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Routine diagnostics for neural antibodies,clinical correlates,treatment and functional outcome |
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| Authors: | Bien Christian G. Bien Corinna I. Dogan Onugoren Müjgan De Simoni Desiree Eigler Verena Haensch Carl-Albrecht Holtkamp Martin Ismail Fatme S. Kurthen Martin Melzer Nico Mayer Kristina von Podewils Felix Rauschka Helmut Rossetti Andrea O. Schäbitz Wolf-Rüdiger Simova Olga Witt Karsten Höftberger Romana May Theodor W. |
| Affiliation: | 1.Epilepsy Center Bethel, Krankenhaus Mara, Maraweg 17-21, 33617, Bielefeld, Germany ;2.Laboratory Krone, Bad Salzuflen, Germany ;3.Department of Neurology, Epilepsy Center, Friedrich-Alexander-Universität, Erlangen-Nürnberg, Germany ;4.Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria ;5.Department of Neurology, University Hospital St. Poelten, St. Poelten, Austria ;6.Department of Neurology, Städtisches Klinikum Ludwigshafen Am Rhein, Ludwigshafen, Germany ;7.Department of Neurology, Kliniken Maria Hilf Moenchengladbach, Faculty of Health, University of Witten/Herdecke, Moenchengladbach, Germany ;8.Epilepsy-Center Berlin-Brandenburg, Institute for Diagnostics of Epilepsy, Evangelisches Krankenhaus Königin Elisabeth Herzberge, Berlin, Germany ;9.Department of Neurology, University Hospital Bochum, Knappschaftskrankenhaus, Bochum, Germany ;10.Swiss Epilepsy Center, Zurich, Switzerland ;11.Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany ;12.Department of Neurology, University Hospital of Augsburg, Augsburg, Germany ;13.Department of Neurology, University Medicine Greifswald, Greifswald, Germany ;14.Department of Neurology and Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Sozialmedizinisches Zentrum Ost, Donauspital, Vienna, Austria ;15.Department of Clinical Neurosciences, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland ;16.Department of Neurology, EvKB-Bethel, Bielefeld, Germany ;17.Protestant Hospital Alsterdorf, Epilepsy Center Hamburg, Hamburg, Germany ;18.Department of Neurology and Research Centre of Neurosensory Sciences, Carl Von Ossietzky University, Oldenburg, Germany ;19.Society of Epilepsy Research, Bielefeld, Germany ; |
| Abstract: | Objective To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions. MethodsEarliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters. ResultsPositive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6–46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-d-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention. ConclusionsThis novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient. |
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