title: Axonal dysfunction with voltage gated potassium channel complex antibodies.
abstract: OBJECTIVE
  Although autoantibodies targeted against voltage-gated potassium channel (VGKC)-associated proteins have been identified in limbic encephalitis (LE) and acquired neuromyotonia (aNMT), the role of these antibodies in disease pathophysiology has not been elucidated. The present study investigated axonal function across the spectrum of VGKC-complex antibody associated disorders.
  
  
  METHODS
  Peripheral axonal excitability studies were undertaken in a cohort of patients with LE (N=6) and aNMT (N=11), compared to healthy controls (HC; N=20).
  
  
  RESULTS
  Patients with LE demonstrated prominent abnormalities in peripheral axonal excitability during the acute phase, with reduced threshold change in threshold electrotonus (depolarizing 10-20 LE: 58.5±3.1%; HC: 67.4±0.9%; P<.005; S2 accommodation LE: 17.2±1.4%; HC: 22.2±0.6%; P≤.005) and in recovery cycle parameters (superexcitability LE: -16.0±0.9%; HC: -23.4±1.1%; P<.01; subexcitability LE: 8.5±1.2%; HC: 13.8±0.7%; P≤.005). The pattern of change in LE patients was dissimilar to the effects of antiepileptic medications, suggesting that these factors did not underlie excitability changes in LE. Normalization of excitability parameters was associated with recovery (TEd peak correlation coefficient=.868; P=.002), suggesting that peripheral excitability studies may provide a marker associated with clinical improvement. In contrast, patients with aNMT demonstrated no significant changes at the site of stimulation.
  
  
  CONCLUSIONS
  The lack of prominent excitability abnormalities in patients with aNMT likely reflects a distal origin of hyperexcitability, expected to be at the motor nerve terminal, while the prominent changes observed in patients with LE likely represent a complex disturbance at the level of the axonal membrane, combined with electrolyte imbalance and adaptive change.
authors.affiliation: Institute of Neurology, University College London, United Kingdom; Neuroscience Research Australia & Prince of Wales Clinical School, University of New South Wales, Australia.
authors.forename: Susanna B
authors.initials: SB
authors.lastname: Park
authors.affiliation: School of Medical Sciences, University of New South Wales, Australia.
authors.forename: Cindy S-Y
authors.initials: CS
authors.lastname: Lin
authors.affiliation: School of Medical Sciences, University of New South Wales, Australia.
authors.forename: Arun V
authors.initials: AV
authors.lastname: Krishnan
authors.affiliation: Neuroscience Research Australia & Prince of Wales Clinical School, University of New South Wales, Australia.
authors.forename: Neil G
authors.initials: NG
authors.lastname: Simon
authors.affiliation: Institute of Neurology, University College London, United Kingdom.
authors.forename: Hugh
authors.initials: H
authors.lastname: Bostock
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Vincent
authors.affiliation: Brain and Mind Research Institute, University of Sydney, Australia. Electronic address: matthew.kiernan@sydney.edu.au.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Kiernan
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood*; D015331:Cohort Studies; D004576:Electromyography; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage; D020386:Isaacs Syndrome / Q000188:drug therapy / Q000209:etiology*; D020363:Limbic Encephalitis / Q000097:blood* / Q000150:complications* / Q000188:drug therapy; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009431:Neural Conduction / Q000502:physiology; D010525:Peripheral Nerves / Q000503:physiopathology*; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology*; D012964:Sodium / Q000097:blood
chemical_list: D000906:Antibodies; C403049:CNTNAP2 protein, human; D016756:Immunoglobulins, Intravenous; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D024642:Potassium Channels, Voltage-Gated; D012964:Sodium
keywords: Axonal excitability; Leucine-rich glioma inactivated 1; Limbic encephalitis; Neuromyotonia; Voltage gated potassium channels