(older age and somewhat larger hematoma size) [89-91]. Mortality Overall mortality in acute lobar hemorrhage due to CAA is in the range of 10 to 30 percent [90,91], with the best prognosis for patients with smaller hematomas (<50 mL) and higher level of consciousness on admission (Glasgow coma scale 8). Recurrence CAA carries a substantially higher risk of hemorrhage recurrence than for hypertensive hemorrhage. In two case series of ICH survivors, recurrence rates were 21 percent at 2 years and 24 percent at a median 2.6 years, respectively [34,92]. Another report of 104 survivors of primary lobar ICH found that patients with history of ICH prior to the index event were at approximately six times the risk as those without a previous history. The risk for recurrent ICH was even higher in those who had more than one prior ICH [75]. https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 12/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Recurrent hemorrhages have a tendency to arise in areas of prior hemorrhage [44]. Areas of high amyloid deposition on amyloid imaging appear to predict sites for future hemorrhage [68]. Recurrent ICH is more likely with increasing number of CMBs and disseminated cSS (see 'Incidental chronic imaging features' below). In a study of 94 consecutive survivors of primary lobar hemorrhage, the three-year cumulative risk of recurrent hemorrhage for patients with one, two, three to five, and six or greater CMBs on the baseline gradient-echo MRI was 14, 17, 38, and 51 percent, respectively (hazard ratio 1.7, 95% CI 1.2-2.4 for each increase in category) [93]. In a study of 118 patients diagnosed with CAA (104 with a symptomatic lobar ICH), the cumulative risk of new ICH at four years was 74 percent for the 27 individuals with disseminated cSS (defined as involving more than three cortical sulci) versus only 25 percent for the 77 without siderosis at baseline [94]. Similarly, the presence of cSAH in patients with CAA is associated with an increased risk of recurrent ICH [95]. Carriers of the e2 or e4 APOE alleles are also at increased risk compared with the more common APOE e3/e3 genotype [34]. (See 'Genetic susceptibilities' above.) Incident dementia The association of subsequent dementia in patients with lobar ICH may reflect an elevated rate of ICH recurrence and/or the relationship of CAA with cognitive impairment. In a study of 255 patients with lobar and nonlobar ICH followed for five years, patients with lobar ICH had higher rates of dementia (36 versus 21 percent) and higher rates of disability (60 versus 31 percent) compared with those with nonlobar ICH [96]. This finding is consistent with a prior study of 218 ICH survivors with one-year incidence of new- onset dementia of 23.4 percent for lobar ICH versus 9.2 percent for nonlobar ICH [97]. In another cohort of 97 patients with lobar ICH, the rate of dementia after median 2.5-year follow-up was 26 percent [98]. (See 'Cognitive impairment' below.) INCIDENTAL CHRONIC IMAGING FEATURES Patients with CAA are frequently asymptomatic unless they develop a specific clinical episode. Evidence suggestive of CAA may be identified in asymptomatic patients who undergo brain MRI for unrelated symptoms (eg, chronic headaches). Microbleeds Chronic evidence of tiny asymptomatic bleeding within the brain can be detected on brain MRI and may reflect CAA. These microbleeds (or microhemorrhages) appear as 2 to 10 mm focal areas of hemosiderin deposition on gradient echo or other T2*-weighted https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 13/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate sequences ( image 7). In population-based studies, cerebral microbleeds are detected in 5 to 23 percent of older individuals [99-102]. Microbleeds can arise from small-vessel disease (CAA or hypertensive vasculopathy) and may represent a milder and somewhat distinct manifestation from overt (macro-)hemorrhage. Analysis of CAA patients in a neuroimaging study who underwent autopsy showed those with a large number of microbleeds had thicker-walled vessels due to beta-amyloid deposition compared with patients with a lower proportion or absence of microbleeds [103]. Microbleeds are also more prevalent among those using antiplatelet agents than nonusers [104,105]. Evaluation and differential diagnosis Focal areas of hemosiderin deposition on MRI should be reviewed with some care since lesions and structures other than hemorrhage can produce signal dropout. These include mineralization (particularly of the basal ganglia), flow-void from a cortical vessel, or adjacent air in the nasal sinuses. When establishing the presence of at least two hemorrhages, lesions that do not clearly represent independent hemorrhagic foci (for example, small blood deposits close to a larger hematoma) should not be counted. Cerebral microbleeds are not specific for CAA as they can be seen in multiple conditions. Such conditions may include: Hypertension [106,107] Cerebral cavernous malformations [108] Coagulopathy [109,110] Thrombocytopenia [111,112] Anticoagulant medications [113] Central nervous system vasculitis [114] Infective endocarditis [115] End-stage kidney failure [116] Traumatic brain injury [117] Prior cardiac surgery [118] While microbleeds in general are not specific to CAA, cortical microbleeds (CMBs; (ie, those restricted to the cerebral cortex or superficial cerebellar regions [cerebellar cortex and vermis]), suggest CAA [106,107]. In contrast, microbleeds that involve the basal ganglia, thalamus, or pons are believed to result from hypertensive microangiopathy. The association between lobar microbleeds and APOE e4 in the Rotterdam and other studies support the hypothesis that these more superficial lesions often originate from CAA [30,101,102,119,120]. https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 14/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Management and prognosis For patients with acute ischemic stroke and a known history of CAA with CMBs only (ie, without a history of lobar hemorrhage or cortical superficial siderosis), we do not withhold systemic intravenous thrombolytic therapy if they otherwise meet eligibility criteria ( table 4), in agreement with guideline statements from the American Heart Association [80]. Over the long-term, the risk of incident hemorrhage in patients with multiple CMBs is nonetheless substantial [121]. Thus, other measures for primary prevention are similar as for patients with an ICH presentation. (See 'Prevention of recurrent hemorrhage' above.) CMBs are associated with an elevated risk of death. One study found that an incidental finding of multiple CMBs in an older adult was associated with a sevenfold risk of stroke- related death compared to individuals without CMBs [122]. Cortical superficial siderosis Evidence of chronic bleeding at the surface of the brain seen on imaging as foci of cSS may be seen in patients with CAA. They likely reflect the chronic form of acute convexity subarachnoid hemorrhage ( image 6) [54,123,124]. cSS is typical at the convexities of the cerebral hemispheres in patients with CAA but may also be found along the cerebellar folia [51]. cSS is frequently found in CAA patients with microbleeds and appears to signal higher risk for future ICH, particularly disseminated cSS. (See 'Microbleeds' above and 'Prognosis' above.) cSS typically is an asymptomatic imaging finding but is also detected in many CAA patients who present with transient neurologic symptoms [124,125]. (See 'Transient focal neurologic episodes' below.) Evaluation and differential diagnosis cSS is common in patients with CAA (40 to 60 percent) but is unusual in patients with ICH of other cause (0 to 4 percent) [54,125]. However, cSS and superficial siderosis involving the cerebellum or brainstem can also arise from several other unrelated causes. These are discussed separately. (See "Superficial siderosis", section on 'Etiology'.) Patients with isolated hemorrhagic imaging findings such as a single CMB or equivocal focus of cSS may develop progressive subclinical findings to further support the diagnosis of CAA. As an example, in one cohort of 118 patients with probable CAA who underwent follow-up imaging at a mean interval of 2.2 years, progression of cSS was found in 28 percent and new CMBs were found in 18 percent [126]. Management and prognosis For patients with acute ischemic stroke and a known history of CAA with cSS, we do not routinely offer systemic thrombolytic therapy. cSS https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 15/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate represents an imaging marker of prior ICH, a contraindication for intravenous thrombolysis ( table 4). Endovascular mechanical thrombectomy may be an option for such patients when treatment benefits are felt to outweigh the hemorrhagic risks. For patients with cSS and a history of ischemic stroke, we individualize the use of antithrombotic therapy based on overall risks and benefits. Retrospective data on such patients who resume antiplatelets or anticoagulants have shown a higher subsequent risk of recurrent ischemic stroke than hemorrhage, suggesting that use of antithrombotics may be considered [127]. The approach to primary stroke prevention in patients with cSS is similar as that for patients with a prior ICH presentation. (See 'Prevention of recurrent hemorrhage' above.) cSS is associated with poor functional outcome in CAA [128]. Disseminated cSS in CAA appears to be an independent predictor of recurrent ICH [94,129], and radiologic progression of cSS on serial imaging has been associated with an increased risk of subsequent ICH [126]. cSS has also associated with an elevated risk of epilepsy in patients with CAA [130]. Nonhemorrhagic imaging findings Nonhemorrhagic findings on brain MRI may also be found in patients with CAA [56]. Acute ischemic micro-infarcts Asymptomatic punctate hyperintense lesions on diffusion-weighted image (DWI) sequencing are occasionally found in patients with CAA [131]. In one retrospective review of brain MRIs from 78 patients with probable CAA, subacute infarcts were identified on DWI in 15 percent [132]. Brain atrophy Cerebral atrophy of white matter is associated with CAA. In one study, white matter volume was lower in patients with CAA than age-matched patients with Alzheimer disease and healthy controls [133]. In CAA patients, atrophy was most pronounced in occipital regions and was more severe in those with higher cortical microbleeds. White matter hyperintensities Chronic white matter hyperintensities on T2-weighted sequences of brain MRI frequently represent small-vessel disease related to multiple conditions. Imaging patterns suggestive of CAA include the "multispot" pattern of multiple (ie, >10), typically bilateral lesions with a round or ovoid appearance [134]. In more advanced cases, white matter hyperintensities may be confluent. Such prominent findings may be seen preferentially in the subcortical parietal and occipital lobes of patients with advanced CAA [135]. https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 16/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Centrum semiovale perivascular spaces Dilated perivascular spaces are identified typically on brain MRI as hyperintense lesions on T2-weighted sequences. They have been associated with vascular disease and aging, but the presence of multiple (>20) dilated perivascular spaces in the subcortical centrum semiovale regions has been associated with CAA with and without ICH [56,129,136-138]. TRANSIENT FOCAL NEUROLOGIC EPISODES A less common clinical manifestation of CAA is transient focal neurologic episodes (TFNE) [139- 141]. These have also been called "amyloid spells." Pathogenesis and clinical features Patients report recurrent, brief, and often stereotyped spells of weakness, numbness, paresthesias, or other cortical symptoms that can spread smoothly over contiguous body parts over several minutes. In one cohort, transient neurologic symptoms occurred in 14 percent of patients with CAA, and positive symptoms (positive visual aura, limb jerking) were as common as negative symptoms (vision loss, limb weakness, dysphasia) [142]. These episodes may reflect abnormal activity (ie, cortical spreading depression) of the surrounding cortex typically in response to the small hemorrhages [143]. In one study, CAA patients with cortical superficial siderosis (cSS) or convexity subarachnoid hemorrhage (cSAH) were more likely to have transient neurologic symptoms compared with CAA patients without these symptoms (50 versus 19 percent) [142]. Evaluation and diagnosis The description of TFNEs can be similar to other transient neurologic attacks such as transient ischemic attacks (TIAs), seizures, and migraine auras. Clinical features more suggestive of TFNE over other diagnoses include the smooth spread of the symptoms over minutes and the stereotypic recurrence of symptoms over time. Symptoms of TFNE tend to localize to the site of a cSAH, prior lobar hemorrhage, or focus of cSS [144]. (See 'Incidental chronic imaging features' above.) Additionally, diagnostic evaluation at the time of acute symptoms can support the diagnosis of TFNE and exclude alternative causes. This may include: Brain MRI with gradient echo or other T2*-weighted sequences to identify cSAH, cSS, or cortical microbleeds (CMBs) in the region of cortex corresponding to TFNE symptoms Vascular imaging to exclude hemodynamically significant stenosis in the relevant vascular supply https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 17/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Electroencephalogram showing no epileptiform activity or seizure in the brain region corresponding to TFNE symptoms Additional testing may be performed to exclude TIA or ischemic stroke if indicated by clinical features or patient risk profile. (See "Differential diagnosis of transient ischemic attack and acute stroke" and "Initial evaluation and management of transient ischemic attack and minor ischemic stroke".) Features that support an alternative diagnosis include: TIAs may present in a patient with vascular risk factors as sudden loss of focal neurologic function attributable to a specific cerebrovascular arterial territory. Seizures may occur in a patient with a history of epilepsy or seizures as focal or diffuse symptoms. They may be associated with temporary postictal weakness or other loss of function. Migraines typically occur in younger patients with a prior history of migraines. Neurologic symptoms typifying the aura may wax over minutes prior to the onset of a headache. The differential diagnosis and evaluation of patients with transient neurologic episodes is discussed in greater detail separately. (See "Differential diagnosis of transient ischemic attack and acute stroke", section on 'Transient neurologic events' and "Differential diagnosis of transient ischemic attack and acute stroke", section on 'Distinguishing transient attacks'.) Management Avoiding misdiagnosis is critical since the administration of antithrombotics for TFNE symptoms presumed to be a TIA may increase the risk of hemorrhagic stroke from CAA [144]. In one series, transient neurologic symptoms in a patient with CAA appeared to predict a high early risk of symptomatic intracerebral hemorrhage, which occurred in 50 percent of patients over a median follow-up period of 14 months [142]. TFNE are typically brief and self-limited but may recur. Patients should be reassured that TFNE that recur typically resolve within weeks [143]. Medications used for seizures or migraine such as topiramate or levetiracetam have been used for those with recurrent or bothersome attacks [143,145]. Other general measures, applicable to patients with hemorrhagic features of CAA, are discussed separately. (See 'Prevention of recurrent hemorrhage' above.) CEREBRAL AMYLOID ANGIOPATHY-RELATED INFLAMMATION https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 18/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Cerebral amyloid angiopathy-related inflammation (CAA-ri) appears to represent a distinct manifestation of CAA characterized by an inflammatory response to amyloid deposition in the brain with subacute and often progressive neurologic symptoms [146,147]. CAA-ri may be a milder form of a condition called Abeta-related angiitis. CAA-ri is characterized by perivascular inflammation, while Abeta-related angiitis is a true vasculitis with inflammation throughout the vessel wall [148-150]. These two inflammatory syndromes share similar clinical presentations, imaging properties, and response to treatment, except that Abeta-related angiitis typically requires more aggressive immunosuppressive treatment. (See 'Management' below.) Clinical and diagnostic features The clinical presentation of a CAA-ri syndrome is that of acute or subacute cognitive decline rather than hemorrhage [151,152]. Patients or family members may report memory impairment, personality changes, confusion, or alterations in level of consciousness. Seizures, new and persistent headaches, and focal and progressive neurologic signs are common. Patients with CAA-ri are younger than those with other manifestations of CAA. In a systematic review of 21 studies that included 378 patients with CAA-ri, the mean age at diagnosis was 66 years [153]. Cognitive decline was reported in 70 percent, encephalopathy in 54 percent, focal neurologic symptoms in 55 percent, headaches in 31 percent, and seizures in 37 percent. The differential diagnosis includes primary, viral, and autoimmune encephalitides as well as cerebral neoplasm and other causes of rapidly progressive dementia [154-156]. (See "Primary angiitis of the central nervous system in adults", section on 'Diagnostic approach'.) Diagnostic studies in this setting typically include brain MRI with contrast, serologic, and cerebrospinal fluid (CSF) analysis. Brain biopsy may be performed both to make a positive diagnosis of CAA-related inflammation as well to exclude other conditions. Findings that support the diagnosis of CAA-ri include: Brain MRI typically shows a (potentially reversible) leukoencephalopathy consisting of patchy or confluent white matter hyperintensities on T2-weighted sequences, characteristically in subcortical white matter, often asymmetric; multiple microbleeds and/or cortical superficial siderosis are seen on gradient echo sequences ( image 8). Gadolinium enhancement may be found in up to half of cases [153,157]. Angiography or magnetic resonance angiography does not show evidence of large- or medium-vessel vasculitis. Neuropathology shows perivascular inflammation with multinucleated giant cells that is associated with amyloid-laden vessels. https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 19/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate Erythrocyte sedimentation rate and C-reactive protein are normal [152]. CSF analysis may be normal but often shows a pleocytosis and/or mildly elevated protein. Anti-amyloid autoantibodies have been detected in the CSF during the acute phase of inflammation and return to control levels during remission [158-160]. CSF assay for anti- amyloid antibodies is not yet commercially available but may eventually emerge as a diagnostic test. Clinical and radiographic improvement may occur with immunosuppressive treatment [146,147,152,161]. (See 'Management' below.) The diagnosis of CAA-ri is made in symptomatic patients with diagnostic imaging evidence of inflammation and hemorrhagic features of CAA who have undergone evaluation to exclude other sources ( table 5). A validation study of proposed criteria for the diagnosis of probable CAA-related inflammation showed high sensitivity (82 percent) and specificity (97 percent) [157]. Management We typically treat patients with suspected CAA-related inflammation with a course of high-dose glucocorticoids followed by a gradual oral taper. Our treatment protocol is usually methylprednisolone 1000 mg per day for three to five days, followed by an oral glucocorticoid taper over approximately 6 to 12 weeks. A repeat brain MRI scan approximately four to six weeks after treatment onset use clinical symptoms and changes in the subcortical white matter hyperintensities as evidence for treatment response. Although glucocorticoid therapy is most often used in this setting [160,162-164], other immunosuppressive treatments, such as cyclophosphamide, methotrexate, and mycophenolate mofetil, have also been used with a favorable response in isolated cases [152,165,166]. While data are limited, available evidence from observational studies supports treating inflammatory forms of CAA with immunosuppressive therapy [147,162-167]. In one series of 48 patients with CAA-related inflammation, those who were treated with immunosuppression (mostly glucocorticoids) were more likely to improve clinically (94 versus 50 percent) and radiographically (86 versus 29 percent) [167]. Treated patients were also less likely to have recurrent symptoms during a median of 2.7 years of follow-up (26 versus 71 percent). The response to therapy may be seen within the first few months and may be more durable when glucocorticoids are tapered slowly. In an observational study of 113 patients with CAA- related inflammation of whom 88 percent received immunosuppressive therapy, clinical recovery was reported by three months in 70 percent and resolution of inflammatory features on neuroimaging occurred in 45 percent [162]. By 12 months, the rates of clinical and radiologic recovery were 84 and 77 percent, respectively. Symptomatic recurrence was likelier in patients treated with high-dose pulse of intravenous glucocorticoids alone than those treated with pulse https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 20/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate intravenous glucocorticoids followed by a gradual oral glucocorticoid taper (hazard ratio 4.68, 95% CI 1.57 13.93). Additional measures to mitigate the associated risks of future bleeding associated with CAA should be based on the risks associated with hemorrhagic features. (See 'Prevention of recurrent hemorrhage' above.) COGNITIVE IMPAIRMENT Advanced CAA is associated with cognitive impairment. The majority of patients diagnosed with CAA appear to have cognitive impairment in at least one domain on neuropsychological testing [17]. An autopsy series found that moderate to severe CAA (present in one-third of the study population) was associated with faster rates of decline in global cognition, perceptual speed, episodic memory, and semantic memory, independently of age, sex, education, Alzheimer disease pathology, and other potential covariates [168]. Pathogenesis The pathogenesis of cognitive impairment in CAA may be multifactorial, with contributions from both vascular injury and Alzheimer disease pathology. Relationship to Alzheimer disease CAA is common in conjunction with Alzheimer disease, appearing in moderate to severe form in 30 of 117 (26 percent) Alzheimer disease brains in an autopsy series; CAA with hemorrhage occurred in six (5.1 percent) [5,169]. Another autopsy study found that patients with both CAA and Alzheimer disease had more severe cognitive impairment than patients with Alzheimer disease alone [170]. Similarly, an MRI study in Alzheimer disease patients found that the presence of multiple microbleeds was associated with worse cognitive performance [171]. However, only about 25 percent of CAA patients appear to have clinical histories of dementia prior to their first hemorrhage [89]. (See "Clinical features and diagnosis of Alzheimer disease".) Relationship to vascular dementia Cerebrovascular disease may contribute to cognitive impairment in patients with CAA. Studies in population- and hospital-based subjects have correlated the number and presence of microbleeds with cognitive impairment and dementia, raising the possibility that these lesions are contributors to neurologic dysfunction, as well as markers of small-vessel disease [172,173]. In one study of patients who underwent MRI because of transient ischemic attack or stroke, a finding of lobar microhemorrhage but not deep microhemorrhage was associated with cognitive impairment [174]. Additionally, clinically silent acute or subacute cerebral infarcts on diffusion-weighted imaging have been detected in 15 to 23 percent of patients with CAA [132,175], and cerebral https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 21/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate microinfarcts on T1 and fluid-attenuated inversion recovery (FLAIR) imaging have been found in 35 to 39 percent [176,177]. These data are consistent with autopsy and imaging studies showing an association between CAA severity and volume of white matter hyperintensity and/or microinfarct burden [139,178-182]. Cognitive impairment in CAA is also associated with ultrastructural white matter abnormalities measured by diffusion-tensor imaging-based methods [183,184]. Vascular dementia is discussed in more detail separately. (See "Etiology, clinical manifestations, and diagnosis of vascular dementia".) Evaluation and management The evaluation and management of patients with cognitive impairment in the setting of CAA does not differ from other settings. Supportive care is the mainstay for patients with cognitive impairment related to CAA, like that of patients with other forms of cognitive impairment and dementia. This is discussed in greater detail separately. (See "Management of the patient with dementia".) Other general measures, applicable to all patients with CAA, are discussed separately. (See 'Prevention of recurrent hemorrhage' above.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults".) SUMMARY AND RECOMMENDATIONS Definition Cerebral amyloid angiopathy (CAA) is characterized by amyloid beta-peptide deposits within small- to medium-sized blood vessels of the brain and leptomeninges. CAA is an important cause of lobar intracerebral hemorrhage in older adults. (See 'Introduction' above.) Diagnosis The diagnosis of probable CAA can be made with clinical evaluation and magnetic resonance imaging (MRI) of the brain ( table 2). Follow-up MRI examinations may be helpful if the initial study is equivocal. (See 'Diagnostic approach' above.) Acute intracerebral hemorrhage The most common clinical manifestation of CAA is acute lobar intracerebral hemorrhage (ICH) ( image 1). CAA-related lobar hemorrhages most commonly arise in posterior lobar brain regions. Because of their superficial location, CAA-related hemorrhages often extend beyond the brain tissue into the subarachnoid and https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 22/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate subdural spaces and less frequently rupture into ventricles. (See 'Acute intracerebral hemorrhage' above.) Because of the risk of spontaneous lobar hemorrhage in patients with CAA, we weigh the risks and benefits of using of anticoagulant and antiplatelet agents at an individual level. We reserve anticoagulation in CAA patients for those at high risk for thromboembolic complications related to specific indications. (See 'Managing anticoagulant and antiplatelet medications' above.) Incidental imaging features Chronic evidence of asymptomatic bleeding and other imaging findings can be detected on brain MRI in CAA patients with or without lobar hemorrhage. (See 'Incidental chronic imaging features' above.) Microbleeds (or microhemorrhages) appear as 2 to 10 mm focal areas of hemosiderin deposition on gradient echo or other T2*-weighted sequences ( image 7) and have an anatomic distribution similar to that of intracerebral hemorrhage, with a predilection for the cerebral cortex. Cortical superficial siderosis (cSS) can represent a focus of remote bleeding related to CAA ( image 6) and is thought to be the chronic form of acute convexity subarachnoid hemorrhage. Nonhemorrhagic imaging findings such as ischemic microinfarcts, cerebral atrophy, white matter hyperintensities, and multiple dilated perivascular spaces may also be found in patients with CAA. Transient focal neurologic episodes Patients with CAA may present with transient focal neurologic episodes (TFNE) described as recurrent, brief, and often stereotyped spells of weakness, numbness, paresthesias, or other cortical symptoms. Symptoms spread smoothly over contiguous body parts over several minutes and tend to localize to the site of a prior lobar hemorrhage or focus of cSS. (See 'Transient focal neurologic episodes' above.) Cerebral amyloid angiopathy-related inflammation Cerebral amyloid angiopathy- related inflammation (CAA-ri) is a distinct manifestation of CAA. Patients present with acute or subacute cognitive decline, seizures, new persistent headaches, or other progressive neurologic signs ( table 5); imaging demonstrates a patchy or confluent immediately subcortical leukoencephalopathy along with lobar microhemorrhages ( image 8). For patients with suspected CAA-ri, we suggest treatment with a course of immunosuppressive therapy, most often with glucocorticoids (Grade 2C). (See 'Cerebral https://www.uptodate.com/contents/cerebral-amyloid-angiopathy/print 23/61 7/5/23, 12:19 PM Cerebral amyloid angiopathy - UpToDate amyloid angiopathy-related inflammation' above.) 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