Carsten Finke1, Harald Prüss2, Josephine Heine3, Sigrid Reuter4, Ute A Kopp3, Florian Wegner5, Florian Then Bergh6, Sebastian Koch7, Olav Jansen8, Thomas Münte9, Günther Deuschl4, Klemens Ruprecht10, Winfried Stöcker11, Klaus-Peter Wandinger12, Friedemann Paul13, Thorsten Bartsch4. 1. Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany2Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany3Berlin Center for Advanced Neuroimaging, Charité-Universitätsmedizin Berlin, Berlin, Germany. 2. Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany4German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany. 3. Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany. 4. Department of Neurology, Memory Disorders and Plasticity Group, University Hospital Schleswig-Holstein, Kiel, Germany. 5. Department of Neurology, Hannover Medical School, Hannover, Germany. 6. Department of Neurology, University of Leipzig, Leipzig, Germany. 7. Department of Neurology, Memory Disorders and Plasticity Group, University Hospital Schleswig-Holstein, Kiel, Germany8Medical Student, Department of Neurology, Memory Disorders and Plasticity Group, University Hospital Schleswig-Holstein, Kiel, Germany. 8. Institute of Neuroradiology, University Hospital Schleswig-Holstein, Kiel, Germany. 9. Department of Neurology, University Hospital Schleswig-Holstein, Lübeck, Germany. 10. Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany11Clinical and Experimental Multiple Sclerosis Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany. 11. Institute for Experimental Immunology, Euroimmun AG, Lübeck, Germany. 12. Department of Neurology, University Hospital Schleswig-Holstein, Lübeck, Germany13Institute of Clinical Chemistry, Neuroimmunology Unit, University Hospital Schleswig-Holstein, Lübeck, Germany. 13. Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany3Berlin Center for Advanced Neuroimaging, Charité-Universitätsmedizin Berlin, Berlin, Germany11Clinical and Experimental Multiple Sclerosis Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany14Neurocure Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany15Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany.
Abstract
IMPORTANCE: Limbic encephalitis with leucine-rich, glioma-inactivated 1 (LGI1) antibodies is one of the most frequent variants of autoimmune encephalitis with antibodies targeting neuronal surface antigens. However, the neuroimaging pattern and long-term cognitive outcome are not well understood. OBJECTIVE: To study cognitive outcome and structural magnetic resonance imaging (MRI) alterations in patients with anti-LGI1 encephalitis. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study was conducted at the Departments of Neurology at Charité-Universitätsmedizin Berlin and University Hospital Schleswig-Holstein, Kiel, Germany. Data on 30 patients with anti-LGI1 encephalitis and 27 healthy control individuals matched for age, sex, and educational level were collected from June 1, 2013, through February 28, 2015. MAIN OUTCOMES AND MEASURES: Clinical assessment, cognitive testing, and high-resolution MRI data, including whole-brain, hippocampal and basal ganglia volumetry; white matter integrity (diffusion tensor imaging); gray matter density (voxel-based morphometry); and hippocampal microstructural integrity (mean diffusivity and fractional anisotropy). RESULTS: Of the 30 patients included in the study, 19 were male (63%); mean (SD) age was 65.7 (12.3) years. Patients with anti-LGI1 encephalitis had incomplete recovery with significant and persisting verbal (mean [SE] Rey Auditory Verbal Learning Test [RAVLT], delayed recall: patients, 6.52 [1.05]; controls, 11.78 [0.56], P < .001) and visuospatial (Rey-Osterrieth Complex Figure Test [ROCF], delayed recall: patients, 16.0 [1.96]; controls, 25.86 [1.24]; P < .001) memory deficits. These deficits were accompanied by pronounced hippocampal atrophy, including subfields cornu ammonis 2/3 (CA2/3) and CA4/dentate gyrus (DG), as well as impaired hippocampal microstructural integrity. Higher disease severity correlated with larger verbal memory deficits (RAVLT delayed recall, r = -0.40; P = .049), decreased volumes of left hippocampus (r = -0.47; P = .02) and left CA2/3 (r = -0.41; P = .04) and CA4/DG (r = -0.43; P = .03) subfields, and impaired left hippocampal microstructural integrity (r = 0.47; P = .01). In turn, decreased volume of the left CA2/3 subfield (RAVLT delayed recall, r = 0.40; P = .047) and impaired left hippocampal microstructural integrity (RAVLT recognition, r = -0.41; P = .04) correlated with verbal memory deficits. Basal ganglia MRI signal abnormalities were observed in only 1 patient, but a longer duration of faciobrachial dystonic seizures correlated with a reduction of pallidum volume (r = -0.71; P = .03). In contrast, no abnormalities of cortical gray matter or white matter were found. The latency between disease onset and initiation of immunotherapy was significantly correlated with verbal (RAVLT recall after interference, r = -0.48; P = .02) and visuospatial (ROCF delayed recall, r = -0.46; P = .03) memory deficits. CONCLUSIONS AND RELEVANCE: Anti-LGI1 encephalitis is associated with cognitive deficits and disability as a result of structural damage to the hippocampal memory system. This damage might be prevented by early immunotherapy.
IMPORTANCE: Limbic encephalitis with leucine-rich, glioma-inactivated 1 (LGI1) antibodies is one of the most frequent variants of autoimmune encephalitis with antibodies targeting neuronal surface antigens. However, the neuroimaging pattern and long-term cognitive outcome are not well understood. OBJECTIVE: To study cognitive outcome and structural magnetic resonance imaging (MRI) alterations in patients with anti-LGI1 encephalitis. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study was conducted at the Departments of Neurology at Charité-Universitätsmedizin Berlin and University Hospital Schleswig-Holstein, Kiel, Germany. Data on 30 patients with anti-LGI1 encephalitis and 27 healthy control individuals matched for age, sex, and educational level were collected from June 1, 2013, through February 28, 2015. MAIN OUTCOMES AND MEASURES: Clinical assessment, cognitive testing, and high-resolution MRI data, including whole-brain, hippocampal and basal ganglia volumetry; white matter integrity (diffusion tensor imaging); gray matter density (voxel-based morphometry); and hippocampal microstructural integrity (mean diffusivity and fractional anisotropy). RESULTS: Of the 30 patients included in the study, 19 were male (63%); mean (SD) age was 65.7 (12.3) years. Patients with anti-LGI1 encephalitis had incomplete recovery with significant and persisting verbal (mean [SE] Rey Auditory Verbal Learning Test [RAVLT], delayed recall: patients, 6.52 [1.05]; controls, 11.78 [0.56], P < .001) and visuospatial (Rey-Osterrieth Complex Figure Test [ROCF], delayed recall: patients, 16.0 [1.96]; controls, 25.86 [1.24]; P < .001) memory deficits. These deficits were accompanied by pronounced hippocampal atrophy, including subfields cornu ammonis 2/3 (CA2/3) and CA4/dentate gyrus (DG), as well as impaired hippocampal microstructural integrity. Higher disease severity correlated with larger verbal memory deficits (RAVLT delayed recall, r = -0.40; P = .049), decreased volumes of left hippocampus (r = -0.47; P = .02) and left CA2/3 (r = -0.41; P = .04) and CA4/DG (r = -0.43; P = .03) subfields, and impaired left hippocampal microstructural integrity (r = 0.47; P = .01). In turn, decreased volume of the left CA2/3 subfield (RAVLT delayed recall, r = 0.40; P = .047) and impaired left hippocampal microstructural integrity (RAVLT recognition, r = -0.41; P = .04) correlated with verbal memory deficits. Basal ganglia MRI signal abnormalities were observed in only 1 patient, but a longer duration of faciobrachial dystonic seizures correlated with a reduction of pallidum volume (r = -0.71; P = .03). In contrast, no abnormalities of cortical gray matter or white matter were found. The latency between disease onset and initiation of immunotherapy was significantly correlated with verbal (RAVLT recall after interference, r = -0.48; P = .02) and visuospatial (ROCF delayed recall, r = -0.46; P = .03) memory deficits. CONCLUSIONS AND RELEVANCE: Anti-LGI1 encephalitis is associated with cognitive deficits and disability as a result of structural damage to the hippocampal memory system. This damage might be prevented by early immunotherapy.
Authors: L Ernst; B David; J Gaubatz; I Domínguez-Narciso; G Lüchters; A J Becker; B Weber; E Hattingen; C E Elger; T Rüber Journal: AJNR Am J Neuroradiol Date: 2019-11-14 Impact factor: 3.825
Authors: Thomas D Miller; Trevor T-J Chong; Anne M Aimola Davies; Michael R Johnson; Sarosh R Irani; Masud Husain; Tammy Wc Ng; Saiju Jacob; Paul Maddison; Christopher Kennard; Penny A Gowland; Clive R Rosenthal Journal: Elife Date: 2020-01-24 Impact factor: 8.140
Authors: Gregory S Day; Melanie Y Yarbrough; Peter Körtvelyessy; Harald Prüss; Robert C Bucelli; Marvin J Fritzler; Warren Mason; David F Tang-Wai; Claude Steriade; Julien Hébert; Rachel L Henson; Elizabeth M Herries; Jack H Ladenson; A Sebastian Lopez-Chiriboga; Neill R Graff-Radford; John C Morris; Anne Fagan Journal: Neurology Date: 2021-04-01 Impact factor: 9.910