Background and purpose Cortical superficial siderosis (cSS) is a key neuroimaging marker of cerebral amyloid angiopathy (CAA) detected on blood-sensitive magnetic resonance imaging (MRI). We aimed to assess cSS in advanced CAA patients and explore differences in its evaluation between susceptibility weighted imaging (SWI) and gradient recalled echo-T2* (GRE-T2*). Materials and methods Neuroimaging data gathered from a prospective cohort of CAA patients with probable or definite CAA were retrospectively analyzed by two independent raters. SWI and GRE-T2* were used to assess presence and severity (absent, focal [<= 3 sulci] or disseminated [> 3 sulci]) of cSS and number of foci. Ratings were compared between sequences and inter-rater agreement was determined. Post hoc analysis explored differences in cSS multifocality scores. Results We detected cSS in 38 patients with SWI and in 36 with GRE-T2* (70.4% versus 66.7%; P = 0.5). The two raters agreed in detecting more disseminated cSS when using SWI: 16 focal (29.63%) and 20 disseminated (37.04%) cases of cSS seen on GRE-T2* and 11 (20.37%) focal and 27 (50%) disseminated cSS cases seen using SWI (P = 0.008). Inter-rater agreement was equivalent for the two sequences (kappa(presence) 0.7 versus 0.69; kappa(severity) 0.74 versus 0.66) for assessing both presence and severity of cSS. Post hoc analysis showed higher multifocality scores from both raters' SWI evaluations, with agreement equivalent to that for T2* evaluations. Conclusions Our findings suggest that SWI ratings could show more disseminated cSS and higher multifocality scores in advanced CAA patients with inter-rater reliability equivalent to that obtained using GRE-T2*, regardless of level of experience.

BACKGROUND AND PURPOSE: Whole-brain network connectivity has been shown to be a useful biomarker of cerebral amyloid angiopathy and related cognitive impairment. We evaluated an automated DTI-based method, peak width of skeletonized mean diffusivity, in cerebral amyloid angiopathy, together with its association with conventional MRI markers and cognitive functions. MATERIALS AND METHODS: We included 24 subjects (mean age, 74.7 [SD, 6.0] years) with probable cerebral amyloid angiopathy and mild cognitive impairment and 62 patients with MCI not attributable to cerebral amyloid angiopathy (non-cerebral amyloid angiopathy?mild cognitive impairment). We compared peak width of skeletonized mean diffusivity between subjects with cerebral amyloid angiopathy?mild cognitive impairment and non-cerebral amyloid angiopathy?mild cognitive impairment and explored its associations with cognitive functions and conventional markers of cerebral small-vessel disease, using linear regression models. RESULTS: Subjects with Cerebral amyloid angiopathy?mild cognitive impairment showed increased peak width of skeletonized mean diffusivity in comparison to those with non-cerebral amyloid angiopathy?mild cognitive impairment (P < .001). Peak width of skeletonized mean diffusivity values were correlated with the volume of white matter hyperintensities in both groups. Higher peak width of skeletonized mean diffusivity was associated with worse performance in processing speed among patients with cerebral amyloid angiopathy, after adjusting for other MRI markers of cerebral small vessel disease. The peak width of skeletonized mean diffusivity did not correlate with cognitive functions among those with non-cerebral amyloid angiopathy?mild cognitive impairment. CONCLUSIONS: Peak width of skeletonized mean diffusivity is altered in cerebral amyloid angiopathy and is associated with performance in processing speed. This DTI-based method may reflect the degree of white matter structural disruption in cerebral amyloid angiopathy and could be a useful biomarker for cognition in this population.

Objective To investigate whether acute convexity subarachnoid hemorrhage (cSAH) associated with acute lobar intracerebral hemorrhage (ICH) increases the risk of ICH recurrence in patients with cerebral amyloid angiopathy (CAA). Methods We analyzed data from a prospective cohort of consecutive survivors of acute spontaneous lobar ICH fulfilling the Boston criteria for possible or probable CAA (CAA-ICH). We analyzed baseline clinical and MRI data, including cSAH (categorized as adjacent or remote from ICH on a standardized scale), cortical superficial siderosis (cSS), and other CAA MRI markers. Multivariable Cox regression models were used to assess the association between cSAH and recurrent symptomatic ICH during follow-up. Results We included 261 CAA-ICH survivors (mean age 76.2 ± 8.7 years). Of them, 166 (63.6%, 95% confidence interval [CI] 57.7%–69.5%) had cSAH on baseline MRI. During a median follow-up of 28.3 (interquartile range 7.2–57.0) months, 54 (20.7%) patients experienced a recurrent lobar ICH. In Cox regression, any cSAH, adjacent cSAH, and remote cSAH were independent predictors of recurrent ICH after adjustment for other confounders, including cSS. Incidence rate of recurrent ICH in patients with cSAH was 9.9 per 100 person-years (95% CI 7.3–13.0) compared with 1.2 per 100 person-years (95% CI 0.3–3.2) in those without cSAH (adjusted hazard ratio 7.5, 95% CI 2.6–21.1). Conclusion In patients with CAA-related acute ICH, cSAH (adjacent or remote from lobar ICH) is commonly observed and heralds an increased risk of recurrent ICH. cSAH may help stratify bleeding risk and should be assessed along with cSS for prognosis and clinical management.

Background and Purpose— We investigated cortical superficial siderosis (cSS) progression and its clinical relevance for incident lobar intracerebral hemorrhage (ICH) risk, in probable cerebral amyloid angiopathy presenting with neurological symptoms and without ICH at baseline. Methods— Consecutive patients meeting modified Boston criteria for probable cerebral amyloid angiopathy from a single-center cohort who underwent magnetic resonance imaging (MRI) at baseline and during follow-up were analyzed. cSS progression was assessed by comparison of the baseline and follow-up images. Patients were followed prospectively for incident symptomatic ICH. cSS progression and first-ever ICH risk were investigated in Cox proportional hazard models adjusting for confounders. Results— The cohort included 118 probable cerebral amyloid angiopathy patients: 72 (61%) presented with transient focal neurological episodes and 46 (39%) with cognitive complaints prompting the baseline MRI investigation. Fifty-two patients (44.1%) had cSS at baseline. During a median scan interval of 2.2 years (interquartile range, 1.2–4.4 years) between the baseline (ie, first) MRI and the latest MRI, cSS progression was detected in 33 (28%) patients. In multivariable logistic regression, baseline cSS presence (odds ratio, 4.04; 95% CI, 1.53–10.70; P=0.005), especially disseminated cSS (odds ratio, 9.12; 95% CI, 2.85–29.18; P<0.0001) and appearance of new lobar microbleeds (odds ratio, 4.24; 95% CI, 1.29–13.9; P=0.017) were independent predictors of cSS progression. For patients without an ICH during the interscan interval (n=105) and subsequent follow-up (median postfinal MRI time, 1.34; interquartile range, 0.3–3 years), cSS progression independently predicted increased symptomatic ICH risk (hazard ratio, 3.76; 95% CI, 1.37–10.35; P=0.010). Conclusions— Our results suggest that cSS evolution may be a useful biomarker for assessing disease progression and ICH risk in cerebral amyloid angiopathy patients and a candidate biomarker for clinical studies and trials.

We read with interest the article by Ng et al, in which the authors investigated associations between the “swirl sign” and hematoma growth. Ng et al found that patients positive for the swirl sign demonstrated larger hemorrhage volumes and higher odds of subsequent hemorrhage expansion (HE).[1][

AimsCortical microinfarcts (CMI) are frequently observed in the ageing brain independent of cognitive decline, but their aetiology is not fully elucidated. To examine the potential role of different vessel pathologies, including cerebral amyloid angiopathy (CAA), arteriolosclerosis‐hyalinosis and thromboembolism in the development of CMI, we examined 80 autopsy cases with more than one CMI on routine neuropathological examination.MethodsPial and intracortical vessels around CMI were assessed for their integrity with haematoxylin–eosin staining and antibodies against amyloid‐β protein and fibrinogen using a semiquantitative four‐level rating scale (absent to severe) in the hippocampus, and the frontal, temporal and occipital cortex. Four histological categories of changes were defined: CAA, vessel pathology other than CAA, thromboembolism and absence of vessel pathology near CMI.ResultsA differential distribution of microvascular pathology was observed depending on brain regions. In the occipital cortex, CAA was commonly associated with CMI. In contrast, in the hippocampus and the frontal cortex, cases without any vascular pathology in pial and intracortical vessels were significantly more frequent.ConclusionsThe aetiology of CMI differs depending on brain location. CAA may play a role principally in the occipital cortex. The large number of intact vessels around the CMI (mainly in the frontal cortex and hippocampus) raises the possibility that pathologies other than structural microangiopathy, including hypoperfusion/arterial hypotension or large vessel atherosclerosis, play a role in the development of microvascular lesions. These results are relevant in the context of aetiopathogenesis of vascular changes associated with conditions like vascular dementia.

Background: The distribution of cerebral microbleeds (CMBs) on MRI is hypothesized to indicate the pattern of underlying small vessel disease (SVD), with CMBs in deep regions reflecting hypertensive arteriopathy, and CMBs in strictly lobar regions reflecting cerebral amyloid angiopathy (CAA).

With great interest, I read the recent article by Inoue et al[1][1] on the diagnostic significance of cortical superficial siderosis (cSS) for Alzheimer disease in a memory clinic setting. In line with other recent studies on the topic, the authors found cSS in 12 of 347 (3.5%) patients in the

Background— We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in patients with ischemic stroke on non-vitamin K antagonist oral anticoagulants (NOACs, last intake <48 hours) in comparison with patients (1) taking vitamin K antagonists (VKAs) or (2) without previous anticoagulation (no-OAC). Methods and Results— This is a multicenter cohort pilot study. Primary outcome measures were (1) occurrence of intracranial hemorrhage (ICH) in 3 categories: any ICH (ICHany), symptomatic ICH according to the criteria of the European Cooperative Acute Stroke Study II (ECASS-II) (sICHECASS-II) and the National Institute of Neurological Disorders and Stroke (NINDS) thrombolysis trial (sICHNINDS); and (2) death (at 3 months). Cohorts were compared by using propensity score matching. Our NOAC cohort comprised 78 patients treated with IVT/IAT and the comparison groups of 441 VKA patients and 8938 no-OAC patients. The median time from last NOAC intake to IVT/IAT was 13 hours (interquartile range, 8–22 hours). In VKA patients, median pre-IVT/IAT international normalized ratio was 1.3 (interquartile range, 1.1–1.6). ICHany was observed in 18.4% NOAC patients versus 26.8% in VKA patients and 17.4% in no-OAC patients. sICHECASS-II and sICHNINDS occurred in 2.6%/3.9% NOAC patients, in comparison with 6.5%/9.3% of VKA patients and 5.0%/7.2% of no-OAC patients, respectively. At 3 months, 23.0% of NOAC patients in comparison with 26.9% of VKA patients and 13.9% of no-OAC patients had died. Propensity score matching revealed no statistically significant differences. Conclusions— IVT/IAT in selected patients with ischemic stroke under NOAC treatment has a safety profile similar to both IVT/IAT in patients on subtherapeutic VKA treatment or in those without previous anticoagulation. However, further prospective studies are needed, including the impact of specific coagulation tests. # CLINICAL PERSPECTIVES {#article-title-52}