Adrian Budhram

Objectives: This study evaluates immunotherapy in drug‐resistant epilepsy (DRE) patients with concern for autoimmune encephalitis‐associated epilepsy (AEAE) but negative neural antibody testing (−Ab). Methods: A retrospective cohort study, focusing on patients treated at our Epilepsy Monitoring Unit (EMU) from January 2018 to May 2022. Of 39 patients with DRE who received immunotherapy, 27 had clinical concern for AEAE. After excluding patients with absent or incomplete neural antibody testing ( n = 7) or positive neural antibodies ( n = 8), 12 antibody‐negative patients constituted the final study cohort. Results: Among the final 12 patients, 41.7% were female (median age 43.5 years, IQR = 28.8–63.3). The median age of epilepsy onset was 39.5 years (IQR = 23.8–60.3), and patients began immunomodulatory treatment (IMT) at a median of 15.5 months after seizure onset (IQR = 12.8–21.8). Distribution of treatments was 41.6% both intravenous immunoglobulin (IVIg) and methylprednisolone (IVMP), 33.3% IVIG alone, 16.6% IVIG, IVMP, and plasma exchanges (PLEX), and 8.3% IVIG, IVMP, and rituximab. After a median follow‐up of 25 months (IQR = 24–31.3), the majority (10/12) had non‐sustained responses beyond 6 months, with only 2/12 showing sustained (>50% reduction in seizures) responses. Confounding factors (e.g., concomitant ASM addition/change, lack of temporal relationship to immunotherapy) were identified in both cases. Significance: The study reveals IMT has limited success in patients with DRE and concern for AEAE but Ab‐. Critical evaluation of IMT is essential in suspected AEAE cases with Ab‐ to avoid unnecessary administration of potentially hazardous immunotherapy in patients who are unlikely to benefit.

Objective: Despite advancements in “autoimmune epilepsy,” more accurately referred to herein as seizures or epilepsy of autoimmune etiology, significant variability exists in its recognition, diagnosis, and management internationally. This study assessed clinicians' understanding, access to diagnostic tools, and treatment practices across global regions. Methods: An online survey, “Recognizing Autoimmune Seizures” was disseminated globally through professional networks including the Canadian League Against Epilepsy (CLAE), International League Against Epilepsy (ILAE), Young Epilepsy Section (YES), and American Epilepsy Society (AES). Results: The survey included 157 respondents: adult neurologists (50%), pediatric neurologists (38%), other healthcare professionals (8%), and trainees (6%). Although 69% reported familiarity with updated ILAE definitions for seizures or epilepsy of autoimmune etiology, 43% noted difficulty with clinical identification. Familiarity varied significantly by region ( p = 0.024) and was highest in Europe (76%) and Asia/South/Central America (73%) versus North America (50%). In Asia and South/Central America, 66% of respondents reported difficulty accessing neural antibody testing, compared with 22% in North America and 17% in Europe ( p < 0.001), largely due to financial barriers in resource‐limited regions (87%; p < 0.001). As a result, clinicians in these settings more frequently treated patients empirically with immunotherapy without confirmatory testing (72%; p < 0.001). Further, adult providers more often identified anti‐GAD65 (73% vs. 52%), anti‐LGI1 (83% vs. 36%), and paraneoplastic antibodies (79% vs. 31%), whereas pediatric clinicians more frequently encountered anti‐MOG‐associated seizures (84% vs. 58%; all p ≤ 0.015). Significance: The survey highlights a clear knowledge‐to‐practice gap in the recognition and diagnosis of seizures or epilepsy of autoimmune etiology. While many are familiar with conceptual definitions, a substantial proportion lack confidence in clinical identification. Respondents emphasized that both knowledge gaps and limited access to diagnostic resources contribute to ongoing disparities in care. There is a pressing need for regionally tailored international initiatives to facilitate clinician education and improve equitable access to neural antibody testing. Plain Language Summary: This global survey of 157 clinicians found that while familiarity with conceptual definitions of seizures and epilepsy of autoimmune etiology was high, clinical recognition remained limited, revealing a clear knowledge‐to‐practice gap. Familiarity varied by region, highest in Europe and South/Central America and Asia, and lowest in North America. Access to neural antibody testing was most constrained in Asia and South/Central America, where limited public funding and high out‐of‐pocket costs were major barriers, leading clinicians to rely more often on empirical immunotherapy. These regional differences highlight the need for context‐specific strategies rather than one‐size‐fits‐all solutions to improve equitable care.

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.

Progressive multifocal leukoencephalopathy (PML) is an infectious disease of the central nervous system that is typically severe and classically occurs in the setting of overt immunocompromise. It is caused by the John Cunningham virus (JCV), a ubiquitous polyomavirus that only rarely leads to neurological complications. Prompt diagnosis of PML is essential for patient management, but can be complicated by disease development in individuals who are relatively immunocompetent, the lack of highly specific clinical symptoms, unfamiliarity with recently described neuroimaging signs and the imperfect sensitivity of assays used to detect JCV in cerebrospinal fluid (CSF). We review the supportive clinical features, neuroimaging findings and confirmatory testing for PML and propose an algorithm to facilitate accurate diagnosis in clinical practice.

Trigeminal Neuralgia Associated with a Solitary Pontine Lesion