Psychosomatics 2017:58:228–244 © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.
Review Article
Autoimmune Encephalopathy for
Psychiatrists: When to Suspect
Autoimmunity and What to Do Next
Mark Oldham, M.D.
Objective: To provide a critical review of autoimmune
encephalopathy—broadly defined as neuropsychiatric
features directly related to an autoimmune process—
relevant for psychiatric practice. Methods: We con-
sulted rheumatology textbooks to define the scope of
autoimmune conditions and identified recent reviews of
rheumatic conditions, autoimmune vasculitis, and
autoimmune encephalitis. We integrated these with
primary reports to provide a clinically relevant overview
of autoimmune encephalopathy. We focus on clinical
features that should raise suspicion for autoimmunity.
Results: Despite outlying conditions, 2 categories of
autoimmune encephalopathy are described: (1) neu-
ropsychiatric symptoms associated with rheumatic
conditions and (2) antibody-associated autoimmune
encephalitis. Rheumatic conditions principally include
Key words: autoimmune encephalopathy, encephalitis, rheumatic disease, anti-NMDA receptor, limbic
encephalitis, paraneoplastic encephalitis.
INTRODUCTION
Autoimmune encephalopathy is increasingly recog-
nized for its early psychiatric symptoms.1,2 It should
be noted that many of the citations herein are from
neurological sources, which prefer the term encephal-
opathy. Encephalopathy is not operationalized, so
it is used here in its broadest sense to include
any clinically significant neuropsychiatric features.
However, the heterogeneity of symptoms encountered
228 www.psychosomaticsjournal.org
connective tissue disease and other vasculitides. These
may present variously such as with unexplained delir-
ium, cognitive decline, or depression. Autoimmune
encephalitis may be diffuse or localized as in limbic,
brainstem, or basal ganglia encephalitis. Unexplained
delirium, psychosis, catatonia, strokes, and seizures are
among common presenting symptoms. Conclusions:
Prompt identification and management of autoim-
munity are critical for optimal outcomes. The fact that
undiagnosed and, therefore, untreated autoimmunity
leads to debilitation demands vigilance for these con-
ditions. Close attention to the unusual nature and course
of neuropsychiatric symptoms, associated neurological
features, and review of systems as reviewed here should
guide the skillful clinician.
(Psychosomatics 2017; 58:228–244)
in autoimmune conditions makes recognition difficult.
Delayed diagnosis may lead debilitating symptoms to
persist or recur for decades,3 and neurocognitive
Received February 6, 2017; revised February 22, 2017; accepted
February 22, 2017. From the Yale School of Medicine (MO), New
Haven, CT. Send correspondence and reprint requests to Mark
Oldham, M.D., Yale School of Medicine, 20 York St, Fitkin 615,
New Haven, CT 06510; e-mail: mark.oldham@yale.edu
© 2017 The Academy of Psychosomatic Medicine. Published by
Elsevier Inc. All rights reserved.
Psychosomatics 58:3, May/June 2017

decline may become irreversible with prolonged brain
inflammation.4 The fact that prompt recognition of an
autoimmune etiology can lead to effective treatment
demands that psychiatric clinicians maintain a high
degree of suspicion for autoimmunity, especially in
unusual neuropsychiatric syndromes. Here, we identify
key clinical features that raise suspicion for autoim-
munity, provide an overview of autoimmune encepha-
lopathies for the psychiatric clinician, and conclude with
recommendations on evaluation and management.
TWO CATEGORIES OF AUTOIMMUNE
ENCEPHALOPATHY
Despite several outlying conditions, 2 categories of
encephalopathy due to the direct effect of autoim-
munity are recognized: (1) rheumatic conditions with
neuropsychiatric symptoms and (2) antibody-
associated autoimmune encephalitis (AAE). Rheu-
matic conditions with neuropsychiatric symptoms
include collagen vascular disease, vasculitides with
cerebral involvement, and outliers such as neuro-
sarcoidosis. These syndromes are defined by the nature
and extent of systemic disease. Although psychiatric
symptoms may be the presenting feature, systemic
evidence of disease is typically evident concurrent with
psychiatric symptoms.5 Delirium and cognitive
impairment are the most common neuropsychiatric
presentations, but other psychiatric syndromes, such
as depression and anxiety disorders, are defined.6,7
AAEs describe conditions of brain inflammation
associated with IgG autoantibodies targeting either
neuronal surface epitopes or intracellular antigens.
Antineuronal surface epitope antibodies are infre-
quently paraneoplastic, whereas anti-intracellular
antigen antibodies are often known as onconeural
antibodies for their close association with malig-
nancy.8 Importantly, proposed diagnostic criteria
for AAE identify psychiatric symptoms as a primary
criterion for diagnosis. These criteria also allow for
probable diagnosis and treatment of many types of
AAE while awaiting antibody confirmation.9
CLINICAL OVERVIEW
Autoimmune encephalopathy usually has a subacute
onset, progressing over the course of 1–3 months,
though it may present acutely as in the case of acute
disseminated encephalomyelitis. Further, the atypical
Psychosomatics 58:3, May/June 2017
Oldham
nature of neuropsychiatric symptoms may alert clini-
cians to possible autoimmunity; diagnosis requires
objective findings. Critically, computed tomography
and magnetic resonance imaging (MRI) are insuffi-
ciently sensitive to rule out autoimmune encephalop-
athy. In fact, reviews indicate that a single brain MRI
may have less than 50% sensitivity for detecting several
of these conditions.10
Many rheumatic conditions have been associated
with neuropsychiatric symptoms; however, multi-
organ involvement, complex histopathology, and
overlap syndromes make rheumatic conditions diffi-
cult to classify. Given intraclass and intrasyndrome
diversity in these conditions, each syndrome has a
unique pattern of associations with neuropsychiatric
symptoms (Table 1).
The neuropsychiatric features of AAE often
reflect brain regions affected, which may be diffuse
or focal (Table 2). Diffuse encephalitis implies broad or
multifocal inflammation. It may affect brain only
(encephalitis), extend to the meninges (meningoence-
phalitis), or extend to the spinal cord (encephalomye-
litis). Brain involvement presents with delirium and
seizures. Involvement of the meninges and spinal cord
causes meningismus and localizing neurological def-
icits, respectively.
Focal encephalitis may involve the medial temporal
lobes (typically bilateral in AAE; limbic encephalitis),
basal ganglia (basal ganglia encephalitis), or brainstem
(brainstem encephalitis or rhombencephalitis). Limbic
encephalitis is known for its common triad of ante-
rograde amnesia, seizures, and psychiatric symptoms
ranging from personality change to delirium. Features
of brainstem encephalitis are variable because inflam-
mation may involve any number of closely nestled
brainstem tracts and nuclei. Cranial nerve palsies are
seen in three-quarters of all patients with brainstem
encephalitis, but the presence of altered arousal, long
tract signs, cerebellar ataxia, or fever varies with
cause.11 Basal ganglia encephalitis is a poorly under-
stood syndrome that causes dystonia, parkinsonism,
chorea, emotional dysregulation, or psychosis.12 Ence-
phalitis lethargica may be one subtype.13
FEATURES THAT SUGGEST
AUTOIMMUNITY
Unusual psychiatric symptoms often cue suspicion of
an underlying autoimmune process (Table 3). These
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Autoimmune Encephalopathy for Psychiatrists

TABLE 1. Rheumatic Conditions With Psychiatric Relevance (References in Text)

Connective tissue General features Psychiatric features
disease
Systemic lupus Z4 of 11 diagnostic criteria Neurolupus case definitions:
erythematosus Serological markers: Cognitive impairment
ANA Mood disorder
Anti-Sm Anxiety disorder
Anti-dsDNA Psychotic disorder
Encephalopathy

Antiphospholipid Primary or comorbid with other rheumatic disease Strokes

Ab syndrome (e.g., lupus) or cancer

Sjögren syndrome Sicca syndrome (dry eyes and mouth) Meningoencephalitis, limbic encephalitis, and
brainstem encephalitis reported
Serological markers: Though not case definitions as in lupus, cognitive
Anti-SS-A (Ro) impairment, mood disorders, and anxiety disorders
Anti-SS-B (La) are common

Polymyositis Anti-Jo antibodies Progressive multifocal leukoencephalopathy due to

corticosteroid use reported

Vasculitis syndrome Systemic features Psychiatric features

Large-sized vessels
Takayasu arteritis Constitutional symptoms: dizziness, fever, myalgia, Anergic depression
arthralgia, and upper extremity claudication Posterior reversible encephalopathy syndrome
reported
Giant cell arteritis Amaurosis fugax, headache, and jaw claudication Rare delirium, delusions, and memory impairment

Medium-sized vessels
Polyarteritis nodosa Involves kidneys, skin, and peripheral neuropathy Encephalopathy
Kawasaki disease Pediatric fever plus Z4 of 5: Encephalopathy or listlessness
Conjunctivitis
Orolingual erythema
Swollen, red hands/feet
Truncal rash
Cervical lymphadenopathy

Small-sized vessels
ANCA-associated Leukocytoclastic vasculitis Rare encephalopathy
(also “pauci- Conflicting evidence suggests ANCA-negativity associated
immune”) with CNS involvement
Immune complex Leukocytoclastic vasculitis Rare encephalopathy due to systemic inflammation
(rare CNS deposition)

Variable-sized vessels
Behçet syndrome Painful oral ulcers (necrotic base, red halo; Z3/y), genital Brainstem encephalitis with reduced arousal and fever
ulcers, eye lesions, and skin lesions
Cogan syndrome Keratitis and pseudo-Ménière disease Cerebral vasculitis
Primary angiitis of May occur with β-amyloid deposition Multifocal strokes, headache, cognitive impairment,
the CNS and personality change

Unclassified
Susac syndrome Branch retinal artery infarct (100%), hearing loss, headache Encephalopathy, multifocal vasculitis
“Snowballs” in corpus callosum on T2/FLAIR MRI
Histology: gass plaques
Sweet syndrome Fever, painful red plaques or nodules, elevated ESR, CRP, or Benign recurrent encephalitis
WBC with neutrophilic predominance

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 Oldham

TABLE 1 (Continued )
Connective tissue General features Psychiatric features
disease
Outliers
Sarcoidosis Granulomatous disease with central pulmonary involvement Cognitive impairment
in 90% Personality change
Relapsing Auricular, nasal, and respiratory chondritis, audiovestibular Brainstem encephalitis, cerebral arteritis
polychondritis damage, ocular inflammation, seronegative inflammatory
polyarthritis
Scleromyxedema Flesh-colored papules due to mucin deposition, myositis, Unexplained delirium
dysphagia, and restrictive lung disease
Serology: IgG paraproteinemia with gamma light chains
Auto-anti- Severe thrombocytopenia and macroangiopathic hemolytic Delirium
ADAMTS13 anemia
Ab Cerebrovascular events more common
ADEM Multifocal neurological deficits Encephalopathy

ADEM ¼ acute demyelinating encephalomyelitis; anti-dsDNA ¼ anti–double stranded DNA; ANA ¼ antinuclear antibodies; ANCA
¼ anti-neutrophil cytoplasmic antibodies; CNS ¼ central nervous system; CRP ¼ C-reactive protein; ESR ¼ erythrocyte sedimentation rate;
FLAIR ¼ fluid-attenuated inversion recovery.

can include delirium whose first-line workup is unre-
vealing, catatonic features not attributable to a pri-
mary psychiatric disorder especially when comorbid
with delirium,14 subacute anterograde amnesia,9 per-
sonality change,9 abnormal age of symptom onset
such as late-onset mania,15 multisymptom presenta-
tions particularly with early neurocognitive decline
and nonauditory hallucinations,16 abrupt or florid
symptom onset,17 rapid progression of symptoms,18
fluctuating symptoms that change over days to
weeks,10 or symptoms resistant to conventional psy-
chiatric interventions.4
Neurological examination may provide important
clues to underlying cause. Focal neurological signs
may define involved central nervous system (CNS)
regions (e.g., cranial nerve palsy accompanying brain-
stem encephalitis), or they may reflect the extent of
inflammation (e.g., meningismus due to meningeal
involvement). Seizures in the context of altered men-
tation may herald encephalitis or cerebral vasculitis.19
Although generalized tonic-clonic seizures declare
themselves, nonconvulsive seizures can manifest with
paraictal catatonia, intermittent unresponsiveness, or
stereotypies.20 Long-term video electroencephalogra-
phy is often necessary to characterize epileptic events.
Medical evaluation may similarly suggest auto-
immunity. Elevations in the inflammatory markers,
erythrocyte sedimentation rate (ESR), and C-reactive
protein (CRP) are expected. However, acuity of illness
may lead to elevated CRP and normal ESR, in part
because CRP rises more acutely in response to
inflammation,21 and cases with normal CRP and
ESR are reported.22 Similarly, cerebral vasculitis
may present with normal ESR, CRP, or both.23,24
The syndrome of inappropriate antidiuretic hormone
secretion can suggest intracranial or thoracic pathol-
ogy, and progressive hypoventilation of unclear cause
may be due to anti–N-methyl-D-aspartate receptor
(NMDAR) antibody encephalitis. Because rheumatic
conditions rarely present with isolated neuropsychi-
atric symptoms, evaluation for systemic features of
rheumatic disease is warranted.
The value of a detailed review of systems and
medical and family histories bears reinforcing. Viral
prodromes are seen in more than half of patients with
anti-NMDAR antibody encephalitis. Diffuse arthral-
gia is common in connective tissue disease, sicca
syndrome in Sjögren syndrome, and headache in
cerebral vasculitis. Systemic vasculitis often causes
inanition, fever, and myalgias. Personal or family
history of autoimmunity or cancer associated with
paraneoplastic syndromes should be inquired.
Patients with unexplained delirium and tobacco
use history should also be assessed for recent unin-
tended weight loss, cough, and hemoptysis: tobacco
can cause small cell lung cancer that metastasizes to
brain and is associated with paraneoplastic
encephalomyelitis.

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Autoimmune Encephalopathy for Psychiatrists

TABLE 2. Antibody-Associated Autoimmune Encephalitis

Neuronal surface Clinical syndromes Notable features
antigens
NMDA receptor, Diffuse encephalitis (DE), limbic encephalitis (LE) Triphasic illness
NR1 subunit Viral prodrome
Psychiatric features
Neurological and medical complications
Teratoma in approximately half of women
Tumor rare in men and children
Relapses in 10-20%
May be postinfectious (HSV1, VZV, and β-hemolytic
Strep)
AMPA, GluA1, or DE or LE Lung, breast, and thymoma (50%)
GluA2
mGlu1 Cerebellar ataxia, rare encephalopathy Lymphoma, leukemia, and prostate
May be postinfectious (VZV)
mGlu5 LE Ophelia syndrome defined by LE plus Hodgkin lymphoma
GAD-65* LE or cerebellar ataxia (?) Antibody titer associated with likelihood of
neuropsychiatric presentation
Stiff person syndrome (SPS) Often co-occurs with other autoantibodies
Thymoma or small cell (25%)
LGI1 (Kv1.1) LE, faciobrachial dystonic seizures Tumor rare
Caspr2 (Kv1.1 or Neuromyotonia, Morvan syndrome, less common LE Thymoma, endometrial carcinoma (30%)
Kv1.2)
Contactin 2 (Kv1.1) Poorly characterized Unclear
DPPX (Kv4.2) Delirium, amnesia, and depression Dysautonomia with severe diarrhea
Tumors not reported
GABAA Encephalitis, prominent seizures Lung, breast, thymoma, and Hodgkin lymphoma (450%)
GABAB Encephalitis, prominent seizures Lung and neuroendocrine (50%)
Glycine-α1 Hyperekplexia, SPS Tumor rare
IgLON5 REM sleep behavior disorder, insomnia, sleep apnea, and Tumors not reported
dysautonomia
D2 Basal ganglia encephalitis with movement disorder and Tumors not reported
psychosis May be postinfectious (β-hemolytic Strep)
Neurexin 3α Delirium Prodromal fever, headache, GI symptoms

Intracellular Paraneoplastic syndromes Tumors

epitopes

Classic antibodies
Anti-Hu (ANNA-1) Encephalomyelitis (EM), LE Small cell,† thymoma
Anti-Ri (ANNA-2) Dementing illness/EM, brainstem encephalitis (BE), LE, Gyn, breast adenocarcinoma, small cell†
cerebellar degeneration (CD)
Anti-Yo (PCA-1) CD Gyn, breast adenocarcinoma
Anti-CV2/CRMP5 EM with subacute dementia and personality change, LE, Small cell,† thymoma
CD, and chorea
Anti-Ma1 or Ma2 Cognitive impairment/EM, LE, BE, and hypothalamic Testicular germ cell tumor, non–small cell lung cancer
encephalitis
Amphiphysin Cognitive impairment/EM, LE Small cell,† breast adenocarcinoma

Nonclassic antibodies
ANNA-3 EM Small cell†
PCA-2 LE, BE, CD Small cell†
AGNA (SOX1) LE, CD Small cell†

Outlying syndromes Clinical syndromes Notable features

Hashimoto Encephalopathy with seizures, myoclonus, Steroid-responsive

encephalopathy hallucinations, or stroke-like episodes
Anti-TPO (85%)

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TABLE 2 (Continued )
Neuronal surface Clinical syndromes
antigens
Anti-TG (70%)
Gluten Cognitive impairment
encephalopathy
Antigliadin Ab
Bickerstaff BE
encephalitis
Antibody-negative Variable
AAE
AAE ¼antibody-associated autoimmune encephalitis; AGNA ¼ antiglial nuclear antibody (here, specifically antibodies to SOX1);
ANNA ¼ antineuronal nuclear antibodies; anti-TPO ¼ antithyroid peroxidase; BE ¼ brainstem encephalitis; CD ¼ cerebellar degeneration;
CSF ¼ cerebrospinal fluid; DE ¼ diffuse encephalitis; EM ¼ encephalomyelitis; HSV ¼ herpes simplex virus; IgLON5 ¼ immunoglobulin
LON family of cell adhesion molecules member 5; LE ¼ limbic encephalitis; PCA-1 ¼ prostate cancer antigen; REM ¼ rapid eye movement;
SPS ¼ stiff person syndrome; VZV ¼ varicella zoster virus.
n
Intracellular antigen.
†
Small cell tumor may be pulmonary or extrapulmonary.
SPECIFIC CONDITIONS
Rheumatic Conditions With Neuropsychiatric
Symptoms
Unlike AAE, which involves direct CNS inflamma-
tion (i.e., encephalitis), rheumatic conditions tend to
cause neuropsychiatric symptoms by inflammation of
connective tissue and, in particular, blood vessels
(Table 2). The neurophysiology of connective tissue
disease remains incompletely understood. Neuropsychi-
atric symptoms may be the result of vasculopathy-
related brain ischemia, systemic inflammation disrupting
neurotransmission, or neurological inflammation itself.
Vasculitis may occur in connective tissue disease or as an
independent autoimmune vasculitis syndrome. Finally,
outlying rheumatic conditions with neuropsychiatric
import such as neurosarcoidosis are described.
Rheumatic Conditions: Connective Tissue Disease
Neuropsychiatric lupus, historically lupus cerebritis,
occurs in roughly half of patients with systemic lupus
erythematosus.25 Of the 19 neuropsychiatric case defini-
tions for neurolupus,7 headache is the most common (87%
of patients with lupus) followed by cognitive impairment
(46%), mood disorders (26%), and anxiety disorders
(12%).16 At least 20 antibodies have been associated with
Psychosomatics 58:3, May/June 2017
Oldham
Notable features
Associated migraines and white matter hyperintensities
Associated with Miller-Fisher syndrome, which is a
variant of Guillain-Barre syndrome
Albuminocytologic dissociation in CSF
Diagnosis requires:
Neuropsychiatric features
2 of 3 objective findings
Other syndromes ruled out
neurolupus.26 Antiphospholipid antibodies, found in half
of patients with lupus, have been inconsistently associated
with neuropsychiatric syndromes.27 These antibodies
confer hypercoagulability and may cause strokes, seiz-
ures, headache, or vascular cognitive impairment. Contra-
dictory evidence suggests an association between
antiribosomal P protein antibodies and psychosis.26
Drug-induced lupus, which presents with antihistone
antibodies in 495% of cases, has a lower prevalence of
neuropsychiatric features. Psychotropics that cause drug-
induced lupus include bupropion, chlorpromazine, lith-
ium, olanzapine, and valproic acid.
Neuropsychiatric symptoms are seen in a fifth of
patients with Sjögren syndrome, and among the fea-
tures of neuro-Sjögren are cognitive impairment (50%),
mood disorders (26%), and anxiety disorders (12%).16
Rarely, Sjögren syndrome has been reported in asso-
ciation with autoimmune encephalitis, which may be
either a focal limbic or brainstem encephalitis or diffuse
encephalitis of brain, meninges, or spinal cord.28
Psychiatric presentations in other connective tissue
disease, such as polymyositis, systemic scleroderma,
or rheumatoid arthritis, remain poorly characterized.
Rheumatic Conditions: Cerebral Vasculitis
Vasculitis syndromes are categorized by size of
affected vessels and by organs involved.29 Given the
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Autoimmune Encephalopathy for Psychiatrists
TABLE 3. Clinical Features That Raise Suspicion for
Autoimmune Cause
Psychiatric Personality change
symptoms Multisymptom presentations
Nonauditory hallucinations
History Viral prodrome
Severe diarrhea
Fever
Personal/family history of autoimmunity
Personal/family history of neoplasm
associated with paraneoplastic syndromes
Current or significant history of tobacco use
Natural history Abnormal age of symptom onset
Abrupt or florid symptom onset
Rapid symptom progression
Changing neuropsychiatric symptoms
Treatment resistance
Neuropsychiatric Unexplained delirium
symptoms Premature cognitive impairment
Subacute anterograde amnesia
Catatonic features
REM sleep behavior disorder
Neurological Seizures
features Unexplained stroke-like events, particularly
multifocal
Headache
Localizing neurological signs including
cranial nerve palsies
Sensorimotor findings
Movement disorder
Medical features Hyponatremia
Central sleep apnea
Dysphagia
Dysautonomia
REM ¼ rapid eye movement.
multisystemic nature of these syndromes, clinical
features are determined by the distribution of inflamed
vessels. Ultimate pathology is due to end-organ
ischemia. CNS involvement leads to strokes including
subcortical infarcts presenting as psychiatric syn-
dromes.30 Vasculitis outside the CNS can cause organ
failure resulting in psychiatric symptoms, and systemic
inflammation itself can cause delirium.31,32
The 2 large-vessel syndromes are Takayasu arter-
itis and giant cell arteritis. Takayasu affects the aorta
and main branches in patients younger than 40 years
of age and presents with nonspecific symptoms includ-
ing dizziness, fever, myalgia, arthralgia, and upper
extremity claudication.33 Common reasons for
234 www.psychosomaticsjournal.org
psychiatric involvement may include torpor, depres-
sion, or anergia, and cases of posterior reversible
encephalopathy syndrome have been described.34
Giant cell arteritis, also called temporal arteritis,
principally affects temporal arteries causing amaurosis
fugax, jaw claudication, and headache localized to the
temples with associated tenderness to touch. Though
psychiatric presentations are rare, it has been reported
to cause delirium, delusions, and impaired memory.35
The 2 medium-sized vasculitis syndromes include
polyarteritis nodosa and Kawasaki disease. Polyarter-
itis nodosa preferentially affects kidneys, skin, and the
peripheral nervous system, causing neuropathy. CNS
involvement is a late finding and presents with
systemic features including fever, malaise, myalgias,
and wasting syndrome.36 CNS symptoms are expected
to cause delirium, focal deficits, or seizures. Kawasaki
disease is typically a time-limited vasculitis of child-
hood. Psychiatric features are rare but may include
delirium or torpor.
Small-vessel vasculitides are characterized by
leukocytoclastic inflammation and include (1) 3
anti-neutrophil cytoplasmic antibodies (ANCA)–
associated vasculitides and (2) 4 syndromes related
to immune complex deposition including cryoglobu-
linemic vasculitis. Systemic features of these condi-
tions are the rule though they may rarely present as
delirium or stroke syndromes of unclear etiology.
Cryoglobulinemia deserves note for its 3 subtypes.
Type 1 is defined by monoclonal antibody elaboration
due to liquid neoplasia. In this syndrome, accumulat-
ing antibodies in the blood cause hyperviscosity, which
in turn causes ischemia because of vessel sludging.
Patients may have headache, retinopathy, spontane-
ous mucosal bleeding, vertigo, delirium, or coma.37
Neuropathology of cryoglobulinemia types 2 and
3 may occur due to immune complex deposition.
Vasculitides of variable-sized vessels include Beh-
çet and Cogan syndromes. Behçet syndrome, charac-
terized by uveitis and ulceration of the mouth and
genitals, involves cerebral vessels in 5–30% of patients.
Acute neuro-Behçet syndrome presents with menin-
goencephalitis and has a predilection for the brain-
stem, whereas chronic neuro-Behçet causes progres-
sive neurocognitive impairment associated with ataxia
and dysarthria.38 Cerebral inflammation in neuro-
Behçet may also lead to dural sinus thrombosis or
other stroke-like syndromes.39 A quarter of patients
with Cogan syndrome are estimated to have cerebral
Psychosomatics 58:3, May/June 2017

involvement.40 Delirium can occur because of diffuse
encephalitis, but stroke syndromes are more common.
Primary angiitis of the CNS is defined by vasculitis
restricted to the CNS. Its most common presenting
symptoms are headache, encephalopathy, and com-
monly multifocal strokes suggesting diffuse cerebro-
vascular involvement.41 The index diagnostic criterion
includes unexplained neuropsychiatric symptoms, but
diagnosis requires angiographic or histopathological
evidence of CNS angiitis. Subacute headache with
progressive subcortical cognitive impairment and
evidence of systemic or cerebrospinal fluid (CSF)
inflammation raise suspicion for primary angiitis of
the CNS. Cerebral amyloid angiopathy may present
with a syndrome of CNS angiitis indistinguishable
from primary angiitis of the CNS but whose course is
inexorable due to progressive amyloid deposition.41
Two additional autoimmune cerebral vasculitis
syndromes of psychiatric relevance are Susac and
neuro-Sweet syndrome. Susac syndrome, also retino-
cochleocerebral syndrome, is a vasculitis affecting
retinal, inner ear, and cerebral arteries, and accord-
ingly causes vision loss, sensorineural hearing loss, and
often unexplained encephalopathy with headache.42 It
classically presents with “snowballs” in the corpus
callosum on T2-weighted brain MRI.43 Neuro-Sweet
syndrome presents as acute encephalitis or meningitis
in patients with abrupt-onset fever and characteristic
painful, erythematous plaques or nodules on the
skin.44 Unlike small-vessel vasculitides mentioned
earlier, histopathology reveals neutrophilic infiltrate
without leukocytoclastic vasculitis.
Rheumatic Conditions: Outliers
Sarcoidosis is a noncaseating granulomatous dis-
ease with pulmonary involvement in 90% of patients.
Extrapulmonary disease is common and involves the
nervous system in up to 15% of patients. The most
common feature of neurosarcoid is cranial neuro-
pathy. Roughly 1 in 5 with neurosarcoid presents with
cognitive or behavioral features.45 Relapsing poly-
chondritis, which usually first presents with auricular
chondritis, has been reported as a rare cause of limbic
encephalitis, cerebral vasculitis, or meningoencepha-
litis with fever.46–48
Scleromyxedema is a dermatological condition
with hallmark flesh-colored papules because of mucin
deposition that may cause unexplained delirium and
Psychosomatics 58:3, May/June 2017
Oldham
myositis. Associated clinical features include dyspha-
gia and restrictive lung disease, and serology usually
reveals IgG paraproteinemia with gamma light
chains.49 Anti-ADAMTS13 autoantibodies cause
acquired thrombotic thrombocytopenic purpura, a
medical emergency defined by severe thrombocytope-
nia and microangiopathic hemolytic anemia due to
shearing of red blood cells. Thrombotic thrombocy-
topenic purpura presents with neuropsychiatric fea-
tures in two-thirds of cases; in half of the cases it
involves seizures or cerebrovascular accidents, the
other half with nonfocal symptoms including delirium
or headache.50
Finally, encephalopathy may follow infections as
in the case of acute demyelinating encephalomyelitis,
Bickerstaff brainstem encephalitis (described later), or
several AAE syndromes (Table 1).51 For instance,
anti-NMDAR antibody encephalitis has been
reported as the cause of encephalitis following herpes
simplex virus encephalitis.52 Acute demyelinating
encephalomyelitis is an immune-mediated demyeli-
nating disorder that presents with delirium. Its asso-
ciated multifocal neurological deficits should alert
clinicians to diffuse CNS disease.53 Symptoms may
be severe, but outcome is generally favorable. A severe
form of acute demyelinating encephalomyelitis,
though, acute hemorrhagic leukoencephalitis is not
uncommonly fatal, and those that survive are func-
tionally devastated.51
Antibody-Associated Autoimmune Encephalitis:
Neuronal Cell Surface Antibodies
Neuronal surface autoantibodies, most of which
alter channel activity, cause downstream effects that
are reversible with antibody removal.54 These anti-
bodies have varied associations with malignancy.8
Furthermore, given the reliance on case series,
reported clinical associations remain provisional,
and recognition bias currently prevents a clear picture
of disease spectrum. Interestingly, though the number
of identified synaptic antigens continues to expand,
most center on the excitatory neurotransmitter gluta-
mate (NMDA, AMPA, mGluR5, and GAD-65
[enzyme that converts glutamate to gamma-amino-
butyric acid {GABA}]), the inhibitory neurotransmit-
ters GABA/glycine (GABAA, GABAB, and glyα1),
and voltage-gated potassium channel complexes
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Autoimmune Encephalopathy for Psychiatrists
(Kv1.1, Kv1.2, and Kv4.2), and many of these are
often co-localized within synapses.55
The most commonly described AAE is anti-
NMDAR antibody encephalitis. In upwards of 80%
of patients with this condition, patients present to
psychiatric providers first,20,56,57 and an estimated
40% are admitted to a psychiatric hospital at presen-
tation.58 In fact, psychiatric and behavioral distur-
bances account for most symptom burden in adults.4
Anti-NMDAR antibody encephalitis typically causes
diffuse encephalitis though limbic encephalitis may
occur.20 Onset begins with a viral prodrome in more
than half of patients. This is followed by psychiatric
symptoms including psychosis, mania, depression, or
catatonia. The condition often progresses to seizures,
dysautonomia, and hypoventilation.59 Despite initial
reports of concurrent ovarian teratoma, subsequent
reports have suggested this relationship to be weaker
than initially thought. Further, only a small propor-
tion of men and children have an associated tumor.4
Four other glutamate-related targets include the
AMPA receptor, mGlu1, mGluR5, and GAD-65.
Anti-AMPAR antibodies target either ionotropic
glutamate receptor 1 (GluA1) or 2 (GluA2). Like
anti-NMDAR antibodies, these antibodies are asso-
ciated with limbic encephalitis or diffuse encephali-
tis.60,61 Autoantibodies to metabotropic Glu1
(mGlu1) receptors preferentially cause cerebellar dys-
function, with only 3 of 11 patients described exhibit-
ing cognitive impairment and 1 with paranoia and
auditory hallucinations.62 Anti-mGlu5 receptor anti-
bodies are a biomarker for Ophelia syndrome, char-
acterized by Hodgkin lymphoma and limbic
encephalitis including hallucinations.63 GAD-65 is a
unique target because it is intracellular, yet anti-GAD-
65 antibodies seldom suggest cancer. Although the
pathogenicity of such antibodies remains controver-
sial, it is curious that antibody titer correlates with the
likelihood of limbic encephalitis or cerebellar ataxia.64
Known as a single entity until 2010, anti-voltage-
gated potassium channel complex (anti-VGKCC)
antibody encephalitis is now know to comprise anti-
bodies targeting at least 3 antigens: LGI1, Caspr2, and
contactin 2.18 Each of these 3 antigens represents a
distinct accessory protein in the Kv1.1 or Kv1.2
VGKCC. The binding sites of an additional 20% of
anti-VGKCC antibodies remain undefined.65 Anti-
LGI1 antibodies are closely associated with limbic
encephalitis and seizures, including generalized tonic-
236 www.psychosomaticsjournal.org
clonic. Faciobrachial dystonic seizures, characterized
by brief, recurrent synchronous arm and ipsilateral
facial twitch, are considered pathognomonic for anti-
LGI1 antibody syndrome.66 Antibodies against
Caspr2 are a cause of neuromyotonia that presents
as muscle hyperexcitability with fasciculations appear-
ing as a “bag of worms” rippling under the skin. They
also cause the broader Morvan syndrome that is
defined by neuromyotonia, insomnia, dysautonomia,
and delirium. Anti-Caspr 2 antibodies may cause
limbic encephalitis though less commonly than anti-
LGI1 antibodies. Clinical associations with anti-
contactin 2 remain unclear. Finally, antibodies to
dipeptidyl-peptidase-like protein-6 (DPPX), the reg-
ulatory unit of a separate potassium channel Kv4.2,
have also been implicated in AAE. Most of these
patients have some combination of amnesia, delirium,
psychosis, or depression.67 A key clinical finding for
this condition is dysautonomia that presents variously
as severe diarrhea, gastroparesis, bladder dysfunction,
or temperature dysregulation.
Antibodies to epitopes associated with inhibitory
neurotransmitter activity—GABAA, GABAB, and
glycine α1—are described infrequently. Autoantibod-
ies to GABAA can cause rapidly progressive severe
delirium and treatment-refractory seizures. Several
such patients have required pharmacologically
induced coma for seizure control.68 Anti-GABAB
antibodies cause limbic encephalitis with prominent
seizures as well.69 Although also a cause of limbic
encephalitis, antibodies to glycine α1 have a unique
association with progressive encephalomyelitis with
rigidity and myoclonus.70 Glycine is the major inhib-
itory neurotransmitter in the spinal cord, explaining
why these antibodies may also cause hyperekplexia
(i.e., brisk startle) and stiff person syndrome.
Antibody-Associated Autoimmune Encephalitis:
Intracellular Epitopes
Antibodies against intracellular antigens do not
directly cause neuropsychiatric symptoms. Rather,
associated neuropsychiatric symptoms are attributed
to cytotoxic T-cell response.71 Small cell cancer,
thymoma, breast cancer, and Hodgkin lymphoma
have well-documented associations with paraneoplas-
tic CNS syndromes.72 CNS paraneoplastic syndromes
are categorized as classic or nonclassic,73 and classic
syndromes relevant for psychiatric features include
Psychosomatics 58:3, May/June 2017

encephalomyelitis and limbic encephalitis. Brainstem
encephalitis is a nonclassic syndrome and may be a
cause of unexplained confusion.74 Paraneoplastic anti-
bodies are similarly divided into classic or nonclassic
(Table 2). Identifying the clinical syndrome is the first
step, followed by serological investigation for associ-
ated antibodies and a workup for occult malignancy
guided by the antibody identified.
Antibody-Associated Autoimmune Encephalitis:
Outliers
Three other AAE deserve mention: Hashimoto
encephalopathy (HE), gluten encephalopathy, and
Bickerstaff brainstem encephalitis. The first of these,
HE, is also known by the more illustrative name
steroid-responsive encephalopathy associated with
thyroid antibodies.75 At least 85% of patients with
HE have antithyroid peroxidase antibodies and 70%
have antithyroglobulin antibodies. Notably, 1 in 10
healthy adults in the community will be positive for
one or both antibodies.9 The index criterion for HE is
broad: encephalopathy with seizures, myoclonus,
hallucinations, or stroke-like episodes. Psychiatric
symptoms, including depression, psychotic mania,
rapidly progressive dementia, or even a decades-
long schizophrenia-like illness, have been reported
as the presenting feature of HE.75 Patients are typically
euthyroid or mildly hypothyroid at presentation, and
symptoms generally respond within days to high-dose
corticosteroids.
Less common than gluten ataxia, gluten encephal-
opathy occurs in association with antigliadin anti-
bodies (either IgG or IgA). This form of cognitive
impairment can occur in either celiac disease or
nonceliac gluten sensitivity.76 Interestingly, white
matter hyperintensities are found in this condition,
and these patients may present with migraine-like
headaches along with peripheral neuropathy. Symp-
toms typically improve with a gluten-free diet.77,78
Lastly, Bickerstaff brainstem encephalitis, along with
Miller-Fisher syndrome, comprise the anti-GQ1b
antibody syndrome where Bickerstaff encephalitis
describes central involvement and Miller-Fisher
peripheral involvement.79 Beyond reduced arousal,
clinical features of Bickerstaff encephalitis include
external ophthalmoplegia and ataxia.
Seronegative autoimmune encephalitides exist
whose corresponding antibodies are yet to be
Psychosomatics 58:3, May/June 2017
Oldham
described; such cases have included both limbic
encephalitis and panencephalitis.80 Early identifica-
tion of autoimmune encephalitis is critical because
prompt treatment is consistently associated with
improved neurocognitive and functional outcomes.81
To avoid further delay in treatment, a probable
diagnosis of antibody-negative autoimmune encepha-
litis may be given if a patient has symptoms of
encephalitis (short-term memory impairment, altered
mentation, or psychiatric symptoms [This diagnostic
criterion is broad though, by analogy with other
defined syndromes, delirium, or features described
under the first paragraph of the section Features That
Suggest Autoimmunity may be considered.]) and at
least 2 of the following 3 findings are present (brain
MRI suggestive of encephalitis; CSF pleocytosis,
oligoglonal bands, or elevated IgG index; or brain
biopsy with evidence of inflammation), and other
defined syndromes mentioned earlier are excluded.9
WORKUP
Rather than conducting the “million-dollar workup”
for each patient, we recommend thoughtful testing
guided by clinical syndromes (i.e., concurrent features
that suggest, for instance, limbic encephalitis) and
further guided by detailed psychosocial and medical
history. Table 4 organizes common clinical findings
that may suggest specific autoimmune encephalopa-
thies. Guidance on performing medical workup for
altered mental status is beyond the scope of this
article,82,83 and specialized workup should be com-
pleted and interpreted by providers with expertise in
those conditions. Here, we provide general consider-
ations for investigating autoimmunity as the cause of
unexplained neuropsychiatric symptoms.9,19,30,84
Where a rheumatic condition is suspected, evi-
dence of systemic disease should guide consideration
of specific disease states. Nonspecific features includ-
ing arthralgias, fatigue, or weight loss may be seen
with systemic inflammation. Serological evaluation
for rheumatic disease includes antinuclear antibodies
with reflex extractible nuclear antigen panel (i.e., anti-
SS-A, anti-SS-B, anti-Scl-70, anti-Jo-1, anti-RNP, and
anti-Sm). Anti–double stranded DNA antibodies may
also be seen in lupus, and antihistone antibodies
suggest drug-induced lupus. Additional laboratory
tests may include cytoplasmic ANCA or perinuclear
ANCA for ANCA-associated small-vessel vasculitis,
www.psychosomaticsjournal.org 237
Autoimmune Encephalopathy for Psychiatrists

TABLE 4. Clinical Features That May Suggest Specific Autoimmune Encephalopathies

History and review of systems

Constitutional
Unintended weight loss
Viral prodrome
Fulminant progression
REM sleep behavior disorder
Recently stopped immunosuppression
Recently started antiretroviral therapy
Heavy smoking
Paraneoplastic syndrome, systemic vasculitis
Anti-NMDAR, postinfectious encephalitis
Acute hemorrhagic leukoencephalitis (i.e., severe ADEM)
Anti-IgLON5, -LGI1
Immune reconstitution inflammatory syndrome (IRIS)
IRIS
Small-cell-related paraneoplastic syndrome, cerebral Buerger

Neuromuscular
Myasthenia gravis Anti-Caspr2
Refractory epilepsy Anti-GABAA or -GABAB
Strokes Vasculitis, antiphospholipid antibody syndrome

Head, ears, eyes, nose, and throat

Photosensitivity Lupus, Cogan syndrome
Dry eyes and mouth Sjögren syndrome
Jaw claudication and amaurosis fugax Giant cell arteritis
Painful oral ulcers Beçhet syndrome
Visual field deficit and hearing Susac syndrome
impairment
Dizziness Takayasu arteritis, Cogan syndrome
Headache Vasculitis (giant cell arteritis with temporal headache)
Migraines Antigliadin antibody

Gastrointestinal
Diarrheal prodrome Anti-DPPX
Chronic GI symptoms Antigliadin antibody

Cardiopulmonary
Dyspnea Connective tissue disease, sarcoidosis, scleromyxedema, and relapsing polychondritis

Musculoskeletal
Raynaud phenomenon Connective tissue disease, cryoglobulinemia
Arthralgia Connective tissue disease, vasculitis
Myalgia (often proximal) Connective tissue disease, vasculitis

Obstetric
Recurrent spontaneous abortion Antiphospholipid antibody syndrome

Mental status examination

Catatonia Encephalitis
Dense anterograde amnesia Limbic encephalitis (consider antibody-associated autoimmune encephalitis)
Prominent psychosis Anti-AMPAR

Laboratory evidence
Hyponatremia SIADH due to cerebral process (nonspecific)
Blood dyscrasia Thrombocytopenia or hemolytic anemia in lupus, macroangiopathic hemolytic anemia in
vasculitides
Renal impairment (otherwise unexplained) Lupus and vasculitis (often small-vessel vasculitides)
Pulmonary granuloma Sarcoidosis
Albuminocytologic dissociation in CSF Anti-GQ1b (i.e., Miller-Fisher/Bickerstaff)

Physical findings
General
Dysautonomia Anti-NMDAR, -DPPX, -Caspr2, and IgLON5

238 www.psychosomaticsjournal.org Psychosomatics 58:3, May/June 2017

 Oldham

TABLE 4. Continued

Head, ears, eyes, nose, and throat

Cranial nerve palsies Brainstem encephalitis or ADEM
Symmetric ophthalmoplegia Bickerstaff
Interstitial keratitis (eye pain and redness) Cogan syndrome, relapsing polychondritis
Vestibular disturbance Cogan syndrome, relapsing polychondritis
Auricular chondritis Relapsing polychondritis
Nasal chondritis Relapsing polychondritis
Oral ulcers Lupus or Beçhet syndrome

Cardiopulmonary
Pericarditis or pleurisy Lupus
Hypventilation Anti-NMDAR
Dry cough Sarcoidosis, paraneoplastic syndrome associated with small cell lung cancer

Neuromuscular
Meningismus Meningoencephalitis (broad differential though ruling out infection is paramount)
Quadriparesis Bickerstaff or other brainstem encephalitis
Faciobrachial dystonic seizures Anti-LGI1
Neuromyotonia (“bag of worms” Anti-Caspr2
appearance)
Cerebellar ataxia Paraneoplastic cerebellar degeneration, brainstem encephalitis, and antigliadin antibodies
Seizure Broad differential but may suggest temporal lobe involvement such as limbic encephalitis
Dystonia, parkinsonism, and myoclonus Basal ganglia encephalitis, antiglycine α1
Chorea Basal ganglia encephalitis, anti-CV2/CRMP5
Myalgia (typically proximal) Connective tissue disease, vasculitis
Hyperekplexia Antiglycine α1

Dermatologic
Malar (butterfly) or discoid rash Lupus
Livedo reticularis or racemosa Vasculitis, antiphospholipid antibody syndrome (including Sneddon syndrome)
Digital necrosis Cryoglobulinemia
Painful red plaques and nodules Sweet syndrome
Flesh-colored papules Scleromyxedema

Genitourinary
Genital ulceration Beçhet syndrome

ADEM ¼ acute demyelinating encephalomyelitis; CSF ¼ cerebrospinal fluid; IgLON5 ¼ immunoglobulin LON family of cell adhesion
molecules member 5; NMDAR ¼ N-methyl-D-aspartate receptor; REM ¼ rapid eye movement.

angiotensin converting enzyme activity or chest X-ray
for sarcoidosis, serum or urinary protein electropho-
resis or both with immunofixation for confirmation to
assess for oligoclonal bands, or serum cryoglobulins to
rule out cryoglobulinemia.
Cerebral vasculitis is suggested by headache,
seizures, cognitive and personality change, and cere-
brovascular events—either transient ischemic attacks
or strokes. Standard assessment for thrombophilia is
warranted for cerebrovascular events. Brain MRI with
and without contrast, electroencephalography, and
lumbar puncture additionally assess for evidence of
cerebral inflammation. Cerebral angiography (arterio-
gram, magnetic resonance angiography, or computed
tomography angiogram) provides radiographic evi-
dence of cerebral vasculitis. Definitive diagnosis of
vasculitis not uncommonly requires biopsy.
AAE may be suggested by leukocytosis, lympho-
cytosis, or other evidence of systemic inflammation
such as tachycardia or fever. Most patients have
elevated CRP and ESR, but these are not universal.
Routine electroencephalogram should be considered
to rule out nonconvulsive seizures or evidence of
encephalopathy.85 Long-term monitoring with
video-electroencephalogram may be performed where
clinical suspicion for occult epileptic activity is high.
Sensitivity of brain MRI for individual subtypes of
AAE varies, but where present, findings include

Psychosomatics 58:3, May/June 2017 www.psychosomaticsjournal.org 239

Autoimmune Encephalopathy for Psychiatrists
hyperintensities on T2-weighted or fluid-attenuated
inversion recovery sequences. Lumbar puncture
should be considered to evaluate for leukocytes in
the CSF (operationalized as Z5/mm3)9 and particu-
larly lymphocytic pleocytosis. Oligoclonal bands or
elevated IgG index in the CSF may provide further
evidence in support of AAE. Antibodies may be
produced by intrathecal lymphocytes, so CSF is
preferred for send-out evaluation of antibody panels.86
Academic centers such as the Mayo Clinic offer
thorough antibody panels defined by clinical scenario
(e.g., encephalopathy, paraneoplastic syndromes, or
early/rapidly progressive dementia).
MANAGEMENT OF PSYCHIATRIC
SYMPTOMS
A patient with autoimmunity should be managed by a
clinician with expertise treating the condition in
question. Additionally, because managing autoim-
munity involves immunosuppression, ruling out con-
current infection is critical87 (discussed in Ref. 88 for
thorough review of encephalitic causes). Best evidence
management recommendations for autoimmune ence-
phalopathies rely on observational studies and expert
opinion.84
Management of neuropsychiatric symptoms asso-
ciated with rheumatic conditions involves immuno-
therapy tailored to specific autoimmune condition plus
symptomatic treatment of neuropsychiatric symp-
toms. See, for instance, clinical guidelines for manag-
ing neurolupus.89 Most cerebral vasculitides are
treated with corticosteroids, often combined with
other agents such as cyclophosphamide.30
AAE treatment involves acute and maintenance
immunotherapy,84 and neurological examination
should be completed before starting treatment to gauge
response and inform subsequent treatment decisions.
High-dose corticosteroids are first-line along with
removal of associated tumor where identified, espe-
cially ovarian teratomas associated with anti-NMDAR
antibody encephalitis. Onconeural antibodies strongly
suggest malignancy, but paraneoplastic syndromes are
likely to precede tumor identification for months to
years.74 Steroids may be combined with intravenous
immunoglobulin (IVIg) or, less commonly, therapeutic
plasma exchange, but clinical decisions are strongly
influenced by physician specialty and geography.90
Because IVIg and therapeutic plasma exchange
240 www.psychosomaticsjournal.org
neutralize or remove circulating antibodies, they are
best reserved for conditions with pathogenic antibodies
(e.g., those that target neuronal surface antigens).91
IVIg or therapeutic plasma exchange may be
used as acute monotherapy where steroids are
contraindicated.84
Up to half of patients with AAE have a satisfactory
response to acute, first-line therapy, but maintenance
immunotherapy is recommended for 6 months or
longer for continued symptom improvement and
relapse prevention.81 It usually involves a gradual
steroid taper and initiation of second-line agents, chiefly
rituximab and cyclophosphamide. The antimetabolites
(azathioprine, mycophenolate mofetil, and methotrexate)
are used less frequently. Readers are referred to recent
reviews that outline treatment algorithms and immuno-
therapy regimens used for AAE.9,73,81,84
Paradoxically, corticosteroids initiated to treat
autoimmune conditions with neuropsychiatric symp-
toms may themselves cause neuropsychiatric symp-
toms. Steroid-induced neuropsychiatric symptoms are
dose-dependent and commonly present within days of
starting therapy.92 The temporal association between
neuropsychiatric symptoms (improvement, worsen-
ing, or change in character) and corticosteroids
(initiation or dose change) often illuminates whether
symptoms are due to underlying autoimmunity or an
adverse effect of treatment. Where steroid dose reduc-
tion or switch to alternative immunotherapy is infea-
sible, management of steroid-induced symptoms is
symptomatic. Of note, rituximab may rarely cause the
devastating condition progressive multifocal
leukoencephalopathy.
No randomized trials for autoimmune encephal-
opathy treatment have been conducted. Response rates
to symptomatic treatment are lower in this population
than in primary psychiatric disorders.10,93 Encephalitis
and vasculitis commonly cause seizures, so mood-
stabilizing antiepileptics, such as valproic acid or
carbamazepine, and benzodiazepines may be preferred
for agitation. Atypical neuroleptics are generally pre-
ferred to typical antipsychotics for reduced risk of
extrapyramidal symptoms. Even still, recent findings
suggest that features of neuroleptic malignant syn-
drome may be seen in upwards of half of patients with
anti-NMDAR antibody encephalitis treated with either
typical or atypical neuroleptics.58 This should also be
borne in mind when treating steroid-induced psychosis.
Catatonia warrants treatment with benzodiazepines,
Psychosomatics 58:3, May/June 2017

and electroconvulsive therapy has been used success-
fully in this population.
Disease course and degree of recovery are dictated
by the underlying autoimmune condition, and this
limits generalizability of comments. Nevertheless,
many autoimmune encephalopathies are incompletely
resolved with treatment, leaving patients with chronic
neuropsychiatric symptoms and functional impair-
ment. For instance, although roughly 4 in 5 patients
with anti-NMDAR antibody encephalitis may be
functionally independent at 2-year follow-up, many
of these patients still have persisting impairment.4
Interventions to improve quality of life in postautoim-
mune encephalopathy population deserve further
investigation.
CONCLUSIONS
Many autoimmune conditions have relevance for
psychiatric clinicians, particularly those practicing in
medical settings. Although secondary causes should be
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