No relevant financial relationship(s) with ineligible companies to disclose. Scott E Kasner, MD Grant/Research/Clinical Trial Support: Bayer [Stroke]; Bristol Meyers Squibb [Stroke]; Medtronic [Stroke]; WL Gore and Associates [Stroke]. Consultant/Advisory Boards: Abbvie [Stroke]; AstraZeneca [Stroke]; BMS [Stroke]; Diamedica [Stroke]; Medtronic [Stroke]. All of the relevant financial relationships listed have been mitigated. John F Dashe, MD, PhD No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/intracranial-large-artery-atherosclerosis-epidemiology-clinical-manifestations-and-diagnosis/print 24/24