Precision Laboratory Diagnostics for Autoimmune Encephalitis and Paraneoplastic Neurological Syndromes: Autoantibody Testing, Fluid Biomarkers, and AI-Assisted Integration

Autoimmune encephalitis (AE) and paraneoplastic neurological syndromes (PNS) are leading causes of potentially reversible but frequently misdiagnosed neurological disability, and delayed recognition worsens outcomes and impedes timely tumor detection. This narrative review is written from a laboratory medicine perspective and focuses on the analytical determinants of early and accurate diagnosis: appropriate test selection, dual-method confirmation combining tissue-based and cell-based assays, phenotype-guided interpretation, and assay harmonization. We summarize the expanding spectrum of neuronal and glial autoantibodies, quantitative biomarkers of neuroaxonal injury—most notably neurofilament light chain—and investigational cerebrospinal fluid markers, including cytokine profiles, kappa free light chains, and markers of astrocytic injury, whose ability to discriminate AE from infectious mimics has not been established. We highlight novel autoantibody discovery through phage immunoprecipitation sequencing, research-stage multi-omics approaches, and early, retrospectively evaluated artificial intelligence-assisted classifiers, and we address the growing challenge of neurological adverse events triggered by immune checkpoint inhibitors. Priorities for translation into routine care include external quality assurance, certified reference materials, age-adjusted reference intervals, and prospective validation of integrated biomarker panels within reference-center networks. The review provides a structured framework to support precision laboratory diagnostics in neuroimmunology.