Paramasivan, Naveen Kumar

AbstractObjectiveTo describe the phenotypes, oncological associations, biomarker profiles, and outcomes across different age groups in patients with ANNA1 (anti‐Hu) autoimmunity.MethodsA retrospective review of patients with ANNA1‐IgG in serum/CSF between January 1, 2001, and December 31,2019 was performed. Patients were classified into three groups based on the age of symptom onset. Phage immunoprecipitation sequencing (PhIP‐Seq) and neurofilament light chain (NfL) measurements were done in patient sera/CSF with archived samples.ResultsOf 122 patients, 81 (66%), 20 (16%), and 21 (17%) patients belonged to older adults, young adults, and pediatric groups, respectively. Lung cancer and neuromuscular presentations were more common in older adults (p < 0.001), while limbic encephalitis and neuroblastoma were more common in pediatric patients (p < 0.005). Most young adults (75%) did not have cancer identified. Proportions of patients with a favorable response to immunotherapy were 20%, 30%, and 52% among older adults, young adults, and pediatric groups, respectively. PhIP‐Seq demonstrated significant enrichment for ELAVL4 peptides especially for amino acids 240–289, in the majority of samples evaluated (36/67, 54%). ZIC and SOX2 peptides were significantly enriched in those with central nervous system presentations. Serum NfL levels were elevated in patients with cancer and those with poor long‐term outcomes.InterpretationYoung adults with ANNA1 autoimmunity phenotypically resembled older adults but rarely had an underlying cancer. Pediatric patients frequently presented with limbic encephalitis and neuroblastoma and often responded favorably to immunotherapy. Distinct antigenic signatures may underlie differences in clinical presentations. Serum NfL levels may be a biomarker of poor long‐term outcomes in ANNA1 autoimmunity.

The administration of intravenous thrombolysis (IVT) for patients with acute ischemic stroke who have recently ingested direct oral anticoagulants (DOACs) presents a clinical challenge due to the perceived increased risk of intracranial hemorrhage (ICH). Traditional guidelines from the US and European authorities advise against IVT within 48 h of last DOAC ingestion, unless specific coagulation tests indicate safety. However, emerging observational studies suggest that IVT might be safe in selected patients. A US stroke registry study and a global multicenter cohort study both reported no significant increase in symptomatic ICH among patients on DOACs compared to those not on anticoagulants. A systematic review of all published observational studies further supported these findings, showing comparable bleeding rates and functional outcomes in DOAC-treated patients. Reversal agents like idarucizumab for dabigatran have demonstrated potential in facilitating safer IVT administration, though logistical and cost-related barriers limit their widespread use. The variability in global guidelines reflects differing approaches to risk assessment and resource availability, highlighting the need for individualized treatment decisions. In India, the increasing prevalence of atrial fibrillation and stroke as well as prescription of DOACs necessitate adapted guidelines that consider local health-care infrastructure. Despite the promising observational data, the lack of randomized controlled trials underscores the need for further research to establish robust evidence for IVT use in this context. Collaborative international efforts and inclusion of diverse patient populations in future studies will be crucial to refine treatment protocols and improve outcomes for stroke patients on DOACs.