Outcome of limbic encephalitis with VGKC-complex antibodies: relation to antigenic specificity

J Neurol. 2014 Sep;261(9):1695-705. doi: 10.1007/s00415-014-7408-6. Epub 2014 Jun 17.

Abstract

In limbic encephalitis (LE) with antibodies (Abs) to the voltage-gated potassium channel complex (VGKC), the Abs are mainly directed to the VGKC-complex proteins, leucine-rich, glioma inactivated 1 protein (LGI1) or contactin-associated protein-like 2 (CASPR-2) or neither. Here, we relate the outcomes of VGKC-LE patients to the presence of Abs to LGI1, CASPR-2 or neither antigen (LGI1/CASPR-2-Ab(-)). Clinical, neuropsychology and MRI data were obtained from patient records for all LE patients from the Bonn Epilepsy Centre positive for VGKC-Abs by radioimmunoprecipitation assay between 2002 and 2011. Eighteen VGKC-LE patients were identified: nine patients (50 %) had LGI1-Abs, three (16 %) had CASPR-2-Abs; and six (33 %) were negative for both LGI1- and CASPR-2-Abs. At first assessment, the groups did not differ clinically or radiologically, but faciobrachial dystonic seizures were only observed in two LGI1-Ab(+) patients. All patients received monthly intravenous methylprednisolone (MP) pulses. At the most recent follow up (median 26 months), thirteen (72 %) were seizure-free, and seizure-freedom rates did not differ between the Ab groups. Hippocampal atrophy had developed in 7/9 LGI1-Ab(+) patients, but in none of the CASPR-2-Ab(+) or LGI/CASPR-2-Ab(-) patients (p = 0.003). While all subgroups improved, memory scores only normalized in six patients (33 %) and LGI1-Ab(+) patients were left with significantly poorer memory than the other two subgroups. Most VGKC-LE patients become seizure-free with pulsed monthly MP, but memory outcome is less favourable. Hippocampal atrophy and poor memory recovery is common in patients with LGI1-Abs and suggests permanent functional damage. More intense immunotherapies could improve outcomes in LGI1-Ab(+)-LE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Antibodies / immunology*
  • Atrophy / pathology
  • Epitopes*
  • Female
  • Glucocorticoids / pharmacology
  • Hippocampus / drug effects
  • Humans
  • Limbic Encephalitis / complications
  • Limbic Encephalitis / drug therapy*
  • Limbic Encephalitis / immunology*
  • Limbic Encephalitis / pathology
  • Magnetic Resonance Imaging
  • Male
  • Membrane Proteins / immunology
  • Memory / drug effects
  • Methylprednisolone / administration & dosage
  • Methylprednisolone / pharmacology*
  • Middle Aged
  • Nerve Tissue Proteins / immunology
  • Potassium Channels, Voltage-Gated / immunology*
  • Proteins / immunology
  • Seizures / drug therapy
  • Seizures / etiology
  • Treatment Outcome

Substances

  • Antibodies
  • CNTNAP2 protein, human
  • Epitopes
  • Glucocorticoids
  • LGI1 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Potassium Channels, Voltage-Gated
  • Proteins
  • Methylprednisolone