title: Outcome of limbic encephalitis with VGKC-complex antibodies: relation to antigenic specificity.
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.
authors.affiliation: Department of Epileptology, University of Bonn Medical Center, Bonn, Germany, michael.malter@gmx.de.
authors.forename: M P
authors.initials: MP
authors.lastname: Malter
authors.forename: C
authors.initials: C
authors.lastname: Frisch
authors.forename: J C
authors.initials: JC
authors.lastname: Schoene-Bake
authors.forename: C
authors.initials: C
authors.lastname: Helmstaedter
authors.forename: K P
authors.initials: KP
authors.lastname: Wandinger
authors.forename: W
authors.initials: W
authors.lastname: Stoecker
authors.forename: H
authors.initials: H
authors.lastname: Urbach
authors.forename: R
authors.initials: R
authors.lastname: Surges
authors.forename: C E
authors.initials: CE
authors.lastname: Elger
authors.forename: A V
authors.initials: AV
authors.lastname: Vincent
authors.forename: C G
authors.initials: CG
authors.lastname: Bien
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology*; D001284:Atrophy / Q000473:pathology; D000939:Epitopes; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020363:Limbic Encephalitis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D008568:Memory / Q000187:drug effects; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000276:immunology; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology*; D011506:Proteins / Q000276:immunology; D012640:Seizures / Q000188:drug therapy / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; C403049:CNTNAP2 protein, human; D000939:Epitopes; D005938:Glucocorticoids; D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D024642:Potassium Channels, Voltage-Gated; D011506:Proteins; D008775:Methylprednisolone