Le-Duy Do1, Eve Chanson1, Virginie Desestret1, Bastien Joubert1, François Ducray1, Sabine Brugière1, Yohann Couté1, Maité Formaglio1, Veronique Rogemond1, Catherine Thomas-Antérion1, Laura Borrega1, Brice Laurens1, Francois Tison1, Jonathan Curot1, Thomas De Brouker1, Christine Lebrun-Frenay1, Jean-Yves Delattre1, Jean-Christophe Antoine1, Jerome Honnorat2. 1. From the French Reference Center on Paraneoplastic Neurological Syndrome (L.-D.D., E.C., V.D., B.J., F.D., V.R., J.-Y.D., J.-C.A., J.H.) and Service de Neurologie D (V.D., M.F.), Hôpital Neurologique, Hospices Civils de Lyon; Institut NeuroMyoGene INSERM U1217/CNRS UMR 5310 (L.-D.D., E.C., V.D., B.J., F.D., V.R., J.-Y.D., J.-C.A., J.H.), Université de Lyon-Université Claude Bernard Lyon 1; Université Grenoble Alpes (S.B., Y.C.), CEA, iRTSV-BGE, Inserm 1038, Grenoble; EA 3082 (C.T.-A.), Université Lyon 2, France; Service of Neurology (L.B.), Hospital Universitario Fundación Alcorcón, Madrid, Spain; Service de Neurologie (B.L., F.T.), CHU Bordeaux and UMR CNRS 5293 Université de Bordeaux; Unité de Neurologie Cognitive, Epilepsie et Pathologie du Mouvement (J.C.), Explorations Fonctionnelles Neurologiques, Hôpital Pierre Paul Riquet, Toulouse; Service de Neurologie (T.D.B.), Hopital Delafontaine, Saint-Denis; Neurology (C.L.-F.), University Hospital Pasteur 2, Nice; Département de Neurologie (J.-Y.D.), Groupe Hospitalier Pitié-Salpêtrière, Paris; and Neurology Department (J.-C.A.), CHU Saint-Etienne, France. 2. From the French Reference Center on Paraneoplastic Neurological Syndrome (L.-D.D., E.C., V.D., B.J., F.D., V.R., J.-Y.D., J.-C.A., J.H.) and Service de Neurologie D (V.D., M.F.), Hôpital Neurologique, Hospices Civils de Lyon; Institut NeuroMyoGene INSERM U1217/CNRS UMR 5310 (L.-D.D., E.C., V.D., B.J., F.D., V.R., J.-Y.D., J.-C.A., J.H.), Université de Lyon-Université Claude Bernard Lyon 1; Université Grenoble Alpes (S.B., Y.C.), CEA, iRTSV-BGE, Inserm 1038, Grenoble; EA 3082 (C.T.-A.), Université Lyon 2, France; Service of Neurology (L.B.), Hospital Universitario Fundación Alcorcón, Madrid, Spain; Service de Neurologie (B.L., F.T.), CHU Bordeaux and UMR CNRS 5293 Université de Bordeaux; Unité de Neurologie Cognitive, Epilepsie et Pathologie du Mouvement (J.C.), Explorations Fonctionnelles Neurologiques, Hôpital Pierre Paul Riquet, Toulouse; Service de Neurologie (T.D.B.), Hopital Delafontaine, Saint-Denis; Neurology (C.L.-F.), University Hospital Pasteur 2, Nice; Département de Neurologie (J.-Y.D.), Groupe Hospitalier Pitié-Salpêtrière, Paris; and Neurology Department (J.-C.A.), CHU Saint-Etienne, France. jerome.honnorat@chu-lyon.fr.
Abstract
OBJECTIVE: To report 10 patients with limbic encephalitis (LE) and adenylate kinase 5 autoantibodies (AK5-Abs). METHODS: We conducted a retrospective study in a cohort of 50 patients with LE with uncharacterized autoantibodies and identified a specific target using immunohistochemistry, Western blotting, immunoprecipitation, mass spectrometry, and cell-based assay. RESULTS: AK5 (a known autoantigen of LE) was identified as the target of antibodies in the CSFs and sera of 10 patients with LE (median age 64 years; range 57-80), which was characterized by subacute anterograde amnesia without seizure and sometimes preceded by a prodromal phase of asthenia or mood disturbances. Anterograde amnesia can be isolated, but some patients also complained of prosopagnosia, paroxysmal anxiety, or abnormal behavior. No associated cancer was observed. All 10 patients had bilateral hippocampal hypersignal on a brain MRI. CSF analysis generally showed a mild pleiocytosis with elevated immunoglobulin G index and oligoclonal bands, as well as high levels of tau protein with normal concentration of Aβ42 and phospho-tau, suggesting a process of neuronal death. Except for one patient, clinical response to immunotherapy was unfavorable, with persistence of severe anterograde amnesia. Two patients evolved to severe cognitive decline. Hippocampal atrophy was observed on control brain MRI. Using in vitro tests on hippocampal neurons, we did not identify clues suggesting a direct pathogenic role of AK5-Abs. CONCLUSIONS: AK5-Abs should be systematically considered in aged patients with subacute anterograde amnesia. Recognition of this disorder is important to develop new treatment strategies to prevent irreversible limbic damage.
OBJECTIVE: To report 10 patients with limbic encephalitis (LE) and adenylate kinase 5 autoantibodies (AK5-Abs). METHODS: We conducted a retrospective study in a cohort of 50 patients with LE with uncharacterized autoantibodies and identified a specific target using immunohistochemistry, Western blotting, immunoprecipitation, mass spectrometry, and cell-based assay. RESULTS:AK5 (a known autoantigen of LE) was identified as the target of antibodies in the CSFs and sera of 10 patients with LE (median age 64 years; range 57-80), which was characterized by subacute anterograde amnesia without seizure and sometimes preceded by a prodromal phase of asthenia or mood disturbances. Anterograde amnesia can be isolated, but some patients also complained of prosopagnosia, paroxysmal anxiety, or abnormal behavior. No associated cancer was observed. All 10 patients had bilateral hippocampal hypersignal on a brain MRI. CSF analysis generally showed a mild pleiocytosis with elevated immunoglobulin G index and oligoclonal bands, as well as high levels of tau protein with normal concentration of Aβ42 and phospho-tau, suggesting a process of neuronal death. Except for one patient, clinical response to immunotherapy was unfavorable, with persistence of severe anterograde amnesia. Two patients evolved to severe cognitive decline. Hippocampal atrophy was observed on control brain MRI. Using in vitro tests on hippocampal neurons, we did not identify clues suggesting a direct pathogenic role of AK5-Abs. CONCLUSIONS:AK5-Abs should be systematically considered in aged patients with subacute anterograde amnesia. Recognition of this disorder is important to develop new treatment strategies to prevent irreversible limbic damage.
Authors: Alberto Vogrig; Gian Luigi Gigli; Samantha Segatti; Elisa Corazza; Alessandro Marini; Andrea Bernardini; Francesca Valent; Martina Fabris; Francesco Curcio; Francesco Brigo; Donatella Iacono; Paolo Passadore; Michele Rana; Jérôme Honnorat; Mariarosaria Valente Journal: J Neurol Date: 2019-09-24 Impact factor: 4.849
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
Authors: Alex Vicino; Valentin Loser; Paolo Salvioni Chiabotti; Jean Philippe Brouland; Renaud Du Pasquier Journal: Neurol Neuroimmunol Neuroinflamm Date: 2021-05-11
Authors: Gerda Ricken; Tobias Zrzavy; Stefan Macher; Patrick Altmann; Johannes Troger; Kim Kristin Falk; Andreas Kiefer; Andreas Fichtenbaum; Goran Mitulovic; Helmut Kubista; Klaus-Peter Wandinger; Paulus Rommer; Thorsten Bartsch; Thomas Berger; Jörg Weber; Frank Leypoldt; Romana Höftberger Journal: Neurol Neuroimmunol Neuroinflamm Date: 2021-05-20