Fig. 3.

Genetic, biochemical and therapeutic aspects of LGI1, CASPR2 and double-negative voltage-gated potassium channel-complex antibodies. a CASPR2 and LGI1 are cell-surface-exposed proteins complexed with voltage-gated potassium channels (VGKC). LGI1 is a secreted protein which binds a disintregin and metalloprotease (ADAM) 22 and 23. The patients typically have immunotherapy-responsive diseases with strong HLA associations. In contrast, patients with VGKC-complex antibodies but without LGI1 or CASPR2 reactivities frequently bind intracellular components, do not have specific HLA associations and do not have characteristic immunotherapy-responsive clinical associations. b Faciobrachial dystonic seizures (FBDS) are highly responsive to immunotherapy (IT) but not to antiepileptic drugs (AED) alone. c Often, FBDS precede the onset of cognitive impairment. Achieving cessation of FBDS usually prevents progression to cognitive impairment. b and c Reproduced with permission from [8]. RIA radioimmunoassay, AED antiepileptic drug, IT immunotherapy, FBDS faciobrachial dystonic seizures, CI cognitive impairment