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We read with interest the review by Le Doare et al. discussing the
presentation and management of neonatal and childhood herpes simplex
encephalitis (HSE). The article nicely outlines the importance of timely
treatment of this potentially catastrophic infection. The authors have
provided practical advice that is applicable for many of the challenges
that clinicians might be faced with.
Although they mentioned...
Although they mentioned the possibility of autoimmune encephalitis
following HSE, it is important to emphasise this likelihood. More
specifically, there is growing evidence to show an association between HSE
and subsequent N-methyl-D-aspartate receptor (NMDAR) antibody
encephalitis. The NMDAR is a type of glutamate receptor found throughout
the brain. Its role in autoimmune encephalitis has only been recently
described by Dalmau et al in 2007 (1) as a paraneoplastic phenomenon
leading to autoimmune encephalitis, although the presence of a causative
tumour is less likely in younger patients (2).
Pruss et al described the presence of NMDAR antibodies occurring in
the course of 30% of individuals with HSE (3). In a paediatric sample, 7
out of 20 individuals (35%) relapsed and 3 out of those 7 patients were
found to be NMDAR antibodies positive (4). This highlights the importance
of considering this diagnosis in patients presenting with a possible
relapse of HSE or even in patients not responding to appropriate antiviral
therapy. Common symptoms may include a movement disorder, seizures and
encephalopathy. Antibodies can be tested in serum and CSF specimens.
Early recognition and referral of autoimmune encephalitis of this
entity is paramount as early aggressive immunotherapy can lead to good
1. Dalmau J, Tuzun E and Wu H et al. Paraneoplastic anti-N-methyl-D-
aspartate receptor encephalitis associated with ovarian teratoma. Ann
Neurol 2007; 6(1): 25-36
2. 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):
3. Pruss H, Finke C, Holtje M et al. N-methyl-D-aspartate receptor
antibodies in herpes simplex encephalitis. Ann Neurol 2012; 72(6): 902-911
4. Hacohen U, 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
5. Titulaer M, 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):