Evidence map›Paper›PMID 39984135›Full record

ArticleBrain, behavior, and immunity2025

Patient-derived monoclonal LGI1 autoantibodies elicit seizures, behavioral changes and brain MRI abnormalities in rodent models.

Manoj Upadhya, Alexander Stumpf, Jack O'Brien-Cairney, César Cordero Gómez, Jan Döring, Julius Hoffmann, Susanne Mueller, Yuko Fukata, Scott van Hoof, Divya Dhangar and 11 more

Abstract read
In one paragraph

Article in Brain, behavior, and immunity, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Entropy of the resting state cortex in epilepsy.Biomedical physics & engineering express · 2026
    Article
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Manoj UpadhyaInstitute of Health and Neurodevelopment, School of Health and Life Sciences, Aston University, Birmingham, United Kingdom.
Alexander StumpfCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Neuroscience Research Center, Berlin, Germany.
Jack O'Brien-CairneyInstitute of Health and Neurodevelopment, School of Health and Life Sciences, Aston University, Birmingham, United Kingdom.
César Cordero GómezDepartment of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
Jan DöringGerman Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
Julius HoffmannDepartment of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Susanne MuellerDepartment of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Charité 3R - Replace | Reduce | Refine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Charité Core Facility 7T Experimental MRIs, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Yuko FukataDivision of Molecular and Cellular Pharmacology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Division of Membrane Physiology, Department of Molecular and Cellular Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan.
Scott van HoofDepartment of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
Divya DhangarInstitute of Health and Neurodevelopment, School of Health and Life Sciences, Aston University, Birmingham, United Kingdom.
Max A WilsonInstitute of Health and Neurodevelopment, School of Health and Life Sciences, Aston University, Birmingham, United Kingdom.
Arunvir AtwalInstitute of Health and Neurodevelopment, School of Health and Life Sciences, Aston University, Birmingham, United Kingdom.
Richard RoschDepartment of Clinical Neurophysiology, King's College Hospital London NHS Foundation Trust, London, United Kingdom; Departments of Neurology and Pediatrics, Columbia University, NY, USA.
Gavin WoodhallInstitute of Health and Neurodevelopment, School of Health and Life Sciences, Aston University, Birmingham, United Kingdom.
Philipp Boehm-SturmDepartment of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Charité 3R - Replace | Reduce | Refine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Charité Core Facility 7T Experimental MRIs, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Masaki FukataDivision of Membrane Physiology, Department of Molecular and Cellular Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Division of Neuropharmacology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Jakob KreyeDepartment of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany; Department of Pediatric Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Dietmar SchmitzCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Neuroscience Research Center, Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
Sukhvir K WrightInstitute of Health and Neurodevelopment, School of Health and Life Sciences, Aston University, Birmingham, United Kingdom; Birmingham Women's and Children's Hospital NHS Trust, Birmingham, United Kingdom. Electronic address: s.wright5@aston.ac.uk.
Hans-Christian KornauCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Neuroscience Research Center, Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
Harald PrüssDepartment of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.

Funding

Wellcome Trust 216613
6 · The paper itself

Abstract

objectiveLimbic encephalitis with leucine-rich glioma inactivated 1 (LGI1) protein autoantibodies is associated with cognitive impairment, psychiatric symptoms, and seizures, including faciobrachial dystonic seizures (FBDS). Patient-derived LGI1-autoantibodies cause isolated symptoms of memory deficits in mice and seizures in rats. Using a multimodal experimental approach, we set out to improve the validity of existing in vivo rodent models to further recapitulate the full clinical syndrome of anti-LGI1 antibody mediated disease.

methodsA monoclonal anti-LGI1 antibody (anti-LGI1 mAb) derived from a patient's CSF antibody-secreting cell was infused intracerebroventricularly (ICV) into rats and mice for one or two weeks, respectively. Cellular excitability of CA3 pyramidal neurons was determined in hippocampal slices. Structural changes in mouse brains were explored using MRI. Antibody effects on behavior and brain activity of rats were studied using video-EEG.

resultsAnti-LGI1 mAbs augmented the excitability of CA3 pyramidal neurons and elicited convulsive and non-convulsive spontaneous epileptic seizures in mice and rats. Mice displayed a hypoactive and anxious phenotype during behavioral testing. MRI revealed acutely increased hippocampal volume after ICV anti-LGI1 mAb infusion. Video-EEG recordings of juvenile rats uncovered two peaks of seizure frequency during the 7-day antibody infusion period resembling the natural progression of seizures in human anti-LGI1 encephalitis.

interpretationOur data strongly corroborate and extend our understanding of the direct pathogenic and epileptogenic role of human LGI1 autoantibodies.

Indexed as

Antibodies, MonoclonalAutoantibodiesBrainProteinsSeizuresAnimalsBehavior, AnimalDisease Models, AnimalFemaleHippocampusHumansIntracellular Signaling Peptides and ProteinsLimbic EncephalitisMagnetic Resonance ImagingMaleMiceAntibodies, MonoclonalAutoantibodiesIntracellular Signaling Peptides and ProteinsLGI1 protein, humanProteinsAnimal modelHuman monoclonal antibodyLGI1Limbic encephalitisSeizure

Identifiers

PMID39984135
PMCPMC7618076

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.