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Outcome of limbic encephalitis with VGKC-complex antibodies: relation to antigenic specificity

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Abstract

In limbic encephalitis (LE) with antibodies (Abs) to the voltage-gated potassium channel complex (VGKC), the Abs are mainly directed to the VGKC-complex proteins, leucine-rich, glioma inactivated 1 protein (LGI1) or contactin-associated protein-like 2 (CASPR-2) or neither. Here, we relate the outcomes of VGKC-LE patients to the presence of Abs to LGI1, CASPR-2 or neither antigen (LGI1/CASPR-2-Ab−). Clinical, neuropsychology and MRI data were obtained from patient records for all LE patients from the Bonn Epilepsy Centre positive for VGKC-Abs by radioimmunoprecipitation assay between 2002 and 2011. Eighteen VGKC-LE patients were identified: nine patients (50 %) had LGI1-Abs, three (16 %) had CASPR-2-Abs; and six (33 %) were negative for both LGI1- and CASPR-2-Abs. At first assessment, the groups did not differ clinically or radiologically, but faciobrachial dystonic seizures were only observed in two LGI1-Ab+ patients. All patients received monthly intravenous methylprednisolone (MP) pulses. At the most recent follow up (median 26 months), thirteen (72 %) were seizure-free, and seizure-freedom rates did not differ between the Ab groups. Hippocampal atrophy had developed in 7/9 LGI1-Ab+ patients, but in none of the CASPR-2-Ab+ or LGI/CASPR-2-Ab− patients (p = 0.003). While all subgroups improved, memory scores only normalized in six patients (33 %) and LGI1-Ab+ patients were left with significantly poorer memory than the other two subgroups. Most VGKC-LE patients become seizure-free with pulsed monthly MP, but memory outcome is less favourable. Hippocampal atrophy and poor memory recovery is common in patients with LGI1-Abs and suggests permanent functional damage. More intense immunotherapies could improve outcomes in LGI1-Ab+-LE.

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Acknowledgments

The authors would like to thank Dr. Bethan Lang and Ms. Linda Clover, Nuffield Department of Clinical Neurosciences, for Ab determinations.

Conflicts of interest

MPM received payments for congress participation, travel expenses, lecture and manuscript preparation from UCB and EISAI.

CF reports no disclosure.

JCSB was funded by grants from Transregio SFB TR3 (Projects A1 and A8) and as part of the Gerok programme (BONFOR commission, University of Bonn). He received payments for travel expenses from Desitin.

CH was funded by grants from Transregio SFB TR3 A1, BMBF and DFG, he received payments for board membership, consultancy, lectures, manuscript preparation and royalties from UCB Pharma, Desitin, VIAMED GmbH, EISAI, Glaxo Smith Kline.

KPW is a full-time employee of and hold stock in EUROIMMUN AG.

WS is a full-time employee of and hold stock in EUROIMMUN AG.

HU reports no disclosure.

RS has received support for congress participation and speaker fees from EISAI and had a consultancy agreement with UCB.

CEE received honoraria for consultancy, expert testimony and lectures from UCB Pharma, Desitin and Pfizer. He is an employee of the Life and Brain Institute Bonn.

AV and the University of Oxford hold patents and receive royalties and payments for antibody testing. AV receives funding from Euroimmun AG and has consultancy agreement with Athena Diagnostics.

CGB served on a scientific advisory board of UCB and EISAI, Germany, undertook industry-funded travel with support of Eisai, UCB, Desitin and Grifols (all Germany), and obtained honoraria for speaking engagements from Eisai, UCB, GlaxoSmithKline and Desitin (all Germany). As part of his present position, he performs serum and cerebrospinal fluid tests for antibodies as those described in the text; for this, his employer charges fees from external senders.

Ethical standard

Studies have been approved by the ethics committee and have, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study.

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Authors and Affiliations

  1. Department of Epileptology, University of Bonn Medical Center, Bonn, Germany

    M. P. Malter, C. Frisch, J. C. Schoene-Bake, C. Helmstaedter, R. Surges, C. E. Elger & C. G. Bien

  2. Institute of Experimental Immunology, Affiliated to Euroimmun AG Luebeck, Luebeck, Germany

    K. P. Wandinger & W. Stoecker

  3. Department of Neuroradiology, University of Freiburg Medical Center, Freiburg, Germany

    H. Urbach

  4. Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK

    A. V. Vincent

  5. Epilepsy Centre Bethel, Krankenhaus Mara, Bielefeld, Germany

    C. G. Bien

  6. Department of Pediatrics, Braunschweig City Hospitals, Brunswick, Germany

    J. C. Schoene-Bake

  7. Department of Neurology, Marien-Krankenhaus Bergisch Gladbach, Dr.-Robert-Koch-Straße 18, 51465, Bergisch Gladbach, Germany

    M. P. Malter

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  1. M. P. Malter
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Correspondence to M. P. Malter.

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Malter, M.P., Frisch, C., Schoene-Bake, J.C. et al. Outcome of limbic encephalitis with VGKC-complex antibodies: relation to antigenic specificity. J Neurol 261, 1695–1705 (2014). https://doi.org/10.1007/s00415-014-7408-6

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  • DOI: https://doi.org/10.1007/s00415-014-7408-6

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