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Outcomes After Endovascular Thrombectomy With or Without Alteplase in Routine Clinical Practice. JAMA Neurol 2022; 79:768. 98. Katsanos AH, Sarraj A, Froehler M, et al. IV Thrombolysis Initiated Before Transfer for Endovascular Stroke Thrombectomy: A Systematic Review and Meta-analysis. Neurology 2023; 100:e1436. 99. Harris J. A review of mobile stroke units. J Neurol 2021; 268:3180. 100. Fassbender K, Merzou F, Lesmeister M, et al. Impact of mobile stroke units. J Neurol Neurosurg Psychiatry 2021. 101. Grotta JC, Yamal JM, Parker SA, et al. Prospective, Multicenter, Controlled Trial of Mobile Stroke Units. N Engl J Med 2021; 385:971. 102. Ebinger M, Siegerink B, Kunz A, et al. Association Between Dispatch of Mobile Stroke Units and Functional Outcomes Among Patients With Acute Ischemic Stroke in Berlin. JAMA 2021; 325:454. 103. Turc G, Hadziahmetovic M, Walter S, et al. 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Endovascular Treatment and Thrombolysis for Acute Ischemic Stroke in Patients With Premorbid Disability or Dementia: A Scientific Statement From the American Heart Association/American Stroke Association. Stroke 2022; 53:e204. Topic 115775 Version 43.0 https://www.uptodate.com/contents/approach-to-reperfusion-therapy-for-acute-ischemic-stroke/print 30/43 7/5/23, 12:09 PM Approach to reperfusion therapy for acute ischemic stroke - UpToDate GRAPHICS 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 https://www.uptodate.com/contents/approach-to-reperfusion-therapy-for-acute-ischemic-stroke/print 31/43 7/5/23, 12:09 PM Approach to reperfusion therapy for acute ischemic stroke - UpToDate Evidence of hemorrhage 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 https://www.uptodate.com/contents/approach-to-reperfusion-therapy-for-acute-ischemic-stroke/print 32/43 7/5/23, 12:09 PM Approach to reperfusion therapy for acute ischemic stroke - UpToDate 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 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/approach-to-reperfusion-therapy-for-acute-ischemic-stroke/print 33/43 7/5/23, 12:09 PM Approach to reperfusion therapy for acute ischemic stroke - UpToDate Modified Rankin Scale Score Description 0 No symptoms at all 1 No significant disability despite symptoms; able to carry out all usual duties and activities 2 Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance 3 Moderate disability; requiring some help, but able to walk without assistance 4 Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance 5 Severe disability; bedridden, incontinent, and requiring constant nursing care and attention 6 Dead Reproduced with permission from: Van Swieten JC, Koudstaa PJ, Visser MC, et al. Interobserver agreement for the assessment of handicap in stroke patients. Stroke 1988; 19:604. Copyright 1988 Lippincott Williams & Wilkins. Graphic 75411 Version 13.0 https://www.uptodate.com/contents/approach-to-reperfusion-therapy-for-acute-ischemic-stroke/print 34/43 7/5/23, 12:09 PM Approach to reperfusion therapy for acute ischemic stroke - UpToDate Stroke treatment delay and outcome Relation of stroke onset to start of treatment (OTT) with treatment effect after adjustment for prognostic variables assessed by A) day 90 modified Rankin score 0-1 versus 2-6 (interaction p=0.0269, n=3530 [excluding EPITHET data p=0.0116, n=3431]); B) global test that incorporates modified Rankin score 0-1 versus 2-6, Barthel Index score 95-100 versus 90 or lower and NIHSS score 0-1 versus 2 or more (interaction p=0.0111, n=3535 [excluding EPITHET data p=0.0049, n=3436]); C) mortality (interaction p=0.0444, n=3530 [excluding EPITHET data p=0.0582, n=3431]); and D) parenchymal hemorrhage type 2 (interaction p=0.4140, n=3531 [excluding EPITHET data p=0.4578, n=3431]). Thus, for parenchymal hemorrhage type 2, the fitted line is not statistically distinguishable from a horizontal line. For each graph, the adjusted odds ratio is shown with the 95% CIs. CIs from the models will differ from those shown in the tables because the model uses data from all patients treated within 0-360 min whereas the categorized analyses in the tables are based on subsets of patients: the modeled CIs are deemed to be more reliable. %: percent. Lees, KR, Bluhmki, E, von Kummer, R, et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010; 375:1695. Illustration used https://www.uptodate.com/contents/approach-to-reperfusion-therapy-for-acute-ischemic-stroke/print 35/43 7/5/23, 12:09 PM Approach to reperfusion therapy for acute ischemic stroke - UpToDate with permission of Elsevier Inc. All rights reserved. Graphic 66764 Version 2.0 https://www.uptodate.com/contents/approach-to-reperfusion-therapy-for-acute-ischemic-stroke/print 36/43 7/5/23, 12:09 PM Approach to reperfusion therapy for acute ischemic stroke - UpToDate National Institutes of Health Stroke Scale (NIHSS) Administer stroke scale items in the order listed. Record performance in each category after each subscale exam. Do not go back and change scores. Follow directions provided for each exam technique. Scores should reflect what the patient does, not what the clinician thinks the patient can do. The clinician should record answers while administering the exam and work quickly. Except where indicated, the patient should not be coached (ie, repeated requests to patient to make a special effort). Instructions Scale definition Score 1a. Level of consciousness: The 0 = Alert; keenly responsive. investigator must choose a response if a full evaluation is prevented by such obstacles as 1 = Not alert; but arousable by minor stimulation to obey, answer, or respond. an endotracheal tube, language barrier, 2 = Not alert; requires repeated stimulation orotracheal trauma/bandages. A 3 is scored only if the patient makes no movement to attend, or is obtunded and requires strong or painful stimulation to make movements (not stereotyped). _____ (other than reflexive posturing) in response to noxious stimulation. 3 = Responds only with reflex motor or autonomic effects or totally unresponsive, flaccid, and areflexic. 1b. Level of consciousness questions: The 0 = Answers both questions correctly. patient is asked the month and his/her age. The answer must be correct - there is no partial credit for being close. Aphasic and stuporous patients who do not comprehend the questions will score 2. Patients unable to speak because of endotracheal intubation, orotracheal trauma, severe dysarthria from 1 = Answers one question correctly. 2 = Answers neither question correctly. _____ any cause, language barrier, or any other problem not secondary to aphasia are given a 1. It is important that only the initial answer be graded and that the examiner not "help" the patient with verbal or non-verbal cues. 1c. Level of consciousness commands: The 0 = Performs both tasks correctly. _____ patient is asked to open and close the eyes and then to grip and release the non-paretic 1 = Performs one task correctly. 2 = Performs neither task correctly. hand. Substitute another one step command if the hands cannot be used. Credit is given if an unequivocal attempt is made but not completed due to weakness. If the patient does not respond to command, the task should be demonstrated to him or her (pantomime), and the result scored (ie, https://www.uptodate.com/contents/approach-to-reperfusion-therapy-for-acute-ischemic-stroke/print 37/43 7/5/23, 12:09 PM Approach to reperfusion therapy for acute ischemic stroke - UpToDate follows none, one or two commands). Patients with trauma, amputation, or other physical impediments should be given suitable one-step commands. Only the first attempt is scored. 2. Best gaze: Only horizontal eye movements will be tested. Voluntary or 0 = Normal. 1 = Partial gaze palsy; gaze is abnormal in reflexive (oculocephalic) eye movements will one or both eyes, but forced deviation or total gaze paresis is not present. be scored, but caloric testing is not done. If the patient has a conjugate deviation of the 2 = Forced deviation, or total gaze paresis not overcome by the oculocephalic eyes that can be overcome by voluntary or reflexive activity, the score will be 1. If a maneuver. patient has an isolated peripheral nerve paresis (cranial nerves III, IV or VI), score a 1. _____ Gaze is testable in all aphasic patients. Patients with ocular trauma, bandages, pre- existing blindness, or other disorder of visual acuity or fields should be tested with reflexive movements, and a choice made by the investigator. Establishing eye contact and then moving about the patient from side to side will occasionally clarify the presence of a partial gaze palsy. 3. Visual: Visual fields (upper and lower quadrants) are tested by confrontation, using finger counting or visual threat, as appropriate. Patients may be encouraged, 0 = No visual loss. 1 = Partial hemianopia. 2 = Complete hemianopia. but if they look at the side of the moving fingers appropriately, this can be scored as normal. If there is unilateral blindness or enucleation, visual fields in the remaining eye are scored. Score 1 only if a clear-cut 3 = Bilateral hemianopia (blind including cortical blindness). _____ asymmetry, including quadrantanopia, is found. If patient is blind from any cause, score 3. Double simultaneous stimulation is performed at this point. If there is extinction, patient receives a 1, and the results are used to respond to item 11. 4. Facial palsy: Ask - or use pantomime to encourage - the patient to show teeth or 0 = Normal symmetrical movements. _____ 1 = Minor paralysis (flattened nasolabial raise eyebrows and close eyes. Score symmetry of grimace in response to noxious fold, asymmetry on smiling). 2 = Partial paralysis (total or near-total paralysis of lower face). stimuli in the poorly responsive or non- comprehending patient. If facial trauma/bandages, orotracheal tube, tape or https://www.uptodate.com/contents/approach-to-reperfusion-therapy-for-acute-ischemic-stroke/print 38/43 7/5/23, 12:09 PM Approach to reperfusion therapy for acute ischemic stroke - UpToDate other physical barriers obscure the face, 3 = Complete paralysis of one or both sides these should be removed to the extent (absence of facial movement in the upper possible. and lower face). 5. Motor arm: The limb is placed in the appropriate position: extend the arms 0 = No drift; limb holds 90 (or 45) degrees for full 10 seconds. (palms down) 90 degrees (if sitting) or 45 degrees (if supine). Drift is scored if the arm 1 = Drift; limb holds 90 (or 45) degrees, but drifts down before full 10 seconds; does not falls before 10 seconds. The aphasic patient hit bed or other support. is encouraged using urgency in the voice and pantomime, but not noxious 2 = Some effort against gravity; limb cannot get to or maintain (if cued) 90 (or 45) degrees, drifts down to bed, but has some stimulation. Each limb is tested in turn, beginning with the non-paretic arm. Only in _____ effort against gravity. the case of amputation or joint fusion at the shoulder, the examiner should record the 3 = No effort against gravity; limb falls. score as untestable (UN), and clearly write 4 = No movement. the explanation for this choice. UN = Amputation or joint fusion, explain:________________ 5a. Left arm 5b. Right arm 6. Motor leg: The limb is placed in the appropriate position: hold the leg at 30 degrees (always tested supine). Drift is scored if the leg falls before 5 seconds. The 0 = No drift; leg holds 30-degree position for full 5 seconds. 1 = Drift; leg falls by the end of the 5-second period but does not hit bed. aphasic patient is encouraged using urgency in the voice and pantomime, but not noxious stimulation. Each limb is tested in turn, beginning with the non-paretic leg. Only in the case of amputation or joint fusion at the hip, the examiner should 2 = Some effort against gravity; leg falls to bed by 5 seconds, but has some effort against gravity. _____ 3 = No effort against gravity; leg falls to bed immediately. record the score as untestable (UN), and clearly write the explanation for this choice. 4 = No movement. UN = Amputation or joint fusion, explain:________________ 6a. Left leg 6b. Right leg 7. Limb ataxia: This item is aimed at finding 0 = Absent. _____ evidence of a unilateral cerebellar lesion. Test with eyes open. In case of visual defect, 1 = Present in one limb. 2 = Present in two limbs. ensure testing is done in intact visual field. The finger-nose-finger and heel-shin tests UN = Amputation or joint fusion, explain:________________ are performed on both sides, and ataxia is scored only if present out of proportion to weakness. Ataxia is absent in the patient https://www.uptodate.com/contents/approach-to-reperfusion-therapy-for-acute-ischemic-stroke/print 39/43 7/5/23, 12:09 PM Approach to reperfusion therapy for acute ischemic stroke - UpToDate who cannot understand or is paralyzed. Only in the case of amputation or joint fusion, the examiner should record the score as untestable (UN), and clearly write the explanation for this choice. In case of blindness, test by having the patient touch nose from extended arm position. 8. Sensory: Sensation or grimace to pinprick 0 = Normal; no sensory loss. when tested, or withdrawal from noxious stimulus in the obtunded or aphasic patient. 1 = Mild-to-moderate sensory loss; patient feels pinprick is less sharp or is dull on the affected side; or there is a loss of superficial Only sensory loss attributed to stroke is scored as abnormal and the examiner pain with pinprick, but patient is aware of being touched.