Anti-N-Methyl-d-Aspartate Receptor Encephalitis that Developed after Herpes Encephalitis: A Case Report and Literature Review

Abstract

Herpes encephalitis (HE) is among the most common forms of viral encephalitis. Earlier publications indicate the development of acyclovir-refractory choreoathetosis in patients with HE. These reports suggest the development of secondary autoimmunity in the pathogenesis of HE. Combined methylprednisolone and acyclovir treatment reduced the appearance of brain abnormalities relative to treatment with acyclovir alone in a mouse model of encephalitis. We describe a case of a 19-month-old previously healthy girl presenting with sudden onset seizures and loss of consciousness. Initial polymerase chain reaction (PCR) tests for the presence of herpes simplex virus (HSV) were negative as were the tests for the limbic encephalitis antibodies. Steroids were administered with acyclovir to treat suspected autoimmune encephalitis as a result of the patient history of varicella vaccination. HSV PCR testing was positive on the 5th day; however, steroid treatment was continued due to the positive response seen in the patient. Steroid therapy was reduced on the 25th day of treatment due to the development of upper respiratory tract infection and the patient developed orofacial dyskinesia and choreoathetoid movements on the 28th day. Antibodies against N-methyl-d-aspartate receptor were detected in the in the serum and cerebrospinal fluid (CSF) on the 28th day. This case is an example of the emergence of autoimmune symptoms in the pathogenesis of HE.

Keywords

herpes encephalitis - autoimmune encephalitis - pediatric - choreoathetoid movements - relapse - dyskinesia

• References

• 1 Steiner I, Kennedy PG, Pachner AR. The neurotropic herpes viruses: herpes simplex and varicella-zoster. Lancet Neurol 2007; 6 (11) 1015-1028
• 2 Raschilas F, Wolff M, Delatour F , et al. Outcome of and prognostic factors for herpes simplex encephalitis in adult patients: results of a multicenter study. Clin Infect Dis 2002; 35 (3) 254-260
• 3 Prüss H, Finke C, Höltje M , et al. N-methyl-D-aspartate receptor antibodies in herpes simplex encephalitis. Ann Neurol 2012; 72 (6) 902-911
• 4 Fiser DH, Long N, Roberson PK, Hefley G, Zolten K, Brodie-Fowler M. Relationship of pediatric overall performance category and pediatric cerebral performance category scores at pediatric intensive care unit discharge with outcome measures collected at hospital discharge and 1- and 6-month follow-up assessments. Crit Care Med 2000; 28 (7) 2616-2620
• 5 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
• 6 Lai M, Hughes EG, Peng X , et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol 2009; 65 (4) 424-434
• 7 Lancaster E, Lai M, Peng X , et al. Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurol 2010; 9 (1) 67-76
• 8 Leypoldt F, Titulaer MJ, Aguilar E , et al. Herpes simplex virus-1 encephalitis can trigger anti-NMDA receptor encephalitis: case report. Neurology 2013; 81 (18) 1637-1639
• 9 Armangue T, Titulaer MJ, Málaga I , et al; Spanish Anti-N-methyl-D-Aspartate Receptor (NMDAR) Encephalitis Work Group. Pediatric anti-N-methyl-D-aspartate receptor encephalitis-clinical analysis and novel findings in a series of 20 patients. J Pediatr 2013; 162 (4) 850-856 , e2
• 10 Hacohen Y, Deiva K, Pettingill P , et al. N-methyl-D-aspartate receptor antibodies in post-herpes simplex virus encephalitis neurological relapse. Mov Disord 2014; 29 (1) 90-96
• 11 Armangue T, Leypoldt F, Málaga I , et al. Herpes simplex virus encephalitis is a trigger of brain autoimmunity. Ann Neurol 2014; 75 (2) 317-323
• 12 Mohammad SS, Sinclair K, Pillai S , et al. Herpes simplex encephalitis relapse with chorea is associated with autoantibodies to N-Methyl-D-aspartate receptor or dopamine-2 receptor. Mov Disord 2014; 29 (1) 117-122
• 13 Florance NR, Davis RL, Lam C , et al. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 2009; 66 (1) 11-18
• 14 Bseikri MR, Barton JR, Kulhanjian JA , et al. Anti-N-methyl D-aspartate receptor encephalitis mimics viral encephalitis. Pediatr Infect Dis J 2012; 31 (2) 202-204
• 15 Gable MS, Sheriff H, Dalmau J, Tilley DH, Glaser CA. 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 2012; 54 (7) 899-904
• 16 Sellner J, Dvorak F, Zhou Y , et al. Acute and long-term alteration of chemokine mRNA expression after anti-viral and anti-inflammatory treatment in herpes simplex virus encephalitis. Neurosci Lett 2005; 374 (3) 197-202
• 17 Reiber H, Ungefehr S, Jacobi C. The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis. Mult Scler 1998; 4 (3) 111-117
• 18 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 (2) 157-165
• 19 Hargrave DR, Webb DW. Movement disorders in association with herpes simplex virus encephalitis in children: a review. Dev Med Child Neurol 1998; 40 (9) 640-642
• 20 De Tiège X, Rozenberg F, Des Portes V , et al. Herpes simplex encephalitis relapses in children: differentiation of two neurologic entities. Neurology 2003; 61 (2) 241-243
• 21 De Tiège X, De Laet C, Mazoin N , et al. Postinfectious immune-mediated encephalitis after pediatric herpes simplex encephalitis. Brain Dev 2005; 27 (4) 304-307
• 22 Sköldenberg B, Aurelius E, Hjalmarsson A , et al. Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults. J Neurol 2006; 253 (2) 163-170
• 23 Meyding-Lamadé UK, Oberlinner C, Rau PR , et al. Experimental herpes simplex virus encephalitis: a combination therapy of acyclovir and glucocorticoids reduces long-term magnetic resonance imaging abnormalities. J Neurovirol 2003; 9 (1) 118-125