How to cite this article: Khalsi F, Ayari A, Trabelsi I, Klaa H, Turki I Bousetta K. Anti-NMDA Receptor Encephalitis Occurring after Herpetic Encephalitis
in a Child: A Case Report. Acad J Ped Neonatol. 2018; 7(2): 555764. DOI: 10.19080/AJPN.2018.07.555764
Background: We describe a child with severe generalized choreoathetosis and anti-Nmethyl-D-aspartate receptor encephalitis after herpes simplex virus type 1 encephalitis recent evidence supports an autoimmune trigger for anti-N-methyl-D-aspartate receptor encephalitis following a viral infection.
Patient description: A 7-year-old girl presented with fever and partial seizures and was subsequently treated for proven herpes simplex virus type 1 encephalitis. Shortly thereafter, she developed irritability, orolingual and facial choreodystonic movements, and choreoathetoid movements of her trunk and limbs. Cerebrospinal fluid analysis confirmed anti-N-methyl-D-aspartate receptor antibodies. Management of her movements required titrated doses of clobazam, valproate, tetrabenazine, and immunotherapy. At 3 months’ follow-up, her abnormal movements had incompletely resolved.
Conclusion: Our patient adds to recent evidence linking a viral trigger for brain autoimmunity. Movement disorders appear early, leading to early immunothearpy management. Symptomatic treatment for persistent or severe generalized choreodystonic movements is challenging, and no prospective clinical trials are available in the pediatric literature
Since its description in children in 2009 , encephalitis with antibodies against N-methyl-D- aspartate receptor (NMDAR) that success herpes encephalitis (HE) has entered the mainstream of neurology.It is responsible for clinical worsening that progress from abnormal movements, seizure to a comatose state.
A girl of seven-year-old was brought to emergency department for fever and focal then generalized seizures. She had no remarquable history and her developmental milestones were normal. She was hospitalized, and an initial cranial CT scan was performed and showed cortical and subcortical hypo density involving temporal and parietal lobes and suggesting an herpes encephalitis.
The patient received 20mg/kg of phenobarbital because of the recurrence of seizures. The Acyclovir was started with the dose of 500mg/m2 thrice a day. Complete blood count and biochemical analysis were normal. A lumbar puncture was performed after the cessation of seizures and revealed a pleocytosis with 310 leucocyte
(80% lymphocyte) and Herpes simplex virus type 1 polymerase
chain reaction (PCR) testing was positive in the cerebrospinal fluid (CSF). The cerebral MRI performed three days later revealed the same lesions seen in the CT scan, Acyclovir was maintained for there weeks then the patient was discharged home.
One week later, she was brought by her parents for abnormal movements, anxiety, irritability and a very poor sleep. Physical examination in the first day didn’t show any abnormality, two days later the patient become unconscious (Glasgow Coma Scale = 08), deep tendon reflexes were normal. Cerebral MRI didn’t show any new cortical lesions neither white matter abnormality. CSF analysis revealed protein and glucose levels of 0.9g/L and 3.05mmol/L, respectively. On microscopic examination of CSF, fifty leucocyte with 80% lymphocytes. Herpes PCR testing was negative. CSF sample was positive for autoantibodies Anti-NMDAR seen in the limbic encephalitis. The patient was treated with methylprednisolone 30mg/Kg, intravenous Immunoglobuline 0.5g/Kg for five days and Acyclovir treatment was reconducted.
After a week of treatment, the patient showed an improvement: Glasgow coma scale improved to 14 and she had no longer dysautonomia. Few days later, she developed abnormal
and involuntary movements, they were fast, large amplitude
and interest limbs, trunk and the neck of the right side of the
body. These movements responded to immunoglobulins and
At 3 months’ followup, her abnormal movements were
completely resolved, and she was seizure- free. At 9 months’ followup,
she has global developmental delay but appears more social
and interactive. She is tolerating a slow taper from tetrabenazine,
and valproate continues to be her primary antiepileptic therapy.
The outcome was excellent after two years of the diagnostic
with minor langage sequaele, the patient returned to school after
10 months and had a good insertion.
Herpes encephalitis is the most common fatal encephalitis
. Despite the improvement of prognosis since the advent of
the Acyclovir, 35% of patient still suffer a poor outcome with
heavy sequelae or even death. However, symptoms seen during
HE are not resulting only from the direct cytotoxicity of the
HSV1. In 2009, Florance NR et al.  described anti-NMDAR
encephalitis in children and young adolescent then in 2012, Pruss
et al. , described cases of limbic encephalitis with anti-NMDAR
antibodies following an HE. Armangue et al.  published a case
series in 2014, he concluded that “relapsing post-HE” is often anti-
NMDAR encephalitis which may occur 1 to 4 weeks after the HE in
both adult and children.
It seems that the mechanism for development of anti-NMDAR
encephalitis following HE is probably that the virus induces
destruction of the neurons and initiates a primary autoimmune
response against NMDAR by presentation of tissue that is normally
shielded from systemic immunity . The presence of NMDAR
antibodies is not equivalent to the diagnosis of anti-NMDAR
encephalitis, a distinct disorder associated with the presence of
IgG anti NR1-subunit of the receptor in the CSF .
Those antibodies are responsible of psychiatric signs and
seizures in adults and explain abnormal movement (choreoathetosis
in 90%) and seizures in pediatric population. There is no standard
approach for treatment, but it consists generally in a first line
immunotherapy and second line immunotherapy. First line
immune therapy repose on Intra veinous Immunoglobuline 0.4g/
Kg for five days associated with Methylprednisolone 30mg/Kg.
Many studies discuss plasma exchange but it still challenging in
pediatric population. If no response after two weeks, Rituximab
(375mg/m2) should be started.
Finally, the association between NMDAR antibodies and
hampered neurocognitive recovery could also have therapeutical
implications. Symptoms related to autoimmune reactions are
potentially responsive to immune therapy and clinical trials
should be designed to find out if the frequency and magnitude of
neurocognitive herpetic damage can decrease in the future.