Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Recent biochemical observations have helped redefine antigenic components within the voltage-gated potassium channel (VGKC) complex. The related autoantibodies may be now divided into likely pathogenic entities, which target the extracellular domains of leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2), and species that target intracellular neuronal components and are likely non-pathogenic. This distinction has enhanced clinical practice as direct determination of LGI1 and CASPR2 antibodies offers optimal sensitivity and specificity. In this review, we describe and compare the clinical features associated with pathogenic LGI1 and CASPR2 antibodies, illustrate emerging laboratory techniques for antibody determination and describe the immunological mechanisms that may mediate antibody-induced pathology. We highlight marked clinical overlaps between patients with either LGI1 or CASPR2 antibodies that include frequent focal seizures, prominent amnesia, dysautonomia, neuromyotonia and neuropathic pain. Although occurring at differing rates, these commonalities are striking and only faciobrachial dystonic seizures reliably differentiate these two conditions. Furthermore, the coexistence of both LGI1 and CASPR2 antibodies in an individual occurs surprisingly frequently. Patients with either antibody respond well to immunotherapies, although systematic studies are required to determine the magnitude of the effect beyond placebo. Finally, data have suggested that CASPR2 and LGI1 modulation via genetic or autoimmune mechanisms may share common intermediate molecules. Taken together, the biochemical distinction of antigenic targets has led to important clinical advances for patient care. However, the striking syndrome similarities, coexistence of two otherwise rare antibodies and molecular insights suggest the VGKC complex may yet be a common functional effector of antibody action. Hence, we argue for a molecular evolution alongside a clinical and phenotypic re-evaluation.

Original publication

DOI

10.1136/jnnp-2017-315720

Type

Journal article

Journal

J Neurol Neurosurg Psychiatry

Publication Date

05/2018

Volume

89

Pages

526 - 534

Keywords

autoimmune encephalitis, epilepsy, limbic system, neuroimmunology, paraneoplastic syndrome