Dubey, Divyanshu

Objective The aim of this study was to assess the diagnostic utility of cerebrospinal fluid (CSF) myelin oligodendrocyte glycoprotein antibodies (MOG‐IgG) testing. Methods We retrospectively identified patients for CSF MOG‐IgG testing from January 1, 1996, to May 1, 2023, at Mayo Clinic and other medical centers that sent CSF MOG‐IgG for testing including: controls, 282; serum MOG‐IgG positive MOG antibody‐associated disease (MOGAD), 74; serum MOG‐IgG negative high‐risk phenotypes, 73; serum false positive MOG‐IgG with alternative diagnoses, 18. A live cell‐based assay assessed CSF MOG‐IgG positivity (IgG‐binding‐index [IBI], ≥2.5) using multiple anti‐human secondary antibodies and end‐titers were calculated if sufficient sample volume. Correlation of CSF MOG‐IgG IBI and titer was assessed. Results The pan‐IgG Fc‐specific secondary was optimal, yielding CSF MOG‐IgG sensitivity of 90% and specificity of 98% (Youden's index 0.88). CSF MOG‐IgG was positive in: 4/282 (1.4%) controls; 66/74 (89%) serum MOG‐IgG positive MOGAD patients; and 9/73 (12%) serum MOG‐IgG negative patients with high‐risk phenotypes. Serum negative but CSF positive MOG‐IgG accounted for 9/83 (11%) MOGAD patients, and all fulfilled 2023 MOGAD diagnostic criteria. Subgroup analysis of serum MOG‐IgG low‐positives revealed CSF MOG‐IgG positivity more in MOGAD (13/16[81%]) than other diseases with false positive serum MOG‐IgG (3/15[20%]) ( p = 0.01). CSF MOG‐IgG IBI and CSF MOG‐IgG titer (both available in 29 samples) were correlated (Spearman's r = 0.64, p < 0.001). Interpretation CSF MOG‐IgG testing has diagnostic utility in patients with a suspicious phenotype but negative serum MOG‐IgG, and those with low positive serum MOG‐IgG results and diagnostic uncertainty. These findings support a role for CSF MOG‐IgG testing in the appropriate clinical setting. ANN NEUROL 2024;96:34–45

ImportanceRapid and accurate diagnosis of autoimmune encephalitis encourages prompt initiation of immunotherapy toward improved patient outcomes. However, clinical features alone may not sufficiently narrow the differential diagnosis, and awaiting autoantibody results can delay immunotherapy.ObjectiveTo identify simple magnetic resonance imaging (MRI) characteristics that accurately distinguish 2 common forms of autoimmune encephalitis, LGI1- and CASPR2-antibody encephalitis (LGI1/CASPR2-Ab-E), from 2 major differential diagnoses, viral encephalitis (VE) and Creutzfeldt-Jakob disease (CJD).Design, Setting, and ParticipantsThis cross-sectional study involved a retrospective, blinded analysis of the first available brain MRIs (taken 2000-2022) from 192 patients at Oxford University Hospitals in the UK and Mayo Clinic in the US. These patients had LGI1/CASPR2-Ab-E, VE, or CJD as evaluated by 2 neuroradiologists (discovery cohort; n = 87); findings were validated in an independent cohort by 3 neurologists (n = 105). Groups were statistically compared with contingency tables. Data were analyzed in 2023.Main Outcomes and MeasuresMRI findings including T2 or fluid-attenuated inversion recovery (FLAIR) hyperintensities, swelling or volume loss, presence of gadolinium contrast enhancement, and diffusion-weighted imaging changes. Correlations with clinical features.ResultsAmong 192 participants with MRIs reviewed, 71 were female (37%) and 121 were male (63%); the median age was 66 years (range, 19-92 years). By comparison with VE and CJD, in LGI1/CASPR2-Ab-E, T2 and/or FLAIR hyperintensities were less likely to extend outside the temporal lobe (3/42 patients [7%] vs 17/18 patients [94%] with VE; P &amp;lt; .001, and 3/4 patients [75%] with CJD; P = .005), less frequently exhibited swelling (12/55 [22%] with LGI1/CASPR2-Ab-E vs 13/22 [59%] with VE; P = .003), and showed no diffusion restriction (0 patients vs 16/22 [73%] with VE and 8/10 [80%] with CJD; both P &amp;lt; .001) and rare contrast enhancement (1/20 [5%] vs 7/17 [41%] with VE; P = .01). These findings were validated in an independent cohort and generated an area under the curve of 0.97, sensitivity of 90%, and specificity of 95% among cases with T2/FLAIR hyperintensity in the hippocampus and/or amygdala.Conclusions and RelevanceIn this study, T2 and/or FLAIR hyperintensities confined to the temporal lobes, without diffusion restriction or contrast enhancement, robustly distinguished LGI1/CASPR2-Ab-E from key differential diagnoses. These observations should assist clinical decision-making toward expediting immunotherapy. Their generalizability to other forms of autoimmune encephalitis and VE should be examined in future studies.