title: N-methyl-d-aspartate receptor autoimmunity affects cognitive performance in herpes simplex encephalitis.
abstract: OBJECTIVE
  To investigate the prevalence and temporal development of N-methyl-d-aspartate receptor (NMDAR) autoantibodies in relation to neurocognitive performance in patients with herpes simplex encephalitis (HSE).
  
  
  METHODS
  This prospective observational study enrolled a total of 49 HSE patients within a randomized controlled trial of valacyclovir. Cerebrospinal fluid and serum samples were drawn in the initial stage of disease, after 2 to 3 weeks and after 3 months. Anti-NMDAR IgG was detected with HEK293 cells transfected with plasmids encoding the NMDA NR1 type glutamate receptor. A batch of neurocognitive tests, including the Mattis Dementia Rating Scale (MDRS), Glasgow Coma Scale (GCS), Reaction Level Scale (RLS85), Mini-Mental State Examination (MMSE) and National Institutes of Health (NIH) stroke scale, was performed during 24 months' follow-up.
  
  
  RESULTS
  Anti-NMDAR IgG was detected in 12 of 49 participants. None were antibody positive in the initial stage of disease. In ten of 12 positive cases, specific antibodies were detectable only after 3 months. Notably, the development of NMDAR autoantibodies was associated with significantly impaired recovery of neurocognitive performance. After 24 months' follow-up, the median increase in MDRS total score was 1.5 vs. 10 points in antibody-positive and -negative participants (p=0.018).
  
  
  CONCLUSIONS
  Anti-NMDAR autoimmunity is a common complication to HSE that develops within 3 months after onset of disease. The association to impaired neurocognitive recovery could have therapeutical implications, as central nervous system autoimmunity is potentially responsive to immunotherapy.
authors: Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden. Electronic address: gabriel.westman@medsci.uu.se.
authors: G
authors: G
authors: Westman
authors: Department of Infectious Diseases, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors: M
authors: M
authors: Studahl
authors: Department of Clinical Microbiology, Infectious Diseases, Umeå University, Umeå, Sweden.
authors: C
authors: C
authors: Ahlm
authors: Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden.
authors: B M
authors: BM
authors: Eriksson
authors: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors: B
authors: B
authors: Persson
authors: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors: J
authors: J
authors: Rönnelid
authors: Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden.
authors: S
authors: S
authors: Schliamser
authors: Unit of Infectious Diseases, Department of Medicine, Karolinska Institutet, Sweden.
authors: E
authors: E
authors: Aurelius
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000378:metabolism*; D020803:Encephalitis, Herpes Simplex / Q000188:drug therapy / Q000276:immunology* / Q000523:psychology*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011446:Prospective Studies; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology*; D013548:Sweden; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D001323:Autoantibodies; D016194:Receptors, N-Methyl-D-Aspartate; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir
keywords: Autoantibodies; Autoimmunity; Herpes simplex encephalitis; IgG; Mattis Dementia Rating Scale; N-methyl-d-aspartate receptor; NMDAR; Neurocognitive impairment