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Background: Fatigue is a major complaint in stroke survivors, but data focusing on intracerebral haemorrhage (ICH) survivors are scarce. In a cohort of spontaneous ICH survivors, we assessed the long-term prevalence of fatigue and its associated factors., Methods: We included consecutive 1-year ICH survivors from the prospective, observational, single-centre Prognosis of Intracerebral Haemorrhage (PITCH) study. We evaluated fatigue (defined as a score ≥ 4 in Chalder Fatigue Scale); the severity of neurological, depressive, and anxiety symptoms; and functional disability 1, 3, and 6 years after ICH. We performed univariable and multivariable models to evaluate clinical factors and brain magnetic resonance imaging (MRI) small vessel disease (SVD) markers associated with fatigue., Results: Of 255 1-year ICH survivors, 153 (60%) underwent fatigue screening and were included in this study. Seventy-eight patients (51%) reported fatigue at 1-year, 56/110 (51%) at 3-year, and 27/67 (40%) at 6-year follow-up. Patients with fatigue exhibited more severe concomitant depressive/anxiety symptoms, but the severity of depressive symptoms was the only clinical factor significantly associated with 1-year fatigue in multivariable analysis (adjusted odds ratio 1.4 for one-point increase; 95% confidence interval 1.2-1.6). Patients with severe cortical atrophy at baseline had increased risk of fatigue at 1-year follow-up compared to patients with mild/no cortical atrophy (adjusted odds ratio 2.5; 95% confidence interval 1.1-5.8)., Conclusions: Fatigue after ICH is frequent and long-lasting, and it is associated with cortical atrophy (but not with other MRI markers of cerebral SVD). The link between fatigue and depressive symptoms may represent a potential therapeutic target., (© 2023. Fondazione Società Italiana di Neurologia.)

Objective: Neuropsychiatric (NP) symptoms are prominent features of cognitive decline, but they have been understudied in patients with spontaneous intracerebral haemorrhage (ICH). In ICH survivors, we aimed at assessing NP symptoms prevalence and profiles, and their influence on long-term outcomes., Methods: We analysed data from consecutive 6-month ICH survivors enrolled in the Prognosis of Intracerebral Haemorrhage study. We performed NP evaluation using the Neuropsychiatric Inventory Questionnaire. Patients underwent long-term clinical follow-up after ICH (median follow-up time 7.2 years, IQR 4.8-8.2)., Results: Out of 560 patients with ICH, 265 survived at 6 months. NP evaluation 6 months after ICH was feasible in 202 patients. NP symptoms were present in 112 patients (55%), and in 36 out of 48 patients (75%) with post-ICH dementia. Affective symptoms were present in 77 patients (38%), followed by vegetative symptoms (52 patients, 26%) and hyperactivity (47 patients, 23%). Apathy and hyperactivity were associated with post-ICH dementia and cerebral amyloid angiopathy MRI profile (all p<0.05). Apathy and hyperactivity prevailing over affective symptoms at 6-month follow-up were associated with higher risks of developing new-onset dementia (HR 5.40; 95% CI 2.27 to 12.84), while presence or severity of NP symptoms were not., Conclusion: NP symptoms were present in more than half of 6-month ICH survivors, with higher prevalence and severity in patients with post-ICH dementia. Distinctive NP profile might be associated to cognitive status and inform on long-term dementia risk., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To identify in patients who survived 6 months after a spontaneous intracerebral haemorrhage (ICH) baseline characteristics and new clinical events associated with functional decline., Methods: In a single-centre study, we prospectively included 6-month survivors with a modified Rankin Scale (mRS) score 0-3. We defined functional decline by a transition to mRS 4-5. We evaluated associations of baseline characteristics and new clinical events with functional decline, using univariate and multivariable models., Results: Of 560 patients, 174 (31%) had an mRS score 0-3 at 6 months. During a median follow-up of 9 years (IQR 8.1-9.5), 40 (23%) converted to mRS 4-5. Age, diabetes mellitus, ICH volume and higher mRS scores at 6 months were independently associated with functional decline. Among baseline MRI markers, presence of strictly lobar cerebral microbleeds (CMBs), and mixed lobar and deep CMBs were independently associated with functional decline. When new clinical events occurring during follow-up were added in multivariable models, age (cause-specific HR (CSHR): 1.07; 95% CI: 1.03 to 1.11), ICH volume (CSHR: 1.03; 95% CI: 1.01 to 1.06), mRS score at 6 months (CSHR per 1 point increase 1.61, 95% CI 1.07 to 2.43), occurrence of dementia (CSHR: 3.81, 95% CI: 1.78 to 8.16) and occurrence of any stroke (CSHR: 4.29, 95% CI: 1.80 to 10.22) remained independently associated with transition to mRS 4-5., Interpretation: Almost one-fourth of patients with spontaneous ICH developed a functional decline over time. Age, ICH volume, higher mRS score at 6 months and new clinical events after ICH are the major determinants., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objective: Predictors of symptomatic haemorrhagic transformation (s-HT) of cerebral ischaemia after intravenous recombinant tissue-plasminogen activator (rt-PA) were identified in studies using CT scans. We evaluated whether MRI can identify other predictors., Method: We analysed predictors of s-HT in a cohort of consecutive patients who received intravenous rt-PA for cerebral ischaemia after MRI at baseline. We used receiver operating characteristic curves considering an area under the curve (AUC) of 0.70 or higher as indicating acceptable discrimination., Results: Of 944 patients, 49 patients (5.2%) developed s-HT. Clinical factors independently associated with s-HT were age (adjusted OR (adjOR) 1.03 for 1 year increase; 95% CI 1.01 to 1.05), excessive alcohol consumption (adjOR 3.13; 95% CI 1.32 to 7.42), recent transient ischaemic attack (adjOR 2.88; 95% CI 1.04 to 7.95) and baseline national institutes of health stroke scale score (adjOR 1.06 for 1 point increase; 95% CI 1.02 to 1.10). MRI predictors were vascular hyperintensities (adjOR 3.89; 95% CI 1.50 to 10.08), old infarcts (adjOR 2.01; 95% CI 1.11 to 3.66) and volume of diffusion-weighted imaging (DWI) abnormality (adjOR 1.02 for 1 cm 3 increase; 95% CI 1.01 to 1.03). The only variable with an acceptable discrimination was volume of DWI abnormality (AUC 0.72; 95% CI 0.64 to 0.79), a value of 4 cm 3 predicting s-HT with a 78% sensitivity and 58% specificity. Variables that can be assessed only with MRI did not predict s-HT., Conclusion: Although the volume of DWI abnormality predicts s-HT, other imaging characteristics that can only be assessed with MRI were not significantly associated with s-HT. Trial registration number NCT01614080., Competing Interests: Competing interests: ND-P and HH reports participation in drug trials with Boehringer-Ingelheim (honoraria paid to the hospital). CC reports participation in symposia organised by Boehringer-Ingelheim and Pfizer, advisory board by BMS (honoraria paid to ADRINORD), drug trials with Boehringer-Ingelheim, Servier, Astra-Zeneca, Biogen (honoraria paid to the hospital), vice president of the European Stroke Organisation (unpaid), member of DSMBs for institutional trials (unpaid): ATTEST 2 (UK), FIV-HeMA (France). Research support from the French Ministry of Health (A3ICH). DL reports participation in symposia organised by Boehringer Ingelheim, Bayer, BMS and Pfizer (honoraria paid to Adrinord), drug trials with Boehringer-Ingelheim (honoraria paid to the hospital), vice editor of the European Stroke Journal (honoraria paid to Adrinord), vice president of the scientific committee of the Fondation de Recherche sur les AVC (unpaid) and member of the scientific committee of the Servier Institute (unpaid). Member of DSMBs for institutional trials (unpaid): INCH (Germany), TARDIS (UK), and TO-ACT (the Netherlands). Research support from a grant of the University of Heidelberg (Germany) for the ECASS4 trial., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

While being increasingly recognized in clinical routine, brain microbleeds remain a puzzling finding for physicians. These small dot-like lesions are thought to be old perivascular collections of hemosiderin deposits. They can be found in different neurological settings such as cerebrovascular or neurodegenerative diseases. While their microscopic size would suggest considering these lesions as anecdotal, they are now regarded as biomarkers of severity of an underlying cerebrovascular disease. Their natural history and the interactions with surrounding brain cells remain unknown. However, their presence may impact therapeutic decisions. Deciphering the biological mechanisms leading to, or following microbleeds would enable us to address a key question: do microbleeds arise and impact the surrounding parenchyma like a miniature version of intracerebral hemorrhages or do they represent a different kind of injury? We hereby discuss, based on both clinical and experimental literature, the gap between the definition of microbleeds coming from neuroimaging and the pathophysiological hypotheses raised from histopathological and experimental data. Our analysis supports the need for a convergent effort from clinicians and basic scientists to go beyond the current "macro" view and disclose the cellular and molecular insights of these cerebral hemorrhagic microlesions.

Background and Purpose- We aimed to determine incidences and predictors of major vascular events in intracerebral hemorrhage (ICH) survivors. Methods- We did a prospective observational cohort study in patients with spontaneous ICH from the Prognosis of Intracerebral Hemorrhage cohort in Lille, France. We studied incidences and predictors of long-term vascular events (cerebral and extracerebral, ischemic and hemorrhagic) in patients alive at 30 days with a prespecified subgroup analysis according to ICH location. We performed multivariable analyses (competing risk analyses, with death during follow-up as a competing event). Results- From the 560 patients with spontaneous ICH enrolled between November 2004 and March 2009, we included 310 patients (median age, 70 years). Eighty-two patients presented at least 1 major vascular event leading to an incidence rate of 20.0% (95% CI, 15.7-24.7) at 5 years after ICH. In the overall cohort, ischemic events were more frequent than hemorrhagic events. However, the incidence strikingly differed according to ICH location: deep ICH was associated with future ischemic events (subhazard ratio, 1.85; 95% CI, 1.01-3.40), whereas lobar ICH with hemorrhagic events (subhazard ratio, 2.38; 95% CI, 1.17-4.86). In deep ICH, the incidence of ischemic events at 5 years was 6× higher than the incidence of hemorrhagic events. Conclusions- ICH survivors are at high risk of both cerebral and extracerebral vascular events. The ischemic or hemorrhagic risk profile varies according to the index ICH location with a stronger ischemic risk in deep ICH. Secondary prevention, tailored on ICH location, should target not only cerebral recurrences but also extracerebral vascular events.

Objective: To determine the prevalence of cortical superficial siderosis (cSS), its clinical and neuroimaging associated markers, and its influence on the risk of recurrent intracerebral hemorrhage (ICH) in a prospective observational ICH cohort., Methods: We investigated clinical and radiologic markers associated with cSS using multivariable analysis. In survival analyses, we used Cox models to identify predictors of recurrent ICH after adjusting for potential confounders., Results: Of the 258 patients included in the study, 49 (19%; 95% confidence interval [CI] 14%-24%) had cSS at baseline. Clinical factors independently associated with the presence of cSS were increasing age (odds ratio [OR] 1.03 per 1-year increase, 95% CI 1.001-1.06, p = 0.044), preexisting dementia (OR 2.62, 95% CI 1.05-6.51, p = 0.039), and history of ICH (OR 4.02, 95% CI 1.24-12.95, p = 0.02). Among radiologic biomarkers, factors independently associated with the presence of cSS were ICH lobar location (OR 24.841, 95% CI 3.2-14.47, p < 0.001), severe white matter hyperintensities score (OR 5.51, 95% CI 1.17-5.78, p = 0.019), and absence of lacune (OR 4.46, 95% CI 1.06-5.22, p = 0.035). During a median follow-up of 6.4 (interquartile range 2.9-8.4) years, recurrent ICH occurred in 19 patients. Only disseminated cSS (hazard ratio 4.69, 95% CI 1.49-14.71, p = 0.008), not the presence or absence of cSS or focal cSS on baseline MRI, was associated with recurrent symptomatic ICH., Conclusion: In a prospective observational cohort of spontaneous ICH, clinical and radiologic markers associated with cSS suggest the implication of underlying cerebral amyloid angiopathy. Disseminated cSS may become a key prognostic neuroimaging marker of recurrent ICH that could be monitored in future clinical trials dedicated to patients with ICH., (© 2018 American Academy of Neurology.)

Objective: We evaluated recurrent intracerebral hemorrhage (ICH) risk in ICH survivors, stratified by the presence, distribution, and number of cerebral microbleeds (CMBs) on MRI (i.e., the presumed causal underlying small vessel disease and its severity)., Methods: This was a meta-analysis of prospective cohorts following ICH, with blood-sensitive brain MRI soon after ICH. We estimated annualized recurrent symptomatic ICH rates for each study and compared pooled odds ratios (ORs) of recurrent ICH by CMB presence/absence and presumed etiology based on CMB distribution (strictly lobar CMBs related to probable or possible cerebral amyloid angiopathy [CAA] vs non-CAA) and burden (1, 2-4, 5-10, and >10 CMBs), using random effects models., Results: We pooled data from 10 studies including 1,306 patients: 325 with CAA-related and 981 CAA-unrelated ICH. The annual recurrent ICH risk was higher in CAA-related ICH vs CAA-unrelated ICH (7.4%, 95% confidence interval [CI] 3.2-12.6 vs 1.1%, 95% CI 0.5-1.7 per year, respectively; p = 0.01). In CAA-related ICH, multiple baseline CMBs (versus none) were associated with ICH recurrence during follow-up (range 1-3 years): OR 3.1 (95% CI 1.4-6.8; p = 0.006), 4.3 (95% CI 1.8-10.3; p = 0.001), and 3.4 (95% CI 1.4-8.3; p = 0.007) for 2-4, 5-10, and >10 CMBs, respectively. In CAA-unrelated ICH, only >10 CMBs (versus none) were associated with recurrent ICH (OR 5.6, 95% CI 2.1-15; p = 0.001). The presence of 1 CMB (versus none) was not associated with recurrent ICH in CAA-related or CAA-unrelated cohorts., Conclusions: CMB burden and distribution on MRI identify subgroups of ICH survivors with higher ICH recurrence risk, which may help to predict ICH prognosis with relevance for clinical practice and treatment trials., (Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Spontaneous intracerebral haemorrhage is defined as a collection of blood in the cerebral parenchyma that is not caused by trauma. It represents roughly 10-20% of all strokes. The clinical presentation is unspecific and the diagnosis requires brain imaging. ICH is a medical emergency and ICH patients have to be admitted in an acute stroke unit. The priority is to fight against ICH expansion. The first step consists in the administration of a specific antagonist of the antithrombotic treatment when available, and in the strict control of blood pressure. Clinicians should keep in mind that the concept of so-called "primary" ICH is misleading since many causes should be searched for. During follow-up, the risk of recurrence may depend on the underlying vessel disease and blood pressure should be strictly managed. ICH patients are at high risk of dementia: cognitive evaluation should regularly be performed during follow-up., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objectives: To identify associated factors and influence on long-term outcome of heavy alcohol intake in a large prospective cohort of consecutive patients with a spontaneous intracerebral hemorrhage (ICH)., Methods: Between November 2004 and March 2009, we prospectively recruited 562 consecutive adults with a spontaneous ICH. We excluded patients without information on drinking habit (n = 22). Heavy alcohol intake was defined as a regular consumption of more than 300 g alcohol/week. We performed bivariate and multivariate analyses (logistic regression) based on demographic and radiologic models. Survival analyses were performed using Kaplan-Meier statistics., Results: Among 540 patients with ICH, 137 (25) were heavy alcohol drinkers (median age 60 vs 74 years in nonabusers; p < 0.0001). In the multivariate demographic model, heavy alcohol drinkers were less likely to be older (odds ratio [OR] 0.97 per 1-year increase, 95% confidence interval [CI] 0.95-0.98) and to have a history of ischemic heart disease (OR 0.34, 95% CI 0.15-0.77) and more likely to be smokers (OR 3.96, 95% CI 2.43-6.46). In the radiologic model, independent factors were nonlobar location of ICH (OR 1.71, 95% CI 1.05-2.77) and less severe leukoaraiosis (OR 0.76 per 1-step increase, 95%CI 0.62-0.73). Platelet counts and prothrombin ratio were significantly lower among heavy alcohol drinkers (respectively, p = 0.01 and p = 0.017). Heavy alcohol intake was predictive of 2 years mortality only among patients younger than 60 years with nonlobar ICH (hazard ratio 1.96, 95% CI 1.06-3.63)., Conclusion: Heavy alcohol intake is associated with the occurrence of ICH at a young age. However, the underlying vasculopathy remains unexplored in these patients. Indirect markers suggest small-vessel disease at an early stage that might be enhanced by moderate hemostatic disorders.

Background and purpose: Guidelines help physicians to provide optimal care for stroke patients, but implementation is challenging due to the quantity of recommendations. Therefore a practical overview related to applicability of recommendations can be of assistance. Methods: A systematic review was performed on ischaemic stroke guidelines published in scientific journals, covering the whole acute care process for patients with ischaemic stroke. After data extraction, experts rated the recommendations on dimensions of applicability, that is, actionability, feasibility and validity, on a 9‐point Likert scale. Agreement was defined as a score of ≥8 by ≥80% of the experts. Results: Eighteen articles were identified and 48 recommendations were ultimately extracted. Papers were included only if they described the whole acute care process for patients with ischaemic stroke. Data extraction and analysis revealed variation in terms of both content and comprehensiveness of this description. Experts reached agreement on 34 of 48 (70.8%) recommendations in the dimension actionability, for 16 (33.3%) in feasibility and for 15 (31.3%) in validity. Agreement on all three dimensions was reached for seven (14.6%) recommendations: use of a stroke unit, exclusion of intracerebral haemorrhage as differential diagnosis, administration of intravenous thrombolysis, performance of electrocardiography/cardiac evaluation, non‐invasive vascular examination, deep venous thrombosis prophylaxis and administration of statins if needed. Discussion and conclusion: Substantial variation in agreement was revealed on the three dimensions of the applicability of recommendations. This overview can guide stroke physicians in improving the care process and removing barriers where implementation may be hampered by validity and feasibility. [ABSTRACT FROM AUTHOR]

Stroke affects up to one in five people during their lifetime in some high-income countries, and up to almost one in two in low-income countries. Globally, it is the second leading cause of death. Clinically, the disease is characterised by sudden neurological deficits. Vascular aetiologies contribute to the most common causes of ischaemic stroke, including large artery disease, cardioembolism, and small vessel disease. Small vessel disease is also the most frequent cause of intracerebral haemorrhage, followed by macrovascular causes. For acute ischaemic stroke, multimodal CT or MRI reveal infarct core, ischaemic penumbra, and site of vascular occlusion. For intracerebral haemorrhage, neuroimaging identifies early radiological markers of haematoma expansion and probable underlying cause. For intravenous thrombolysis in ischaemic stroke, tenecteplase is now a safe and effective alternative to alteplase. In patients with strokes caused by large vessel occlusion, the indications for endovascular thrombectomy have been extended to include larger core infarcts and basilar artery occlusion, and the treatment time window has increased to up to 24 h from stroke onset. Regarding intracerebral haemorrhage, prompt delivery of bundled care consisting of immediate anticoagulation reversal, simultaneous blood pressure lowering, and prespecified stroke unit protocols can improve clinical outcomes. Guided by underlying stroke mechanisms, secondary prevention encompasses pharmacological, vascular, or endovascular interventions and lifestyle modifications. [ABSTRACT FROM AUTHOR]

Background: Although anxiety is common in several neurological conditions, it has been poorly investigated after spontaneous intracerebral hemorrhage (ICH). Aims: In consecutive ICH survivors, we assessed the long-term prevalence of anxiety and its clinical and radiological determinants. Methods: Using the Hospital Anxiety and Depression Scale (HADS), we evaluated ICH survivors enrolled in the prospective, single-center Prognosis of Intracerebral Hemorrhage (PITCH) study. The prevalence of anxiety (defined as a HADS-anxiety subscale score >7) was evaluated at three time points (1–2, 3–5, and 6–8 years after ICH), along with neurological symptoms severity, functional disability, and cognitive impairment scores. Clinical and radiological characteristics associated with anxiety were evaluated in univariate and multivariable models. Results: Of 560 patients with spontaneous ICH, 255 were alive 1 year later, 179 of whom completed the HADS questionnaire and were included in the study. Thirty-one patients (17%; 95% confidence interval (CI) = 12–23) had anxiety 1–2 years, 38 (27%; 95% CI = 19–34) 3–5 years, and 18 (21%; 95% CI = 12–30) 6–8 years after ICH. In patients with anxiety, the prevalence of associated depressive symptoms was 48% 1–2 years, 61% 3–5 years, and 56% 6–8 years after ICH. Among clinical and radiological baseline characteristics, only lobar ICH location was significantly associated with anxiety 1–2 years after ICH (odds ratio = 2.8; 95% CI = 1.2–6.5). Anxiety was not associated with concomitant neurological symptoms severity, functional disability, or cognitive impairment. Conclusion: Anxiety is frequent in ICH survivors, often in association with depressive symptoms, even many years after the index event. [ABSTRACT FROM AUTHOR]

Objective: This study aimed at identifying the incidence, predictors, and impact on long-term mortality and dementia of early-onset delirium in a cohort of patients with spontaneous intracerebral hemorrhage. Methods: We prospectively recruited consecutive patients in the Prognosis of InTra-Cerebral Hemorrhage (PITCH) cohort and analyzed incidence rate of early-onset delirium (i.e. during the first seven days after intracerebral hemorrhage onset) with a competing risk model. We used a multivariable Fine-Gray model to identify baseline predictors, a Cox regression model to study its impact on the long-term mortality risk, and a Fine-Gray model adjusted for pre-specified confounders to analyze its impact on new-onset dementia. Results: The study population consisted of 248 patients (mean age 70 years, 54% males). Early-onset delirium incidence rate was 29.8% (95% confidence interval (CI) 24.3–35.6). Multivariate analysis showed that pre-existing dementia (subhazard ratio (SHR) 2.08, 95%CI 1.32–3.32, p = 0.002), heavy alcohol intake (SHR 1.79, 95%CI 1.13–2.82, p = 0.013), and intracerebral hemorrhage lobar location (SHR 1.56, 95%CI 1.01–2.42, p = 0.049) independently predicted early-onset delirium. Median follow-up was 9.5 years. Early-onset delirium was associated with higher mortality rates during the first five years of follow-up (HR 1.52, 95%CI 1.00–2.31, p = 0.049), but did not predict new-onset dementia (SHR 1.31, 95%CI 0.60–2.87). Conclusion: Early-onset delirium is a frequent complication after intracerebral hemorrhage; it is associated with markers of pre-existing brain vulnerability and with higher mortality risk, but not with higher dementia rates during long-term follow-up. [ABSTRACT FROM AUTHOR]

Background: Factors associated with long-term mortality after spontaneous intracerebral hemorrhage (ICH) have been poorly investigated. Aim: Our objective was to identify variables associated with long-term mortality in a prospective cohort of 30-day ICH survivors. Methods: We prospectively included consecutive 30-day spontaneous ICH survivors. We evaluated baseline and follow-up clinical characteristics and magnetic resonance imaging (MRI) markers of chronic brain injury as variables associated with long-term mortality using univariate and multivariable Cox proportional hazard regression models. Results: Of 560 patients with spontaneous ICH, 304 (54.2%) survived more than 30 days and consented for follow-up. During a median follow-up of 10 years (interquartile range: 8.0–10.5), 176 patients died. The cumulative survival rate at 10 years was 38%. In multivariable analysis, variables independently associated with long-term mortality were age (hazard ratio (HR) per 10-year increase: 1.68, 95% confidence interval (CI): 1.45–1.95), male gender (HR: 1.41, CI: 1.02–1.95), prestroke dependency (HR: 1.66, CI: 1.15–2.39), National Institutes of Health Stroke Scale score (HR per 1-point increase: 1.03, CI: 1.01–1.04), occurrence of any stroke (HR: 2.24, CI: 1.39–3.60), and dementia (HR: 1.51, CI: 1.06–2.16) during follow-up. Among MRI markers, only cerebral atrophy (HR per 1-point increase: 1.50, CI: 1.13–2.00) was independently associated with long-term mortality. Conclusions: Preexisting comorbidities, clinical severity at presentation, and significant clinical event during follow-up are associated with long-term mortality. Among MRI markers of chronic brain injury, only cerebral atrophy is associated with long-term mortality. [ABSTRACT FROM AUTHOR]

Background: Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid β in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report an international collaborative study aiming to update and externally validate the Boston diagnostic criteria across the full spectrum of clinical CAA presentations.Methods: In this multicentre, hospital-based, retrospective, MRI and neuropathology diagnostic accuracy study, we did a retrospective analysis of clinical, radiological, and histopathological data available to sites participating in the International CAA Association to formulate updated Boston criteria and establish their diagnostic accuracy across different populations and clinical presentations. Ten North American and European academic medical centres identified patients aged 50 years and older with potential CAA-related clinical presentations (ie, spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathological assessment for CAA diagnosis. MRI scans were centrally rated at Massachusetts General Hospital (Boston, MA, USA) for haemorrhagic and non-haemorrhagic CAA markers, and brain tissue samples were rated by neuropathologists at the contributing sites. We derived the Boston criteria version 2.0 (v2.0) by selecting MRI features to optimise diagnostic specificity and sensitivity in a prespecified derivation cohort (Boston cases 1994-2012, n=159), then externally validated the criteria in a prespecified temporal validation cohort (Boston cases 2012-18, n=59) and a geographical validation cohort (non-Boston cases 2004-18; n=123), comparing accuracy of the new criteria to the currently used modified Boston criteria with histopathological assessment of CAA as the diagnostic standard. We also assessed performance of the v2.0 criteria in patients across all cohorts who had the diagnostic gold standard of brain autopsy.Findings: The study protocol was finalised on Jan 15, 2017, patient identification was completed on Dec 31, 2018, and imaging analyses were completed on Sept 30, 2019. Of 401 potentially eligible patients presenting to Massachusetts General Hospital, 218 were eligible to be included in the analysis; of 160 patient datasets from other centres, 123 were included. Using the derivation cohort, we derived provisional criteria for probable CAA requiring the presence of at least two strictly lobar haemorrhagic lesions (ie, intracerebral haemorrhages, cerebral microbleeds, or foci of cortical superficial siderosis) or at least one strictly lobar haemorrhagic lesion and at least one white matter characteristic (ie, severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern). The sensitivity and specificity of these criteria were 74·8% (95% CI 65·4-82·7) and 84·6% (71·9-93·1) in the derivation cohort, 92·5% (79·6-98·4) and 89·5% (66·9-98·7) in the temporal validation cohort, 80·2% (70·8-87·6) and 81·5% (61·9-93·7) in the geographical validation cohort, and 74·5% (65·4-82·4) and 95·0% (83·1-99·4) in all patients who had autopsy as the diagnostic standard. The area under the receiver operating characteristic curve (AUC) was 0·797 (0·732-0·861) in the derivation cohort, 0·910 (0·828-0·992) in the temporal validation cohort, 0·808 (0·724-0·893) in the geographical validation cohort, and 0·848 (0·794-0·901) in patients who had autopsy as the diagnostic standard. The v2.0 Boston criteria for probable CAA had superior accuracy to the current Boston criteria (sensitivity 64·5% [54·9-73·4]; specificity 95·0% [83·1-99·4]; AUC 0·798 [0·741-0854]; p=0·0005 for comparison of AUC) across all individuals who had autopsy as the diagnostic standard.Interpretation: The Boston criteria v2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their specificity in our cohorts of patients aged 50 years and older presenting with spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes. Future studies will be needed to determine generalisability of the v.2.0 criteria across the full range of patients and clinical presentations.Funding: US National Institutes of Health (R01 AG26484). [ABSTRACT FROM AUTHOR]