with leukoaraiosis: a positron emission tomography/magnetic resonance imaging study. Ann Neurol 2013; 73:529. https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 36/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate 183. McCreary CR, Beaudin AE, Subotic A, et al. Cross-sectional and longitudinal differences in peak skeletonized white matter mean diffusivity in cerebral amyloid angiopathy. Neuroimage Clin 2020; 27:102280. 184. Raposo N, Zanon Zotin MC, Schoemaker D, et al. Peak Width of Skeletonized Mean Diffusivity as Neuroimaging Biomarker in Cerebral Amyloid Angiopathy. AJNR Am J Neuroradiol 2021; 42:875. Topic 1128 Version 45.0 https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 37/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate GRAPHICS Lobar hemorrhage in cerebral amyloid angiopathy Acute superficial lobar hemorrhage in the left frontal lobe seen on computed tomography scan in a patient with cerebral amyloid angiopathy (A). Flair magnetic resonance image performed one week later shows the high signal intensity of subacute hemorrhage with surrounding edema extending into the subcortical white matter (B). Hemorrhage (now low signal intensity consistent with hemosiderin) and edema are mostly resolved on a three-month follow-up study (C). Courtesy of Eric D Schwartz, MD. Graphic 50480 Version 4.0 https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 38/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Characteristic features and initial diagnostic imaging for common underlying causes of spontaneous isolated convexity subarachnoid hemorrhage Suspected Choice of initial diagnostic Characteristic feature(s) etiology imaging test(s) Age >60 years CAA MRI brain with T2*-weighted SWI or GRE sequences Baseline cognitive impairment Recurrent thunderclap headache (>2 RCVS CTA or MRA of head within 1 week) MRI brain Exposure to vasoactive substance Risk factor for venous thrombosis* CVT CTV or MRV of head Head CT features suggestive of venous thrombosis (eg, hyperdense venous sinus; venous infarction) MRI brain New heart murmur Mycotic aneurysm MRI brain with contrast or cerebral DSA Systemic/cutaneous evidence of embolism Clinical history of active cancer Brain tumor MRI brain with contrast Clinical history of new persistent headaches Head CT features suggestive of tumor (eg, vasogenic edema) Headache prior to neurologic deficits Intracranial dissection CTA of head or cerebral DSA Clinical history of connective tissue disorder Head CT features suggestive of AVM AVM Cerebral DSA (calcification or hypodense flow voids adjacent to SAH) History of minor/occult trauma may be Occult trauma MRI brain elicited Evidence of extracranial bleeding or systemic injuries Clinical history of new persistent headaches Vasculitis MRI brain with contrast Cerebral DSA Progressive cognitive or other neurologic impairments Brain and meningeal biopsy https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 39/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Patients with spontaneous isolated convexity SAH present with bleeding restricted to the surface of the cerebral hemispheres. The suspected underlying cause of convexity SAH may be identified by initial diagnostic imaging test. Additional imaging and/or other testing may be warranted if initial imaging is nondiagnostic. Refer to specific UpToDate topics for additional information on the diagnostic evaluation of conditions that may present with convexity SAH. SAH: subarachnoid hemorrhage; CAA: cerebral amyloid angiopathy; MRI: magnetic resonance imaging; SWI: susceptibility-weighted imaging; GRE: gradient recall echo imaging; RCVS: reversible cerebral vasoconstriction syndrome; CTA: computed tomographic angiography; MRA: magnetic resonance angiography; CT: computed tomography; CVT: cerebral venous thrombosis; CTV: computed tomography venography; MRV: magnetic resonance venography; DSA: digital subtraction angiography; AVM: arteriovenous malformation. Refer to UpToDate topic on the causes of venous thrombosis. Graphic 140108 Version 2.0 https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 40/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Old hemorrhages on gradient echo MRI Comparison of CT scan (A), T2- weighted MRI (B), and gradient echo MRI (C) demonstrates the utility of the last for detecting old hemorrhages consistent with cerebral amyloid angiopathy. In addition to the the left frontoparietal hemorrhage seen on all studies (arrowheads), the gradient- echo sequence demonstrates multiple areas of decreased signal in gray- white regions (arrows) consistent with chronic hemorrhage. CT: computed tomography; MRI: magnetic resonance imaging. Reproduced with permission from Greenberg SM, Finklestein SP, Schaefer PW. Petechial hemorrhages accompanying lobar hemorrhage: detection by gradient-echo MRI. Neurology 1996; 46:1751. Graphic 81579 Version 12.0 https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 41/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Acute and subacute lobar hemorrhage Noncontrast head CT shows acute right parietal ICH (A). T2* susceptibility-weighted sequence on MRI performed one day later shows an acute ICH in the right frontal and parietal hemisphere (B) as well as a subacute hemorrhage in the left occipital lobe (thick arrow) and chronic ICH in right inferior parietal lobule (C; arrow). In addition, multiple microbleeds at cerebral corticomedullary junctions (B, C) are consistent with cerebral amyloid angiopathy. CT: computed tomography; ICH: intracerebral hemorrhage; MRI: magnetic resonance imaging. Courtesy of Glenn A Tung, MD, FACR. Graphic 132283 Version 1.0 https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 42/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Distinctive distribution of cerebral microbleeds (A-C) CMBs on T2*-weighted gradient echo MRI sequences suggestive of deep penetrating (hypertensive) vasculopathy. CMBs predominate in bilateral thalami (A), brainstem (B), and dentate nucleus of cerebellum (C). (D-F) CMBs on T2*-weighted gradient echo MRI sequences suggestive of cerebral amyloid angiopathy. CMBs predominate in cerebral hemispheres (D, E). Associated findings include lobar hemorrhage (D; arrow and thick arrow) and superficial siderosis (F; circles). CMB: cerebral microbleeds; MRI: magnetic resonance imaging. Courtesy of Glenn A Tung, MD, FACR. https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 43/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Graphic 132282 Version 1.0 https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 44/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Various radiologic patterns of subarachnoid hemorrhage on noncontrast compu tomography (CT) of the head (A) Obvious large SAH: hyperdense blood in all the basal cisterns, with some dilatation of the temporal horn the lateral ventricles, suggesting early hydrocephalus. (B) More subtle, smaller SAH: small hyperdense collection of blood in the basal cistern adjacent to the left p and suprasellar cistern (short solid arrow). (C) Perimesencephalic SAH: the long solid arrows indicate a perimesencephalic (sometimes called a pretrun SAH. These hemorrhages represent approximately 10% of nontraumatic SAHs. They are thought to be caused venous bleeding, will have a negative CTA result, and usually have an excellent outcome. However, the radiographic pattern is also observed with posterior circulation aneurysms, so all of these patients require neurosurgical consultation and vascular imaging. (D) Convexal SAH: the arrowheads indicate a high convexal SAH. This pattern is observed in two groups of patients. In younger patients, it is usually due to RCVS, but in older ones, it often indicates amyloid angiopath a patient presenting with a severe rapid-onset headache, RCVS would be the likely diagnosis. (E) Traumatic SAH: the history usually suggests a traumatic SAH (the most common cause). However, if this pattern (dashed arrows indicate small amounts of SAH abutting bone, often in the anterior frontal and temp bones) is observed in a patient without a clear history of trauma, the likely cause is a traumatic SAH. https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 45/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate SAH: subarachnoid hemorrhage; CTA: computed tomography angiography; RCVS: reversible cerebral vasoconstriction syndrome. Reproduced from: Edlow JA. Managing Patients With Nontraumatic, Severe, Rapid-Onset Headache. Ann Emerg Med 2018; 71:400. Illus used with the permission of Elsevier Inc. All rights reserved. Graphic 121315 Version 1.0 https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 46/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Brain MRI findings in cortical superficial siderosis Axial susceptibility-weighted images from a patient with cortical superficial siderosis showing bilateral frontoparietal superficial cortical hypointensity due to hemosiderin deposition (A, B) and sparing of the infratentorial region (C). MRI: magnetic resonance imaging. Courtesy of Neeraj Kumar, MD. Graphic 130369 Version 1.0 https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 47/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Boston Criteria for cerebral amyloid angiopathy Boston criteria for Modified Boston criteria [3] sporadic CAA version 2.0, Boston criteria, 2001 [2] version 1.5, 2010 [1] 2022 Definite CAA Full postmortem examination Full postmortem examination demonstrating: Full postmortem examination demonstrating: demonstrating: Lobar, cortical, or cortico- Lobar, cortical, or cortico- Spontaneous ICH, TFNE, subcortical hemorrhage subcortical hemorrhage cSAH, cognitive impairment Severe CAA with Severe CAA with vasculopathy vasculopathy Severe CAA with Absence of other diagnostic lesion Absence of other diagnostic lesion vasculopathy Absence of other diagnostic lesion Probable CAA with supporting pathology Clinical data and pathologic tissue Clinical data and pathologic tissue (evacuated hematoma Clinical data and pathologic tissue (evacuated hematoma (evacuated hematoma or cortical biopsy): or cortical biopsy): or cortical biopsy): Lobar, cortical, or cortico- subcortical hemorrhage Lobar, cortical, or cortico- subcortical hemorrhage Presentation with spontaneous ICH, TFNE, cSAH, or cognitive impairment Some degree of CAA in specimen Some degree of CAA in specimen Absence of other diagnostic lesion Absence of other diagnostic lesion Some degree of CAA in specimen Absence of other diagnostic lesion Probable CAA Clinical data and MRI demonstrating: Clinical data and MRI demonstrating: Clinical data and MRI demonstrating: Age 50 years Age 55 years Age 55 years Plus either: Plus either: Multiple hemorrhages restricted to lobar, cortical, Presentation with spontaneous ICH, Multiple hemorrhages restricted to lobar, or cortico-subcortical regions (cerebellar TFNE, or cognitive impairment cortical, or cortico- subcortical regions hemorrhage allowed) (cerebellar Absence of other cause of Two or more lobar hemorrhagic lesions hemorrhage allowed) hemorrhage https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 48/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate on T2*-weighted or imaging (eg, ICH, Single lobar, cortical, or CMB, cSS, cSAH) cortico-subcortical hemorrhage and focal Absence of other cause of or disseminated superficial siderosis hemorrhage or Absence of other cause of hemorrhage or superficial One lobar hemorrhagic lesion on T2*-weighted siderosis imaging (eg, ICH, CMB, cSS, cSAH) One white matter feature (eg, >20 perivascular spaces in centrum semiovale or WMH in a multispot pattern) Absence of any deep hemorrhagic lesions on T2*- weighted imaging (eg, ICH, CMB) Absence of other cause of hemorrhagic lesions Possible CAA Clinical data and MRI Clinical data and MRI Clinical data and MRI demonstrating: demonstrating: demonstrating: Age 50 years Age 55 years Age 55 years Plus either: Plus either: Single lobar, cortical, or cortico-subcortical Presentation with spontaneous ICH, Single lobar, cortical, or cortico-subcortical hemorrhage TFNE, cSAH, or cognitive hemorrhage Absence of other cause of hemorrhage or impairment Focal or One lobar disseminated superficial siderosis hemorrhagic lesion on T2*-weighted Absence of other cause of imaging (eg, ICH, CMB, cSS, cSAH) hemorrhage or superficial siderosis https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 49/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Absence of other cause of hemorrhage or One white matter feature (eg, >20 perivascular spaces in centrum semiovale or WMH in a multispot pattern) Absence of any deep hemorrhagic lesions on T2*- weighted imaging (eg, ICH, CMB) Absence of other cause of hemorrhagic lesions The Boston criteria incorporate clinical, radiologic, and pathologic data to provide diagnostic certainty for patients with suspected CAA. Successive iterations of these criteria reflect the evolving understanding of these diagnostic features. Refer to UpToDate topics for additional information on the diagnosis and evaluation of patients with suspected CAA. CAA: cerebral amyloid angiopathy; ICH: intracerebral hemorrhage; TFNE: transient focal neurologic event; cSAH: convexity subarachnoid hemorrhage; MRI: magnetic resonance imaging; cSS: cortical superficial siderosis; WMH: white matter hyperintensity. Hemorrhagic lesion in the cerebellum is not counted as either lobar or deep hemorrhagic lesion. Other causes of hemorrhagic lesion: antecedent head trauma, hemorrhagic transformation of an ischemic stroke, arteriovenous malformation, hemorrhagic tumor, and vasculitis. Other causes of cortical superficial siderosis and acute convexity subarachnoid hemorrhage should also be excluded. Other causes of intracerebral hemorrhage: excessive warfarin (INR >3.0); antecedent head trauma or ischemic stroke; central nervous system tumor, vascular malformation, or vasculitis; and blood dyscrasia or coagulopathy. (INR >3.0 or other nonspecific laboratory abnormalities permitted for diagnosis of possible CAA.) Siderosis restricted to 3 or fewer sulci. Siderosis affecting at least 4 sulci. References: 1. Charidimou A, Boulouis G, Frosch MP, et al. The Boston criteria version 2.0 for cerebral amyloid angiopathy: A multicentre, retrospective, MRI-neuropathology diagnostic accuracy study. Lancet Neurol 2022; 21:714. https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 50/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate 2. Linn J, Halpin A, Demaerel P, et al. Prevalence of super cial siderosis in patients with cerebral amyloid angiopathy. Neurology 2010; 74:1346. 3. Knudsen KA, Rosand J, Karluk D, Greenberg SM. Clinical diagnosis of cerebral amyloid angiopathy: Validation of the Boston criteria. Neurology 2001; 56:537. Graphic 139328 Version 1.0 https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 51/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Goal blood pressure according to baseline risk for cardiovascular disease and method of measuring blood pressure Routine/conventional office blood pressure Unattended AOBPM, (manual measurement daytime ABPM, or home with stethoscope or blood pressure oscillometric device)* Higher-risk population 125 to 130/<80 120 to 125/<80 Known ASCVD Heart failure Diabetes mellitus Chronic kidney disease Age 65 years Calculated 10-year risk of ASCVD event 10% Lower-risk 130 to 139/<90 125 to 135/<90 None of the above risk factors All target ranges presented above are in mmHg. On average, blood pressure readings are 5 to 10 mmHg lower with digital, unattended, or out-of- office methods of measurement (ie, AOBPM, daytime ABPM, home blood pressure) than with routine/standard methods of office measurement (ie, manual auscultatory or oscillometric measurement), presumably due to the "white coat effect." However, it is critical to realize that this average difference in blood pressures according to the methodology of measurement applies to the population and not the individual. Some patients do not experience a white coat effect, and, therefore, there is some uncertainty in setting goals that are specific to the method of measurement. When treating to these goals, a patient may (inadvertently) attain a blood pressure below the given target. Provided the patient does not develop symptoms, side effects, or adverse events as a result of the treatment regimen, then reducing or withdrawing antihypertensive medications is unnecessary. Less aggressive goals than those presented in the table may be appropriate for specific groups of patients, including those with postural hypotension, the frail older adult patient, and those with side effects to multiple antihypertensive medications. AOBPM: automated oscillometric blood pressure monitoring; ABPM: ambulatory blood pressure monitoring; ASCVD: atherosclerotic cardiovascular disease; ACC/AHA: American College of Cardiology/American Heart Association. https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 52/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Office blood pressure must be performed adequately in order to use such measurements to manage patients. Critical to an adequate office assessment of blood pressure are proper patient positioning (eg, seated in a chair, feet flat on the floor, arm supported, remove clothing covering the location of cuff placement) and proper technique (eg, calibrated device, proper-sized cuff). The average of multiple measurements should be used for management. Refer to UpToDate topics on measurement of blood pressure. Office readings should not be used to manage blood pressure unless it is performed adequately. Home blood pressure, like office blood pressure, must be performed adequately in order for the measurements to be used to manage patients. First, the accuracy of the home blood pressure device must be verified in the clinician's office. Second, the clinician should verify that the cuff and bladder that the patient will use are the appropriate size. Third, patients should measure their pressure after several minutes of rest and while seated in a chair (back supported and feet flat on the floor) with their arm supported (eg, resting on a table). Fourth, the blood pressure should be measured at different times per day and over multiple days. The average value of these multiple measurements is used for management. Home blood pressure readings should not be used to manage blood pressure unless it is performed adequately and in conjunction with office blood pressure or ambulatory blood pressure. The level of evidence supporting the lower goal in higher-risk individuals is stronger for some risk groups (eg, patients with known coronary heart disease, patients with a calculated 10-year risk 15%, chronic kidney disease) than for other risk groups (eg, patients with diabetes, patients with a prior stroke). Refer to UpToDate topics on goal blood pressure for a discussion of the evidence. Prior history of coronary heart disease (acute coronary syndrome or stable angina), prior stroke or transient ischemic attack, prior history of peripheral artery disease. In older adults with severe frailty, dementia, and/or a limited life expectancy, or in patients who are nonambulatory or institutionalized (eg, reside in a skilled nursing facility), we individualize goals and share decision-making with the patient, relatives, and caretakers, rather than targeting one of the blood pressure goals in the table. The 2013 ACC/AHA cardiovascular risk assessment calculator should be used to estimate 10-year cardiovascular disease risk. In the large subgroup of patients who have an initial (pretreatment) blood pressure 140/ 90 mmHg, but who do not have any of the other listed cardiovascular risk factors, some experts would set a more aggressive blood pressure goal of <130/<80 mmHg rather than those presented in the table. This more aggressive goal would likely reduce the chance of developing severe hypertension and ultimately lower the relative risk of cardiovascular events in these lower-risk patients over the long term. However, the absolute benefit of more aggressive blood pressure lowering in these patients is comparatively small, and a lower goal would require more intensive pharmacologic therapy and corresponding side effects. Graphic 117101 Version 3.0 https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 53/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Lobar versus nonlobar hemorrhage and microbleeds Axial SWI magnetic resonance imaging from two different patients. In panel A, there are multiple lobar hemorrhages including a left parietal lobar hematoma (arrowhead) and many lobar microbleeds (arrows), without microbleeds in the basal ganglia or brainstem (not shown), meeting criteria for probable cerebral amyloid angiopathy. In panel B, there is a left thalamic hematoma (arrowhead) with microbleeds in the basal ganglia (arrows). This pattern of nonlobar hemorrhages is not consistent with cerebral amyloid angiopathy, and instead is probably caused by hypertension. SWI: susceptibility-weighted imaging. Courtesy of Eric Smith, MD. Graphic 119376 Version 1.0 https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 54/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - 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/cerebral-amyloid-angiopathy/print 55/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - 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/cerebral-amyloid-angiopathy/print 56/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - 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/cerebral-amyloid-angiopathy/print 57/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate CAA-related perivascular inflammation (A) T2 weighted axial MR image shows periventricular white matter hyperintensity in a patient who presented with memory difficulties. (B) Gradient echo MR image from the same patient shows multiple low intensity foci (arrows) consistent with microhemorrhages, which are not seen on the T2 weighted image (A). The microhemorrhages are located peripherally, as opposed to hypertensive related hemorrhages that may occur centrally. (C) FLAIR MR image demonstrates patchy and confluent periventricular white matter hyperintensity. CAA: cerebral amyloid angiopathy; MR: magnetic resonance; FLAIR: fluid- attenuated inversion recovery. https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 58/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Courtesy of Eric D Schwartz, MD. Graphic 55227 Version 3.0 https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 59/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Criteria for the diagnosis of cerebral amyloid angiopathy-related inflammation (CAA-ri) Diagnosis Criteria Probable CAA-ri 1. Age 40 years 2. Presence of one or more of the following clinical features: headache, decrease in consciousness, behavioral change, or focal neurological signs and seizures; the presentation is not directly attributable to an acute ICH 3. MRI shows unifocal or multifocal WMH lesions (corticosubcortical or deep) that are asymmetric and extend to the immediately subcortical white matter; the asymmetry is not due to past ICH 4. Presence of one or more of the following corticosubcortical hemorrhagic lesions: cerebral macrobleed, cerebral microbleed, or cortical superficial siderosis [1] 5. Absence of neoplastic, infectious, or other cause Possible CAA-ri 1. Age 40 years 2. Presence of one or more of the following clinical features: headache, decrease in consciousness, behavioral change, or focal neurological signs and seizures; the presentation is not directly attributable to an acute ICH 3. MRI shows WMH lesions that extend to the immediately subcortical white matter 4. Presence of one or more of the following corticosubcortical hemorrhagic lesions: cerebral macrobleed, cerebral microbleed, or cortical superficial siderosis [1] 5. Absence of neoplastic, infectious, or other cause CAA-ri: cerebral amyloid angiopathy-related inflammation; ICH: intracerebral hemorrhage; MRI: magnetic resonance imaging; WMH: white matter hyperintensity. Reference: 1. Charidimou A, Linn J, Vernooij MW, et al. Cortical super cial siderosis: detection and clinical signi cance in cerebral amyloid angiopathy and related conditions. Brain 2015; 138:2126. Reproduced with permission from: Auriel E, Charidimou A, Gurol ME, et al. Validation of clinicoradiological criteria for the diagnosis of cerebral amyloid angiopathy-related in ammation. JAMA Neurol 2016; 73(2):197-202. Copyright 2016 American Medical Association. All rights reserved. Graphic 118977 Version 10.0 https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 60/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Contributor Disclosures Steven M Greenberg, MD, PhD 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. Richard P Goddeau, Jr, DO, FAHA 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/cerebral-amyloid-angiopathy/print 61/61