Original article
Initial clinical presentation of young children with N-methyl-d-aspartate receptor encephalitis

https://doi.org/10.1016/j.ejpn.2017.12.014Get rights and content

Highlights

  • First clinical symptom of young children with NMDA-R-Abs encephalitis is different than adult female.

  • Generalized or focal seizures are the most frequent first neurological symptom of young children with NMDA-R-Abs encephalitis.

  • Focal seizures are difficult to diagnose because of presentation with transient unilateral dystonic or tonic posturing.

Abstract

Autoimmune encephalitis with anti-N-methyl-d-aspartate receptor autoantibodies (NMDA-R-Abs) is a recently described disease affecting adult and pediatric patients. Symptoms of the disease are now perfectly described in the adult population but the clinical presentation is less known in young children. The aim of the present study was to describe the clinical presentation and the specificities of symptoms presented by young children with NMDA-R-Abs encephalitis to improve diagnosis of this disease, and to compare these to a series of previously published female adult patients. Fifty cases of children younger than twelve years of age diagnosed with NMDA-R-Abs encephalitis between January 1, 2007 and December 31, 2016 (27 females and 23 males) were retrospectively studied. The first neurological symptoms observed in young children with NMDA-R-Abs encephalitis were characterized by seizure (72%), especially focal seizure (42%), within a median of 15 days before other encephalitis symptoms; other patients mostly had behavioral disorders (26%). The seizures were frequently difficult to diagnose because of the transient unilateral dystonic or tonic posturing presentation or sudden unilateral pain in the absence of clonic movements. A post-ictal motor deficit was also frequently observed. This clinical presentation is different from that observed in adult females with NMDA-R-Abs encephalitis who initially present mainly psychiatric disorders (67%) or cognitive impairment (19%), and less frequently seizures (14%). The diagnosis of NMDA-R-Abs encephalitis should be systematically considered in young children of both sexes who present neurological symptoms suggesting recent seizures (focal or generalized) without obvious other etiology.

Introduction

Autoimmune encephalitis with anti-N-methyl-d-aspartate receptor antibodies (NMDA-R-Abs) was described for the first time in 2007 in 13 women presenting an ovarian teratoma.1 NMDA-R-Abs encephalitis represents about 4% of all encephalitis2 and it is the most common autoimmune encephalitis.3, 4 The course of the disease is very well known in the adult population especially in young women who typically present prodromal symptoms followed a few days later by psychiatric disorders then seizures and autonomic dysfunctions.5, 6 Several studies have reported clinical and laboratory data in children and adolescents with NMDA-R-Abs encephalitis7, 8, 9, 10, 11 but none of them has precisely described the course of the disease in young children.

The aim of this study was to describe the clinical and paraclinical presentation as well as outcome of NMDA-R-Abs encephalitis in young children in order to increase the accuracy of the disease diagnosis, knowing that prognosis seems to be related to the early initiation of immunomodulatory treatment.6, 8, 9

Section snippets

Population

We retrospectively studied all the children with NMDA-R-Abs encephalitis younger than 12 years old diagnosed in the French Paraneoplastic Neurological Syndrome Reference Center between January 1, 2007 and December 31, 2016. The diagnosis of NMDA-R-Abs encephalitis was confirmed by the presence of NMDA-R-Abs in the patient's cerebrospinal fluid (CSF), as previously described,7, 13 using two methods: i) specific staining pattern by immunohistochemistry of the hippocampus on rat brain tissue; ii)

Population

Fifty children were included in the study (Fig. 1). The median age at diagnosis was 5.9 years (interquartile range, IQR [3.8–8.3]), 27/50 patients (54%) were female, and most were of caucasian (40%) or african (34%) ethnicity.

Clinical presentation

Prodromal symptoms were present in 20 patients (40%): fever in 10/20 patients (50%), headache and ear, nose and throat (ENT) disorders in 6/20 (30%), digestive disorders in 5/20 (25%), cough and sleep disorders in 2/20 patients (10%), and deterioration of the general state

Discussion

The present study identified the specific characteristics of young children with NMDA-R-Abs encephalitis. As compared to adult patients who are mostly female and present behavioral and cognitive disorders a few days before the main symptoms of encephalitis,5, 6, 13, 14 young children are equally male and female and present mainly seizures as the first neurological symptom. However, the diagnosis of seizures can be difficult because young children may present atypical seizures, such as

Conclusion

The study demonstrates that presentation of NMDA-R-Abs encephalitis is particular in young children and different than in adults. The diagnosis should be systematically considered in both male and female patients, and not only in case of abnormal behavior or abnormal movements as is the case in adult patients, but also in case of neurological symptoms suggesting recent seizures (focal or generalized) in the absence of obvious other etiology. The diagnosis must be also considered in the presence

Conflict of interest

None of the authors have any conflicts of interests to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Study funding

This study is supported by research grants from the Agence Nationale de la Recherche (ANR-14-CE15-0001-MECANO), the Fondation pour la recherche sur le cerveau (FRC-Neurodon2014) and CSL Behring France, FRM (Fondation pour la recherche médicale) DQ20170336751.

Acknowledgments

The authors would like to thank all the patients, relatives, and physicians who helped to collect the clinical data and particularly Drs Barneiras, Gitiaux, Hully, Simmonet (Hôpital Necker Enfants Malades); Drs Bellavoine, Bonheur, Germanaud, Pichard (Hôpital Robert Debré); Drs Barraud, Lepine, Milh (Hôpitaux de Marseille); Dr Barthez (CHRU Tours); Dr Benezit (Hospices Civils de Lyon); Drs Cheuret, Majorel (CHU Toulouse); Drs Deiva, Maurey, Metreau, Tardieu (CHU Bicêtre); Dr Desprez (Hôpitaux

References (21)

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