Dubey, Divyanshu

Abstract Background Autoimmunity is an increasingly recognized cause of encephalitis with a similar prevalence to that of infectious etiologies. Over the past decade there has been a rapidly expanding list of antibody biomarker discoveries that have aided in the identification and characterization of autoimmune encephalitis. As the number of antibody biomarkers transitioning from the research setting into clinical laboratories has accelerated, so has the demand and complexity of panel-based testing. Clinical laboratories are increasingly involved in discussions related to test utilization and providing guidance on which testing methodologies provide the best clinical performance. Content To ensure optimal clinical sensitivity and specificity, comprehensive panel-based reflexive testing based on the predominant neurological phenotypic presentation (e.g., encephalopathy) is ideal in the workup of cases of suspected autoimmune neurological disease. Predictive scores based on the clinical workup can aid in deciding when to order a test. Testing of both CSF and serum is recommended with few exceptions. Appropriate test ordering and interpretation requires an understanding of both testing methodologies and performance of antibody testing in different specimen types. Summary This review discusses important considerations in the design and selection of neural antibody testing methodologies and panels. Increased collaboration between pathologists, laboratorians, and neurologists will lead to improved utilization of complex autoimmune neurology antibody testing panels.

Background: Myelitis accompanied by a negative spinal cord MRI may lead to diagnostic uncertainty. Objective and Methods: We retrospectively investigated the frequency of negative spinal cord MRI (performed <6 weeks from onset) in Mayo Clinic patients with myelin oligodendrocyte glycoprotein (MOG)-IgG-associated myelitis (2000–2019). Results: The initial spinal cord MRI was negative in 7/73 (10%) patients, despite severe acute disability (median EDSS, 7 (range, 4.5–8)); myelitis symptoms/signs were frequent (paraparesis, neurogenic bladder, sensory level, Lhermitte’s phenomenon). Myelitis lesions became overt at follow-up MRI in three patients. Conclusions: A negative spinal cord MRI should not dissuade from MOG-IgG testing in patients with acute/subacute myelitis.

Expanding use of immune‐checkpoint inhibitors (ICIs) underscores the importance of accurate diagnosis and timely management of neurological immune‐related adverse events (irAE‐N). We evaluate the real‐world frequency, phenotypes, co‐occurring immune‐related adverse events (irAEs), and long‐term outcomes of severe, grade III to V irAE‐N at a tertiary care center over 6 years. We analyze how our experience supports published literature and professional society guidelines. We also discuss these data with regard to common clinical scenarios, such as combination therapy, ICI rechallenge and risk of relapse of irAE‐N, and corticosteroid taper, which are not specifically addressed by current guidelines and/or have limited data. Recommendations for management and future irAE‐N reporting are outlined. ANN NEUROL 2020;87:659–669

ObjectiveDrug‐resistant seizures are common in patients with leucine‐rich, glioma‐inactivated 1 (LGI1)‐IgG associated and contactin‐associated protein‐like 2 (CASPR2)‐IgG associated encephalitis. We performed the first randomized double‐blind placebo‐controlled trial to evaluate efficacy of intravenous immunoglobulin (IVIG) in reducing seizure frequency.MethodsOur enrollment goal was 30 LGI1/CASPR2‐IgG–seropositive adult patients with ≥2 seizures per week. Patients were randomized to receive IVIG (0.5g/kg day 1, 1g/kg day 2, 0.6g/kg weeks 3 and 5) or volume‐matched intravenous normal saline. Following the blinded phase, the nonresponders in the placebo group received IVIG. The primary clinical outcome was 50% reduction in seizure frequency from baseline to 5 weeks.ResultsAfter enrollment of 17 patients (LGI1‐IgG, 14; CASPR2‐IgG, 3) over 34 months, the study was terminated due to slow enrollment. Six of 8 patients in the IVIG group were responders, compared to 2 of 9 in the placebo group (p = 0.044, odds ratio = 10.5, 95% confidence interval = 1.1–98.9). For the LGI1‐IgG seropositive subgroup, 6 of 8 patients in the IVIG group were responders, compared to zero of 6 in the placebo group. Two LGI1‐IgG–seropositive patients receiving IVIG, but none receiving placebo, were seizure‐free at the end of the blinded phase. Four of the 6 patients entering the open‐label IVIG arm reported ≥50% reduction in seizure frequency. There were no correlations with LGI1/CASPR2‐IgG1–4 subclasses.InterpretationSuperiority of IVIG to placebo reached statistical significance for the primary endpoint for all patients and the subset with LGI1‐IgG. These results have to be interpreted with the caveat that the study did not reach its originally selected sample size. ANN NEUROL 2020;87:313–323