Inactivated COVID-19 vaccine induced acute stroke-like focal neurologic symptoms: a case series.

BACKGROUND: A subgroup of individuals experienced stroke-like symptoms after receiving an inactivated COVID-19 vaccine. We present clinical characteristics, neuroimaging, and outcome of these patients. METHODS: Medical personals who had neurological symptoms after receiving inactivated COVID-19 vaccine were enrolled. Clinical, laboratory investigation and neuroimaging were collected. Subjects were prospectively followed-up on clinical and neuroimaging to detect brain parenchymal or cerebrovascular abnormality. RESULTS: Nineteen out of 385 subjects (4.9%) developed neurological symptoms after vaccination. There was a female predominance (89.5%) with mean age of 34 ± 7.5 years. Majority of patients (52.6%) had symptoms within 60 min after vaccination. The most common neurological symptoms were numbness (94.7%) followed by headache (52.6%) and weakness (47.4%). The most common neurological signs were sensory deficit (79%) followed by motor weakness (52.6%) and tongue deviation (26.3%). Recurrent headache was observed in most patients (89.5%) during followed up. Serial brain imaging was done in all patients with median follow-up interval of 18 days. There was no evidence of acute brain infarction in any of the patients, 84.2% had no vascular abnormality, 15.8% had transient focal narrowing of cerebral vessels. Outcome was favorable, modified ranking scale 0-1 for all patients at 4 weeks after vaccination. CONCLUSIONS: Transient focal neurological symptoms and deficits can be found after COVID-19 vaccination. However, benefit to stop COVID-19 pandemic by vaccination is outweighed by these seemingly reversible side effects. The pathophysiology underlined these phenomena should be further investigated.

Cortical Superficial Siderosis Evolution.

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.

Reversible Cerebral Vasoconstriction Syndrome: A Report on Three Cases.

Reversible cerebral vasoconstriction syndrome (RCVS), a recently recognized syndrome, is defined as an intermittent segmental vasospasm of cerebral arteries accompanied by thunderclap headache. The major complications of RCVS include ischemic or hemorrhagic stroke, which may cause morbidity and mortality. It is important to detect RCVS in clinical practice because misdiagnosis may lead to inappropriate treatment. In Thailand, there are only two reported cases of RCVS, which may reflect an underdiagnosis of this syndrome. To raise awareness of RCVS, we reported a case series of three RCVS cases. Two of the presented cases had interesting precipitating factors, and two cases had an unusual delayed clinical course.

Idiopathic hypertrophic pachymeningitis at King Chulalongkorn Memorial Hospital.

BACKGROUND: Idiopathic Hypertrophic Pachymeningitis (IHP) is a rare chronic inflammatory disorder of the dura. Classic clinical symptoms include headaches and cranial neuropathy. Because of scarce clinical data from Thailand, the present study aimed to determine the clinical features, neuroimaging findings, natural histories, therapeutic options, and outcomes for treatment of IHP in a tertiary care center. MATERIAL AND METHOD: A retrospective study was carried out on all adult IHP patients hospitalized at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between January 2000 and November 2011. Diagnostic criteria included 1) clinical symptom compatibility with IHP, 2) neuroimaging to reveal enhanced hypertrophic dura compatible with clinical syndrome, and 3) ruled out secondary causes of LHP, using appropriate clinical profiles and investigations including tissue biopsy. RESULTS: Thirty-two patients were enrolled with 21 females and 11 males, mean age of 49.03 +/- 16.12 years. The two most common symptoms were headache (93.8%) and diplopia (43.8%). The most common neurological finding was multiple cranial neuropathies (84.4%). Cranial nerve III was affected in 56.3% of the patients, followed by other cranial nerves including CN VI, IV, V and II. Headache without a neurological deficit was observed in 12.5% of the cases. Focal and diffuse enhanced thickening of the dura were observed in 96.9% and 3.1% of the cases respectively. Focal thickening in the supratentorium included the cavernous sinus, orbital apex, sphenoid wing, and superior orbital fissure. Focal thickening in the infratentorium included the falx cerebelli, the dura at the base of the skull, Meckel's cave, and foramen magnum. CSF examination showed lymphocyte pleocytosis with a slight increase in CSF proteins. Headache subsided in all of the patients after treatment with corticosteroid In relapsing and recurrent patients, a combined treatment of steroids and azathioprine was prescribed. With the combined treatment, clinical complete recovery, relapsing and recurrence were detected in 40%, 40% and 20% of the cases respectively. All relapsing and recurrence were due to rapid tapering of for early discontinuation of the steroids treatment. Only one patient had a spontaneous remission. CONCLUSION: The most common clinical manifestations of IHP were headache and multiple cranial nerve involvement. Almost all of the patients had good initial response to steroid therapy. Relapse or recurrence was usually caused by rapid tapering off or early discontinuation of the steroid treatment. Long-term treatment with combined immunosuppression may be necessary in some cases.

Cross-Cultural Translation and Validation of the Thai Version of the Scale for the Assessment and Rating of Ataxia (SARA-TH).

OBJECTIVE: To culturally adapt the original English Scale for the Assessment and Rating of Ataxia to Thai (SARA-TH) and to evaluate the reliability and validity of the SARA-TH in assessing ataxia in acute ischemic stroke or transient ischemic attack (TIA) patients, as assessed by three healthcare professionals. METHODS: The SARA underwent translation and cross-cultural adaptation to Thai according to established guidelines. Reliability (e.g., internal consistency, intrarater reliability, interrater reliability) and validity (e.g., content validity, convergent validity) were assessed in a sample of 50 participants with ataxia after acute ischemic stroke or TIA. Spearman correlation analysis was used to examine the relationships between the SARA-TH and the Barthel Index (BI-TH), the National Institutes of Health Stroke Scale (NIHSS-TH), and the International Cooperative Ataxia Rating Scale (ICARS) to assess convergent validity. Interrater and intrarater reliability among experienced and novice neurologists, physiotherapists, and occupational therapists were assessed using weighted kappa. RESULTS: The SARA-TH demonstrated good comprehension and exhibited no significant floor or ceiling effects. It showed excellent internal consistency (Cronbach's α≥0.776). Significant correlations were found between the SARA-TH score and the BI-TH score (rs=-0.743 to -0.665), NIHSS- TH score (rs=0.404-0.513), and ICARS score (rs=0.859-0.917). The intrarater reliability for each rater ranged from 0.724 to 1.000 (p<0.01), and the interrater reliability varied from 0.281 to 0.927 (p<0.01). CONCLUSION: The SARA-TH has excellent internal consistency, validity, and intrarater reliability, as well as acceptable interrater reliability among health professionals with varying levels of experience. It is recommended for assessing ataxia severity in individuals following acute ischemic stroke or TIA.

Convexity subarachnoid hemorrhage in lobar intracerebral hemorrhage: A prognostic marker.

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.

Cortical superficial siderosis and recurrent intracerebral hemorrhage risk in cerebral amyloid angiopathy: Large prospective cohort and preliminary meta-analysis.

BACKGROUND: We aimed to investigate cortical superficial siderosis as an MRI predictor of lobar intracerebral hemorrhage (ICH) recurrence risk in cerebral amyloid angiopathy (CAA), in a large prospective MRI cohort and a systematic review. METHODS: We analyzed a single-center MRI prospective cohort of consecutive CAA-related ICH survivors. Using Kaplan-Meier and Cox regression analyses, we investigated cortical superficial siderosis and ICH risk, adjusting for known confounders. We pooled data with eligible published cohorts in a two-stage meta-analysis using random effects models. Covariate-adjusted hazard rations (adj-HR) from pre-specified multivariable Cox proportional hazard models were used. RESULTS: The cohort included 240 CAA-ICH survivors (cortical superficial siderosis prevalence: 36%). During a median follow-up of 2.6 years (IQR: 0.9-5.1 years) recurrent ICH occurred in 58 patients (24%). In prespecified multivariable Cox regression models, cortical superficial siderosis presence and disseminated cortical superficial siderosis were independent predictors of increased symptomatic ICH risk at follow-up (HR: 2.26; 95% CI: 1.31-3.87, p = 0.003 and HR: 3.59; 95% CI: 1.96-6.57, p < 0.0001, respectively). Three cohorts including 443 CAA-ICH patients in total were eligible for meta-analysis. During a mean follow-up of 2.5 years (range: 2-3 years) 92 patients experienced recurrent ICH (pooled risk ratio: 6.9% per year, 95% CI: 4.2%-9.7% per year). In adjusted pooled analysis, any cortical superficial siderosis and disseminated cortical superficial siderosis were the only independent predictors associated with increased lobar ICH recurrence risk (adj-HR: 2.4; 95% CI: 1.5-3.7; p < 0.0001, and adj-HR: 4.4; 95% CI: 2-9.9; p < 0.0001, respectively). CONCLUSIONS: In CAA-ICH patients, cortical superficial siderosis presence and extent are the most important MRI prognostic risk factors for lobar ICH recurrence. These results can help guide clinical decision making in patients with CAA.

Dementia incidence and predictors in cerebral amyloid angiopathy patients without intracerebral hemorrhage.

Cerebral amyloid angiopathy (CAA) is a common cause of cognitive impairment in older individuals. This study aimed to investigate predictors of dementia in CAA patients without intracerebral hemorrhage (ICH). A total of 158 non-demented patients from the Stroke Service or the Memory Clinic who met the modified Boston Criteria for probable CAA were included. At baseline, neuroimaging markers, including lobar microbleeds (cerebral microbleeds (CMBs)), white matter hyperintensities (WMH), cortical superficial siderosis (cSS), magnetic resonance imaging (MRI)-visible centrum semiovale perivascular spaces (CSO-PVS), lacunes, and medial temporal atrophy (MTA) were assessed. The overall burden of small vessel disease (SVD) for CAA was calculated by a cumulative score based on CMB number, WMH severity, cSS presence and extent and CSO-PVS severity. The estimated cumulative dementia incidence at 1 year was 14% (95% confidence interval (CI): 5%-23%), and 5 years 73% (95% CI: 55%, 84%). Age (hazard ratio (HR) 1.05 per year, 95% CI: 1.01-1.08, p = 0.007), presence of MCI status (HR 3.40, 95% CI: 1.97-6.92, p < 0.001), MTA (HR 1.71 per point, 95% CI: 1.26-2.32, p = 0.001), and SVD score (HR 1.23 per point, 95% CI: 1.20-1.48, p = 0.030) at baseline were independent predictors for dementia conversion in these patients. Cognitive deterioration of CAA patients appears attributable to cumulative changes, from both vasculopathic and neurodegenerative lesions.

Evolution of cerebral microbleeds after cranial irradiation in medulloblastoma patients.

OBJECTIVE: To characterize the temporal and spatial pattern of cerebral microbleeds (CMBs) after cranial irradiation in patients with medulloblastoma. METHODS: We retrospectively identified patients with medulloblastoma treated with craniospinal irradiation at the Massachusetts General Hospital between 1999 and 2015. Longitudinal MRI including T2*-weighted gradient-recalled echo (GRE) sequences were reviewed, and the prevalence, spatial pattern, and risk factors associated with CMBs were characterized. RESULTS: We identified a total of 27 patients; 5 patients were children (median age 6.3 years) and 22 patients were adults (median age 28.8 years). CMBs were found in 67% (18/27) of patients, who were followed for a median of 4.1 years. Patients with CMBs had longer GRE follow-up time compared to those without CMBs (4.9 vs 1.7 years, p = 0.035). The median latency of the appearance of CMBs was 2.79 years (interquartile range 1.76-4.26). The prevalence of CMBs increased with each year from time of radiation therapy, and the cumulative prevalence was highest in patients age <20 years (100% cumulative prevalence, vs 59% in adult patients treated at age ≥20 years). CMBs were mostly found in lobar distribution and predominately in bilateral occipital lobes. Patients using antithrombotic medications developed CMBs at a significantly higher rate (p = 0.041). CONCLUSIONS: Our data demonstrate a high prevalence of CMBs following cranial irradiation, progressively increasing with each year from time of radiation therapy.

Cortical superficial siderosis and first-ever cerebral hemorrhage in cerebral amyloid angiopathy.

OBJECTIVE: To investigate whether cortical superficial siderosis (cSS) is associated with increased risk of future first-ever symptomatic lobar intracerebral hemorrhage (ICH) in patients with cerebral amyloid angiopathy (CAA) presenting with neurologic symptoms and without ICH. METHODS: Consecutive patients meeting modified Boston criteria for probable CAA in the absence of ICH from a single-center cohort were analyzed. cSS and other small vessel disease MRI markers were assessed according to recent consensus recommendations. Patients were followed prospectively for future incident symptomatic lobar ICH. Prespecified Cox proportional hazard models were used to investigate cSS and first-ever lobar ICH risk adjusting for potential confounders. RESULTS: The cohort included 236 patients with probable CAA without lobar ICH at baseline. cSS prevalence was 34%. During a median follow-up of 3.26 years (interquartile range 1.42-5.50 years), 27 of 236 patients (11.4%) experienced a first-ever symptomatic lobar ICH. cSS was a predictor of time until first ICH (p = 0.0007, log-rank test). The risk of symptomatic ICH at 5 years of follow-up was 19% (95% confidence interval [CI] 11%-32%) for patients with cSS at baseline vs 6% (95% CI 3%-12%) for patients without cSS. In multivariable Cox regression models, cSS presence was the only independent predictor of increased symptomatic ICH risk during follow-up (HR 4.04; 95% CI 1.73-9.44, p = 0.001), after adjusting for age, lobar cerebral microbleeds burden, and white matter hyperintensities. CONCLUSIONS: cSS is consistently associated with an increased risk of future lobar ICH in CAA with potentially important clinical implications for patient care decisions such as antithrombotic use.

Small vessel disease burden in cerebral amyloid angiopathy without symptomatic hemorrhage.

OBJECTIVE: Cerebral amyloid angiopathy (CAA) is a common age-related small vessel disease (SVD). Patients without intracerebral hemorrhage (ICH) typically present with transient focal neurologic episodes (TFNEs) or cognitive symptoms. We sought to determine if SVD lesion burden differed between patients with CAA first presenting with TFNEs vs cognitive symptoms. METHODS: A total of 647 patients presenting either to a stroke department (n = 205) or an outpatient memory clinic (n = 442) were screened for eligibility. Patients meeting modified Boston criteria for probable CAA were included and markers of SVD were quantified, including cerebral microbleeds (CMBs), perivascular spaces, cortical superficial siderosis (cSS), and white matter hyperintensities (WMHs). Patients were classified according to presentation symptoms (TFNEs vs cognitive). Total CAA-SVD burden was assessed using a validated summary score. Individual neuroimaging markers and total SVD burden were compared between groups using univariable and multivariable models. RESULTS: There were 261 patients with probable CAA included. After adjustment for confounders, patients first seen for TFNEs (n = 97) demonstrated a higher prevalence of cSS (p < 0.0001), higher WMH volumes (p = 0.03), and a trend toward higher CMB counts (p = 0.09). The total SVD summary score was higher in patients seen for TFNEs (adjusted odds ratio per additional score point 1.46, 95% confidence interval 1.16-1.84, p = 0.013). CONCLUSIONS: Patients with probable CAA without ICH first evaluated for TFNEs bear a higher burden of structural MRI SVD-related damage compared to those first seen for cognitive symptoms. This study sheds light on neuroimaging profile differences across clinical phenotypes of patients with CAA without ICH.

Cortical superficial siderosis multifocality in cerebral amyloid angiopathy: A prospective study.

OBJECTIVE: In order to explore the mechanisms of cortical superficial siderosis (cSS) multifocality and its clinical implications for recurrent intracerebral hemorrhage (ICH) risk in patients with cerebral amyloid angiopathy (CAA), we used a new rating method that we developed specifically to evaluate cSS extent at spatially separated foci. METHODS: Consecutive patients with CAA-related ICH according to Boston criteria from a single-center prospective cohort were analyzed. The new score that assesses cSS multifocality (total range 0-4) showed excellent interrater reliability (k = 0.87). The association of cSS with markers of CAA and acute ICH was investigated. Patients were followed prospectively for recurrent symptomatic ICH. RESULTS: The cohort included 313 patients with CAA. Multifocal cSS prevalence was 21.1%. APOE ε2 allele prevalence was higher in patients with multifocal cSS. In probable/definite CAA, cSS multifocality was independently associated with neuroimaging markers of CAA severity, including lobar microbleeds, but not with acute ICH features, which conversely, were determinants of cSS in possible CAA. During a median follow-up of 2.6 years (interquartile range 0.9-5.1 years), the annual ICH recurrence rates per cSS scores (0-4) were 5%, 6.5%, 13.5%, 16.2%, and 26.9%, respectively. cSS multifocality (presence and spread) was the only independent predictor of increased symptomatic ICH risk (hazard ratio 3.19; 95% confidence interval 1.77-5.75; p < 0.0001). CONCLUSIONS: The multifocality of cSS correlates with disease severity in probable CAA; therefore cSS is likely to be caused by discrete hemorrhagic foci. The new cSS scoring system might be valuable for clinicians in determining annual risk of ICH recurrence.

Hemorrhage recurrence risk factors in cerebral amyloid angiopathy: Comparative analysis of the overall small vessel disease severity score versus individual neuroimaging markers.

INTRODUCTION: An MRI-based score of total small vessel disease burden (CAA-SVD-Score) in cerebral amyloid angiopathy (CAA) has been demonstrated to correlate with severity of pathologic changes. Evidence suggests that CAA-related intracerebral hemorrhage (ICH) recurrence risk is associated with specific disease imaging manifestations rather than overall severity. We compared the correlation between the CAA-SVD-Score with the risk of recurrent CAA-related lobar ICH versus the predictive role of each of its components. METHODS: Consecutive patients with CAA-related ICH from a single-center prospective cohort were analyzed. Radiological markers of CAA related SVD damage were quantified and categorized according to the CAA-SVD-Score (0-6 points). Subjects were followed prospectively for recurrent symptomatic ICH. Adjusted Cox proportional hazards models were used to investigate associations between the CAA-SVD-Score as well as each of the individual MRI signatures of CAA and the risk of recurrent ICH. RESULTS: In 229 CAA patients with ICH, a total of 56 recurrent ICH events occurred during a median follow-up of 2.8years [IQR 0.9-5.4years, 781 person-years). Higher CAA-SVD-Score (HR=1.26 per additional point, 95%CI [1.04-1.52], p=0.015) and older age were independently associated with higher ICH recurrence risk. Analysis of individual markers of CAA showed that CAA-SVD-Score findings were due to the independent effect of disseminated superficial siderosis (HR for disseminated cSS vs none: 2.89, 95%CI [1.47-5.5], p=0.002) and high degree of perivascular spaces enlargement (RR=3.50-95%CI [1.04-21], p=0.042). CONCLUSION: In lobar CAA-ICH patients, higher CAA-SVD-Score does predict recurrent ICH. Amongst individual elements of the score, superficial siderosis and dilated perivascular spaces are the only markers independently associated with ICH recurrence, contributing to the evidence for distinct CAA phenotypes singled out by neuro-imaging manifestations.

Cognitive Profile and its Association with Neuroimaging Markers of Non-Demented Cerebral Amyloid Angiopathy Patients in a Stroke Unit.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is increasingly recognized as a cause of cognitive impairment in the elderly, but the cognitive profile in patients with the disease has not been well characterized. OBJECTIVE: To characterize the neuropsychological profile of CAA patients without dementia and to determine the association between cognitive performance in different domains and neuroimaging lesions characteristic of CAA. METHODS: Fifty-eight non-demented CAA patients were compared to 138 cognitively normal subjects using a standard neuropsychological test battery. Total brain volume (TBV), white matter hyperintensities, number of lobar cerebral microbleeds, hippocampal volume, and cortical superficial siderosis in all CAA patients were assessed. The association between these neuroimaging markers and neuropsychological performance in different cognitive domains in the CAA group were analyzed. RESULTS: Patients with CAA had significantly worse performance on all individual neuropsychological domains tested, when compared to the cognitive normal group. The cognitive decline of CAA patients was most noticeable in tests for processing speed with a Z score of -1.92±1.56 (mean±SD), then followed by executive function (-0.93±1.01), episodic memory (-0.87±1.29), semantic fluency (-0.73±1.06), and attention (-0.42±0.98). TBV of the CAA patients was correlated with processing speed (ß= 0.335, p = 0.03) and executive function (ß= 0.394, p = 0.01). CONCLUSIONS: Non-demented patients with CAA had cognitive deficits in multiple areas. Lower TBV was related to slower processing speed and worse executive function.

Microbleeds on MRI are associated with microinfarcts on autopsy in cerebral amyloid angiopathy.

OBJECTIVES: To identify in vivo MRI markers that might correlate with cerebral microinfarcts (CMIs) on autopsy in patients with cerebral amyloid angiopathy (CAA). METHODS: We included patients with neuropathologic evidence of CAA on autopsy and available antemortem brain MRI. Clinical characteristics and in vivo MRI markers of CAA-related small vessel disease were recorded, including white matter hyperintensities, cerebral microbleeds, cortical superficial siderosis, and centrum semiovale perivascular spaces. In addition, the presence of intracerebral hemorrhage on MRI was assessed. Evaluation of the presence and number of CMIs was performed in 9 standard histology sections. RESULTS: Of 49 analyzed patients with CAA, CMIs were present in 36.7%. The presence of ≥1 CMIs on autopsy was associated with higher numbers of microbleeds on antemortem MRI (median 8 [interquartile range 2.5-33.0] vs 1 [interquartile range 0-3], p = 0.003) and with the presence of intracerebral hemorrhage (44.4% vs 16.1%, p = 0.03). No associations between CMIs and other in vivo MRI markers of CAA were found. In a multivariable model adjusted for severe CAA pathology, higher numbers of microbleeds were independent predictors of the presence of CMIs on pathology. CONCLUSIONS: CMIs are a common finding at autopsy in patients with CAA. The strong association between MRI-observed microbleeds and CMIs at autopsy may suggest a shared underlying pathophysiologic mechanism between these lesions.

Total Magnetic Resonance Imaging Burden of Small Vessel Disease in Cerebral Amyloid Angiopathy: An Imaging-Pathologic Study of Concept Validation.

IMPORTANCE: Cerebral amyloid angiopathy (CAA) is characteristically associated with magnetic resonance imaging (MRI) biomarkers of small vessel brain injury, including strictly lobar cerebral microbleeds, cortical superficial siderosis, centrum semiovale perivascular spaces, and white matter hyperintensities. Although these neuroimaging markers reflect distinct pathophysiologic aspects in CAA, no studies to date have combined these structural imaging features to gauge total brain small vessel disease burden in CAA. OBJECTIVES: To investigate whether a composite score can be developed to capture the total brain MRI burden of small vessel disease in CAA and to explore whether this score contributes independent and complementary information about CAA severity, defined as intracerebral hemorrhage during life or bleeding-related neuropathologic changes. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, cross-sectional study examined a single-center neuropathologic CAA cohort of eligible patients from the Massachusetts General Hospital from January 1, 1997, through December 31, 2012. Data analysis was performed from January 2, 2015, to January 9, 2016. Patients with pathologic evidence of CAA (ie, any presence of CAA from routinely collected brain biopsy specimen, biopsy specimen at hematoma evacuation, or autopsy) and available brain MRI sequences of adequate quality, including T2-weighted, T2*-weighted gradient-recalled echo, and/or susceptibility-weighted imaging and fluid-attenuated inversion recovery sequences, were considered for the study. MAIN OUTCOMES AND MEASURES: Brain MRIs were rated for lobar cerebral microbleeds, cortical superficial siderosis, centrum semiovale perivascular spaces, and white matter hyperintensities. All 4 MRI lesions were incorporated into a prespecified ordinal total small vessel disease score, ranging from 0 to 6 points. Associations with severity of CAA-associated vasculopathic changes (fibrinoid necrosis and concentric splitting of the wall), clinical presentation, number of intracerebral hemorrhages, and other imaging markers not included in the score were explored using logistic and ordinal regression. RESULTS: In total, 105 patients with pathologically defined CAA were included: 52 with autopsies, 22 with brain biopsy specimens, and 31 with pathologic samples from hematoma evacuations. The mean (range) age of the patients was 73 (71-74) years, and 55 (52.4%) were women. In multivariable ordinal regression analysis, severity of CAA-associated vasculopathic changes (odds ratio, 2.40; 95% CI, 1.06-5.45; P = .04) and CAA presentation with symptomatic intracerebral hemorrhage (odds ratio, 2.23; 95% CI, 1.07-4.64; P = .03) were independently associated with the total MRI small vessel disease score. The score was associated with small, acute, diffusion-weighted imaging lesions and posterior white matter hyperintensities in adjusted analyses. CONCLUSIONS AND RELEVANCE: This study provides evidence of concept validity of a total MRI small vessel disease score in CAA. After further validation, this approach can be potentially used in prospective clinical studies.

Cortical superficial siderosis predicts early recurrent lobar hemorrhage.

OBJECTIVE: To identify predictors of early lobar intracerebral hemorrhage (ICH) recurrence, defined as a new ICH within 6 months of the index event, in patients with cerebral amyloid angiopathy (CAA). METHODS: Participants were consecutive survivors (age ≥55 years) of spontaneous symptomatic probable or possible CAA-related lobar ICH according to the Boston criteria, drawn from an ongoing single-center cohort study. Neuroimaging markers ascertained in CT or MRI included focal (≤3 sulci) or disseminated (>3 sulci) cortical superficial siderosis (cSS), acute convexity subarachnoid hemorrhage (cSAH), cerebral microbleeds, white matter hyperintensities burden and location, and baseline ICH volume. Participants were followed prospectively for recurrent symptomatic ICH. Cox proportional hazards models were used to identify predictors of early recurrent ICH adjusting for potential confounders. RESULTS: A total of 292 patients were enrolled. Twenty-one patients (7%) had early recurrent ICH. Of these, 24% had disseminated cSS on MRI and 19% had cSAH on CT scan. In univariable analysis, the presence of disseminated cSS, cSAH, and history of previous ICH were predictors of early recurrent ICH (p < 0.05 for all comparisons). After adjusting for age and history of previous ICH, disseminated cSS on MRI and cSAH on CT were independent predictors of early recurrent ICH (hazard ratio [HR] 3.92, 95% confidence interval [CI] 1.38-11.17, p = 0.011, and HR 3.48, 95% CI 1.13-10.73, p = 0.030, respectively). CONCLUSIONS: Disseminated cSS on MRI and cSAH on CT are independent imaging markers of increased risk for early recurrent ICH. These markers may provide additional insights into the mechanisms of ICH recurrence in patients with CAA.

Intracerebral hemorrhage after intravenous thrombolysis in patients with cerebral microbleeds and cardiac myxoma.

BACKGROUND AND PURPOSE: Cardiac myxoma is a rare etiology of stroke. Both cerebral microbleeds and cardiac myxoma may increase the risk of intracerebral hemorrhage after intravenous (IV) thrombolysis. However, data are still limited. We report a case of multiple cerebral microbleeds treated with IV thrombolysis with later findings of cardiac myxoma. SUMMARY OF CASE: A 58-year-old-man presented with right-sided hemiplegia and global aphasia. The presumptive diagnosis of acute left middle cerebral artery (MCA) infarction was made. Previous magnetic resonance imaging showed multiple cerebral microbleeds. The patient received IV thrombolysis. Bilateral cerebellar hemorrhage occurred after thrombolysis, and a median suboccipital craniectomy and hematoma removal was performed. Transthoracic echocardiogram found a left atrial myxoma. The tumor was then surgically removed. Six months later, neurological deficit improved. CONCLUSION: Cerebral microbleeds may be associated with atrial myxoma. IV thrombolysis could benefit acute ischemic stroke patients with both baseline cerebral microbleeds and atrial myxoma.