Clinical spectrum and diagnostic value of antibodies against the potassium channel-related protein complex

Abstract

Introduction: Antibodies against a protein complex that includes voltage-gated potassium channels (VGKC) have been reported in patients with limbic encephalitis, peripheral nerve hyperexcitability, Morvan's syndrome, and a large variety of neurological syndromes.Review summary: In this article, a review is presented of the syndromes associated with antibodies against VGKC-related proteins and the main antigens of this protein complex, the proteins LGI1 (leucine rich glioma inactivated protein 1) and Caspr2 (contactin-associated protein-like 2). The conceptual problems and clinical implications of the description of antibodies against VGKC-related proteins other than LGI1 and Caspr2 are also discussed.Although initial studies indicated the occurrence of antibodies against VGKC, recent investigations have shown that the main antigens are a neuronal secreted protein known as LGI1 which modulates synaptic excitability, and a protein called Caspr2 located on the cell surface and processes of neurons of different brain regions, and at the juxtaparanodal region of myelinated axons. While antibodies against LGI1 preferentially associate with classical limbic encephalitis, antibodies against Caspr2 associate with a wider spectrum of symptoms, including Morvan's syndrome, peripheral nerve hyperexcitability or neuromyotonia, and limbic or more extensive encephalitis. In addition there are reports of patients with antibodies against VGKC-related proteins that are different from LGI1 or Caspr2. In these cases, the identity and location of the antigens are unknown, the syndrome association is not specific, and the response to treatment uncertain.ଝ Please cite this article as: Montojo MT, Petit-Pedrol M, Graus F, Dalmau J. Espectro clínico y valor diagnóstico de los anticuerpos contra el complejo proteico asociado a canales de potasio. Neurología. 2015;30:295-301.

Neuronal Surface Antibody-Mediated Autoimmune Encephalitis

“…For example, it is now known that VGKC antibodies target many proteins, known collectively as the VGKC complex. 85 These include LGI1 and CASPR2 antibodies that have each been identified in the serum or CSF of patients with syndromes consisting of specific constellations of symptoms. 18,19 The identity and location of other antigens in the VGKC complex is unknown.…”

Autoimmune limbic encephalitis in association with acute stroke

“…1 Persistent encephalopathy following multifocal strokes and status epilepticus may represent a unique presentation of anti-CASPR2 limbic encephalitis. [3][4][5] One prior report described autoimmune limbic encephalitis and VGKC antibody detection following an acute ischemic stroke. 6 It is speculated that blood-brain barrier compromise may play a role in pathogenesis.…”

Clinical significance of cation channel antibodies in motor neuron disease

“…Finally, all 3 antibodies represent unique syndromes that are seen uncommonly by physicians, often require further work‐up, and may warrant immunosuppressive treatment. VGKC complex antibodies are commonly associated with limbic encephalitis, neuromyotonia, and Morvan syndrome . VGCC antibodies are often associated with Lambert–Eaton myasthenic syndrome and paraneoplastic cerebellar degeneration .…”