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

Diagnostic algorithms in autoimmune encephalitis

Valentina Damato
Institute of Neurology, Catholic University of Sacred Heart, 00168 Rome, Italy.

A B S T R AC T
Over the past decade the discovery of novel forms of encephalitis associated with neuronal surface antibodies had changed
the paradigms for diagnosing and treating disorders that were previously mischaracterized. Recognition of clinical syndromes,
consistent methods of diagnosis, and early targeted immunotherapy can lead to a favorable outcome in diseases that may be
associated with significant disability or death if left untreated. Here the conditions associated with neuronal surface antibodies are
briefly reviewed, some general aspects of these syndromes are considered and guidelines that could help in the recognition of
these disorders are suggested. Furthermore, a diagnostic algorithm to detect and characterize neuronal cell surface autoantibodies
is suggested and some of the caveats of serum testing are outlined. Future directions will involve the identification of novel
autoantibodies, the standardization of methods to detect and characterize them, as well as evaluation of the most efficacious
therapeutic strategies in patients with established diagnosis of autoimmune encephalitis.

Key words: Autoimmune encephalitis; neuronal surface autoantibodies; paraneoplastic syndromes

INTRODUCTION autoantibodies is often not paraneoplastic and can affect
patients of all ages, including children and young adults. [2]
Anti-neuronal autoimmune encephalitis (AIE) is a
complex syndrome resulting from a self-directed response Over the past ten years, the characterization of encephalitis
to neuronal antigens. These disorders can be associated associated with neuronal surface autoantibodies has
with immunoglobulinG (IgG) autoantibodies specific to changed our perspective on their diagnosis and treatment.
intracellular neuronal antigens (e.g. Hu, Yo, Ri) and to In these disorders, the autoantibodies are associated with
neuronal surface or synaptic antigens [e.g. N-methyl-d- a characteristic phenotype and their detection contributes
aspartate receptor (NMDAR), amino-3-hydroxy-5-hydroxy- to the neurological diagnosis. As early treatment speeds
5-methyl-4-isoxazolepropionic acid receptor (AMPAR), recovery, reduces disability and decreases relapses, it is
gamma-aminobutyric acid B GABA(B)R]. The first group of important that the immune pathogenesis of these disorders
AIE typically occurs in the setting of cancer, resulting from is promptly recognized.
an autoimmune reaction against intracellular antigens co-
expressed by the cancer and the central nervous system In this paper a diagnostical gorithm is proposed for a
(CNS). The autoantibodies are thought to be not pathogenic clinical approach to AIE and screening of the associated
but an epiphenomenon, and patients show limited or autoantibodies.
no response to immunotherapy. Compelling evidence
suggests that in the second group of AIE, the binding DIAGNOSTIC APPROACH
of the autoantibodies to extracellular antigens directly The diagnosis of AIE should be suspected in patients
causes neuronal dysfunction, which can be reversed by developing subacute cognitive impairment, psychiatric
[1]
antibody-depleting therapies, such as plasmapheresis disturbances, movement disorders or seizures. The
and intravenous immunoglobulins. In contrast to classical diagnosis will be further support by the evidence of CNS
paraneoplastic syndromes, AIE associated with synaptic
inflammation from cerebrospinal fluid (CSF) analysis or
magnetic resonance imaging (MRI). Autoantibody testing
Corresponding Author: Dr. Valentina Damato, Institute of
Neurology, Catholic University of Sacred Heart, Largo F. Vito 1, has a critical role in confirming the diagnosis and in leading
00168 Roma, Italy. E-mail: valentina.damato86@gmail.com
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DOI: How to cite this article: Damato V. Diagnostic algorithms in autoimmune
10.20517/2347-8659.2015.43 encephalitis. Neuroimmunol Neuroinflammation 2016;3;93-7.
Received: 03-10-2015; Accepted: 25-12-2015

© 2016 Neuroimmunology and Neuroinflammation | Published by OAE Publishing Inc. 93