Clinical spectrum and diagnostic value of antibodies against the potassium channel related protein complex.
Neurología. 2015-06-01; 30(5): 295-301
DOI: 10.1016/j.nrl.2013.12.007
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Montojo MT(1), Petit-Pedrol M(1), Graus F(1), Dalmau J(2).
Author information:
(1)Institut d́Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona,
España; Servicio de Neurología, Hospital Clínic, Universitat de Barcelona,
Barcelona, España.
(2)Institut d́Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona,
España; Servicio de Neurología, Hospital Clínic, Universitat de Barcelona,
Barcelona, España; Institució Catalana de Recerca i Estudis Avançats (ICREA),
Barcelona, España. Electronic address: .
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.
CONCLUSIONS: The discovery of antigens such as LGI1 and Caspr2 has resulted in a
clinical and molecular definition of the broad group of diseases previously
attributed to antibodies against VGKC. Considering the literature that describes
the presence of antibodies against VGKC other than LGI1 and Caspr2 proteins, we
propose a practical algorithm for the diagnosis and treatment of these patients.
Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.