Background: Severe hematoma expansion (sHE) has the strongest impact on intracerebral hemorrhage (ICH) outcome. We investigated the predictors of sHE. Methods: Retrospective analysis of ICH patients admitted at nine sites in Italy, Germany, China, and Canada. The following imaging features were analyzed: non-contrast CT (NCCT) hypodensities, heterogeneous density, blend sign, irregular shape, and CT angiography (CTA) spot sign. The outcome of interest was sHE, defined as volume increase >66% and/or >12.5 from baseline to follow-up NCCT. Predictors of sHE were explored with logistic regression. Results: A total of 1472 patients were included (median age 73, 56.6% males) of whom 223 (15.2%) had sHE. Age (odds ratio (OR) per year, 95% confidence interval (CI), 1.02 (1.01–1.04)), Anticoagulant treatment (OR 3.00, 95% CI 2.09–4.31), Glasgow Coma Scale (OR 0.93, 95% CI 0.89–0.98), time from onset/last known well to imaging, (OR per h 0.96, 95% CI 0.93–0.99), and baseline ICH volume, (OR per mL 1.02, 95% CI 1.02–1.03) were independently associated with sHE. Ultra-early hematoma growth (baseline volume/baseline imaging time) was also a predictor of sHE (OR per mL/h 1.01, 95% CI 1.00–1.02). All NCCT and CTA imaging markers were also predictors of sHE. Amongst imaging features NCCT hypodensities had the highest sensitivity (0.79) whereas the CTA spot sign had the highest positive predictive value (0.51). Conclusions: sHE is common in the natural history of ICH and can be predicted with few clinical and imaging variables. These findings might inform clinical practice and future trials targeting active bleeding in ICH.

Introduction: Nonketotic hyperglycemic hyperosmolar state (NKHHS) is associated with a wide spectrum of neurological syndromes including acute stroke-like deficits. Clinical features and etiology have not been established yet.Methods: Here we provide a case illustration and systematic review on non-epileptic acute neurological deficits in NKHSS. The systematic literature search followed PRISMA guidelines and a predefined protocol, including cases of NKHSS with acute stroke-like presentation.Results: The database search yielded 18 cases. Hemianopia was the most common clinical presentation (73%), followed by partial or total anterior circulation syndrome (26%). Patients with symptoms of acute anterior circulation infarct were significantly older (69.5 ± 5.1 vs. 52.2 ± 13.9 years;p = 0.03) and showed higher mean glucose levels at the admission vs. those with hemianopia (674.8 ± 197.2 vs. 529.4 ± 190.8 mg/dL;p = 0.16). Brain MRI was performed in 89% of patients, resulting abnormal in 71% of them, especially hemianopic (91%). Subcortical hypointensities in T2-FLAIR MR sequences were present in all the analyzed cases. Cortical DWI hyperintensities were also common (64%). EEG showed diffuse or focal slow wave activity in 68% of patients, especially with visual hallucinations (85%). Neurological symptoms completely resolved in 78% of patients within 6 (IQR 3–10) days, following aggressive treatment and glucose normalization.Conclusions: Our results suggest neuronal dysfunction on a metabolic basis as the leading cause of acute neurological deficits in NKHHS. Despite the generally favorable prognosis, prompt identification and aggressive treatment are crucial to avoid irreversible damage. Larger cohort studies are needed to confirm our findings.

The risk of recurrent ischemic stroke, intracranial hemorrhage, and mortality in people with atrial fibrillation detected after stroke (AFDAS) is still unclear compared with people with known atrial fibrillation (KAF). We systematically reviewed the literature to provide updated estimates for the risk of recurrent stroke, intracerebral hemorrhage, and mortality in AFDAS compared with KAF. Our protocol was registered in PROSPERO (CRD42024583064). Presentation followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. We searched MEDLINE, EMBASE, Cochrane CENTRAL, and MedRxiv up to August 28, 2024, for studies comparing AFDAS and KAF for the following outcomes of interest: recurrent ischemic stroke (primary), intracerebral hemorrhage, mortality, and any stroke recurrence. We included cohort, observational studies (either prospective or retrospective) and randomized controlled trials and excluded studies with less than 15 patients per group. Eligible studies were assessed for bias using the Risk of Bias in Non-Randomized Studies tool. We pooled study-level results through random-effect meta-analysis of risk ratios (RRs). We also performed prespecified sensitivity analysis for study quality, timing of search for AF, propensity score matching, and study data source (administrative vs local data), and we planned meta-regression analysis to test for the interaction of sex, comorbid cardiovascular risk factors, and anticoagulation status on the difference between AFDAS and KAF. Seventeen studies were retrieved (n = 113,365; n_KAF = 80,339; n_AFDAS = 33,026; female in KAF, 49.0%; female in AFDAS, 45.1%), eight of which had low risk of bias. Ischemic stroke recurrence was significantly lower in AFDAS compared with the KAF group (RR = 0.79, 95% CI = 0.66-0.95, I² = 70%; n_studies = 10). Meta-regression analysis revealed no interaction of anticoagulation, CHA₂DS₂-VASc score, or sex on the difference in risk of recurrent ischemic stroke between groups. Mortality was lower in the AFDAS group compared with KAF (RR = 0.84, 95% CI = 0.74-0.95, I² = 74%; n_studies = 14). The rates of any intracerebral bleeding (RR = 0.97, 95% CI = 0.68-1.39, I² = 58%; n_studies = 5) and any stroke recurrence (RR = 0.99, 95% CI = 0.75-1.30; I² = 60; n_studies = 3) were similar in AFDAS and KAF. AFDAS may carry a lower risk of ischemic stroke recurrence and mortality compared with KAF, with similar risk of intracerebral hemorrhage. Stratification through implementation of AF burden measures may support more personalized management for people with AFDAS.

Objectives: Evidence on the activity of patisiran therapy in specific subgroups of patients with hereditary transthyretin amyloidosis variant (ATTRv) is still scarce. This prospective real-world study was designed to provide the first in-depth clinical data on the effectiveness of patisiran in patients with ATTRv reporting the p.Ile88Leu variant, the most widespread variant in the Emilia-Romagna regional area, which has been less represented in previous clinical trials.Patients and methods: This prospective study evaluated all the patients with genetically proven ATTRv (p.Ile88Leu) and polyneuropathy treated with patisiran in the Emilia-Romagna referral centers for ATTRv (Institute of Neurological Sciences in Bologna and Division of Neurology in Rimini) from March 2021 to April 2023. All subjects underwent clinical and neurological evaluations at baseline and after 9–12 months of treatment.Results: A total of 22 patients were included in the study; the median age was 73 years (IQR: 9), the age at diagnosis was 72 years (IQR: 10), and the disease duration was 1.6 years (IQR: 2.3). We observed stability of all considered neurological and cardiological parameters at 9–12 months after the beginning of patisiran treatment.Conclusion: Our findings support the clinical data regarding the effectiveness of patisiran in stabilizing the disease course and extend this activity to the subset of patients with the p.Ile88Leu variant.