title: Cramp-fasciculation syndrome in patients with and without neural autoantibodies.
abstract: BACKGROUND
  We investigated the clinical, electrophysiological and neural autoantibody characteristics in cramp-fasciculation syndrome (CFS) patients.
  
  
  METHODS
  We reviewed Mayo Clinic records from 2000 to 2011 to identify clinically defined CFS patients who underwent neural autoantibody testing. Stored sera of patients who tested positive for antibodies to voltage-gated potassium channel complex (VGKC complex) were analyzed further for leucine-rich glioma-inactivated 1 (LGI1) or contactin-associated protein-2 immunoglobulin G (CASPR2-IgG) antibodies.
  
  
  RESULTS
  Thirty-seven patients were identified. Twelve were seropositive for neural autoantibodies. Clinical manifestations were similar in seropositive and seronegative patients, although central and autonomic neuronal hyperexcitability symptoms were more common in seropositive cases. No patients had a malignancy. Repetitive tibial nerve stimulation at 10 Hz revealed longer afterdischarges in seropositive patients. Two of 7 patients with VGKC-complex autoimmunity demonstrated LGI1 or CASPR2-IgG antibodies. Only 2 of 12 seropositive patients required immunotherapy.
  
  
  CONCLUSIONS
  VGKC-complex autoimmunity occurs in a minority of CFS patients. Antibody positivity was associated with extramuscular manifestations, typically without malignancy. Target antigens within the VGKC complex remain unknown in most patients.
authors.affiliation: Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905, USA; Department of Neurology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Teerin
authors.initials: T
authors.lastname: Liewluck
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Klein
authors.forename: Lyell K
authors.initials: LK
authors.lastname: Jones
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001703:Biophysics; D002648:Child; D015331:Cohort Studies; D003402:Creatine Kinase / Q000097:blood; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D007167:Immunotherapy; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000276:immunology*; D009431:Neural Conduction; D009468:Neuromuscular Diseases / Q000097:blood* / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology; D011506:Proteins / Q000276:immunology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; C403049:CNTNAP2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D024642:Potassium Channels, Voltage-Gated; D011506:Proteins; D003402:Creatine Kinase
keywords: CASPR2 antibody; LGI1 antibody; cramp-fasciculation syndrome; peripheral nerve hyperexcitability syndrome; voltage-gated potassium channel complex antibody