Testing for neural antibodies in autoimmune encephalitis: who, what, where, when, why, and how

In recent decades, neural antibody testing has emerged as a cornerstone of autoimmune encephalitis (AE) diagnosis. Commercially available assays to detect these antibodies are now in widespread use, resulting in dramatically increased test accessibility and reduced turnaround times. However, there remains heterogeneity in testing approach and pitfalls related to test ordering as well as diagnostic test performance, which may vary across laboratories depending on their testing methodologies or algorithms. This creates the potential for both false-negative and false-positive results, which can lead to patient misdiagnosis if clinicians are not familiar with both the strengths and limitations of this testing in practice. In this narrative review, we discuss the approach to patient selection for antibody testing, importance of serum and cerebrospinal fluid testing using appropriately handled specimens, potential limitations of local versus reference laboratory testing, optimal timing of testing, benefit of testing to patient management, and diagnostic performance of different test methodologies and algorithms ( the "who, what, where, when, why, and how" of neural antibody testing in AE), with the aim of providing a practically useful framework for clinicians who order this testing.