Cerebral Amyloid Angiopathy: Multiple neurolgic problems

A 72-Year-old female with a history of migraine headaches presented with an acute onset of expressive aphasia, difficulty with memory and worsening of her headaches. An MRI of the brain was done which revealed diffuse white matter T2 hyperintensities (Figures 1). Due to worsening of the patient’s clinical symptoms a repeat MRI was performed four days later that revealed multiple micro-bleeds (Figure 2), as well as a lobar hemorrhage in left temporal lobe (Figure 2). An extensive workup including HIV testing, CSF examination for infectious etiology including protein 14-3-3 and demylineating disease was negative. Paraneoplastic and autoimmune workup was also non-diagnostic. A brain biopsy was performed due to the extensive white matter disease, which revealed Cerebral Amyloid Angiopathy (CAA) with focal granulomatous angiitis. The patient was treated with intravenous steroids with no significant improvement clinically. Two months after diagnosis, her disease course has remained static, without improvement or deterioration.

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A case of inflammatory cerebral amyloid angiopathy with white matter lesions appearing after brain biopsy

Rinsho Shinkeigaku ◽

10.5692/clinicalneurol.cn-001534 ◽

2021 ◽

Vol 61 (3) ◽

pp. 188-193

Author(s):

Yosuke Takeuchi ◽

Shuei Murahashi ◽

Yasuyuki Hara ◽

Makoto Nakajima ◽

Mitsuharu Ueda

Keyword(s):

White Matter ◽

Cerebral Amyloid Angiopathy ◽

White Matter Lesions ◽

Brain Biopsy ◽

Amyloid Angiopathy ◽

Cerebral Amyloid

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Non-inflammatory cerebral amyloid angiopathy as a cause of rapidly progressive dementia: A case study

Dementia & Neuropsychologia ◽

10.1590/s1980-57642009dn30400015 ◽

2009 ◽

Vol 3 (4) ◽

pp. 352-357 ◽

Cited By ~ 1

Author(s):

Leonel Tadao Takada ◽

Paulo Camiz ◽

Lea T. Grinberg ◽

Claudia da Costa Leite

Keyword(s):

White Matter ◽

Cognitive Decline ◽

Cerebral Amyloid Angiopathy ◽

Brain Mri ◽

White Matter Lesions ◽

Brain Biopsy ◽

Amyloid Angiopathy ◽

Progressive Dementia ◽

Co Morbidity ◽

Cerebral Amyloid

Abstract A 77 year-old men developed a subacute-onset, rapidly progressive cognitive decline. After 6 months of evolution, he scored 6 on the Mini-Mental State Examination and had left hemiparesis and hemineglect. The patient died 11 months after the onset of cognitive symptoms. Brain MRI showed microhemorrhages on gradient-echo sequence and confluent areas of white matter hyperintensities on T2-weighted images. Brain biopsy revealed amyloid-b peptide deposition in vessel walls, some of them surrounded by micro-bleeds. In this case report, we discuss the role of cerebral amyloid angiopathy (CAA) in cognitive decline, due to structural lesions associated with hemorrhages and infarcts, white matter lesions and co-morbidity of Alzheimer's disease, as well as the most recently described amyloid angiopathy-related inflammation.

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Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x20944226 ◽

2020 ◽

pp. 0271678X2094422 ◽

Cited By ~ 1

Author(s):

Hedok Lee ◽

Feng Xu ◽

Xiaodan Liu ◽

Sunil Koundal ◽

Xiaoyue Zhu ◽

...

Keyword(s):

White Matter ◽

Cerebral Amyloid Angiopathy ◽

Rat Model ◽

Distinct Pattern ◽

Transgenic Rat ◽

Amyloid Angiopathy ◽

Diffuse White Matter ◽

Cerebral Amyloid ◽

Transgenic Rat Model

Diffuse white matter (WM) disease is highly prevalent in elderly with cerebral small vessel disease (cSVD). In humans, cSVD such as cerebral amyloid angiopathy (CAA) often coexists with Alzheimer’s disease imposing a significant impediment for characterizing their distinct effects on WM. Here we studied the burden of age-related CAA pathology on WM disease in a novel transgenic rat model of CAA type 1 (rTg-DI). A cohort of rTg-DI and wild-type rats was scanned longitudinally using MRI for characterization of morphometry, cerebral microbleeds (CMB) and WM integrity. In rTg-DI rats, a distinct pattern of WM loss was observed at 9 M and 11 M. MRI also revealed manifestation of small CMB in thalamus at 6 M, which preceded WM loss and progressively enlarged until the moribund disease stage. Histology revealed myelin loss in the corpus callosum and thalamic CMB in all rTg-DI rats, the latter of which manifested in close proximity to occluded and calcified microvessels. The quantitation of CAA load in rTg-DI rats revealed that the most extensive microvascular Aβ deposition occurred in the thalamus. For the first time using in vivo MRI, we show that CAA type 1 pathology alone is associated with a distinct pattern of WM loss.

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Abstract 9: Peak Width of Skeletonized Mean Diffusivity and Cognition in Cerebral Amyloid Angiopathy

Stroke ◽

10.1161/str.52.suppl_1.9 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Mitchell J Horn ◽

Elif Gokcal ◽

J. A Becker ◽

Alvin S Das ◽

Kristin Schwab ◽

...

Keyword(s):

White Matter ◽

Regression Model ◽

Cerebral Amyloid Angiopathy ◽

Mean Diffusivity ◽

Multiple Regression Model ◽

Amyloid Angiopathy ◽

Peak Width ◽

Symbol Substitution ◽

Relevant Variables ◽

Cerebral Amyloid

Background: We hypothesized that Peak Width of Skeletonized Mean Diffusivity (PSMD), an automated marker of cerebral microangiopathy representing microstructural disruption of white matter (WM), would be increased in patients with cerebral amyloid angiopathy (CAA) compared to healthy controls (HCs) and increased PSMD would be associated with lower processing speed scores (PSSs) in patients with CAA. Methods: Seventy-two nondemented probable CAA patients and 23 HCs prospectively underwent high-resolution brain MRIs and cognitive tests. PSMD scores were quantified from a probabilistic skeleton of the WM tracts as previously validated (http://www.psmd-marker.com). In subjects with intracerebral hemorrhage (ICH, n=27), ICH regions were masked and removed from the PSMD pipeline. The analyses were repeated in the non-ICH hemisphere. Raw scores of Trail Making Test-B and Symbol Substitution Test were transformed into standardized z -scores and averaged to obtain PSSs. Results: The mean age (p=0.366) and sex (p=0.811) were similar between CAA patients and HCs. PSMD was higher in the CAA group [(3.95±0.9) х 10 –4 mm 2 /s] compared to HCs [(3.32±0.6) х 10 –4 mm 2 /s] (p=0.003). This association remained significant in a linear regression model corrected for age and sex (β=0.700, 95%CI 0.3-1, p=0.001). Within the CAA cohort, higher PSMD was associated with higher WM hyperintensity volume in a multiple regression model adjusted for all relevant variables (β=0.890, 95%CI 0.7-1, p<0.001). In a regression model corrected for age, sex, years of education and presence of ICH, a lower PSS was independently associated with increased PSMD (β=-0.405, 95%CI {-0.6}-{-0.2}, p<0.001). These results did not change when the non-ICH hemisphere was used for PSMD processing. Conclusion: PSMD is increased in CAA and is associated with worse PSSs supporting the view that disruption of white matter has a significant role in cognitive impairment in CAA.

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Abstract 47: White Matter Atrophy in Cerebral Amyloid Angiopathy

Stroke ◽

10.1161/str.47.suppl_1.47 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Panagiotis Fotiadis ◽

Aaron Schultz ◽

Trey Hedden ◽

Sergi Martinez-Ramirez ◽

Yael Reijmer ◽

...

Keyword(s):

White Matter ◽

Cerebral Amyloid Angiopathy ◽

Cortical Thickness ◽

Tissue Loss ◽

White Matter Hyperintensity ◽

Aging Brain ◽

Amyloid Angiopathy ◽

Intracranial Volume ◽

White Matter Volume ◽

Cerebral Amyloid

Background/Purpose: Cerebral Amyloid Angiopathy (CAA) leads to leukoaraiosis, lacunar infarcts and cortical tissue loss. We hypothesized that CAA is also associated with white matter atrophy (WMA). Methods: We have compared volumetric multimodal MRIs from 72 prospectively enrolled non-demented patients with probable CAA (per Boston criteria), to 3 other well-studied cohorts: 289 Healthy Controls (HC) from the Harvard Aging Brain (HAB) study, 231 HC and 198 patients with AD from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Validated FreeSurfer algorithms were used to calculate White Matter Volume (WMV), white matter hyperintensity volume (WMHv), and cortical thickness. Microbleeds (MBs) were counted on SWI-MRI. Measures were obtained from the contralateral hemisphere if intracerebral hemorrhage present. All volumes were corrected for total intracranial volume (ICV), so reported as percent of ICV. Results: The CAA patients were significantly younger (mean age: 70.1) compared to both HC cohorts (ADNI-HC: 76.0, p<0.001, HAB-HC: 73.8, p < 0.001), and to patients with AD (75.5, p < 0.001). Despite being younger, patients with CAA presented significantly lower global WMV (28% ± 2.6) than both ADNI-HC (29.2% ± 2.2, p < 0.001), HAB-HC (29.0% ± 2.5, p = 0.001), and patients with AD (28.7% ± 2.2, p = 0.02) [Figure]. The association persisted after correcting for age, gender and WMHv. Within the CAA cohort, there was a negative correlation between WMV and lobar MB counts (rho = -0.26, p = 0.03), it remained significant after correcting for age, gender, WMHv (p=0.016). There were no significant associations however between WMV and neither WMHv, nor cortical thickness (both p>0.2). Conclusions: Patients with CAA show WMA when compared to older HC and AD. WMA independently correlates with MBs, a marker of CAA severity. Consistent spatial patterns of atrophy especially in posterior regions when compared to both HC and AD [Figure] might represent the “WMA signature of CAA”.

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White matter atrophy in cerebral amyloid angiopathy

Neurology ◽

10.1212/wnl.0000000000010017 ◽

2020 ◽

Vol 95 (5) ◽

pp. e554-e562 ◽

Cited By ~ 1

Author(s):

Panagiotis Fotiadis ◽

Yael D. Reijmer ◽

Susanne J. Van Veluw ◽

Sergi Martinez-Ramirez ◽

Fikret Isik Karahanoglu ◽

...

Keyword(s):

Executive Function ◽

White Matter ◽

Cerebral Amyloid Angiopathy ◽

Amyloid Angiopathy ◽

Intracranial Volume ◽

White Matter Volume ◽

Cognitive Changes ◽

Important Mediator ◽

Multivariable Analyses ◽

Cerebral Amyloid

ObjectiveWe postulated that cerebral amyloid angiopathy (CAA) is associated with white matter atrophy (WMA) and that WMA can be related to cognitive changes in CAA.MethodsWhite matter volume expressed as percent of intracranial volume (pWMV) of prospectively enrolled patients without dementia diagnosed with probable CAA was compared to age-matched healthy controls (HC) and patients with Alzheimer disease (AD). Cognitive scores were also sought to understand the potential effects of WMA on cognitive function.ResultsPatients with CAA (n = 72) had significantly lower pWMV (27.97% ± 2.63) when compared to age-matched HC (n = 72; mean difference [MD], 2.38%; p < 0.0001) and patients with AD (n = 72; MD, 1.57%; p < 0.0001). Differences were most pronounced in the posterior occipital regions in both comparisons. When comparisons were restricted to groups of patients with CAA but no intracerebral hemorrhage (n = 32) or hypertension (n = 32), and age-matched HC and AD, the significant differences were unaltered. Within the CAA cohort, higher age, lobar microbleed counts, and presence of hypertension were associated with lower pWMV (p = 0.0007, p = 0.031, and p = 0.003, respectively). All associations remained independent in multivariable analyses. Within the CAA cohort, higher pWMV independently correlated with better scores of executive function.ConclusionsPatients with CAA show WMA when compared to age-matched HC and patients with AD. WMA independently correlates with the number of lobar microbleeds, a marker of CAA severity. Consistent spatial patterns of WMA especially in posterior regions might be related to CAA. The association between WMA and measures of executive function suggests that WMA might represent an important mediator of CAA-related neurologic dysfunction.

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Abstract W MP89: Validation of Clinical-Radiological Criteria for the Diagnosis of Cerebral Amyloid Angiopathy-related Inflammation

Stroke ◽

10.1161/str.45.suppl_1.wmp89 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Eitan Auriel ◽

Mahmut Edip Gurol ◽

Jun Ni ◽

Ellis Van Etten ◽

Sergi Martinez-Remirez ◽

...

Keyword(s):

Sensitivity And Specificity ◽

Cerebral Amyloid Angiopathy ◽

Vascular Inflammation ◽

Brain Biopsy ◽

Control Group ◽

Amyloid Angiopathy ◽

Radiological Criteria ◽

Disease Subtype ◽

History Of ◽

Cerebral Amyloid

Introduction: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a disease subtype characterized by rapidly progressive cognitive decline, seizures, headaches, T2-hyperintense MRI lesions, and neuropathologic evidence of CAA-associated vascular inflammation. CAA-ri is an important diagnosis to reach in clinical practice, as many patients respond to immunosuppressive therapy. Definitive diagnosis of CAA-ri generally requires brain biopsy, however, highlighting the importance of developing noninvasive diagnostic criteria. Objectives: To test the sensitivity and specificity of modified criteria (Table 1) for possible and probable CAA-ri in groups of subjects with histologically proven CAA-ri and non-CAA-ri. Methods: After refining previously proposed clinical- radiological criteria we retrospectively analyzed clinical charts and MRI FLAIR and gradient-echo scans obtained from 17 subjects with pathologically confirmed CAA-ri and 37 control subjects with pathologic diagnosis of non-inflammatory CAA. The control group was further divided into those with past intracerebral hemorrhage (ICH) (n=21) and those with cerebral microbleeds (CMB) only and no history of ICH (n=16). Results: In the CAA-ri group 14/17 (82.4%) met criteria for both probable and possible CAA-ri. One (4.7%) of the subjects in the control CAA-ICH group (n=21) met the criteria for possible and none met criteria for probable CAA-ri. In the control CAA-no ICH group 1/16 (6.25%) and 11/16 (68.75%) met criteria for probable and possible CAA-ri respectively. This yields sensitivity and specificity of 82% and of 97.3% respectively for the probable criteria and sensitivity and specificity of 82% and 67.6% respectively for the possible criteria. Conclusions: Our data suggest that a reliable diagnosis of CAA-ri can be reached from basic clinical and radiographic information alone with good sensitivity and excellent specificity.

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Abstract 36: The Boston Criteria V2.0 for Cerebral Amyloid Angiopathy: Updated Criteria and Multicenter MRI-Neuropathology Validation

Stroke ◽

10.1161/str.52.suppl_1.36 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Andreas Charidimou ◽

Gregoire Boulouis ◽

Matthew Frosch ◽

Jean-Claude Baron ◽

Marco Pasi ◽

...

Keyword(s):

White Matter ◽

Intracerebral Hemorrhage ◽

Diagnostic Accuracy ◽

Cerebral Amyloid Angiopathy ◽

Brain Mri ◽

Amyloid Angiopathy ◽

Perivascular Spaces ◽

Validation Sample ◽

Temporal Validation ◽

Cerebral Amyloid

Introduction: The Boston criteria are used worldwide for in vivo diagnosis of cerebral amyloid angiopathy (CAA). Given substantial advances in CAA research, we aimed to update the Boston criteria and externally validate their diagnostic accuracy across the spectrum of CAA-related presentations and across international sites. Methods: As part of an International CAA Association multicenter study, we identified patients age 50 or older with potential CAA-related clinical presentations (spontaneous intracerebral hemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathologic assessment for the diagnosis of CAA. We derived Boston criteria v2.0 by selecting MRI features to optimize diagnostic specificity and sensitivity in a pre-specified derivation sample (Boston cases 1994 to 2012, n=159), then externally validated in pre-specified temporal (Boston cases 2012-2018, n=59) and geographical (non-Boston cases 2004-2018; n=123) validation samples and compared their diagnostic accuracy to the currently used modified Boston criteria. Results: Based on exploratory analyses in the derivation sample, we derived provisional criteria for probable CAA requiring presence of at least 2 strictly lobar hemorrhagic lesions (intracerebral hemorrhage, cerebral microbleed, or cortical superficial siderosis focus) or at least 1 strictly lobar hemorrhagic lesion and 1 white matter characteristic (severe degree of visible perivascular spaces in centrum semiovale or white matter hyperintensities multispot pattern). Sensitivity/specificity of the criteria were 74.8/84.6% in the derivation sample, 92.5/89.5% in the temporal validation sample, 80.2/81.5% in the geographic validation sample, and 74.5/95.0% in cases across all samples with autopsy as the diagnostic gold standard. The v2.0 criteria for probable CAA had superior accuracy to the currently modified Boston criteria (p<0.005) in the autopsied cases. Conclusion: The Boston criteria v.2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their high specificity. Validation of the criteria across independent patient settings firmly supports their adoption into clinical practice and research.

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