Sensitivity and Specificity of the Boston Criteria Version 2.0 for the Diagnosis of Cerebral Amyloid Angiopathy in a Community-Based Sample.

BACKGROUND AND OBJECTIVES: The Boston criteria are a set of clinical and neuroimaging features that enable accurate diagnosis of cerebral amyloid angiopathy (CAA) without invasive methods such as brain biopsies or autopsy. The last updates to the Boston criteria, named version 2.0, were recently released and incorporated new nonhemorrhagic MRI features. These criteria have been validated in symptomatic samples, with improved diagnostic yield. We set out to investigate the accuracy of the Boston criteria v2.0 for the diagnosis of CAA in a community-based sample. METHODS: Participants were recruited from longitudinal clinical-pathologic studies of aging conducted at the Rush Alzheimer's Disease Center in Chicago: the Religious Orders Study and the Rush Memory and Aging Project. Deceased participants with in vivo 3T MRI and detailed pathologic data available were included in the analysis. We compared the diagnostic yield of the current and earlier versions of the Boston criteria in our sample. Among those classified as probable CAA according to the Boston criteria v2.0, we investigated the ability of each neuroimaging marker to distinguish between false-positive and true-positive cases. RESULTS: In total, 134 individuals were included in the study (mean age = 82.4 ± 6.0 years; 69.4% F), and 49 of them were considered pathology-proven definite cases with CAA (mean age = 82.9 ± 6.0 years; 63.3% F). The Boston criteria versions 1.0 and 1.5 yielded similar sensitivity (26.5%, both), specificity (90.6% and 89.4%, respectively), and predictive values (negative: 68.1% and 67.9%; positive: 61.9% and 59.1%, respectively). The recently released Boston criteria v2.0 offered higher sensitivity (38.8%) and slightly lower specificity (83.5%). Among those classified as probable CAA (v2.0), pathology-proven true-positive cases had higher numbers of strictly cortical lobar microbleeds compared with false-positive cases (p = 0.004). DISCUSSION: Similar to findings from symptomatic samples, the inclusion of nonhemorrhagic neuroimaging markers in the updated Boston criteria offered a 12.3% gain in sensitivity among community-dwelling individuals, at the expense of a 5.9% drop in specificity. In cases with probable CAA, the cortical location of microbleeds may represent a promising distinguishing feature between true-positive and false-positive cases. Despite its improved performance, the diagnostic sensitivity of the updated criteria in a community-based sample remains limited. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the Boston criteria v2.0 accurately distinguishes people with CAA from those without CAA.

Association Between Hippocampal Volumes and Cognition in Cerebral Amyloid Angiopathy.

BACKGROUND AND OBJECTIVES: Accumulating evidence suggests that gray matter atrophy, often considered a marker of Alzheimer disease (AD), can also result from cerebral small vessel disease (CSVD). Cerebral amyloid angiopathy (CAA) is a form of sporadic CSVD, diagnosed through neuroimaging criteria, that often co-occurs with AD pathology and leads to cognitive impairment. We sought to identify the role of hippocampal integrity in the development of cognitive impairment in a cohort of patients with possible and probable CAA. METHODS: Patients were recruited from an ongoing CAA study at Massachusetts General Hospital. Composite scores defined performance in the cognitive domains of memory, language, executive function, and processing speed. Hippocampal subfields' volumes were measured from 3T MRI, using an automated method, and multivariate linear regression models were used to estimate their association with each cognitive domain and relationship to CAA-related neuroimaging markers. RESULTS: One hundred twenty patients, 36 with possible (age mean [range]: 75.6 [65.6-88.9]), 67 with probable CAA (75.9 [59.0-94.0]), and 17 controls without cognitive impairment and CSVD (72.4 [62.5-82.7]; 76.4% female patients), were included in this study. We found a positive association between all investigated hippocampal subfields and memory and language, whereas specific subfields accounted for executive function (CA4 [Estimate = 5.43; 95% CI 1.26-9.61; p = 0.020], subiculum [Estimate = 2.85; 95% CI 0.67-5.02; p = 0.022]), and processing speed (subiculum [Estimate = 1.99; 95% CI 0.13-3.85; p = 0.036]). These findings were independent of other CAA-related markers, which did not have an influence on cognition in this cohort. Peak width of skeletonized mean diffusivity (PSMD), a measure of white matter integrity, was negatively associated with hippocampal subfields' volumes (CA3 [Estimate = -0.012; 95% CI -0.020 to -0.004; p = 0.034], CA4 [Estimate = -0.010; 95% CI -0.020 to -0.0007; p = 0.037], subiculum [Estimate = -0.019; 95% CI -0.042 to -0.0001; p = 0.003]). DISCUSSION: These results suggest that hippocampal integrity is an independent contributor to cognitive impairment in patients with CAA and that it might be related to loss of integrity in the white matter. Further studies exploring potential causes and directionality of the relationship between white matter and hippocampal integrity may be warranted.

Histopathological Correlates of Lobar Microbleeds in False-Positive Cerebral Amyloid Angiopathy Cases.

OBJECTIVE: A definite diagnosis of cerebral amyloid angiopathy (CAA), characterized by the accumulation of amyloid ß in walls of cerebral small vessels, can only be obtained through pathological examination. A diagnosis of probable CAA during life relies on the presence of hemorrhagic markers, including lobar cerebral microbleeds (CMBs). The aim of this project was to study the histopathological correlates of lobar CMBs in false-positive CAA cases. METHODS: In 3 patients who met criteria for probable CAA during life, but showed no CAA upon neuropathological examination, lobar CMBs were counted on ex vivo 3T magnetic resonance imaging (MRI) and on ex vivo 7T MRI. Areas with lobar CMBs were next sampled and cut into serial sections, on which the CMBs were then identified. RESULTS: Collectively, there were 25 lobar CMBs on in vivo MRI and 22 on ex vivo 3T MRI of the analyzed hemispheres. On ex vivo MRI, we targeted 12 CMBs for sampling, and definite histopathological correlates were retrieved for 9 of them, of which 7 were true CMBs. No CAA was found on any of the serial sections. The "culprit vessels" associated with the true CMBs instead showed moderate to severe arteriolosclerosis. Furthermore, CMBs in false-positive CAA cases tended to be located more often in the juxtacortical or subcortical white matter than in the cortical ribbon. INTERPRETATION: These findings suggest that arteriolosclerosis can generate lobar CMBs and that more detailed investigations into the exact localization of CMBs with respect to the cortical ribbon could potentially aid the diagnosis of CAA during life. ANN NEUROL 2023;94:856-870.

Peak width of skeletonized mean diffusivity and cognitive performance in cerebral amyloid angiopathy.

Background: Cerebral Amyloid Angiopathy (CAA) is a cerebral small vessel disease that can lead to microstructural disruption of white matter (WM), which can be measured by the Peak Width of Skeletonized Mean Diffusivity (PSMD). We hypothesized that PSMD measures would be increased in patients with CAA compared to healthy controls (HC), and increased PSMD is associated with lower cognitive scores in patients with CAA. Methods: Eighty-one probable CAA patients without cognitive impairment who were diagnosed with Boston criteria and 23 HCs were included. All subjects underwent an advanced brain MRI with high-resolution diffusion-weighted imaging (DWI). PSMD scores were quantified from a probabilistic skeleton of the WM tracts in the mean diffusivity (MD) image using a combination of fractional anisotropy (FA) and the FSL Tract-Based Spatial Statistics (TBSS) algorithm (www.psmd-marker.com). Within CAA cohort, standardized z-scores of processing speed, executive functioning and memory were obtained. Results: The mean of age and sex were similar between CAA patients (69.6 ± 7.3, 59.3% male) and HCs (70.6 ± 8.5, 56.5% male) (p = 0.581 and p = 0.814). PSMD was higher in the CAA group [(4.13 ± 0.94) × 10-4 mm2/s] compared to HCs [(3.28 ± 0.51) × 10-4 mm2/s] (p < 0.001). In a linear regression model corrected for relevant variables, diagnosis of CAA was independently associated with increased PSMD compared to HCs (ß = 0.45, 95% CI 0.13-0.76, p = 0.006). Within CAA cohort, higher PSMD was associated with lower scores in processing speed (p < 0.001), executive functioning (p = 0.004), and memory (0.047). Finally, PSMD outperformed all other MRI markers of CAA by explaining most of the variance in models predicting lower scores in each cognitive domain. Discussion: Peak Width of Skeletonized Mean Diffusivity is increased in CAA, and it is associated with worse cognitive scores supporting the view that disruption of white matter has a significant role in cognitive impairment in CAA. As a robust marker, PSMD can be used in clinical trials or practice.

Apathy in Patients With Cerebral Amyloid Angiopathy: A Multimodal Neuroimaging Study.

BACKGROUND AND OBJECTIVE: To analyze the prevalence and associated clinical characteristics of apathy in sporadic cerebral amyloid angiopathy and investigate whether apathy was associated with disease burden and disconnections of key structures in the reward circuit through a structural and functional multimodal neuroimaging approach. METHODS: Thirty-seven participants with probable sporadic cerebral amyloid angiopathy without symptomatic intracranial hemorrhage or dementia (mean age, 73.3 ± 7.2 years, % male = 59.5%) underwent a detailed neuropsychological evaluation, including measures of apathy and depression, and a multimodal MR neuroimaging study. A multiple linear regression analysis was used to assess the association of apathy with conventional small vessel disease neuroimaging markers. A voxel-based morphometry with a small volume correction within regions previously associated with apathy and a whole-brain tract-based spatial statistics were performed to identify differences in the gray matter and white matter between the apathetic and nonapathetic groups. Gray matter regions significantly associated with apathy were further evaluated for their functional alterations as seeds in the seed-based resting-state functional connectivity analysis. Potential confounders, namely, age, sex, and measures of depression, were entered as covariates in all analyses. RESULTS: A higher composite small vessel disease marker score (CAA-SVD) was associated with a higher degree of apathy (standardized coefficient = 1.35 (0.07-2.62), adjusted R2 = 27.90, p = 0.04). Lower gray matter volume of the bilateral orbitofrontal cortices was observed in the apathetic group than in the nonapathetic group (F = 13.20, family-wise error-corrected p = 0.028). The apathetic group demonstrated a widespread decrease in white matter microstructural integrity compared with the nonapathetic group. These tracts connect key regions within and between related reward circuits. Finally, there were no significant functional alterations between the apathetic and nonapathetic groups. DISCUSSION: Our findings revealed the orbitofrontal cortex as a key region in the reward circuit associated with apathy in sporadic cerebral amyloid angiopathy, independent from depression. Apathy was shown to be associated with a higher CAA-SVD score and an extensive disruption of white matter tracts, which suggested that a higher burden of CAA pathology and the disruption in large-scale white matter networks may underlie manifestations of apathy.

Peak Width of Skeletonized Mean Diffusivity: A Neuroimaging Marker for White Matter Injury.

A leading cause of white matter (WM) injury in older individuals is cerebral small vessel disease (SVD). Cerebral SVD is the most prevalent vascular contributor to cognitive impairment and dementia. Therapeutic progress for cerebral SVD and other WM disorders depends on the development and validation of neuroimaging markers suitable as outcome measures in future interventional trials. Diffusion-tensor imaging (DTI) is one of the best-suited MRI techniques for assessing the extent of WM damage in the brain. But the optimal method to analyze individual DTI data remains hindered by labor-intensive and time-consuming processes. Peak width of skeletonized mean diffusivity (PSMD), a recently developed fast, fully automated DTI marker, was designed to quantify the WM damage secondary to cerebral SVD and reflect related cognitive impairment. Despite its promising results, knowledge about PSMD is still limited in the radiologic community. This focused review provides an overview of the technical details of PSMD while synthesizing the available data on its clinical and neuroimaging associations. From a critical expert viewpoint, the authors discuss the limitations of PSMD and its current validation status as a neuroimaging marker for vascular cognitive impairment. Finally, they point out the gaps to be addressed to further advance the field.

White Matter Hyperintensities and Poststroke Apathy: A Fully Automated MRI Segmentation Study.

INTRODUCTION: Poststroke apathy (PSA) is a common neuropsychiatric disorder that may affect up to 30% of stroke patients. Despite the difficulties of investigating this condition (overlapping with depression, heterogeneity of diagnostic criteria, a small number of studies), some recent diffusion tensor imaging studies have suggested that widespread microstructural white matter (WM) disruption plays a key role in the development of PSA. Therefore, we intended to investigate this hypothesis by evaluating the relationship between WM hyperintensities (WMH) and apathy in patients with cerebrovascular disease. METHODS: We studied patients with apathy (n = 7), depression (n = 13), comorbid apathy and depression (n = 13), and controls (n = 20), and we investigated the variables associated with the volume of WMH measured by an automated brain MRI segmentation software. RESULTS: The overall prevalence of PSA was 37.7% (pure and comorbid). Patients with apathy presented a higher volume of WMH in comparison to controls. Mini-Mental State Examination (MMSE), NPI-A, and the number of cerebral microbleeds were the only variables associated with WMH. Conversely, NPI-D did not correlate to WMH. DISCUSSION/CONCLUSION: This is an exploratory study that supports the view of PSA as a distinct syndrome from PSD mediated mainly by diffuse white matter hyperintensities, which suggests that WM disruption is an important pathway to the development of apathy in stroke patients.

A Causal Classification System for Intracerebral Hemorrhage Subtypes.

OBJECTIVE: Determining the underlying causes of intracerebral hemorrhage (ICH) is of major importance, because risk factors, prognosis, and management differ by ICH subtype. We developed a new causal CLASsification system for ICH Subtypes, termed CLAS-ICH, based on recent advances in neuroimaging. METHODS: CLAS-ICH defines 5 ICH subtypes: arteriolosclerosis, cerebral amyloid angiopathy, mixed small vessel disease (SVD), other rare forms of SVD (genetic SVD and others), and secondary causes (macrovascular causes, tumor, and other rare causes). Every patient is scored in each category according to the level of diagnostic evidence: (1) well-defined ICH subtype; (2) possible underlying disease; and (0) no evidence of the disease. We evaluated CLAS-ICH in a derivation cohort of 113 patients with ICH from Massachusetts General Hospital, Boston, USA, and in a derivation cohort of 203 patients from Inselspital, Bern, Switzerland. RESULTS: In the derivation cohort, a well-defined ICH subtype could be identified in 74 (65.5%) patients, including 24 (21.2%) with arteriolosclerosis, 23 (20.4%) with cerebral amyloid angiopathy, 18 (15.9%) with mixed SVD, and 9 (8.0%) with a secondary cause. One or more possible causes were identified in 42 (37.2%) patients. Interobserver agreement was excellent for each category (kappa value ranging from 0.86 to 1.00). Despite substantial differences in imaging modalities, we obtained similar results in the validation cohort. INTERPRETATION: CLAS-ICH is a simple and reliable classification system for ICH subtyping, that captures overlap between causes and the level of diagnostic evidence. CLAS-ICH may guide clinicians to identify ICH causes, and improve ICH classification in multicenter studies. ANN NEUROL 2023;93:16-28.

Peak width of skeletonized mean diffusivity in cerebral amyloid angiopathy: Spatial signature, cognitive, and neuroimaging associations.

Background: Peak width of skeletonized mean diffusivity (PSMD) is a promising diffusion tensor imaging (DTI) marker that shows consistent and strong cognitive associations in the context of different cerebral small vessel diseases (cSVD). Purpose: Investigate whether PSMD (1) is higher in patients with Cerebral Amyloid Angiopathy (CAA) than those with arteriolosclerosis; (2) can capture the anteroposterior distribution of CAA-related abnormalities; (3) shows similar neuroimaging and cognitive associations in comparison to other classical DTI markers, such as average mean diffusivity (MD) and fractional anisotropy (FA). Materials and methods: We analyzed cross-sectional neuroimaging and neuropsychological data from 90 non-demented memory-clinic subjects from a single center. Based on MRI findings, we classified them into probable-CAA (those that fulfilled the modified Boston criteria), subjects with MRI markers of cSVD not attributable to CAA (presumed arteriolosclerosis; cSVD), and subjects without evidence of cSVD on MRI (non-cSVD). We compared total and lobe-specific (frontal and occipital) DTI metrics values across the groups. We used linear regression models to investigate how PSMD, MD, and FA correlate with conventional neuroimaging markers of cSVD and cognitive scores in CAA. Results: PSMD was comparable in probable-CAA (median 4.06 × 10-4 mm2/s) and cSVD (4.07 × 10-4 mm2/s) patients, but higher than in non-cSVD (3.30 × 10-4 mm2/s; p < 0.001) subjects. Occipital-frontal PSMD gradients were higher in probable-CAA patients, and we observed a significant interaction between diagnosis and region on PSMD values [F(2, 87) = 3.887, p = 0.024]. PSMD was mainly associated with white matter hyperintensity volume, whereas MD and FA were also associated with other markers, especially with the burden of perivascular spaces. PSMD correlated with worse executive function (ß = -0.581, p < 0.001) and processing speed (ß = -0.463, p = 0.003), explaining more variance than other MRI markers. MD and FA were not associated with performance in any cognitive domain. Conclusion: PSMD is a promising biomarker of cognitive impairment in CAA that outperforms other conventional and DTI-based neuroimaging markers. Although global PSMD is similarly increased in different forms of cSVD, PSMD's spatial variations could potentially provide insights into the predominant type of underlying microvascular pathology.

White matter hyperintensities are a prominent feature of autosomal dominant Alzheimer's disease that emerge prior to dementia.

BACKGROUND: To promote the development of effective therapies, there is an important need to characterize the full spectrum of neuropathological changes associated with Alzheimer's disease. In line with this need, this study examined white matter abnormalities in individuals with early-onset autosomal dominant Alzheimer's disease, in relation to age and symptom severity. METHODS: This is a cross-sectional analysis of data collected in members of a large kindred with a PSEN1 E280A mutation. Participants were recruited between September 2011 and July 2012 from the Colombian Alzheimer's Prevention Initiative registry. The studied cohort comprised 50 participants aged between 20 and 55 years, including 20 cognitively unimpaired mutation carriers, 9 cognitively impaired mutation carriers, and 21 non-carriers. Participants completed an MRI, a lumbar puncture for cerebrospinal fluid collection, a florbetapir PET scan, and neurological and neuropsychological examinations. The volume of white matter hyperintensities (WMH) was compared between cognitively unimpaired carriers, cognitively impaired carriers, and non-carriers. Relationships between WMH, age, and cognitive performance were further examined in mutation carriers. RESULTS: The mean (SD) age of participants was 35.8 (9.6) years and 64% were women. Cardiovascular risk factors were uncommon and did not differ across groups. Cognitively impaired carriers [median, 6.37; interquartile range (IQR), 9.15] had an increased volume of WMH compared to both cognitively unimpaired carriers [median, 0.85; IQR, 0.79] and non-carriers [median, 1.07; IQR, 0.71]. In mutation carriers, the volume of WMH strongly correlated with cognition and age, with evidence for an accelerated rate of changes after the age of 43 years, 1 year earlier than the estimated median age of symptom onset. In multivariable regression models including cortical amyloid retention, superior parietal lobe cortical thickness, and cerebrospinal fluid phospho-tau, the volume of WMH was the only biomarker independently and significantly contributing to the total explained variance in cognitive performance. CONCLUSIONS: The volume of WMH is increased among individuals with symptomatic autosomal-dominant Alzheimer's disease, begins to increase prior to clinical symptom onset, and is an independent determinant of cognitive performance in this group. These findings suggest that WMH are a key component of autosomal-dominant Alzheimer's disease that is closely related to the progression of clinical symptoms.

Corpus callosum lesions are associated with worse cognitive performance in cerebral amyloid angiopathy.

The impact of vascular lesions on cognition is location dependent. Here, we assessed the contribution of small vessel disease lesions in the corpus callosum to vascular cognitive impairment in cerebral amyloid angiopathy, as a model for cerebral small vessel disease. Sixty-five patients with probable cerebral amyloid angiopathy underwent 3T magnetic resonance imaging, including a diffusion tensor imaging scan, and neuropsychological testing. Microstructural white-matter integrity was quantified by fractional anisotropy and mean diffusivity. Z-scores on individual neuropsychological tests were averaged into five cognitive domains: information processing speed, executive functioning, memory, language and visuospatial ability. Corpus callosum lesions were defined as haemorrhagic (microbleeds or larger bleeds) or ischaemic (microinfarcts, larger infarcts and diffuse fluid-attenuated inversion recovery hyperintensities). Associations between corpus callosum lesion presence, microstructural white-matter integrity and cognitive performance were examined with multiple regression models. The prevalence of corpus callosum lesions was confirmed in an independent cohort of memory clinic patients with and without cerebral amyloid angiopathy (n = 82). In parallel, we assessed corpus callosum lesions on ex vivo magnetic resonance imaging in cerebral amyloid angiopathy patients (n = 19) and controls (n = 5) and determined associated tissue abnormalities with histopathology. A total number of 21 corpus callosum lesions was found in 19/65 (29%) cerebral amyloid angiopathy patients. Corpus callosum lesion presence was associated with reduced microstructural white-matter integrity within the corpus callosum and in the whole-brain white matter. Patients with corpus callosum lesions performed significantly worse on all cognitive domains except language, compared with those without corpus callosum lesions after correcting for age, sex, education and time between magnetic resonance imaging and neuropsychological assessment. This association was independent of the presence of intracerebral haemorrhage, whole-brain fractional anisotropy and mean diffusivity, and white-matter hyperintensity volume and brain volume for the domains of information processing speed and executive functioning. In the memory clinic patient cohort, corpus callosum lesions were present in 14/54 (26%) patients with probable and 2/8 (25%) patients with possible cerebral amyloid angiopathy, and in 3/20 (15%) patients without cerebral amyloid angiopathy. In the ex vivo cohort, corpus callosum lesions were present in 10/19 (53%) patients and 2/5 (40%) controls. On histopathology, ischaemic corpus callosum lesions were associated with tissue loss and demyelination, which extended beyond the lesion core. Together, these data suggest that corpus callosum lesions are a frequent finding in cerebral amyloid angiopathy, and that they independently contribute to cognitive impairment through strategic microstructural disruption of white-matter tracts.

Radiomic signature of DWI-FLAIR mismatch in large vessel occlusion stroke.

BACKGROUND AND PURPOSE: Ischemic diffusion-weighted imaging-fluid-attenuated inversion recovery (DWI-FLAIR) mismatch may be useful in guiding acute stroke treatment decisions given its relationship to onset time and parenchymal viability; however, it relies on subjective grading. Radiomics is an emerging image quantification methodology that may objectively represent continuous image characteristics. We propose a novel radiomics approach to characterize DWI-FLAIR mismatch. METHODS: Ischemic lesions were visually graded for FLAIR positivity (absent, subtle, obvious) among consecutive large vessel occlusion stroke patients who underwent hyperacute MRI. Radiomic features were extracted from within the lesions on DWI and FLAIR. The DWI-FLAIR mismatch radiomics signature was built with features systematically selected by a cross-validated ElasticNet linear regression model of mismatch. RESULTS: We identified 103 patients with mean age 68 ± 16 years; 63% were female. FLAIR hyperintensity was absent in 25%, subtle in 55%, and obvious in 20%. Inter-rater agreement for visual grading was moderate (Κ = .58). The radiomics signature of DWI-FLAIR mismatch included native FLAIR histogram kurtosis and local binary pattern-filtered FLAIR gray-level cluster shade; both correlated with visual grading (ρ = -.42, p < .001 and ρ = .40, p < .001, respectively). CONCLUSIONS: Radiomics can describe DWI-FLAIR mismatch and may provide objective, continuous biomarkers for infarct evolution using clinical-grade images. These novel biomarkers may prove useful for treatment decisions and future research.

Massive Orbital Infiltration and Trigeminal Enlargement in Churg-Strauss Syndrome Associated With IgG4 Plasma Cell Positivity.

The association of C-antineutrophil cytoplasmic antibody (ANCA) vasculitis and IgG4 positivity is a new condition not well described in clinical terms. The authors examined a 28-year-old man with a previous diagnosis of eosinophilic granulomatosis with polyangiitis, formerly known as Churg-Strauss disease, who presented with bilateral orbital inflammation. Magnetic resonance imaging revealed diffuse orbital infiltration and enlargement of the major divisions of the trigeminal nerve. Biopsy of the orbital contents showed necrotizing granulomatous vasculitis and a high number of IgG4-positive plasma cells (IgG4/IgG = 60%).

Cranial US in Infants Exposed to Zika Virus: The NATZIG Cohort.

Background Studies addressing neuroimaging findings as primary outcomes of congenital Zika virus infection are variable regarding inclusion criteria and confirmatory laboratory testing. Purpose To investigate cranial US signs of prenatal Zika virus exposure and to describe frequencies of cranial US findings in infants exposed to Zika virus compared to those in control infants. Materials and Methods In this single-center prospective cohort study, participants were enrolled during the December 2015-July 2016 outbreak of Zika virus infection in southeast Brazil (Natural History of Zika Virus Infection in Gestation cohort). Eligibility criteria were available cranial US and laboratory findings of maternal Zika virus infection during pregnancy confirmed with RNA polymerase chain reaction testing (ie, Zika virus-exposed infants). The control group was derived from the Zika in Infants and Pregnancy cohort and consisted of infants born to asymptomatic pregnant women who tested negative for Zika virus infection during pregnancy. Two radiologists who were blinded to the maternal Zika virus infection status independently reviewed cranial US scans from both groups and categorized them as normal findings, Zika virus-like pattern, or mild findings. Associations between cranial US findings and prenatal Zika virus exposure were assessed with univariable analysis. Results Two hundred twenty Zika virus-exposed infants (mean age, 53.3 days ± 71.1 [standard deviation]; 113 boys) and born to 219 mothers infected with Zika virus were included in this study and compared with 170 control infants (mean age, 45.6 days ± 45.8; 102 boys). Eleven of the 220 Zika virus-exposed infants (5%), but no control infants, had a Zika virus-like pattern at cranial US. No difference in frequency of mild findings was observed between the groups (50 of 220 infants [23%] vs 44 of 170 infants [26%], respectively; P = .35). The mild finding of lenticulostriate vasculopathy, however, was nine times more frequent in Zika virus-exposed infants (12 of 220 infants, 6%) than in control infants (one of 170 infants, 1%) (P = .01). Conclusion Lenticulostriate vasculopathy was more common after prenatal exposure to Zika virus, even in infants with normal head size, despite otherwise overall similar frequency of mild cranial US findings in Zika virus-exposed infants and in control infants. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Benson in this issue.

Cerebral small vessel disease and vascular cognitive impairment: from diagnosis to management.

PURPOSE OF REVIEW: We present recent developments in the field of small vessel disease (SVD)-related vascular cognitive impairment, including pathological mechanisms, updated diagnostic criteria, cognitive profile, neuroimaging markers and risk factors. We further address available management and therapeutic strategies. RECENT FINDINGS: Vascular and neurodegenerative pathologies often co-occur and share similar risk factors. The updated consensus criteria aim to standardize vascular cognitive impairment (VCI) diagnosis, relying strongly on cognitive profile and MRI findings. Aggressive blood pressure control and multidomain lifestyle interventions are associated with decreased risk of cognitive impairment, but disease-modifying treatments are still lacking. Recent research has led to a better understanding of mechanisms leading to SVD-related cognitive decline, such as blood-brain barrier dysfunction, reduced cerebrovascular reactivity and impaired perivascular clearance. SUMMARY: SVD is the leading cause of VCI and is associated with substantial morbidity. Tackling cardiovascular risk factors is currently the most effective approach to prevent cognitive decline in the elderly. Advanced imaging techniques provide tools for early diagnosis and may play an important role as surrogate markers for cognitive endpoints in clinical trials. Designing and testing disease-modifying interventions for VCI remains a key priority in healthcare.

Association of Memory Impairment With Concomitant Tau Pathology in Patients With Cerebral Amyloid Angiopathy.

OBJECTIVE: Relying on tau-PET imaging, this cross-sectional study explored whether memory impairment is linked to the presence of concomitant tau pathology in individuals with cerebral amyloid angiopathy (CAA). METHODS: Forty-six patients with probable CAA underwent a neuropsychological examination and an MRI for quantification of structural markers of cerebral small vessel disease. A subset of these participants also completed a [11C]-Pittsburgh compound B (n = 39) and [18F]-flortaucipir (n = 40) PET for in vivo estimation of amyloid and tau burden, respectively. Participants were classified as amnestic or nonamnestic on the basis of neuropsychological performance. Statistical analyses were performed to examine differences in cognition, structural markers of cerebral small vessel disease, and amyloid- and tau-PET retention between participants with amnestic and those with nonamnestic CAA. RESULTS: Patients with probable CAA with an amnestic presentation displayed a globally more severe profile of cognitive impairment, smaller hippocampal volume (p < 0.001), and increased tau-PET binding in regions susceptible to Alzheimer disease neurodegeneration (p = 0.003) compared to their nonamnestic counterparts. Amnestic and nonamnestic patients with CAA did not differ on any other MRI markers or on amyloid-PET binding. In a generalized linear model including all evaluated neuroimaging markers, tau-PET retention (ß = -0.85, p = 0.001) and hippocampal volume (ß = 0.64 p = 0.01) were the only significant predictors of memory performance. The cognitive profile of patients with CAA with an elevated tau-PET retention was distinctly characterized by a significantly lower performance on the memory domain (p = 0.004). CONCLUSIONS: These results suggest that the presence of objective memory impairment in patients with probable CAA could serve as a marker for underlying tau pathology. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that tau-PET retention is related to the presence of objective memory impairment in patients with CAA.

CT-Visible Convexity Subarachnoid Hemorrhage is Associated With Cortical Superficial Siderosis and Predicts Recurrent ICH.

OBJECTIVE: To investigate whether acute convexity subarachnoid hemorrhage (cSAH) detected on CT in lobar intracerebral hemorrhage (ICH) related to cerebral amyloid angiopathy (CAA) is associated with recurrent ICH. METHODS: We analyzed data from a prospective cohort of consecutive acute lobar ICH survivors fulfilling the Boston criteria for possible or probable CAA who had both brain CT and MRI at index ICH. Presence of cSAH was assessed on CT blinded to MRI data. Cortical superficial siderosis (cSS), cerebral microbleeds, and white matter hyperintensities were evaluated on MRI. Cox proportional hazard models were used to assess the association between cSAH and the risk of recurrent symptomatic ICH during follow-up. RESULTS: A total of 244 ICH survivors (76.4 ± 8.7 years; 54.5% female) were included. cSAH was observed on baseline CT in 99 patients (40.5%). Presence of cSAH was independently associated with cSS, hematoma volume, and preexisting dementia. During a median follow-up of 2.66 years, 49 patients (20.0%) had recurrent symptomatic ICH. Presence of cSAH was associated with recurrent ICH (hazard ratio 2.64; 95% confidence interval 1.46-4.79; p = 0.001), after adjusting for age, antiplatelet use, warfarin use, and history of previous ICH. CONCLUSION: cSAH was detected on CT in 40.5% of patients with acute lobar ICH related to CAA and heralds an increased risk of recurrent ICH. This CT marker may be widely used to stratify the ICH risk in patients with CAA. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that cSAH accurately predicts recurrent stroke in patients with CAA.

Collateral Scores and Outcomes after Endovascular Treatment for Basilar Artery Occlusion.

BACKGROUND: Basilar artery occlusion (BAO) is a rare stroke subtype with high mortality rates. Best BAO reperfusion strategy is still controversial. OBJECTIVE: We aim to describe outcomes of BAO patients submitted to mechanical thrombectomy (MT) in a comprehensive stroke center in Brazil and analyze which previous published computed tomography angiography (CTA) collateral score better predict functional outcomes. METHODS: Retrospective analysis of consecutive BAO patients. CTA was used to evaluate the posterior circulation collateral score (PC-CS), the basilar artery on CTA score, and for the presence of posterior communicating arteries. A favorable outcome was defined as modified Rankin Score ≤3 at 90-days. After univariate analyses, multivariate logistic regression was used to identify if any collateral score independently predicts favorable outcomes. RESULTS: Between January 2011 and April 2017, 27 (85% male) BAO patients with median NIHSS 26 (IQR 15-32) were identified. Twenty-five (93%) patients were treated with MT devices, and only 2 (7%) patients were treated with angioplasty and stenting. Successful recanalization rate was 85%, and only 1 (3.7%) patient had symptomatic hemorrhagic transformation. Favorable outcomes were reached in 10 (37%) patients. In univariate analysis, female sex, NIHSS, Glasgow coma scale, mild-to-moderate symptoms on admission, onset-to-groin time, and PC-CS predicted favorable outcomes. In multivariate analysis, PC-CS (OR 1.69; 95% CI 1.10-2.60; p = 0.016) and NIHSS (OR 0.84; 95% CI 0.77-0.93; p = 0.001) remained the only independent predictors of favorable outcomes. The PC-CS AUC was 0.80 (95% CI 0.62-0.98; p = 0.012). CONCLUSIONS: MT is a promising strategy for BAO treatment. Among collateral scores, PC-CS was the only independent predictor of favorable outcomes in the present study.