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The last decade has seen significant advances in our understanding of the spectrum of probable antibody-mediated central nervous system disease and the autoantibodies that can help in their identification. In their recent review for this journal, Paul Gozzard and Paul Maddison detailed the wide range of rare neurological conditions associated with paraneoplastic (onconeural) antibodies, which are usually directed at intracellular antigens. Here, the authors focus on antibodies directed against mainly cell-surface neuronal antigens which are associated with central nervous system conditions that often respond to immunotherapies.
Antibodies that target the extracellular domain of neuronal cell-surface proteins and thus are likely to contribute directly to the pathology of the condition. Patients with these antibodies often do not have associated tumours and tend to respond well to immunotherapies, with tumour treatment, if appropriate. Successful treatments are often associated with paralleled reductions in antibody concentrations. Some appear to have a monophasic course but others may relapse and require ongoing immunosuppression.1
By contrast, onconeural antibodies usually target intracellular proteins and represent markers of an associated cancer but have not, in general, been shown to be pathogenic.2 Patients with these onconeural antibodies usually do not respond to immunosuppression even in addition to tumour removal. Nevertheless, because of the importance of identifying an underlying neoplasm, onconeural antibodies are often also requested when an autoimmune condition is suspected, even when a cell-surface neuronal autoantibody is found.
Although all currently recognised antibody-mediated non-paraneoplastic central nervous system (CNS) disorders are rare, numbering perhaps 5–10 per million per year (based on current results of routine antibody screening from the Oxford Clinical Service), it is important to identify these disorders so that appropriate treatments can be offered. Here, we describe the …
This is a reprint of a paper that first appeared in Practical Neurology, February 2012, Volume 12, pages 4–13.
Competing interests AV and the Department of Clinical Neurology in Oxford receive royalties and payments for antibody assays. AV is the inventor on patent application WO/2010/046716 entitled ‘Neurological Autoimmune Disorders’. The patent has been licensed to Euroimmun AG for the development of assays for LGI1 and other VGKC-complex antibodies. AV acts as a paid consultant for Athena Diagnostics and is employed by Oxford University and University College London. AV and SRI may receive royalties for testing of VGKC-complex antibodies.
Provenance and peer review Commissioined by Charles Warlow; this paper was reviewed by Neil Scolding.