C G Bien1, Z Mirzadjanova1, C Baumgartner2, M D Onugoren1,3, T Grunwald4, M Holtkamp5, S Isenmann6, P Kermer7, N Melzer8, M Naumann9, M Riepe10, W R Schäbitz11, T J von Oertzen12, F von Podewils13, H Rauschka14, T W May15. 1. Epilepsy Center Bethel, Krankenhaus Mara, Bielefeld, Germany. 2. Karl Landsteiner Institute for Clinical Epilepsy Research and Cognitive Neurology, 2nd Neurological Department, General Hospital Hietzing with Neurological Center Rosenhügel, Sigmund Freud University, Vienna, Austria. 3. Department of Neurology, University Hospital Erlangen, Erlangen, Germany. 4. Swiss Epilepsy Center, Clinic Lengg and Department of Neurology, University Hospital Zurich, Zurich, Switzerland. 5. Epilepsy-Center Berlin-Brandenburg, Berlin. 6. Department of Neurology, Center for Research in Clinical Medicine (CCM), HELIOS-Universitätsklinikum Wuppertal, University of Witten/Herdecke, Wuppertal. 7. Department of Neurology, Nordwest-Krankenhaus Sanderbusch, Sande. 8. Department of Neurology, University of Münster, Münster. 9. Department of Neurology and Clinical Neurophysiology, Klinikum Augsburg, Augsburg. 10. Department of Psychiatry II Ulm University at Bezirkskrankenhaus Günzburg, Mental Health & Old Age Psychiatry, Günzburg. 11. Department of Neurology, Evangelisches Krankenhaus Bielefeld, Bielefeld, Germany. 12. Department of Neurology 1, Neuromed Campus, Kepler Universitätsklinikum, Linz, Austria. 13. Department of Neurology, Universitätsmedizin Greifswald, Greifswald, Germany. 14. Karl Landsteiner-Institute for Neuroimmunological and Neurodegenerative Disorders, Danube Hospital/Donauspital, Vienna, Austria. 15. Society for Epilepsy Research, Epilepsy Centre Bethel, Bielefeld, Germany.
Abstract
BACKGROUND AND PURPOSE: To clarify the relevance of titres of IgG antibodies against contactin-associated protein-2 (CASPR2) in diagnosing anti-CASPR2 encephalitis and to describe features and outcomes. METHODS: This was a retrospective analysis of 64 patients with CASPR2 antibodies, categorized independently as 'autoimmune encephalitis' or 'other disease'. Logistic regression methods were performed to identify potential predictors of 'autoimmune encephalitis' in addition to CASPR2 antibodies. RESULTS: An upfront CASPR2 antibody serum titre cut-off at ≥1:200 had a diagnostic sensitivity of 85% and a specificity of 81%. Logistic regression analyses indicated that, in addition to titre, encephalitic magnetic resonance imaging (MRI) was a significant predictor of 'autoimmune encephalitis' (Nagelkerke's R2 = 0.81, P < 0.001) with high sensitivity (84%) and very high specificity (100%). Patients with CASPR2 antibodies and an estimated probability of >70% of having anti-CASPR2 encephalitis (n = 22) had limbic encephalitis (n = 18, one patient plus ataxia), Morvan syndrome (n = 2) or a hyperkinetic movement disorder (n = 2). Median modified Rankin score (mRS) at diagnosis was 3 (range 1-4). Twenty patients were male; median age was 64 (range 54-75) years; 5/15 patients with cerebrospinal fluid data had intrathecal CASPR2 antibody synthesis, and 12/19 with follow-ups >3 months (median 12 months, range 4-43 months) improved by ≥1 mRS point resulting in a median mRS of 2 (range 0-6; one death; all but one having received immunotherapy); and 2/15 patients with follow-up MRI developed hippocampal atrophy. CONCLUSIONS: Only higher CASPR2 serum antibody titres indicate anti-CASPR2 encephalitis, and diagnostic accuracy increases if MRI findings are considered. Anti-CASPR2 encephalitis has characteristic features and a favourable outcome with immunotherapy.
BACKGROUND AND PURPOSE: To clarify the relevance of titres of IgG antibodies against contactin-associated protein-2 (CASPR2) in diagnosing anti-CASPR2encephalitis and to describe features and outcomes. METHODS: This was a retrospective analysis of 64 patients with CASPR2 antibodies, categorized independently as 'autoimmune encephalitis' or 'other disease'. Logistic regression methods were performed to identify potential predictors of 'autoimmune encephalitis' in addition to CASPR2 antibodies. RESULTS: An upfront CASPR2 antibody serum titre cut-off at ≥1:200 had a diagnostic sensitivity of 85% and a specificity of 81%. Logistic regression analyses indicated that, in addition to titre, encephalitic magnetic resonance imaging (MRI) was a significant predictor of 'autoimmune encephalitis' (Nagelkerke's R2 = 0.81, P < 0.001) with high sensitivity (84%) and very high specificity (100%). Patients with CASPR2 antibodies and an estimated probability of >70% of having anti-CASPR2encephalitis (n = 22) had limbic encephalitis (n = 18, one patient plus ataxia), Morvan syndrome (n = 2) or a hyperkinetic movement disorder (n = 2). Median modified Rankin score (mRS) at diagnosis was 3 (range 1-4). Twenty patients were male; median age was 64 (range 54-75) years; 5/15 patients with cerebrospinal fluid data had intrathecal CASPR2 antibody synthesis, and 12/19 with follow-ups >3 months (median 12 months, range 4-43 months) improved by ≥1 mRS point resulting in a median mRS of 2 (range 0-6; one death; all but one having received immunotherapy); and 2/15 patients with follow-up MRI developed hippocampal atrophy. CONCLUSIONS: Only higher CASPR2 serum antibody titres indicate anti-CASPR2encephalitis, and diagnostic accuracy increases if MRI findings are considered. Anti-CASPR2encephalitis has characteristic features and a favourable outcome with immunotherapy.
Authors: Niels Hansen; Daniel Luedecke; Berend Malchow; Michael Lipp; Jonathan Vogelgsang; Charles Timäus; Tristan Zindler; Stefan Gingele; Simone Kühn; Jürgen Gallinat; Klaus Wiedemann; Johannes Denk; Nicole Moschny; Jens Fiehler; Thomas Skripuletz; Christian Riedel; Mike P Wattjes; Inga Zerr; Hermann Esselmann; Luise Poustka; Anne Karow; Hans Hartmann; Helge Frieling; Stefan Bleich; Jens Wiltfang; Alexandra Neyazi Journal: J Neural Transm (Vienna) Date: 2021-05-31 Impact factor: 3.575
Authors: Bo Sun; Melanie Ramberger; Kevin C O'Connor; Rachael J M Bashford-Rogers; Sarosh R Irani Journal: Nat Rev Neurol Date: 2020-07-28 Impact factor: 44.711
Authors: Anna Rada; Robert Birnbacher; Claudio Gobbi; Martin Kurthen; Albert Ludolph; Markus Naumann; Ulrike Neirich; Tim J von Oertzen; Gerhard Ransmayr; Matthias Riepe; Mareike Schimmel; Oliver Schwartz; Rainer Surges; Christian G Bien Journal: J Neurol Date: 2020-10-06 Impact factor: 4.849
Authors: Romana Höftberger; Theodor W May; Christian G Bien; Corinna I Bien; Müjgan Dogan Onugoren; Desiree De Simoni; Verena Eigler; Carl-Albrecht Haensch; Martin Holtkamp; Fatme S Ismail; Martin Kurthen; Nico Melzer; Kristina Mayer; Felix von Podewils; Helmut Rauschka; Andrea O Rossetti; Wolf-Rüdiger Schäbitz; Olga Simova; Karsten Witt Journal: J Neurol Date: 2020-04-03 Impact factor: 4.849
Authors: Sumanth Shivaram; Madhu Nagappa; Doniparthi V Seshagiri; Anita Mahadevan; Yashwanth Gangadhar; T N Sathyaprabha; Vijay Kumavat; Rose D Bharath; Sanjib Sinha; Arun B Taly Journal: Ann Indian Acad Neurol Date: 2021-03-31 Impact factor: 1.383