title: New-Onset Headache in Patients With Autoimmune Encephalitis Is Associated With anti-NMDA-Receptor Antibodies.
abstract: OBJECTIVE
  We tested the hypotheses (i) that autoimmune encephalitis is associated with new-onset headache, and (ii) that the occurrence of headache is associated with the presence of anti-N-methyl-D-aspartate (NMDA)-receptor antibodies.
  
  
  BACKGROUND
  Autoimmune encephalitis presents with cognitive dysfunction as well as neuro-psychiatric symptoms. Its pathophysiology might involve antibody-mediated dysfunction of the glutamatergic system as indicated by the presence of anti-NMDA-receptor antibodies in some patients.
  
  
  METHODS
  In this cross-sectional study, patients with autoimmune encephalitis were assessed with a standardized interview for previous headache and headache associated with autoimmune encephalitis. Headache was classified according to the International Classification of Headache Disorders, second edition. Clinical and paraclinical findings were correlated with the occurrence of headache.
  
  
  RESULTS
  Of 40 patients with autoimmune encephalitis, 19 did not have a history of headache. Of those, nine suffered from encephalitis-associated headache. Seven of these nine had anti-NMDA-receptor antibodies in contrast to only two among the remaining 10 patients without new-onset headache (P = .023, odds ratio: 14, 95% confidence interval: 1.5; 127). In most patients headache occurred in attacks on more than 15 days/month, was severe, and of short duration (less than 4 hours). International Headache Society criteria for migraine were met in three patients.
  
  
  CONCLUSIONS
  New-onset headache is a relevant symptom in patients with autoimmune encephalitis who have no history of previous headache, especially in the subgroup with anti-NMDA-receptor antibodies. This indicates a thorough investigation for secondary headaches including anti-NMDA-R antibodies for patients with new-onset headache and neuropsychiatric findings. Glutamatergic dysfunction might be important for the generation of head pain but may only occasionally be sufficient to trigger migraine-like attacks in nonmigraineurs.
authors.affiliation: Department of Neurology, University of Munich Hospital, Großhadern, Munich, Germany (C.J. Schankin, F. Kästele, L. Ann Gerdes, T. Winkler, E. Csanadi, T. Högen, T. Kümpfel, and A. Straube).|Department of Neurology, University Hospital Bern - Inselspital, University of Bern, Bern, Switzerland (C.J. Schankin).
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Schankin
authors.affiliation: Department of Neurology, University of Munich Hospital, Großhadern, Munich, Germany (C.J. Schankin, F. Kästele, L. Ann Gerdes, T. Winkler, E. Csanadi, T. Högen, T. Kümpfel, and A. Straube).
authors.forename: Fabian
authors.initials: F
authors.lastname: Kästele
authors.affiliation: Department of Neurology, University of Munich Hospital, Großhadern, Munich, Germany (C.J. Schankin, F. Kästele, L. Ann Gerdes, T. Winkler, E. Csanadi, T. Högen, T. Kümpfel, and A. Straube).|Institute of Clinical Neuroimmunology, University of Munich Hospital, Großhadern, Munich, Germany (L.A. Gerdes and T. Kümpfel).
authors.forename: Lisa Ann
authors.initials: LA
authors.lastname: Gerdes
authors.affiliation: Department of Neurology, University of Munich Hospital, Großhadern, Munich, Germany (C.J. Schankin, F. Kästele, L. Ann Gerdes, T. Winkler, E. Csanadi, T. Högen, T. Kümpfel, and A. Straube).
authors.forename: Tobias
authors.initials: T
authors.lastname: Winkler
authors.affiliation: Department of Neurology, University of Munich Hospital, Großhadern, Munich, Germany (C.J. Schankin, F. Kästele, L. Ann Gerdes, T. Winkler, E. Csanadi, T. Högen, T. Kümpfel, and A. Straube).
authors.forename: Endy
authors.initials: E
authors.lastname: Csanadi
authors.affiliation: Department of Neurology, University of Munich Hospital, Großhadern, Munich, Germany (C.J. Schankin, F. Kästele, L. Ann Gerdes, T. Winkler, E. Csanadi, T. Högen, T. Kümpfel, and A. Straube).
authors.forename: Tobias
authors.initials: T
authors.lastname: Högen
authors.affiliation: Department of Neurology, University Medical Center, University of Göttingen, Göttingen, Germany (H. Pellkofer).
authors.forename: Hannah
authors.initials: H
authors.lastname: Pellkofer
authors.affiliation: Department of Clinical Neurophysiology, University Medical Center, University of Göttingen, Göttingen, Germany (W. Paulus).
authors.forename: Walter
authors.initials: W
authors.lastname: Paulus
authors.affiliation: Department of Neurology, University of Munich Hospital, Großhadern, Munich, Germany (C.J. Schankin, F. Kästele, L. Ann Gerdes, T. Winkler, E. Csanadi, T. Högen, T. Kümpfel, and A. Straube).|Institute of Clinical Neuroimmunology, University of Munich Hospital, Großhadern, Munich, Germany (L.A. Gerdes and T. Kümpfel).
authors.forename: Tania
authors.initials: T
authors.lastname: Kümpfel
authors.affiliation: Department of Neurology, University of Munich Hospital, Großhadern, Munich, Germany (C.J. Schankin, F. Kästele, L. Ann Gerdes, T. Winkler, E. Csanadi, T. Högen, T. Kümpfel, and A. Straube).
authors.forename: Andreas
authors.initials: A
authors.lastname: Straube
mesh_terms: D000328:Adult; D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis / Q000150:complications*; D000906:Antibodies / Q000097:blood; D004660:Encephalitis / Q000150:complications* / Q000276:immunology*; D005260:Female; D050031:Hashimoto Disease / Q000150:complications* / Q000276:immunology*; D006261:Headache / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology; D018709:Statistics, Nonparametric
chemical_list: D000906:Antibodies; D016194:Receptors, N-Methyl-D-Aspartate
keywords: anti-NMDA-receptor antibodies; autoimmune encephalitis; headache; limbic encephalitis; migraine; secondary headache