Histopathology of diffusion-weighted imaging-positive lesions in cerebral amyloid angiopathy

Telgte, Annemieke ter; Scherlek, Ashley A; Reijmer, Yaël D.; Kouwe, André J van der; Harten, Thijs van; Duering, Marco; Bacskai, Brian J.; Leeuw, Frank‐Erik de; Frosch, Matthew P.; Greenberg, Steven M.; Veluw, Susanne J. van

doi:10.1007/s00401-020-02140-y

Cited by 23 publications

(27 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AIS as the primary manifestation of CAA is likely to be underdiagnosed since DWI lesions in CAA patients are often discussed as an epiphenomenon of CAA. Yet, a former study revealed that 130 DWI and T2* lesions examined histopathologically were in 100% acute microinfarcts [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Index event of cerebral amyloid angiopathy (CAA) determines long-term prognosis and recurrent events (retrospective analysis and clinical follow-up)

Wagner

Groetsch

Wilfling

et al. 2021

Neurol. Res. Pract.

View full text Add to dashboard Cite

Background The modified Boston criteria (mBC) define the probability for the diagnosis of cerebral amyloid angiopathy (CAA). Its initial clinical presentation differs from asymptomatic cerebral microbleedings (cMBs), acute ischemic stroke (AIS), cortical hemosiderosis (cSS), to lobar ICH (lICH). Methods Retrospective analyses and clinical follow-ups of individuals with at least mBC “possible” CAA from 2005 to 2018. Results 149 patients were classified in subgroups due to the index event: lICH (n = 91), AIS (n = 32), > 3 cMBs only (n = 16) and cSS (n = 10). Patients in the lICH subgroup had a significantly higher percentage of single new lICHs compared to other groups, whereas patients in the AIS-group had a significantly higher percentage of multiple new AIS. cMBs as index event predisposed for AIS during follow up (p < 0.0016). Patients of the cMBs- or cSS-group showed significantly more TFNEs (transient focal-neurological episodes) and lower numbers of asymptomatic patients (for epilepsy and TFNEs) at the index event than patients with lICH or AIS (p < 0.0013). At long-term follow-up, the cMBs- and cSS-group were characterized by more TFNEs and fewer asymptomatic patients. Conclusions A new classification system of CAA should add subgroups according to the initial clinical presentation to the mBCs allowing individual prognosis, acute treatment and secondary prophylaxis.

show abstract

Section: Discussionmentioning

confidence: 99%

Index event of cerebral amyloid angiopathy (CAA) determines long-term prognosis and recurrent events (retrospective analysis and clinical follow-up)

Wagner

Groetsch

Wilfling

et al. 2021

Neurol. Res. Pract.

View full text Add to dashboard Cite

show abstract

“…Cerebral microinfarcts manifest as small ovoid or round high intensity areas in the subcortex and cortex on diffusion-weighted MRI [ 38 ]. Analyses of autopsied brains with CAA cases have identified diffusion-weighted imaging-positive lesions that represent acute infarcts [ 39 ].…”

Section: Diagnosis Of Caa: Markers Characteristic Features and Techniquesmentioning

confidence: 99%

Current Management and Therapeutic Strategies for Cerebral Amyloid Angiopathy

Inoue

Ando

Misumi

et al. 2021

IJMS

View full text Add to dashboard Cite

Cerebral amyloid angiopathy (CAA) is characterized by accumulation of amyloid β (Aβ) in walls of leptomeningeal vessels and cortical capillaries in the brain. The loss of integrity of these vessels caused by cerebrovascular Aβ deposits results in fragile vessels and lobar intracerebral hemorrhages. CAA also manifests with progressive cognitive impairment or transient focal neurological symptoms. Although development of therapeutics for CAA is urgently needed, the pathogenesis of CAA remains to be fully elucidated. In this review, we summarize the epidemiology, pathology, clinical and radiological features, and perspectives for future research directions in CAA therapeutics. Recent advances in mass spectrometric methodology combined with vascular isolation techniques have aided understanding of the cerebrovascular proteome. In this paper, we describe several potential key CAA-associated molecules that have been identified by proteomic analyses (apolipoprotein E, clusterin, SRPX1 (sushi repeat-containing protein X-linked 1), TIMP3 (tissue inhibitor of metalloproteinases 3), and HTRA1 (HtrA serine peptidase 1)), and their pivotal roles in Aβ cytotoxicity, Aβ fibril formation, and vessel wall remodeling. Understanding the interactions between cerebrovascular Aβ deposits and molecules that accumulate with Aβ may lead to discovery of effective CAA therapeutics and to the identification of biomarkers for early diagnosis.

show abstract

“…The development of magnetic resonance imaging (MRI) technology has provided the most potent approach to understanding the etiology of hemorrhage. Diffusion-weighted imaging (DWI) hyperintensities distant from the hematoma were considered to be acute ischemic lesions, [1][2][3][4][5] which were identified in 11-41% of patients with acute ICH. 2,4,[6][7][8] They further aggravated brain injury.…”

Section: Introductionmentioning

confidence: 99%

Ischemia in intracerebral hemorrhage: A comparative study of small‐vessel and large‐vessel diseases

Zhang

Ren

Deng

et al. 2022

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Objective: This study aimed to compare effects of cerebral small-vessel disease (cSVD) burden and cerebral artery stenosis (CAS) on acute ischemia in intracerebral hemorrhage (ICH) and their interaction with mean arterial pressure (MAP) change. Methods: We recruited consecutive patients with acute primary ICH. Brain magnetic resonance imaging and angiography were performed to quantify diffusion-weighted imaging (DWI) lesions, CAS, and cSVD markers, which were calculated for the total cSVD score. Multivariable regression models were adopted to explore their associations by DWI lesions size (<15 vs. ≥15 mm) and median MAP change stratification. Results: Of 305 included patients (mean age 59.5 years, 67.9% males), 77 (25.2%) had DWI lesions (small, 79.2%; large, 20.8%) and 67 (22.0%) had moderate and severe CAS. In multivariable analysis, small DWI lesions were independently associated with higher total cSVD score (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.36-2.41). and large DWI lesions were associated with more severe CAS (OR 2.51, 95% CI 1.17-5.38). This association was modified by MAP change (interaction p = 0.016), with stratified analysis showing an increased risk of large DWI lesions in severe CAS with greater MAP change (≥44 mmHg) (OR 3.48, 95% CI 1.13-10.74) but not with mild MAP change (<44 mmHg) (OR 1.21,. Interpretation: Total cSVD burden is associated with small DWI lesions, whereas the degree of CAS is associated with large DWI lesions, specifically with greater MAP change, suggesting that large-artery atherosclerosis may be involved in ischemic brain injury, which is different from small-vessel pathogenesis in ICH.

show abstract

Histopathology of diffusion-weighted imaging-positive lesions in cerebral amyloid angiopathy

Cited by 23 publications

References 40 publications

Index event of cerebral amyloid angiopathy (CAA) determines long-term prognosis and recurrent events (retrospective analysis and clinical follow-up)

Index event of cerebral amyloid angiopathy (CAA) determines long-term prognosis and recurrent events (retrospective analysis and clinical follow-up)

Current Management and Therapeutic Strategies for Cerebral Amyloid Angiopathy

Ischemia in intracerebral hemorrhage: A comparative study of small‐vessel and large‐vessel diseases

Contact Info

Product

Resources

About