None of the patients with LGI1-E showed either probable or definitive quantitative IIS

None of the patients with LGI1-E showed either probable or definitive quantitative IIS. NMDAR-E but only in 36% of LGI1-E patients. Robust quantitative intrathecal immunoglobulin synthesis (IIS, IgG > IgM >> IgA) was characteristic for NMDAR-E, but absent in LGI-E. In NMDAR-E, CSF leukocytes were higher when IIS was present or more pronounced. In addition, in NMDAR-E, CSF leukocytes were lower and IIS occurred less often and if so to a lesser degree at older age. Patients with NMDAR-E with severe functional impairment more often experienced positive OCBs. In CSF obtained later than 3 weeks of onset, leukocytes were lower. In parallel, the correlation of leukocytes with IIS disappeared as IIS was partially impartial of disease duration. The MRZ reaction was positive in 5 (36%) patients with NMDAR-E. All these associations were completely absent in LGI1-E. Here, younger patients showed more blood-CSF barrier dysfunction. In LGI1-E, but not in NMDAR-E, the blood-CSF barrier was more dysfunctional when CSF leukocytes were higher. == Conversation == NMDAR-E and LGI-E differ in their common extent of CSF inflammation. In addition, the patterns created by the different inflammatory CSF parameters and their Seviteronel relationship with disease severity, age, and disease duration are subtype-characteristic. Moreover, indicators for multiple sclerosis-like chronic inflammation are Seviteronel present in a subgroup of patients with NMDAR-E. These CSF patterns might be markers for the different immunopathogeneses of LGI1-E and NMDAR-E. The 2 2 most common subtypes of autoimmune encephalitis (AE) are AE with antibodies against NMDA receptors (NMDAR-E) and AE with leucine-rich glioma inactivated protein-1 Seviteronel (LGI1-E).1,2NMDAR-E and LGI1-E are quite different: NMDAR-E mostly affects young women,3whereas LGI1-E tends to occur more frequently at older age and in men. 2NMDAR-E typically progresses to a global encephalitic syndrome with decreased consciousness, stereotypic movements, and vegetative dysfunction,3whereas LGI1-E is a typical limbic AE.2On cranial MRI, many patients with LGI1-E show mesiotemporal T2-hyperintensities,2whereas in NMDAR-E, the MRI is frequently normal, although heterogeneous lesions also involving white matter are found in about half of the patients.3A recent systematic analysis of diverse AE subtypes with regard to published basic CSF parameters comprising leukocytes, total protein, and oligoclonal bands (OCBs) revealed 2 different clusters: together with AEs with contactin-associated protein-like 2 (CASPR2), -aminobutyric acid (GABAA), and glycine receptor antibodies, LGI1-E typically showed scarce and infrequent CSF inflammation, whereas robust and frequent inflammation was characteristic for NMDAR-E and AEs with dipeptidyl-peptidase-like protein-6 (DPPX, GABAB, and -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antibodies.4To complement this systematic analysis,4we performed a multicentric retrospective analysis of the detailed inflammatory CSF findings in therapy-naive patients with LGI1- and NMDAR-E enrolled in the registry of the German Network of Research on Autoimmune Encephalitis (GENERATE) with CSF obtained within 90 days from clinical onset. The parameters included not only CSF leukocytes, blood-CSF barrier function, and OCBs but also quantitative intrathecal immunoglobulin synthesis for immunoglobulin G (IgG), A (IgA), and M (IgM). For a subset of patients with CSF/serum samples still available, an analysis of the MRZ reaction (M = measles, R = rubella, Z = varicella zoster Rabbit Polyclonal to MASTL [VZV]), a marker for polyspecific intrathecal synthesis of pathogen-specific IgG typical of MS was analyzed. The mutual interactions of different CSF parameters and their associations with disease duration, severity, and age were analyzed. == Methods == == Patient Identification == GENERATE is a multicentric, combined retrospective and prospective registry for patients with AE in Germany (generate-net.de/) recruiting since 2013. For this project, patients were selected according to the following criteria: (1) enrollment before January 1, 2017, (2) NMDAR antibodies in CSF or LGI1 antibodies in serum and/or CSF positive, (3) no recent infectious encephalitis, and (4) complete first CSF examination, including leukocyte count, OCB, and CSF/serum ratios for albumin (QAlb), IgG (QIgG), IgA (QIgA), and IgM (QIgM) obtained within 90 days after onset without prior immunomodulatory therapy (Figure 1). Basic demographic variables, clinical presentation, MRI and EEG findings, as needed to test the fulfillment of recently suggested diagnostic criteria for AE,5and severity of functional impairment at the time of lumbar puncture (LP) as the modified Rankin Scale (mRS) score6were extracted from the GENERATE database. == Figure 1. Study Profile. == Flowchart depicting the enrollment process. AE = autoimmune encephalitis; HSVE.