Among the tumors that are believed to be associated with VGKC complex-IgG, lung carcinoma, thymoma and hematologic malignancies are the most commonly described. Neoplasms are detected only in a minority of seropositive patients for VGKC complex-IgG (16% in the experience of Mayo Clinic) and do not significantly associate with Caspr-2 or LGI-1. demonstrated that T-cell cytotoxicity is not a major contributor for the pathogenesis of the neurological syndromes associated with VGKCs, whereas antibody and complement-mediated neuronal cell damage are prevalent. These three proteins are contactin-associated protein-2 (Caspr-2), which is localized at the juxtaparanodes in myelinated axons and associates with Transient axonal glycoprotein 1,postsynaptic density-95/discs large/zonula occludens-1, and the ankyrin-spectrin protein leucine-rich, glioma inactivated 1 (LGI-1) protein that is most strongly expressed in the hippocampus and the protein Tag-1/contactin-2, associated with Caspr-2.īien et al. In contrast, these autoantibodies more commonly target three proteins that are complexed with alpha-dendrotoxin-labeled potassium channels in brain extracts. VGKCs are complexed with other neuronal proteins, and it is now widely known that serum autoantibodies directed against VGKCs are actually directed against the potassium channel subunits only in a minority of patients. Neurological autoimmune and paraneoplastic syndromes involve only a small number of VGKCs, notably the “Shaker” type Kv1 channels (Kv1.1, Kv1.2, Kv1.6), sensitive to alpha-dendrotoxin. Moreover, VGKCs contribute to the generation of the action potential. Voltage-gated potassium channels (VGKCs) represent a group of tetrameric signaling proteins with several functions, including modulation of neuronal excitability and neurotransmitter release. As a result, VGKC complex-IgG are now part of the investigation of patients with unexplained subacute onset of epilepsy, memory or cognitive problems, or peripheral nerve hyperexcitability syndromes. The vast majority of these conditions are reversible by immunotherapy, and it is becoming increasingly recognized that early diagnosis and detection of VGKC complex-IgG is critical in order to rapidly start the treatment. These include Isaacs’ syndrome, Morvan syndrome, limbic encephalitis, facio-brachial dystonic seizures, chorea and other movement disorders, epilepsy, psychosis, gastrointestinal neuromuscular diseases, a subacute encephalopathy that mimics Creutzfeldt-Jakob prion disease both clinically and radiologically and autoimmune chronic pain. We will review all the major neurological conditions associated with VGKC complex-IgG. Among all the cancers described in association with VGKC complex-IgG, lung carcinoma, thymoma, and hematologic malignancies are the most commonly detected. Neoplasms are detected only in a minority of seropositive patients for VGKC complex-IgG and do not significantly associate with Caspr-2 or LGI-1. These three proteins are contactin-associated protein-2 (Caspr-2), leucine-rich, glioma inactivated 1 (LGI-1)-protein and the protein Tag-1/contactin-2. By contrast, these autoantibodies more commonly target three proteins that are complexed with alpha-dendrotoxin-labeled potassium channels in brain extracts. Moreover, VGKCs give a key contribution to the generation of the action potential.
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