BACKGROUND:Endovascular thrombectomy (EVT) has demonstrated benefits in patients with ischemic stroke and large-vessel occlusions, but its efficacy and safety in patients with the largest baseline infarcts (Alberta Stroke Program Early Computed Tomography Score [ASPECTS] 0-2), remain controversial. This study aimed to evaluate the efficacy and safety of EVT in early presenting patients with ASPECTS 0 to 2 compared with medical care alone. METHODS:This post hoc analysis of the multicenter, randomized LASTE trial ([Large Stroke Therapy Evaluation]; patients ≤80 years, ASPECTS 0-5, proximal anterior circulation large-vessel occlusion, randomization within 6.5 hours of last known well) evaluated the subgroup with ASPECTS 0 to 2, representing those with large baseline infarcts without an upper size limit, randomized to receive EVT plus medical care or medical care alone. Primary outcomes included the distribution of the modified Rankin Scale score at 90 days. Secondary outcomes included mortality, infarct volume growth at 24 hours, the incidence of symptomatic intracranial hemorrhage and modified Rankin Scale score at 180 days. The LASTE trial was conducted and reported in accordance with the CONSORT guidelines (Consolidated Standards of Reporting Trials). RESULTS:Median age was 72 years and 55.8% were women. Among the 181 patients with ASPECTS 0 to 2 (median core volume 156 mL [25th-75th percentiles, 121-204 mL]), at 90 days after randomization, EVT improved functional outcomes (generalized odds ratio, 1.81 [95% CI, 1.32-2.47]) and reduced mortality (38.4% versus 59.6%; relative risk, 0.64 [95% CI, 0.47-0.89]), which translated predominantly into an increase in the proportion of modified Rankin Scale score of 0 to 3 in the EVT group (31.4% versus 8.5%; relative risk, 3.69 [95% CI, 1.77-7.68]). A significant reduction in infarct growth volume was observed in the EVT group compared with medical care (mean difference, -70.3 mL [95% CI, -94.2 to -46.3]). Rates of symptomatic intracranial hemorrhage were 12.9% versus 4.5%, respectively (relative risk, 2.85 [95% CI, 0.94-8.60]). CONCLUSIONS:EVT improves functional outcomes and reduces mortality in patients with ASPECTS 0 to 2. These findings support the concept that in patients aged <80 years presenting within early time window (6.5 hours) with unlimitedly large infarct (predominantly selected using magnetic resonance imaging), the infarct size in isolation should not be used to disqualify patients from endovascular treatment. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03811769.
HLA-B*35:08:18 differs from HLA-B*35:08:01:01 by one nucleotide substitution in codon 284 in exon 5.
We assessed the Pneumocystis jirovecii PCR accuracy on non-invasive oropharyngeal wash (OW) specimens for the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-HIV immunocompromised patients. In this retrospective study, 134 patients with suspected PJP undergoing both OW and deep respiratory sampling were included. PJP was defined by composite criteria. OW P. jirovecii PCR showed a sensitivity of 61.5% (95% CI 42.5-77.6) and a specificity of 97.2% (95% CI 92.2-99.1). Positive and negative predictive values were 84.2% and 91.3%, respectively. These results suggest OW P. jirovecii PCR may support non-invasive diagnosis, but cannot be used to exclude PJP.
HLA-C*05:315 differs from HLA-C*05:01:01:02 by one nucleotide substitution in codon 304 in exon 5.
Background and ObjectivesDevelopmental and epileptic encephalopathies (DEEs) with early burst-suppression EEG (EIDEE-BS) are among the most severe neonatal epileptic syndromes, typically presenting in the first months of life with refractory seizures and profound neurodevelopmental impairment. Although variants in the KCNQ2, STXBP1, and SCN2A genes are recognized as major causes, the full genetic spectrum remains uncertain. We aimed to delineate the electroclinical characteristics, genetic etiologies, and long-term outcomes in a large MRI-negative EIDEE-BS cohort.MethodsWe retrospectively analyzed 110 patients with BS EEG enrolled from a database of 1,540 individuals with suspected genetic epilepsies (2008-2023). Clinical, EEG, and genetic data were systematically collected. Patients were stratified into 4 groups: KCNQ2, STXBP1, "other pathogenic variants," and "without a genetic diagnosis." EEG traces were reviewed independently, and outcomes were assessed through long-term follow-up.ResultsPathogenic or likely pathogenic variants were identified in 62.7% of patients and involved 23 genes, including 2 copy number variants. KCNQ2 (n = 24) and STXBP1 (n = 16) accounted for one-third of diagnoses, whereas SCN2A (n = 3) and KCNT1 (n = 2) were less frequent. In KCNQ2 cases, seizures and BS onset occurred earlier than in STXBP1 cases: mean 2 days vs 6 weeks for seizures and 3 days vs 2 months for BS, respectively. A typical BS pattern (bursts longer than suppressions) strongly correlated with KCNQ2 and STXBP1 variants. Novel associations were found with DPM1, GRIN2A, KCNT2, PIGO, PURA, WWOX, and candidate genes (KMT2E, SNAP25, and SYT1). Most variants were de novo heterozygous; however, recessive and X-linked inheritance patterns were also observed. Mortality was high (25%), primarily from status epilepticus and complications of severe disability. Most patients (72.5%) had persistent seizures at follow-up (a mean of 6.5 years), as well as profound intellectual disabilities, irrespective of genotype.DiscussionThis large series highlights the strong monogenic basis of EIDEE-BS. KCNQ2, STXBP1, and SCN2A were the most commonly affected genes. Early EEG features, particularly BS timing and morphology, can help anticipate the underlying genotype and guide precision therapy, including the early use of sodium channel blockers in selected cases. These findings support recent ILAE reclassification efforts and underscore the importance of comprehensive genomic testing for improved diagnosis and counseling.
