Abstract Background and aims CADASIL is the most common monogenic cerebral small vessel disease and an important cause of ischemic stroke and vascular cognitive impairment in young and middle-aged adults. We aimed to characeterize and evaluate clinical severity of CADASIL in Portugal. Methods We conducted a cross-sectional, multicenter, study including patients with CADASIL and asymptomatic carriers of a NOTCH3 mutation. Demographic, genetic, and clinical data were obtained and brain MRIs were reviewed. Condition severity was assessed by CADASIL Clinical Severity Grading Scale and NOTCH3-SVD Staging System. Statistical analysis was performed using SPSS®. Results We included 138 individuals, 16% asymptomatic carriers of NOTCH3 mutation, 62.3% females, median age of 62 years (IQR 15). Family history of CADASIL was present in 58% of cases. Pathogenic variants c.1672C>T p.(Arg558Cys) and c.1258G>T p.(Gly420Cys) were the most frequently identified. Ischemic stroke and transient ischemic attacks were the predominant clinical presentations. Cognitive impairment and migraine-like headache was observed in 42% and 30% of cases, respectively. Two or more additional cerebrovascular risk factors were present in 60% of cases. Antiplatelet agents, statins and antidementia medication were taken by 66%, 57% and 20%, respectively. High disease severity (stage ≥3) was identified in 20% of cases. Stages 1 and 2 were obtained with the NOTCH3-SVD Staging System in 40% and 30% of cases of asymptomatic carriers, respectively. Conclusions This cohort highlights the high burden of CADASIL in Portugal and suggests a clinico-radiological mismatch in early stages. Early diagnosis may facilitate timely vascular risk factor management and improve neurological outcomes. Conflict of interest Carla Morgado: nothing to disclose, Aurora Costa: nothing to disclose, Daniela Ferro: nothing to disclose, Jorge Machado: nothing to disclose, Mariana Henriques: nothing to disclose, Mariana Perdicoulis: nothing to disclose, Sofia Pinto: nothing to disclose, Bárbara Rodrigues: nothing to disclose , Inês Carvalho: nothing to disclose , José Fins: nothing to disclose , Luís Costa: nothing to disclose , Beatriz Marques: nothing to disclose, Mariana Gomes: nothing to disclose, Miguel Peliteiro: nothing to disclose, André Rego: nothing to disclose, Maria João Lima: nothing to disclose, Luís Maia: nothing to disclose, Elsa Azevedo: nothing to disclose, Miguel Viana-Baptista: nothing to disclose, Ana Rita Silva: nothing to disclose
BACKGROUND AND OBJECTIVES:Severe eosinophilic asthma (SEA) is often inadequately controlled. The BETREAT study evaluated the real-world effectiveness of benralizumab, an anti-IL-5 receptor monoclonal antibody, in Portugal, focusing on treatment persistence, asthma control, exacerbation rates, and quality of life (QoL). STUDY DESIGN AND METHODS:Retrospective, observational study including SEA adults who received benralizumab between July 2019 and October 2020 across 16 sites in Portugal. Data from electronic medical records were analysed over 24 months, with evaluations at 3, 6, 12, and 24 months after treatment initiation. Key outcomes included exacerbation rates, oral corticosteroid use, asthma and lung function, and QoL. RESULTS:Of the 74 patients (mean ± SD age 56 ± 11 years and 73.0% female), 66.2% were biologic-naïve. After initiating benralizumab, median eosinophil counts decreased to 0 cells/µL after 3 months. Exacerbation rates decreased from a mean annual rate of 3.12 at baseline to 0.48 by 24 months. Patient-reported asthma control and QoL improved, with ACT and CARAT scores reaching well-controlled levels in most patients by 24 months. Notably, 20.0% of patients achieved clinical remission by the end of the study. CONCLUSIONS:Benralizumab significantly improved SEA outcomes and contributed to clinical remission over a 24-month period, demonstrating potential for long-term disease control and QoL improvement.
Abstract Background and aims Approximately 30% of ischaemic cerebrovascular events remain of undetermined aetiology, including Embolic Stroke of Undetermined Source (ESUS). Beyond atrial fibrillation (AF), other potential mechanisms have been identified, such as artery-to-artery embolism, patent foramen ovale (PFO), and hypercoagulable states, particularly those associated with malignancy. It is estimated that 5–10% of ESUS cases are related to neoplastic disease. Methods Retrospective study of patients admitted with TIA or ischaemic stroke since 2021, classified as undetermined at discharge from the Stroke Unit, and followed for at least two years. Results Ninety-nine patients were included (47.5% women; mean age 73.1 ± 11.8 years). Five patients had active malignancy at the time of the index event, and eight were diagnosed during follow-up, totalling 13 cases (13.1%). A causal relationship was assumed in three patients, two of whom were anticoagulated. Two additional patients were subsequently diagnosed with AF and anticoagulated. In the remaining cases, no causal relationship was assumed due to localised disease or absence of recognised prothrombotic potential. During follow-up, AF was detected in 11 of 58 patients who underwent rhythm monitoring; PFO was identified in four of 22 investigated patients, and artery-to-artery embolism was presumed in three cases. Stroke recurrence occurred in three patients, one associated with active malignancy. Conclusions Despite the absence of systematic oncological screening, more than 10% of patients initially classified as having ESUS had a diagnosis of cancer at baseline or during follow-up. These findings highlight the relevance of considering malignancy in selected ESUS patients, given its implications for secondary prevention. Conflict of interest Jorge M. Ferreira Machado: nothing to disclose, Teresa Medeiros: nothing to disclose, Sofia Tavares: nothing to disclose, Diogo Fitas: nothing to disclose, Sandra Moreira: nothing to disclose, Cristina Duque: nothing to disclose, Maria João Lima: nothing to disclose
