To determine whether MRI-based cerebral small vessel disease (CSVD) burden assessment, in addition to clinical and CT data, improved prediction of cognitive impairment after spontaneous intracerebral ...hemorrhage (ICH).
We analyzed data from ICH survivors enrolled in a single-center prospective study. We employed 3 validated CSVD burden scores: global, cerebral amyloid angiopathy (CAA)-specific, and hypertensive arteriopathy (HTNA)-specific. We quantified cognitive performance by administering the modified Telephone Interview for Cognitive Status test. We utilized linear mixed models to model cognitive decline rates, and survival models for new-onset dementia. We calculated CSVD scores' cutoffs to maximize predictive performance for dementia diagnosis.
We enrolled 612 ICH survivors, and followed them for a median of 46.3 months (interquartile range 35.5-58.7). A total of 214/612 (35%) participants developed dementia. Higher global CSVD scores at baseline were associated with faster cognitive decline (coefficient -0.25, standard error SE 0.02) and dementia risk (sub-hazard ratio 1.35, 95% confidence interval 1.10-1.65). The global score outperformed the CAA and HTNA scores in predicting post-ICH dementia (all
< 0.05). Compared to a model including readily available clinical and CT data, inclusion of the global CSVD score resulted in improved prediction of post-ICH dementia (area under the curve AUC 0.89, SE 0.02 vs AUC 0.81, SE 0.03,
= 0.008 for comparison). Global CSVD scores ≥2 had highest sensitivity (83%) and specificity (91%) for dementia diagnosis.
A validated MRI-based CSVD score is associated with cognitive performance after ICH and improved diagnostic accuracy for predicting new onset of dementia.
Objective
Oral anticoagulation treatment (OAT) resumption is a therapeutic dilemma in intracerebral hemorrhage (ICH) care, particularly for lobar hemorrhages related to amyloid angiopathy. We sought ...to determine whether OAT resumption after ICH is associated with long‐term outcome, accounting for ICH location (ie, lobar vs nonlobar).
Methods
We meta‐analyzed individual patient data from: (1) the multicenter RETRACE study (n = 542), (2) a U.S.‐based single‐center ICH study (n = 261), and (3) the Ethnic/Racial Variations of Intracerebral Hemorrhage study (n = 209). We determined whether, within 1 year from ICH, OAT resumption was associated with: (1) mortality, (2) favorable functional outcome (modified Rankin Scale = 0–3), and (3) stroke incidence. We separately analyzed nonlobar and lobar ICH cases using propensity score matching and Cox regression models.
Results
We included 1,012 OAT‐related ICH survivors (633 nonlobar and 379 lobar). Among nonlobar ICH survivors, 178/633 (28%) resumed OAT, whereas 86/379 (23%) lobar ICH survivors did. In multivariate analyses, OAT resumption after nonlobar ICH was associated with decreased mortality (hazard ratio HR = 0.25, 95% confidence interval CI = 0.14–0.44, p < 0.0001) and improved functional outcome (HR = 4.22, 95% CI = 2.57–6.94, p < 0.0001). OAT resumption after lobar ICH was also associated with decreased mortality (HR = 0.29, 95% CI = 0.17–0.45, p < 0.0001) and favorable functional outcome (HR = 4.08, 95% CI = 2.48–6.72, p < 0.0001). Furthermore, OAT resumption was associated with decreased all‐cause stroke incidence in both lobar and nonlobar ICH (both p < 0.01).
Interpretation
These results suggest novel evidence of an association between OAT resumption and outcome following ICH, regardless of hematoma location. These findings support conducting randomized trials to explore risks and benefits of OAT resumption after ICH. Ann Neurol 2017;82:755–765
IMPORTANCE: Cerebral amyloid angiopathy–related inflammation (CAA-ri), a distinct subtype of cerebral amyloid angiopathy, is characterized by an autoimmune reaction to cerebrovascular β-amyloid ...deposits. Outcomes and response to immunosuppressive therapy for CAA-ri are poorly understood. OBJECTIVE: To identify clinical, neuroimaging, laboratory, pathologic, or treatment-related associations with outcomes after an episode of CAA-ri. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of prospectively identified individuals who presented from July 3, 1998, to November 27, 2017, with a median follow-up of 2.7 years (interquartile range, 1.0-5.5 years). The study included 48 consecutive patients with CAA-ri meeting diagnostic criteria who had at least 1 disease episode and subsequent outcome data. No patients refused or were excluded. EXPOSURES: Prespecified candidate variables were immunosuppressive therapies, cerebrospinal fluid pleocytosis, magnetic resonance imaging findings of recent infarcts or contrast enhancement, and histopathologic evidence of vessel wall inflammation. MAIN OUTCOMES AND MEASURES: Clinical improvement and worsening were defined by persistent changes in signs or symptoms, radiographic improvement by decreased subcortical foci of T2 hyperintensity or T1 enhancement, and radiographic worsening by increased subcortical T2 hyperintensity, T1 enhancement, or infarcts. Disease recurrence was defined as new-onset clinical symptoms associated with new imaging findings. RESULTS: The 48 individuals in the study included 29 women and had a mean (SD) age of 68.9 (9.9) years. Results of presenting magnetic resonance imaging revealed that 10 of 29 patients with CAA-ri (34%) had T1 contrast enhancement, 30 of 32 (94%) had subcortical T2 hyperintensity (22 of 30 73% asymmetric), 7 of 32 (22%) had acute or subacute punctate infarcts, and 27 of 31 (87%) had microbleeds. Immunosuppressive treatments after first episodes included corticosteroids (33 69%), cyclophosphamide (6 13%), and mycophenolate (2 4%); 14 patients (29%) received no treatment. Clinical improvement and radiographic improvement were each more likely in individuals treated with an immunosuppressive agent than with no treatment (clinical improvement: 32 of 34 94% vs 7 of 14 50%; odds ratio, 16.0; 95% CI, 2.72-94.1; radiographic improvement: 24 of 28 86% vs 4 of 14 29%; odds ratio, 15.0; 95% CI, 3.12-72.1). Recurrence was less likely if CAA-ri was treated with any immunosuppressant agent than not (9 of 34 26% vs 10 of 14 71%; hazard ratio, 0.19; 95% CI, 0.07-0.48). When controlling for treatment, no variables were associated with outcomes aside from an association between APOE ɛ4 and radiographic improvement (odds ratio, 4.49; 95% CI, 1.11-18.2). CONCLUSIONS AND RELEVANCE: These results from a relatively large series of patients with CAA-ri support the effectiveness of immunosuppressive treatment and suggest that early treatment may both improve the initial disease course and reduce the likelihood of recurrence. These results raise the possibility that early blunting of CAA-ri and the autoimmune response may have long-term benefits for the subsequent disease course.
Intracerebral haemorrhage is less common than ischaemic stroke, but it is the most deadly or disabling neurological emergency, with mortality rates exceeding 40% in the acute phase and as few as 12% ...of affected patients able to live independently in the first year after haemorrhage.1 Clinicians have investigated surgery for haematoma evacuation and haemostatic therapies to stop the bleeding in intracerebral haemorrhage early after onset to limit the extent of the brain damage in the acute phase, but these trials have so far been unsuccessful.2,3 Given these results, more data are needed to understand the potential contributors to haematoma growth to identify better treatment targets and enrol the populations most likely to benefit in future studies. The presence of cerebral microbleeds, for instance, almost quadruples the risk of intracerebral haemorrhage in people with atrial fibrillation who take anticoagulants.7 Overall, such studies and meta-analyses of their data clarify the association between anticoagulants and brain bleeds—ie, that oral anticoagulants increase the risk of intracerebral haemorrhage especially in patients at higher baseline risk and they promote the growth of the haematoma, thereby worsening patient outcomes.4–9 In Al-Shahi Salman and colleagues' study,4 antiplatelet use was also associated with a modest increase in risk of haematoma growth (1·68, 95% CI 1·06–2·66; p=0·026), which emphasises the importance of using antiplatelets only when needed. ...even if the heightened growth risk of haematomas greater than 20–30 mL can be considered as an opportunity to treat large bleeds, it should be remembered that large baseline intracerebral haemorrhage also means severe tissue damage which might limit potential clinical benefit from haemostatic therapies.
OBJECTIVETo assess the predominant type of cerebral small vessel disease (SVD) and recurrence risk in patients who present with a combination of lobar and deep intracerebral hemorrhage ...(ICH)/microbleed locations (mixed ICH).
METHODSOf 391 consecutive patients with primary ICH enrolled in a prospective registry, 75 (19%) had mixed ICH. Their demographics, clinical/laboratory features, and SVD neuroimaging markers were compared to those of 191 patients with probable cerebral amyloid angiopathy (CAA-ICH) and 125 with hypertensive strictly deep microbleeds and ICH (HTN-ICH). ICH recurrence and case fatality were also analyzed.
RESULTSPatients with mixed ICH showed a higher burden of vascular risk factors reflected by a higher rate of left ventricular hypertrophy, higher creatinine values, and more lacunes and severe basal ganglia (BG) enlarged perivascular spaces (EPVS) than patients with CAA-ICH (all p < 0.05). In multivariable models mixed ICH diagnosis was associated with higher creatinine levels (odds ratio OR 2.5, 95% confidence interval CI 1.2–5.0, p = 0.010), more lacunes (OR 3.4, 95% CI 1.7–6.8), and more severe BG EPVS (OR 5.8, 95% CI 1.7–19.7) than patients with CAA-ICH. Conversely, when patients with mixed ICH were compared to patients with HTN-ICH, they were independently associated with older age (OR 1.03, 95% CI 1.02–1.1), more lacunes (OR 2.4, 95% CI 1.1–5.3), and higher microbleed count (OR 1.6, 95% CI 1.3–2.0). Among 90-day survivors, adjusted case fatality rates were similar for all 3 categories. Annual risk of ICH recurrence was 5.1% for mixed ICH, higher than for HTN-ICH but lower than for CAA-ICH (1.6% and 10.4%, respectively).
CONCLUSIONSMixed ICH, commonly seen on MRI obtained during etiologic workup, appears to be driven mostly by vascular risk factors similar to HTN-ICH but demonstrates more severe parenchymal damage and higher ICH recurrence risk.
BACKGROUND AND PURPOSE—Magnetic resonance imaging visible perivascular spaces in the centrum semiovale (CSO-PVS) have been associated with cerebral amyloid angiopathy (CAA).We aimed to further ...confirm this link by evaluating CSO-PVS volume in pathologically-demonstrated sporadic and genetically-demonstrated hereditary forms of the disease.
METHODS—We studied a retrospective hospital-based cohort consisting of 63 individuals aged >55 having brain magnetic resonance imaging and pathological assessment of CAA (mean age, 73.6±8.5; 46% female), and a separate cohort consisting of 26 carriers, and 28 noncarriers of the hereditary cerebral hemorrhage with amyloidosis–Dutch type (mean age, 46.7±12.8; 61.1% female). CSO-PVS volume was quantified on a single magnetic resonance imaging slice using a computer-assisted segmentation method and expressed as the relative volume of the intracranial volume in that particular slice (CSO-PVS relative volume). We compared CSO-PVS relative volume (1) between subjects with and without the disease in both cohorts; (2) between non-CAA, CAA without hemorrhage, and CAA with hemorrhage cases in the sporadic CAA cohort. All variables reaching P<0.1 in bivariate analyses were entered in logistic regression models.
RESULTS—In both sporadic and Dutch cohorts, cases with CAA had significantly higher CSO-PVS relative volume than cases without (median IQR3.7% 2.5–5.3 versus 1.8% 1.2–2.4, P<0.0001; 3.8% 0.6–6.2 versus 0.7% 0.4–1.6, P=0.007; respectively). In linear regression models, sporadic CAA was associated with higher CSO-PVS relative volume (P=0.008). In the sporadic CAA cohort, compared with non-CAA cases, CSO-PVS relative volume was higher in both CAA with hemorrhage and without hemorrhage (4.4% 2.6–6.1 and 3% 2.4–3.6 versus 1.8% 1.2–2.4, P<0.001 and P=0.005, respectively). Higher CSO-PVS relative volume was associated with CAA in regression models, both when hemorrhage was present (odds ratio, 2.63; 95% confidence interval, 1.33–5.18; P=0.005) and absent (odds ratio, 4.55; 95% confidence interval, 0.98–21.04; P=0.05).
CONCLUSIONS—Increased CSO-PVS volume is a consistent magnetic resonance imaging marker of cerebrovascular amyloid deposition and a promising diagnostic tool for sporadic CAA without hemorrhagic manifestations.
Objective: We hypothesized that florbetapir, a Food and Drug Administration-approved PET tracer, could distinguish cerebral amyloid angiopathy (CAA)-related intracerebral hemorrhage (ICH) from ...hypertensive ICH (HTN-ICH). Methods: We prospectively enrolled survivors of primary ICH related to probable CAA (per Boston Criteria, n = 10) and HTN-ICH (n = 9) without dementia. All patients underwent florbetapir-PET and multimodal MRI, and patients with CAA had additional Pittsburgh compound B (PiB) PET. Amyloid burden was assessed quantitatively (standard uptake value ratio SUVR) and visually classified as positive or negative. Results: The CAA and HTN-ICH groups had similar age (66.9 vs 67.1), sex, and leukoaraiosis volumes (31 vs 30 mL, all p> 0.8). Florbetapir uptake and PiB retention strongly correlated in patients with CAA both globally within cerebral cortex (r= 0.96, p< 0.001) and regionally in lobar cortices (all r> 0.8, all p< or = 0.01). Mean global cortical florbetapir uptake was substantially higher in CAA than HTN-ICH (SUVR: 1.41 + or - 0.17 vs 1.15 + or - 0.08, p= 0.001), as was mean occipital SUVR (1.44 + or - 0.12 vs 1.17 + or - 0.08, p< 0.001), even after correcting for global SUVR (p= 0.03). Visual rating for positive/negative florbetapir demonstrated perfect interrater agreement (k = 1) and was positive for all 10 patients with CAA vs 1 of 9 HTN-ICH patients (sensitivity 100%, specificity 89%). Conclusions: Florbetapir appears to label vascular amyloid in patients with CAA-related ICH. The approved florbetapir binary visual reading method can have diagnostic value in appropriate clinical settings.
Cerebral amyloid angiopathy is a common small vessel disease in the elderly involving vascular amyloid-β deposition. Cerebral amyloid angiopathy is one of the leading causes of intracerebral ...hemorrhage and a significant contributor to age-related cognitive decline. The awareness of a diagnosis of cerebral amyloid angiopathy is important in clinical practice as it impacts decisions to use lifelong anticoagulation or nonpharmacological alternatives to anticoagulation such as left atrial appendage closure in patients who have concurrent atrial fibrillation, another common condition in older adults. This review summarizes the latest literature regarding the management of patients with sporadic cerebral amyloid angiopathy, including diagnostic criteria, imaging biomarkers for cerebral amyloid angiopathy severity, and management strategies to decrease intracerebral hemorrhage risk. In a minority of patients, the presence of cerebral amyloid angiopathy triggers an autoimmune inflammatory reaction, referred to as cerebral amyloid angiopathy-related inflammation, which is often responsive to immunosuppressive treatment in the acute phase. Diagnosis and management of cerebral amyloid angiopathy-related inflammation will be presented separately. While there are currently no effective therapeutics available to cure or halt the progression of cerebral amyloid angiopathy, we discuss emerging avenues for potential future interventions.
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