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An 11-year retrospective experience of antibodies against the voltage-gated potassium channel (VGKC) complex from a tertiary neurological centre

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Abstract

Acquired diseases classically associated with VGKC-complex antibodies include peripheral nerve hyperexcitability (PNH), Morvan’s syndrome, limbic encephalitis (LE), and epilepsy. However, not all such patients have VGKC-complex antibodies and antibodies have been reported in patients without a defined immune-mediated syndrome. To analyse the clinical relevance of positive VGKC-complex antibodies requested on the basis of initial clinical suspicion. We retrospectively analysed patients with positive VGKC-complex antibodies (>100 pM) referred to our institution between 2001 and 2011. 1,614 VGKC-complex assays were performed in 1,298 patients. Titres >100 pM were detected in 57/1,298 (4 %) patients. A classic VGKC-complex channelopathy (60 %) was associated with VGKC-complex antibody titres >400 pM (p = 0.0004). LGI1 or CASPR2 antibodies were only detected in classic VGKC-complex channelopathies (LE; n = 3/4 and PNH; n = 1/5). VGKC-complex antibody titres <400 pM were seen with PNH (n = 15/22; 68 %) but also a heterogeneous range of central and/or peripheral nervous system disorders. Electromyography was supportive of PNH in 65 % of cases and symptomatic treatment was beneficial in 46 % of patients. Irrespective of titre, the rate of malignancy in patients with VGKC-complex antibodies was higher than the age-matched national incidence of malignancy (OR 19.9, 95 % CI 8.97–44.0 p<0.0001). Clinical phenotyping and antibody titres >400 pM can help determine VGKC-complex antibody relevance. Antibody titres <400 pM are associated with PNH but also a more heterogeneous clinical spectrum. The antibody association in the latter is of doubtful clinical relevance. The rate of malignancy was significantly higher than the national incidence irrespective of titre.

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Acknowledgments

The authors would like to thank Dr. Patrick Waters for providing the constructs used in the CBAs. The authors would also like to thank both Dr. Patrick Waters and Dr. Ester Coutinho for their helpful comments.

Conflicts of interest

SH is funded by a Watney/Myasthenia Gravis Association/Oxford Biomedical Research Centre Fellowship. AV and the University of Oxford hold patents and receive royalties and payments for autoantibody tests including VGKC-complex antibodies. SHW, PP, DO, and MS declare no conflicts of interest.

Ethical standard

The study was approved by the local institutional clinical governance and audit board and performed in accordance with the Helsinki Declaration of 1975, as revised in 2000 and 2008.

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Authors and Affiliations

  1. Department of Neurology, Walton Centre for Neurology and Neurosurgery, Lower Lane, Fazarkerley, Liverpool, L9 7LJ, UK

    S. Huda, D. O’Connell & M. Steiger

  2. Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Level 6 West Wing, Oxford, OX3 9DU, UK

    S. Huda, P. Pettingill & A. Vincent

  3. Department of Neuro-ophthalmology, Moorfields Eye Hospital, 162 City Road, London, EC1V 2PD, UK

    S. H. Wong

Authors
  1. S. Huda
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  2. S. H. Wong
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  3. P. Pettingill
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  4. D. O’Connell
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  5. A. Vincent
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  6. M. Steiger
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Correspondence to S. Huda.

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Huda, S., Wong, S.H., Pettingill, P. et al. An 11-year retrospective experience of antibodies against the voltage-gated potassium channel (VGKC) complex from a tertiary neurological centre. J Neurol 262, 418–424 (2015). https://doi.org/10.1007/s00415-014-7588-0

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  • DOI: https://doi.org/10.1007/s00415-014-7588-0

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