Abstract
Herpes simplex virus (HSV) encephalitis can induce an autoimmune encephalitis mediated by autoantibodies against the N-methyl-D-aspartate receptor (NMDAR). Post-HSV NMDAR encephalitis and de novo NMDAR encephalitis have been more commonly described in children and young adults. We describe the case of a 67-year-old woman with post-HSV NMDAR encephalitis and review the relevant literature. Clinical, serological, neurophysiological, and imaging evaluations were undertaken in the evaluation of this patient. A literature review was performed. Nearly 2 months after a typical course of HSV encephalitis confirmed by HSV polymerase chain reaction studies from the spinal fluid and treated with intravenous acyclovir, a 67-year-old woman suffered neurological deterioration. There was no evidence of active HSV infection, but NMDAR antibodies were found in her serum and spinal fluid. The patient improved after initiation of immunosuppressive therapy. All patients who experience new or recurrent neurological symptoms following recovery from HSV encephalitis should be evaluated for post-infectious autoimmune encephalitis, including NMDAR encephalitis.
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References
Abramson JS, Roach ES, Levy HB (1984) Postinfectious encephalopathy after treatment of herpes simplex encephalitis with acyclovir. Pediatr Infect Dis J 3:146–147
Armangué T, Titulaer MJ, Málaga I et al (2013) Pediatric anti-N-methyl-D-aspartate receptor encephalitis-clinical analysis and novel findings in a series of 20 patients. J Pediatr 162:850–856
Armangue T, Leypoldt F, Malaga I et al (2014) Herpes simplex virus encephalitis is a trigger of brain autoimmunity. Ann Neurol 75:317–323
Aurelius E, Forsgren M, Skoldenberg B et al (1993) Persistent intrathecal immune activation in patients with herpes simplex encephalitis. J Infect Dis 168:1248–1252
Baltagi S, Shoykhet M, Felmet K et al (2010) Neurological sequelae of 2009 influenza A (H1N1) in children: a case series observed during a pandemic. Ped Crit Car Med 11:179–184
Barthez-Carpentier MA, Rozenberg F, Dussaix E et al (1995) Relapse of herpes simplex encephalitis. J Child Neurol 10:363–367
Baxter R, Forsyth RJ, Eyre JA (1994) Movement disorder after herpes simplex virus encephalitis. Dev Med Child Neurol 36:275–276
Dalmau J, Tuzun E, Wu HY et al (2007) Paraneoplastic anti-N-methyl-D aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 61:25–36
Dalmau J, Gleichman AJ, Hughes EG et al (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 7:1091–1098
Dalmau J, Lancaster E, Martinez-Hernandez E et al (2011) Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 10:63–74
Davis LE, McLaren LC (1983) Relapsing herpes simplex encephalitis following antiviral therapy. Ann Neurol 13:192–195
De Tiége XD, Rozenberg F, Des Portes V et al (2003) Herpes simplex encephalitis relapses in children: differentiation of two neurologic entities. Neurology 61:241–243
De Tiege X, De Laet C, Mazoin N, et al. (2005) Postinfectious immune-mediated encephalitis after pediatric herpes simplex encephalitis. Brain Dev 27-304-7
Dennett C, Klapper PE, Cleater GM (1996) Polymerase chain reaction in the investigation of ‘relapse’ following herpes simplex encephalitis. J Med Virol 48:129–132
Desena A, Graves D, Warnack W, Greenberg BM (2014) Herpes simplex encephalitis as a potential cause of anti-N-methyl-D-aspartate receptor antibody encephalitis. JAMA Neurol 71:344–346
Devrim I, Tezer H, Haliloglu G et al (2008) Relapsing herpes simplex virus encephalitis despite high-dose acyclovir therapy: a case report. Turk J Pediatr 50:380–382
Gable SM, Gavali S, Radner A et al (2009) Anti-NMDA receptor encephalitis: report of ten cases and comparison with viral encephalitis. Eur J Clin Microbiol Infect Dis 28:1421–1429
Gable MS, Sheriff H, Dalmau J, Tilley DH, Glaser CA (2012) The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clin Infect Dis 54:899–904
Gresa-Arribas N, Titulaer M, Torrents A et al (2014) Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol 13:167–177
Hacohen Y, Deiva K, Pettingill P et al (2014) N-Methyl-D-aspartate receptor antibodies in post-herpes simplex virus encephalitis neurological relapse. Mov Disord 29:90–96
Hargrave DR, Webb DW (1998) Movement disorders in association with herpes simplex virus encephalitis in children: a review. Dev Med Child Neurol 40:640–642
Ito Y, Kimura H, Yabuta Y et al (2000) Exacerbation of herpes simplex encephalitis after successful treatment with acyclovir. Clin Infect Dis 30:185–187
Joos AAB, Ziyeh S, Rauer S et al (2003) Postinfectious autoimmune-mediated encephalitis eight months after herpes simplex encephalitis. Eur Neurol 50:54–56
Kimura H, Aso K, Kuzushima K et al (1992) Relapse of herpes simplex encephalitis in children. Pediatrics 89:891–894
Knezevic W, Carroll WM (1983) Relapse of herpes simplex encephalitis after acyclovir therapy. Aust N Z J Med 13:625–626
Koenig H, Rabinowitz SG, Day E et al (1979) Post-infectious encephalomyelitis after successful treatment. NEJM 300:1089–1093
Leypoldt F, Titulaer MJ, Aguilar E et al (2013) Herpes simplex virus-1 encephalitis can trigger anti-NMDA receptor encephalitis: case report. Neurology 81:1637–1639
Mohammad SS, Sinclair K, Pillai S et al (2014) Herpes simplex encephalitis relapse with chorea is associated with autoantibodies to N-methyl-D-aspartate receptor or dopamine-2-receptor. Mov Disord 29:117–122
Pike MG, Kennedy CR, Neville BGR et al (1991) Herpes simplex encephalitis with relapse. Arch Dis Child 66:1242–1244
Prüss H, Dalmau J, Harms L (2010) Retrospective analysis of NMDA receptor antibodies in encephalitis of unknown origin. Neurology 751735–9
Prüss H, Finke C, Höltje M (2012) N-methyl-D-aspartate receptor antibodies in herpes simplex encephalitis. Ann Neurol 72:902–911
Ross CAC, Stevenson J (1961) Herpes-simplex meningoencephalitis. Lancet 2:682–685
Schäbitz WR, Rogalewski A, Hagemeister C, Bien CG (2014) VZV brainstem encephalitis triggers NMDA receptor immunoreaction. Neurology 83:2309–2311
Schleede L, Bueter W, Baumgartners-Sigl S et al (2013) Pediatric herpes simplex virus encephalitis: a retrospective multicenter experience. J Child Neurol 28:321–331
Schlesinger Y, Buller RS, Brunstrom JE et al (1995) Expanded spectrum of herpes simplex encephalitis in children. J Pediatr 126:234–241
Sellner J, Dvorak F, Zhou Y et al (2005) Acute and long-term alteration of chemokine mRNA expression after anti-viral and anti-inflammatory treatment in herpes simplex virus encephalitis. Neurosci Lett 374:197–202
Shanks DE, Blasco PA, Chason DP (1991) Movement disorder following herpes simplex encephalitis. Dev Med Child Neurol 33:343–355
Sköldenberg B, Aurelius E, Hjalmarsson A et al (2006) Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults. J Neurol 253:163–170
Valencia I, Miles DK, Melvin J et al (2004) Relapse of herpes encephalitis after acyclovir therapy: report of two new cases and review of the literature. Neuropediatrics 35:371–376
Van Landingham KE, Marsteller HB, Ross GW et al (1988) Relapse of herpes simplex encephalitis after conventional acyclovir therapy. JAMA 259:1051–1053
Wang HS, Kuo MF, Huang SC et al (1994) Choreoathetosis as an initial sign of relapsing of herpes simplex encephalitis. Pediatr Neurol 11:341–345
Whitley RJ, Alford CA, Hirsh MS et al (1986) Vidarabine versus acyclovir therapy in herpes simplex encephalitis. NEJM 314:144–149
Xu CL, Liu L, Zhao WQ et al (2011) Anti-N-methyl-D-aspartate receptor encephalitis with serum and anti-thyroid antibodies and IgM antibodies against Epstein-Barr virus viral capsid antigen: a case report and one year follow-up. BMC Neurol 11:149–155
Yamada S, Kameyama T, Nagaya S (2003) Relapsing herpes simplex encephalitis: pathological confirmation of viral reactivation. J Neurol Neurosurg Psychiatry 74:262–264
Conflict of interest
Nicholas A. Morris, MD, Tamara Kaplan, MD, and Jenny Linnoila, MD, PhD declare that they have no competing interests.
Tracey Cho, MD received compensation as a consultant for Optum Insight, guest editor for Continuum: Lifelong Learning in Neurology, and guest editor for Seminars in Neurology.
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Morris, N.A., Kaplan, T.B., Linnoila, J. et al. HSV encephalitis-induced anti-NMDAR encephalitis in a 67-year-old woman: report of a case and review of the literature. J. Neurovirol. 22, 33–37 (2016). https://doi.org/10.1007/s13365-015-0364-9
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DOI: https://doi.org/10.1007/s13365-015-0364-9