Citations

ObjectiveTo evaluate the cerebrospinal fluid (CSF) cytokine/chemokine profile of central nervous system (CNS) neurosarcoidosis (NS), and its utility in differential diagnosis, treatment, and prognostication.MethodsIn this case–control study, we validated 17 cytokines/chemokines (interleukin [IL]‐1‐beta, IL‐2, IL‐4, IL‐5, IL‐6, IL‐10, IL‐12p70, IL‐13, IL‐17A, BAFF, IL‐8/CXCL8, CXCL9, CXCL10, CXCL13, GM‐CSF, interferon‐gamma, and tumor necrosis factor [TNF]‐alpha) in a multiplexed automated immunoassay system (ELLA; Bio‐Techne, Minneapolis, MN, USA), and assessed them in CSF and serum of symptomatic patients with probable or definite CNS NS (01/2011–02/2023) with gadolinium enhancement and/or CSF pleocytosis. Patients with multiple sclerosis, primary CNS lymphoma, aquaporin‐4 immunoglobulin G positivity, non‐inflammatory disorders, and healthy individuals were used as controls.ResultsA total of 32 NS patients (59% women; median age, 59 years [19–81]) were included; concurrent sera were available in 12. CSF controls consisted of 26 multiple sclerosis, 8 primary CNS lymphoma, 84 aquaporin‐4 immunoglobulin G positive, and 34 patients with non‐inflammatory disorders. Gadolinium enhancement was present in 31 of 32 NS patients, and CSF pleocytosis in 27 of 32 (84%). CSF IL‐2, IL‐6, IL‐10, IL‐13, BAFF, IL‐8/CXCL8, CXCL9, CXCL10, CXCL13, GM‐CSF, interferon‐gamma, and TNF‐alpha levels were significantly higher in NS patients compared with non‐inflammatory controls (p ≤ 0.02); elevations were more common in CSF than serum. Concurrent elevation of IL‐6, CXCL9, CXCL10, GM‐CSF, interferon‐gamma, and TNF‐alpha was present in 18 of 32 NS patients, but only in 1 control. Elevated IL‐6, IL‐10, IL‐13, CXCL9, CXL10, GM‐CSF, and TNF‐alpha associated with measures of disease activity.InterpretationNS CSF cytokine/chemokine profiles suggest T cell (mainly T helper cell type 1), macrophage, and B‐cell involvement. These signatures aid in NS diagnosis, indicate disease activity, and suggest therapeutic avenues. ANN NEUROL 2024;96:704–714

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