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CSF Findings in Acute NMDAR and LGI1 Antibody-Associated Autoimmune Encephalitis
Marc Dürr1, Gunnar Nissen1, Kurt-Wolfram Sühs1
1From the Department of Neurology (M.D., M.S., J.D., H.T., J.L.), Ulm University; Department of Neurosurgery (M.D.), University Hospital Tübingen; Neuroimmunology (G.N., K.-P.W., F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein Kiel/Lübeck; Department of Neurology (K.-W.S., P.S.), Hannover Medical School; Department of Neurology (C.G.), University Hospital Jena; Department of Neurology (M.R., H.-P.H., N.M.), Medical Faculty, Heinrich Heine University Düsseldorf; Department of Neurology (M.R.), Center for Neurology and Neuropsychiatry, LVR-Klinikum Düsseldorf, Düsseldorf; Institute of Neuroimmunology and Multiple Sclerosis (M.A.F., M.K.), University Medical Center Hamburg-Eppendorf; Department of Neurology (M.P.M., M.M.), University of Cologne, Faculty of Medicine and University Hospital; Institute of Clinical Neuroimmunology (F.S.T., T.K.), University Hospital and Biomedical Center, Ludwig-Maximilians University Munich; Department of Pediatrics (M.G.H.), University Hospital RWTH Aachen; Technische Universität Dresden (H.S.), and Department of Neurology, University Hospital Augsburg; Department of Neurology (F.T.B.), University Hospital Leipzig; Department of Neurology (C.K.), Klinikum Osnabrück; Department of Neurology (U.K.Z.), Section for Neuroimmunology, University Hospital Rostock; Department of Neurology with Institute of Translational Neurology (N.M., C.C.G.), University Hospital Münster; Department of Neurology (P.L.), University Hospital Göttingen; Institute of Epidemiology and Medical Biometry, Ulm University; and Department of Neurology (F.L.), University Hospital Schleswig-Holstein and Kiel University, Germany.
Autoimmune encephalitis subtypes show distinct cerebrospinal fluid (CSF) inflammation patterns. NMDAR-E exhibits robust inflammation, while LGI1-E shows mild inflammation, indicating different disease mechanisms.
Area of Science:
- Neurology
- Immunology
- Neuroinflammation
Background:
- Autoimmune encephalitis (AE) subtypes display varying degrees of cerebrospinal fluid (CSF) inflammation.
- N-methyl-D-aspartate receptor encephalitis (NMDAR-E) typically shows robust CSF inflammation, whereas leucine-rich glioma-inactivated protein 1 encephalitis (LGI1-E) presents with rare and mild CSF inflammation.
Purpose of the Study:
- To characterize and compare CSF findings in acute, therapy-naive NMDAR-E and LGI1-E.
- To identify subtype-specific inflammatory patterns in CSF and their correlation with clinical features.
Main Methods:
- Retrospective, cross-sectional analysis of CSF parameters (leukocytes, oligoclonal bands, immunoglobulin ratios) in 82 NMDAR-E and 36 LGI1-E patients.
- Analysis of intrathecal immunoglobulin synthesis (IIS) and blood-CSF barrier function.
- Testing for the MRZ reaction in a subset of patients.
Main Results:
- CSF abnormalities were found in 94% of NMDAR-E patients versus 36% of LGI1-E patients.
- Robust intrathecal immunoglobulin synthesis (IIS) was characteristic of NMDAR-E but absent in LGI1-E.
- NMDAR-E showed correlations between CSF leukocytes, IIS, age, and disease severity; LGI1-E displayed increased blood-CSF barrier dysfunction in younger patients with higher CSF leukocytes.
Conclusions:
- NMDAR-E and LGI1-E exhibit distinct CSF inflammatory profiles, suggesting different underlying immunopathogeneses.
- CSF inflammatory patterns, including IIS and blood-CSF barrier function, may serve as subtype-specific biomarkers.
- A subgroup of NMDAR-E patients showed signs of chronic, multiple sclerosis-like inflammation.
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