RSS-Feed abonnieren
DOI: 10.1055/s-0042-1757706
Autoimmune Encephalitis with Autoantibodies to NMDAR1 following Herpes Encephalitis in Children and Adolescents

Abstract
Herpes simplex virus (HSV) type 1 is a frequent pathogen causing infectious encephalitis (HSVE). Early treatment with intravenous acyclovir has led to a significant decrease in mortality. However, especially in children, deterioration during or after HSVE may occur without any evidence of HSV reactivation or improvement following repeated antiviral therapy. Here, we report 15 patients (age range 3 months to 15 years) who suffered from autoimmune encephalitis with autoantibodies to NMDAR1 following Herpes encephalitis, presenting with movement abnormalities (young children) or neuropsychiatric symptoms (older children) as major complaints, respectively. The diagnosis was based on positive cerebrospinal fluid (CSF) and/or serum anti-NMDAR-antibodies with two children showing only positive CSF antibody findings. The time lag between first symptoms and diagnosis of autoimmune encephalitis was significantly longer than between first symptoms and diagnosis of HSVE (p <0.01). All patients improved during immunosuppressive treatment, during which plasmapheresis or rituximab treatments were applied in 11 patients, irrespective of their age. Despite immunotherapy, no patients relapsed with HSVE. Early diagnosis and treatment of autoimmune encephalitis after HSVE may be associated with a better outcome so that high clinical awareness and routine testing for anti-NMDAR-antibodies after HSVE seems advisable. If autoimmune encephalitis is suspected, antibody testing should also be performed on CSF if negative in serum.
Publikationsverlauf
Eingereicht: 11. November 2021
Angenommen: 12. August 2022
Artikel online veröffentlicht:
21. Dezember 2022
© 2022. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Granerod J, Ambrose HE, Davies NW. et al; UK Health Protection Agency (HPA) Aetiology of Encephalitis Study Group. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis 2010; 10 (12) 835-844
- 2 Boston Interhospital Virus Study Group; NIAID-Sponsored Cooperative Antiviral Clinical Study. Failure of high dose 5-iodo-2′-deoxyuridine in the therapy of herpes simplex virus encephalitis. Evidence of unacceptable toxicity. N Engl J Med 1975; 292 (12) 599-603
- 3 Sköldenberg B, Forsgren M, Alestig K. et al. Acyclovir versus vidarabine in herpes simplex encephalitis. Randomised multicentre study in consecutive Swedish patients. Lancet 1984; 2 (8405): 707-711
- 4 De Tiège X, Rozenberg F, Des Portes V. et al. Herpes simplex encephalitis relapses in children: differentiation of two neurologic entities. Neurology 2003; 61 (02) 241-243
- 5 Gutman LT, Wilfert CM, Eppes S. Herpes simplex virus encephalitis in children: analysis of cerebrospinal fluid and progressive neurodevelopmental deterioration. J Infect Dis 1986; 154 (03) 415-421
- 6 Ito Y, Kimura H, Yabuta Y. et al. Exacerbation of herpes simplex encephalitis after successful treatment with acyclovir. Clin Infect Dis 2000; 30 (01) 185-187
- 7 Schleede L, Bueter W, Baumgartner-Sigl S. et al. Pediatric herpes simplex virus encephalitis: a retrospective multicenter experience. J Child Neurol 2013; 28 (03) 321-331
- 8 Sköldenberg B, Aurelius E, Hjalmarsson A. et al. Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults. J Neurol 2006; 253 (02) 163-170
- 9 Lafaille FG, Pessach IM, Zhang SY. et al. Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells. Nature 2012; 491 (7426): 769-773
- 10 Armangue T, Spatola M, Vlagea A. et al; Spanish Herpes Simplex Encephalitis Study Group. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis. Lancet Neurol 2018; 17 (09) 760-772
- 11 Nosadini M, Mohammad SS, Corazza F. et al. Herpes simplex virus-induced anti-N-methyl-d-aspartate receptor encephalitis: a systematic literature review with analysis of 43 cases. Dev Med Child Neurol 2017; 59 (08) 796-805
- 12 Marcus L, Ness JM. Pediatric N-Methyl-d-Aspartate (NMDA) receptor encephalitis, with and without herpes encephalitis. J Child Neurol 2021; 36 (09) 743-751
- 13 Dalmau J, Tüzün E, Wu HY. et al. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007; 61 (01) 25-36
- 14 Dalmau J, Gleichman AJ, Hughes EG. et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008; 7 (12) 1091-1098
- 15 Favier M, Joubert B, Picard G. et al. Initial clinical presentation of young children with N-methyl-d-aspartate receptor encephalitis. Eur J Paediatr Neurol 2018; 22 (03) 404-411
- 16 Florance NR, Davis RL, Lam C. et al. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 2009; 66 (01) 11-18
- 17 Goenka A, Jain V, Nariai H, Spiro A, Steinschneider M. Extended clinical spectrum of anti-N-methyl-d-aspartate receptor encephalitis in children: a case series. Pediatr Neurol 2017; 72: 51-55
- 18 Hara M, Martinez-Hernandez E, Ariño H. et al. Clinical and pathogenic significance of IgG, IgA, and IgM antibodies against the NMDA receptor. Neurology 2018; 90 (16) e1386-e1394
- 19 Prüss H, Finke C, Höltje M. et al. N-methyl-D-aspartate receptor antibodies in herpes simplex encephalitis. Ann Neurol 2012; 72 (06) 902-911
- 20 Titulaer MJ, McCracken L, Gabilondo I. et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013; 12 (02) 157-165
- 21 Martinez-Hernandez E, Horvath J, Shiloh-Malawsky Y, Sangha N, Martinez-Lage M, Dalmau J. Analysis of complement and plasma cells in the brain of patients with anti-NMDAR encephalitis. Neurology 2011; 77 (06) 589-593
- 22 Al-Obaidi MMJ, Bahadoran A, Wang SM, Manikam R, Raju CS, Sekaran SD. Disruption of the blood brain barrier is vital property of neurotropic viral infection of the central nervous system. Acta Virol 2018; 62 (01) 16-27
- 23 Bartels F, Krohn S, Nikolaus M. et al. Clinical and magnetic resonance imaging outcome predictors in pediatric anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol 2020; 88 (01) 148-159