White matter hyperintensity patterns in cerebral amyloid angiopathy and hypertensive arteriopathy

Charidimou, Andreas; Boulouis, Grégoire; Haley, Kellen; Auriel, Eitan; Etten, Ellis S. van; Fotiadis, Panagiotis; Reijmer, Yaël D.; Ayres, Alison; Vashkevich, Anastasia; DiPucchio, Zora; Schwab, Kristin; Martínez-Ramírez, Sergi; Rosand, Jonathan; Viswanathan, Anand; Greenberg, Steven M.; Gurol, M. Edip

doi:10.1212/wnl.0000000000002362

Cited by 173 publications

(209 citation statements)

References 32 publications

Supporting

Mentioning

202

Contrasting

Unclassified

Order By: Relevance

“…Patients with CAA had higher CMB counts, as in previous studies (p , 0.001). 6,23 No adverse event from any of the study procedures was observed in any participant.…”

Section: Resultsmentioning

confidence: 93%

“…19,20 In our largest analyzed series of consecutive primary ICH patients who had MRI (n 5 526), patients with uncertain diagnoses were common (isolated lobar ICH, n 5 122, 23.2%; mixed location or cerebellar ICH, n 5 76, 14.5%) relative to the more definite diagnostic categories (probable CAA, n 5 191, 36.3%; HTN-ICH, n 5 137, 26%). 6 Older patients with multiple lobar microbleeds without ICH (lobar microbleed-only patients) show clinical, radiologic, and risk factor profiles of CAA, 26 but low microbleed counts on MRI are associated with a decreased probability of confirming CAA on autopsy. 34 These data suggest that for more than one third of primary ICH patients and for lobar microbleed-only patients with low microbleed burden, adjunctive diagnostic methods are needed for establishing the diagnosis of CAA.…”

Section: Resultsmentioning

confidence: 99%

“…6,23 The CAA and HTN-ICH cohorts were well-matched in terms of age, sex, and WMH volumes. Our study also has notable limitations.…”

Section: Resultsmentioning

confidence: 99%

“…4,5 The diagnosis of CAA cannot currently be made safely or ruled out by clinically available imaging methods in more than one-third of primary ICHs. 6 One of the exciting advances in CAA research has been the demonstration of the ability of Pittsburgh compound B (PiB), originally designed to detect plaque amyloid in Alzheimer disease (AD), to label vascular amyloid as well. [7][8][9][10] This PET tracer was shown to bind vascular amyloid by radiologic-pathologic correlation in both the common sporadic form of CAA and Iowa-type hereditary CAA, a form of the disorder with little or no plaque deposits of fibrillar Ab.…”

Section: Classification Of Evidencementioning

confidence: 99%

See 3 more Smart Citations

Florbetapir-PET to diagnose cerebral amyloid angiopathy

et al. 2016

Self Cite

View full text Add to dashboard Cite

Objective: We hypothesized that florbetapir, a Food and Drug Administration-approved PET tracer, could distinguish cerebral amyloid angiopathy (CAA)-related intracerebral hemorrhage (ICH) from hypertensive ICH (HTN-ICH). Methods:We prospectively enrolled survivors of primary ICH related to probable CAA (per Boston Criteria, n 5 10) and HTN-ICH (n 5 9) without dementia. All patients underwent florbetapir-PET and multimodal MRI, and patients with CAA had additional Pittsburgh compound B (PiB) PET. Amyloid burden was assessed quantitatively (standard uptake value ratio [SUVR]) and visually classified as positive or negative. Results:The CAA and HTN-ICH groups had similar age (66.9 vs 67.1), sex, and leukoaraiosis volumes (31 vs 30 mL, all p . 0.8). Florbetapir uptake and PiB retention strongly correlated in patients with CAA both globally within cerebral cortex (r 5 0.96, p , 0.001) and regionally in lobar cortices (all r . 0.8, all p # 0.01). Mean global cortical florbetapir uptake was substantially higher in CAA than HTN-ICH (SUVR: 1.41 6 0.17 vs 1.15 6 0.08, p 5 0.001), as was mean occipital SUVR (1.44 6 0.12 vs 1.17 6 0.08, p , 0.001), even after correcting for global SUVR (p 5 0.03). Visual rating for positive/negative florbetapir demonstrated perfect interrater agreement (k 5 1) and was positive for all 10 patients with CAA vs 1 of 9 HTN-ICH patients (sensitivity 100%, specificity 89%).Conclusions: Florbetapir appears to label vascular amyloid in patients with CAA-related ICH. The approved florbetapir binary visual reading method can have diagnostic value in appropriate clinical settings. Classification of evidence:This study provides Class II evidence that florbetapir-PET provides a sensitivity of 100% (95% confidence interval [CI] 66%-100%) and specificity of 89% (95% CI 51%-99%) for determination of probable CAA among cognitively normal patients. Cerebral amyloid angiopathy (CAA), characterized by accumulation of b-amyloid (Ab) proteins in the walls of cortical/leptomeningeal vessels, is a common cause of vessel wall breakdown and vascular dysfunction in older adults, making it a major contributor to fatal or disabling intracerebral hemorrhages (ICH) as well as ischemic injury and dementia. 1,2 There currently is no specific treatment for CAA, in part because of our inability to identify this condition at early phases prior to appearance of multiple hemorrhagic brain lesions. 3 Accurate early diagnosis of CAA also has direct implications for stroke prevention, as this pathology is an important cause of anticoagulant-associated ICH and might dictate use of alternative nonpharmaceutical approaches such as left atrial appendage closure for patients with nonvalvular atrial fibrillation. 4,5

show abstract

“…Patients with CAA had higher CMB counts, as in previous studies (p , 0.001). 6,23 No adverse event from any of the study procedures was observed in any participant.…”

Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

“…6,23 The CAA and HTN-ICH cohorts were well-matched in terms of age, sex, and WMH volumes. Our study also has notable limitations.…”

Section: Resultsmentioning

confidence: 99%

Section: Classification Of Evidencementioning

confidence: 99%

See 2 more Smart Citations

Florbetapir-PET to diagnose cerebral amyloid angiopathy

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Brain MRI before LAA may be helpful for selecting patients at higher risk of further bleeding after brain hemorrhage [14] as the presence of cerebral CMBs and severe LA are recognized as markers of bleeding risk [16][17][18].…”

Section: Discussionmentioning

confidence: 99%

Magnetic resonance imaging in patients with atrial fibrillation before left atrial appendage closure after brain hemorrhage

Benoit¹,

Rioufol²,

Ong³

et al. 2017

Interventional-Cardiology

View full text Add to dashboard Cite

Association Between Immunosuppressive Treatment and Outcomes of Cerebral Amyloid Angiopathy–Related Inflammation

et al. 2020

Self Cite

View full text Add to dashboard Cite

IMPORTANCE Cerebral amyloid angiopathy-related inflammation (CAA-ri), a distinct subtype of cerebral amyloid angiopathy, is characterized by an autoimmune reaction to cerebrovascular β-amyloid deposits. Outcomes and response to immunosuppressive therapy for CAA-ri are poorly understood. OBJECTIVE To identify clinical, neuroimaging, laboratory, pathologic, or treatment-related associations with outcomes after an episode of CAA-ri. DESIGN, SETTING, AND PARTICIPANTSA retrospective cohort study of prospectively identified individuals who presented from July 3, 1998, to November 27, 2017, with a median follow-up of 2.7 years (interquartile range, 1.0-5.5 years). The study included 48 consecutive patients with CAA-ri meeting diagnostic criteria who had at least 1 disease episode and subsequent outcome data. No patients refused or were excluded.EXPOSURES Prespecified candidate variables were immunosuppressive therapies, cerebrospinal fluid pleocytosis, magnetic resonance imaging findings of recent infarcts or contrast enhancement, and histopathologic evidence of vessel wall inflammation.MAIN OUTCOMES AND MEASURES Clinical improvement and worsening were defined by persistent changes in signs or symptoms, radiographic improvement by decreased subcortical foci of T2 hyperintensity or T1 enhancement, and radiographic worsening by increased subcortical T2 hyperintensity, T1 enhancement, or infarcts. Disease recurrence was defined as new-onset clinical symptoms associated with new imaging findings. RESULTSThe 48 individuals in the study included 29 women and had a mean (SD) age of 68.9 (9.9) years. Results of presenting magnetic resonance imaging revealed that 10 of 29 patients with CAA-ri (34%) had T1 contrast enhancement, 30 of 32 (94%) had subcortical T2 hyperintensity (22 of 30 [73%] asymmetric), 7 of 32 (22%) had acute or subacute punctate infarcts, and 27 of 31 (87%) had microbleeds. Immunosuppressive treatments after first episodes included corticosteroids (33 [69%]), cyclophosphamide (6 [13%]), and mycophenolate (2 [4%]); 14 patients (29%) received no treatment. Clinical improvement and radiographic improvement were each more likely in individuals treated with an immunosuppressive agent than with no treatment (clinical improvement: 32 of 34 [94%] vs 7 of 14 [50%]; odds ratio, 16.0; 95% CI, 2.72-94.1; radiographic improvement: 24 of 28 [86%] vs 4 of 14 [29%]; odds ratio, 15.0; 95% CI, 3.12-72.1). Recurrence was less likely if CAA-ri was treated with any immunosuppressant agent than not (9 of 34 [26%] vs 10 of 14 [71%]; hazard ratio, 0.19; 95% CI, 0.07-0.48). When controlling for treatment, no variables were associated with outcomes aside from an association between APOE ε4 and radiographic improvement (odds ratio, 4.49; 95% CI, 1.11-18.2). CONCLUSIONS AND RELEVANCEThese results from a relatively large series of patients with CAA-ri support the effectiveness of immunosuppressive treatment and suggest that early treatment may both improve the initial disease course and reduce the likelihood of recurrence. These results r...

show abstract

White matter hyperintensity patterns in cerebral amyloid angiopathy and hypertensive arteriopathy

Abstract: Different patterns of subcortical leukoaraiosis visually identified on MRI might provide insights into the dominant underlying microangiopathy type as well as mechanisms of tissue injury in patients with ICH.

Cited by 173 publications

References 32 publications

Florbetapir-PET to diagnose cerebral amyloid angiopathy

Florbetapir-PET to diagnose cerebral amyloid angiopathy

Magnetic resonance imaging in patients with atrial fibrillation before left atrial appendage closure after brain hemorrhage

Association Between Immunosuppressive Treatment and Outcomes of Cerebral Amyloid Angiopathy–Related Inflammation

Contact Info

Product

Resources

About