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N-methyl-d-aspartate receptor autoimmunity affects cognitive performance in herpes simplex encephalitis

Westman, G.; Studahl, M.; Ahlm, C.; Eriksson, B. M.; Persson, B.; Rönnelid, J.; Schliamser, S. LU and Aurelius, E. (2016) In Clinical Microbiology and Infection 22(11). p.934-940
Abstract

Objectives: 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... (More)

Objectives: 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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Autoantibodies, Autoimmunity, Herpes simplex encephalitis, IgG, Mattis Dementia Rating Scale, N-methyl-d-aspartate receptor, Neurocognitive impairment, NMDAR
in
Clinical Microbiology and Infection
volume
22
issue
11
pages
934 - 940
publisher
Wiley-Blackwell
external identifiers
  • scopus:84992187033
  • wos:000388119300009
ISSN
1198-743X
DOI
10.1016/j.cmi.2016.07.028
language
English
LU publication?
yes
id
aa33711e-a359-431e-9926-f9accafc1152
date added to LUP
2016-11-04 12:16:03
date last changed
2017-11-19 04:34:33
@article{aa33711e-a359-431e-9926-f9accafc1152,
  abstract     = {<p>Objectives: 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.</p>},
  author       = {Westman, G. and Studahl, M. and Ahlm, C. and Eriksson, B. M. and Persson, B. and Rönnelid, J. and Schliamser, S. and Aurelius, E.},
  issn         = {1198-743X},
  keyword      = {Autoantibodies,Autoimmunity,Herpes simplex encephalitis,IgG,Mattis Dementia Rating Scale,N-methyl-d-aspartate receptor,Neurocognitive impairment,NMDAR},
  language     = {eng},
  number       = {11},
  pages        = {934--940},
  publisher    = {Wiley-Blackwell},
  series       = {Clinical Microbiology and Infection},
  title        = {N-methyl-d-aspartate receptor autoimmunity affects cognitive performance in herpes simplex encephalitis},
  url          = {http://dx.doi.org/10.1016/j.cmi.2016.07.028},
  volume       = {22},
  year         = {2016},
}