Evaluation of cognitive deficits and structural hippocampal damage in encephalitis with leucine-rich, glioma-inactivated 1 antibodies

Carsten Finke, Harald Prüss, Josephine Heine, Sigrid Reuter, Ute A. Kopp, Florianmd Wegner, Florian Then Bergh, Sebastian Koch, Olav Jansen, Thomas Münte, Günther Deuschl, Klemens Ruprecht, Winfried Stöcker, K. P. Klaus-Peterwandinger, Friedemann Paul, Thorsten Bartsch

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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 studywas 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.

Original languageEnglish (US)
Pages (from-to)50-59
Number of pages10
JournalJAMA Neurology
Volume74
Issue number1
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

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Encephalitis
Leucine
Glioma
Verbal Learning
Memory Disorders
Antibodies
Hippocampus
Dentate Gyrus
Magnetic Resonance Imaging
Basal Ganglia
Immunotherapy
Limbic Encephalitis
Outcome Assessment (Health Care)
Globus Pallidus
Diffusion Tensor Imaging
Anisotropy
Berlin
Surface Antigens
Neurology
Neuroimaging

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Evaluation of cognitive deficits and structural hippocampal damage in encephalitis with leucine-rich, glioma-inactivated 1 antibodies. / Finke, Carsten; Prüss, Harald; Heine, Josephine; Reuter, Sigrid; Kopp, Ute A.; Wegner, Florianmd; Bergh, Florian Then; Koch, Sebastian; Jansen, Olav; Münte, Thomas; Deuschl, Günther; Ruprecht, Klemens; Stöcker, Winfried; Klaus-Peterwandinger, K. P.; Paul, Friedemann; Bartsch, Thorsten.

In: JAMA Neurology, Vol. 74, No. 1, 01.01.2017, p. 50-59.

Research output: Contribution to journalArticle

Finke, C, Prüss, H, Heine, J, Reuter, S, Kopp, UA, Wegner, F, Bergh, FT, Koch, S, Jansen, O, Münte, T, Deuschl, G, Ruprecht, K, Stöcker, W, Klaus-Peterwandinger, KP, Paul, F & Bartsch, T 2017, 'Evaluation of cognitive deficits and structural hippocampal damage in encephalitis with leucine-rich, glioma-inactivated 1 antibodies', JAMA Neurology, vol. 74, no. 1, pp. 50-59. https://doi.org/10.1001/jamaneurol.2016.4226
Finke, Carsten ; Prüss, Harald ; Heine, Josephine ; Reuter, Sigrid ; Kopp, Ute A. ; Wegner, Florianmd ; Bergh, Florian Then ; Koch, Sebastian ; Jansen, Olav ; Münte, Thomas ; Deuschl, Günther ; Ruprecht, Klemens ; Stöcker, Winfried ; Klaus-Peterwandinger, K. P. ; Paul, Friedemann ; Bartsch, Thorsten. / Evaluation of cognitive deficits and structural hippocampal damage in encephalitis with leucine-rich, glioma-inactivated 1 antibodies. In: JAMA Neurology. 2017 ; Vol. 74, No. 1. pp. 50-59.
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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 studywas conducted at the Departments of Neurology at Charit{\'e}-Universit{\"a}tsmedizin 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.",
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T1 - Evaluation of cognitive deficits and structural hippocampal damage in encephalitis with leucine-rich, glioma-inactivated 1 antibodies

AU - Finke, Carsten

AU - Prüss, Harald

AU - Heine, Josephine

AU - Reuter, Sigrid

AU - Kopp, Ute A.

AU - Wegner, Florianmd

AU - Bergh, Florian Then

AU - Koch, Sebastian

AU - Jansen, Olav

AU - Münte, Thomas

AU - Deuschl, Günther

AU - Ruprecht, Klemens

AU - Stöcker, Winfried

AU - Klaus-Peterwandinger, K. P.

AU - Paul, Friedemann

AU - Bartsch, Thorsten

PY - 2017/1/1

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N2 - 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 studywas 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.

AB - 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 studywas 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.

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