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psychiatric symptoms very similar to classical mood One important clinical feature of autoimmune
and psychotic disorders reinforced the hypothesis encephalitis is the strong association between
that innate inflammation/autoimmunity may be autoantibody production and the presence of
relevant to the pathogenesis of psychiatric symptoms teratoma or other neoplasms. Comorbidities of
at least in a subset of patients with bipolar disorder autoimmune encephalitis with small cell lung
[7]
or schizophrenia. [8] carcinoma, neuroblastoma, ovarian carcinoma, breast
carcinoma, thymoma, and testicular cancers have
AUTOIMMUNE ENCEPHALITIS also been reported. [26] These findings suggested that
the autoantibody syndrome may be triggered by
Since 1974, Mitsuda and Fukuda described “atypical cross‑reaction between antibodies produced in response
[9]
psychosis” as some acute and transient psychotic to tumor presence and antigenically similar synaptic
disorders, which cannot be easily classified as either proteins within the central nervous system (CNS).
schizophrenia or mood disorder with psychotic Autoimmune encephalitis can develop, however, with
features. Some important clinical characteristics of or without an underlying tumor, and in the largest case
atypical psychosis include acute onset, emotional series to date, no teratoma or other type of tumor was
and psychomotor disturbances, alternations of detected in 41% of cases. [3,27]
consciousness, high prevalence in women, and
well‑adjusted premorbid personality. In these Different forms of autoimmune encephalitis can affect
conditions, an involvement of neurologic brain changes patients of all ages although some of them seem to
has been hypothesized. preferentially occur in late childhood and young
adulthood. [28,29] The onset of the symptomatology
The identification of autoimmune encephalitis, shows a substantial overlap among the different
a new category of neuropsychiatric diseases that types. Sometimes associated with headache or mild
occurs with focal or widespread involvement of the hyperthermia, the initial clinical picture is characterized
nervous system in association with antibodies against by a rapid development of a set of psychiatric and/
extracellular epitopes of neuronal cell‑surface or or neurological symptoms. Mood disorders, usually
synaptic proteins, have led to changed paradigms for manic or mixed‑manic symptoms, anxiety, behavioral
the diagnosis and treatment for some neuropsychiatric problems, psychotic features, mild to moderate disorders
disorders, and reclassification of syndromes previously of consciousness, and memory loss occur in most types
defined as idiopathic or with descriptive terms. [10] of autoimmune encephalitis, often associated with
Since 2005, there have been 1‑2 discoveries of novel seizures. Demographic information (such as gender
syndromes and associated autoantigens per year, and race), presence or absence of a underlying tumor,
including autoantigens the N‑methyl‑D‑aspartate brain magnetic resonance imaging (MRI) findings,
receptor (NMDAR), [11,12] the subunits Kv1.1 and Kv1.2 CSF examination, and the severity and predominance
of the voltage‑gated potassium channels (VGKCs), of some symptoms over others can suggest a specific
the α‑amino‑3‑hydroxy‑5‑methyl‑4‑isoxazol‑pro subtype.
pionic acid receptor (AMPAR), [13] metabotropic
glutamate receptor 5, [14] or the γ‑amino‑butyric Ultimately, two approaches have been proposed for the
acid B‑receptor (GABAbR), [15] leucine‑rich glioma diagnosis of autoimmune encephalitis: one based on the
inactivated 1 (Lgi1), [16] contactin associated protein laboratory examination as proposed by Lancaster and
2 (CASPR2). [17] The study of these disorders has Dalmau [10] and the other based on clinical diagnostic
revealed novel mechanisms of how antibodies criteria as proposed by Zuliani et al. [30] The latter
might alter memory, behavior, cognition and cause recommend that one should suspect a diagnosis of
mood disorders, psychosis, seizures or abnormal an autoimmune encephalitis when a patient presents
movements. [18,19] However, though obtaining serum to with acute or subacute onset of symptoms, evidence
test for autoantibodies is extremely convenient and of inflammation supported by CSF examination,
relatively noninvasive, the caveats of using serum imaging, or histopathological investigations, and the
antibodies as a diagnostic tool need to be considered. exclusion of other infectious, metabolic, and toxic
Neuronal surface antibodies are not 100% specific. [20‑25] etiologies. Supportive criteria include a history of other
In particular, lower serum titers should be interpreted autoimmune comorbidities, and preceding infectious
with caution, and the role of evaluating cerebrospinal prodromes. Using a combination of these criteria as
fluid (CSF) neuronal surface antibodies rather than well as test of response to therapy, they suggest a model
serum titers may increase diagnostic specificity. [10] The whereby patients can be classified as having definite,
presence of neuronal surface antibodies should always probable or possible neuronal cell surface antibody
be correlated with the clinical picture. related pathology. [30,31]

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