M Dogan Onugoren1, D Deuretzbacher2, C A Haensch3, H J Hagedorn4, S Halve5, S Isenmann6, C Kramme1, H Lohner7, N Melzer8, R Monotti9, S Presslauer10, W R Schäbitz11, S Steffanoni9, K Stoeck12, M Strittmatter13, F Stögbauer14, E Trinka15, T J von Oertzen16, H Wiendl8, F G Woermann1, C G Bien1. 1. Krankenhaus Mara, Epilepsy Center Bethel, Bielefeld, Germany. 2. Department of Neurology, Landeskrankenhaus, Bruck/Mur, Austria. 3. Department of Neurology, Maria Hilf Kliniken GmbH Mönchengladbach, University of Witten/Herdecke, Mönchengladabch, Germany. 4. Laboratory Krone, Bad Salzuflen, Germany. 5. Evangelic Hospital Unna, University of Duisburg-Essen, Unna, Germany. 6. Department of Neurology, Helios Klinikum Wuppertal, Center for Clinical Research, and University Witten/Herdecke, Wuppertal, Germany. 7. Department of Neurology, RoMed Kliniken Rosenheim, Rosenheim, Germany. 8. Department of Neurology, University of Münster, Münster, Germany. 9. Department of Internal Medicine, Ospedale La Carità, Locarno, Switzerland. 10. Department of Neurology, Wilhelminenspital der Stadt Wien, Wien, Austria. 11. Department of Neurology, Bethel-EvKB, Bielefeld, Germany. 12. Department of Neurology, Georg-August-University, Göttingen, Germany. 13. Department of Neurology, Klinikum Merzig, Merzig, Germany. 14. Department of Neurology, Klinikum Osnabrück, Osnabrück, Germany. 15. Department of Neurology, Christian Doppler Medical Centre, Paracelsus Medical University, Salzburg, Austria. 16. Department of Neurology, Wagner-Jauregg Neuroscience Centre, Linz, Austria.
Abstract
BACKGROUND: Two novel antibodies (abs) directed to γ-aminobutyric acid B receptor (GABA(B)R) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in patients with limbic encephalitis (LE) were first described by the Philadelphia/Barcelona groups and confirmed by the Mayo group. We present a novel series for further clinical and paraclinical refinement. METHODS: Serum and cerebrospinal fluid samples from a diagnostic laboratory were selected if found to be positive for GABA(B)R or AMPAR abs within a broad antineuronal ab panel. Data were retrospectively compiled. RESULTS: In 10 patients, we detected abs to GABA(B)R. Median age was 70 years. Five of them were diagnosed with small cell lung cancer (SCLC). Intrathecal GABA(B)R ab synthesis was found in all six patients with sufficient data available (median ab-index: 76.8). On MRI, we found bilateral mediotemporal and in two cases cortical abnormalities. EEG revealed encephalopathy, partly with epileptiform discharges. Five patients received immunotherapy, two patients tumour treatment and three both therapies. Three patients died, in five patients cognitive functions declined, one patient improved slightly and one patient fully recovered. AMPAR abs were detected in three patients with mnestic disturbances. Median age was 60.7 years. The only female patient was diagnosed with ovarian cancer. None of the patients had intrathecal ab synthesis. MRI findings showed bilateral mediotemporal abnormalities. EEG was normal in all patients. Two of the three immunologically treated patients improved, one patient stabilised on a low level. DISCUSSION: GABA(B)R and AMPAR abs are well associated with LE. GABA(B)R abs lead to severe clinical, neuroradiological and EEG abnormalities with poorer outcome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
BACKGROUND: Two novel antibodies (abs) directed to γ-aminobutyric acid B receptor (GABA(B)R) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in patients with limbic encephalitis (LE) were first described by the Philadelphia/Barcelona groups and confirmed by the Mayo group. We present a novel series for further clinical and paraclinical refinement. METHODS: Serum and cerebrospinal fluid samples from a diagnostic laboratory were selected if found to be positive for GABA(B)R or AMPAR abs within a broad antineuronal ab panel. Data were retrospectively compiled. RESULTS: In 10 patients, we detected abs to GABA(B)R. Median age was 70 years. Five of them were diagnosed with small cell lung cancer (SCLC). Intrathecal GABA(B)R ab synthesis was found in all six patients with sufficient data available (median ab-index: 76.8). On MRI, we found bilateral mediotemporal and in two cases cortical abnormalities. EEG revealed encephalopathy, partly with epileptiform discharges. Five patients received immunotherapy, two patientstumour treatment and three both therapies. Three patientsdied, in five patients cognitive functions declined, one patient improved slightly and one patient fully recovered. AMPAR abs were detected in three patients with mnestic disturbances. Median age was 60.7 years. The only female patient was diagnosed with ovarian cancer. None of the patients had intrathecal ab synthesis. MRI findings showed bilateral mediotemporal abnormalities. EEG was normal in all patients. Two of the three immunologically treated patients improved, one patient stabilised on a low level. DISCUSSION: GABA(B)R and AMPAR abs are well associated with LE. GABA(B)R abs lead to severe clinical, neuroradiological and EEG abnormalities with poorer outcome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Authors: F Graus; D Escudero; L Oleaga; J Bruna; A Villarejo-Galende; J Ballabriga; M I Barceló; F Gilo; S Popkirov; P Stourac; J Dalmau Journal: Eur J Neurol Date: 2018-05-21 Impact factor: 6.089