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Topic: Autoimmune neurological diseases associated with
autoantibodies specific for synaptic antigens

Autoimmune encephalopathies in children:

diagnostic clues and therapeutic challenges

Giorgia Olivieri, Ilaria Contaldo, Gloria Ferrantini, Elisa Musto, Roberta Scalise, Maria Chiara Stefanini,
Domenica Battaglia, Eugenio Mercuri
Department of Paediatric Neurology and Psychiatry, Catholic University of Sacred Heart, 00168 Rome, Italy.

A B S T R AC T
Neuronal surface antibody syndromes (NSAS) encompass a variety of disorders associated with “neuronal surface antibodies”.
These share clinical and neuroradiological features that pose challenges related to their recognition and treatment. Recent
epidemiological studies show a clear predominance for the glutamate-N-methyl-D-aspartate receptor encephalitis in both
adults and pediatric population. Despite this, the overall NSAS’s incidence remains underestimated, and diagnosis persists
to be not always easy to achieve. Based on current literature data, in this paper the authors propose a diagnostic pathway to
approach and treat pediatric NSAS. An autoimmune etiology can be suggested through the integration of clinical, immunological,
electrophysiological and neuroradiological data. On that basis, a target treatment can be started, consisting of corticosteroids and
intravenous immunoglobulin or plasma exchange as a first-line immunotherapy, followed by second-line drugs including rituximab,
cyclophosphamide or mycophenolate mophetil, if the case. In children a prompt diagnosis and a targeted treatment may lead to a
better clinical outcome. Nevertheless further studies are required to assess the need of more tailored treatments according to long-
term outcome findings and prognostic factors in different NSAS.

Key words: Autoimmune encephalitis; children; diagnosis

INTRODUCTION proteins with various roles in neuronal function,
ranging from synaptic transmission and plasticity to
Over the last decade there has been an increase in the ions channels’ clustering and modulation, and including
identification of forms of encephalitis associated with also glutamic acid decarboxylase (GAD) enzyme when
“neuronal surface antibodies” (NSAbs). These have exposed on cellular surface during exocitosis. [1,7]
been labelled as “neuronal surface antibody syndromes”
(NSAS). [1] A number of studies reporting NSAS in infancy
suggest that, so far, their incidence has been probably
NSAS differ from encephalitis due to antibodies directed underestimated, due to the fact that they are still often
against intracellular neuronal antigens for a different unrecognized or identified at a later stage. [8,9]
etiopathogenetic mechanism, a weaker association
with paraneoplastic syndromes, a better response to In pediatric forms, as in adults one, females
immunotherapy and a higher incidence in the pediatric can be over-represented, and a history of other
[10]
population. [2-6] Pathogenesis predominantly involves antibody-mediated condition is easily detectable.
humoral immune response, while cellular immune Conversely, in children rather than adults, a
response activation may coexist in a variable proportion, paraneoplastic cause is less probable and the role
according to the different forms. Target antigens include of fever or intercurrent infections in supporting the
autoimmune process is less clear. [1,10]
Corresponding Author: Dr. Giorgia Olivieri, Department of
Child Neurology, Policlinico Gemelli, Largo A. Gemelli, 00168 This is an open access article distributed under the terms of the Creative
Roma, Italy. E-mail: gio.olivieri82@gmail.com Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non-commercially, as long as the
author is credited and the new creations are licensed under the identical terms.
Access this article online
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Website:
http://www.nnjournal.net How to cite this article: Olivieri G, Contaldo I, Ferrantini G, Musto
E, Scalise R, Stefanini MC, Battaglia D, Mercuri E. Autoimmune
encephalopathies in children: diagnostic clues and therapeutic challenges.
Neuroimmunol Neuroinflammation 2016;3:147-55.
DOI: 10.20517/2347-8659.2016.09
Received: 19-02-2016; Accepted: 25-03-2016.
© 2016 Neuroimmunology and Neuroinflammation | Published by OAE Publishing Inc. 147