REVIEW

C URRENT
OPINION Autoimmune and inflammatory neurological
disorders in the intensive care unit
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Camille Legouy a, Anna Cervantes b, Romain Sonneville c,d

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and Kiran T. Thakur e

Purpose of review
The present review summarizes the diagnostic approach to autoimmune encephalitis (AE) in the intensive
care unit (ICU) and provides practical guidance on therapeutic management.
Recent findings
Autoimmune encephalitis represents a group of immune-mediated brain diseases associated with antibodies
that are pathogenic against central nervous system proteins. Recent findings suggests that the diagnosis of
AE requires a multidisciplinary approach including appropriate recognition of common clinical syndromes,
brain imaging and electroencephalography to confirm focal pathology, and cerebrospinal fluid and serum
tests to rule out common brain infections, and to detect autoantibodies. ICU admission may be necessary at
AE onset because of altered mental status, refractory seizures, and/or dysautonomia. Early management in
ICU includes prompt initiation of immunotherapy, detection and treatment of seizures, and supportive care
with neuromonitoring. In parallel, screening for neoplasm should be systematically performed. Despite
severe presentation, epidemiological studies suggest that functional recovery is likely under appropriate
therapy, even after prolonged ICU stays.
Conclusion
AE and related disorders are increasingly recognized in the ICU population. Critical care physicians
should be aware of these conditions and consider them early in the differential diagnosis of patients
presenting with unexplained encephalopathy. A multidisciplinary approach is mandatory for diagnosis, ICU
management, specific therapy, and prognostication.
Keywords
autoimmune, encephalitis, intensive care, outcome

INTRODUCTION this article, we discuss the clinical approach at AE in

Autoimmune encephalitis (AE) represents a group of
immune-mediated brain diseases associated with
antibodies that are pathogenic against central nerv-
ous system (CNS) proteins [1,2]. Once thought to be
associated primarily with malignancies, pathogenic
antibodies have now been found to be triggered by
multiple causes including infectious causes of ence-
phalitis such as Herpes Simplex Virus-1 (HSV-1) and
Japanese Encephalitis virus (JEV) [3–5]. Patients with
AE can present with an array of complex neurological
symptoms, and commonly present to the intensive
care unit (ICU) with coma, new-onset status epilep-
ticus, complex movement disorders, and/or dysau-
tonomia. While there are certain causes of AE
requiring ICU care, which have a distinctive clinical
phenotype, including anti-NMDA receptor encepha-
litis (NMDARE), many cases of AE serve as clinically
challenging to distinguish from infectious encepha-
litis and other causes of systemic inflammation. In
the ICU, a common setting for fulminant presenta-
tions of AE requiring specialized care.
a
GHU Paris Psychiatrie & Neurosciences, Department of Intensive Care
Medicine, Paris, France, bDivisions of Neurocritical Care and Neuro-
infectious Disease, Boston Medical Center, Boston, Massachusetts,
USA, cUniversit
e, IAME, INSERM UMR1137, dAP-HP,
e Paris Cit

H^opital Bichat – Claude Bernard, Department of Intensive Care Med-
icine, Paris, France and eDepartment of Neurology, Columbia University
Irving Medical Center-New York Presbyterian Hospital, New York, New
York, USA
Correspondence to Prof. Romain Sonneville, MD, PhD, Service de
m
edecine intensive – reanimation, H^
opital Bichat – Claude Bernard,
46 rue Henri Huchard, 75877 Paris Cedex, France.
Tel: +33 1 40257702; fax: +33 1 40258782;
e-mail: romain.sonneville@aphp.fr
Curr Opin Crit Care 2024, 30:142–150
DOI:10.1097/MCC.0000000000001139

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Number 2
April 2024

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 Autoimmune and inflammatory neurological disorders in the intensive care unit Legouy et al.
KEY POINTS

Recent findings suggests that the diagnosis of
autoimmune encephalitis (AE) requires a
multidisciplinary approach including appropriate
recognition of common clinical syndromes, brain
imaging and electroencephalography to confirm focal
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pathology, and cerebrospinal fluid and serum tests to
rule out common brain infections, and to
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detect autoantibodies.

Early management of AE in ICU includes prompt
initiation of immunotherapy, detection and treatment of
seizures, and supportive care with neuromonitoring.

A multidisciplinary approach is mandatory for
diagnosis, ICU management, specific therapy,
and prognostication.
WHEN TO CONSIDER AUTOIMMUNE
ENCEPHALITIS?
Epidemiology
The annual incidence of all-cause encephalitis is
estimated to be approximately 5–8 cases per 100
000 persons, with >50% of unknown cause [6]. In
several studies, AE now surpasses the prevalence of
infectious causes of encephalitis, including viral
etiologies. In a study of all-cause encephalitis in
Olmsted County, USA, prevalence of AE similar to
that of infectious encephalitides [7]. AE is increas-
ingly recognized with a study performed in France
finding that the national observed incidence rate for
the antibody-positive AE subgroup increased from
1.4 per million person-years in 2016 to 2.1 per
million person-years in 2018 [8]. NMDARE repre-
sents the most common identified cause of AE in
the ICU setting [9]. Though, important gaps exist
as epidemiological data has been outpaced by newly
identified antibodies and clinical entities. Signifi-
cant gaps also remain given limited diagnostic avail-
ability across resource-limited settings. Research
studies evaluating the epidemiological burden of
encephalitis in the ICU should not be neglected
and are fundamental to understanding the global
& encephalitis by Graus et al.
burden of AE [10 ].
Clinical presentation
A rapid diagnosis and timely initiation of immuno-
therapy are crucial to minimizing severe complica-
tions in patients with AE admitted to the ICU [11].
Despite efforts attempting to characterize etiologies
of encephalitis clinically, multiple modalities are
still required to reach a definitive diagnosis and rule
out alternative diagnoses, including neuroimaging,
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cerebrospinal fluid (CSF) studies, and electroence-
phalogram (EEG). The differential diagnosis of
AE is broad and includes toxic/metabolic, infec-
tious, neoplastic, vascular, or systemic inflamma-
tory conditions.
Delays in identification, diagnosis and early
management of AE led to the development of diag-
nostic criteria in 2016 to aide in distinguishing AE
from other disorders, and to codify associated clin-
ical presentations [12]. Although these criteria have
provided an essential foundational framework for
clinicians to evaluate and manage possible and
probable AE, there continues to be frequent mis-
diagnosis of AE as recently evidenced in a series of
&&
393 adult patients [13 ]. The study identified that
27% of cases originally diagnosed and managed for
AE had alternate etiologies, and that they meet
diagnostic criteria for possible or probable AE
&&
[13 ]. The clinical approach includes a clinical algo-
rithm designed to assist in the differential diagnosis
of AEs and initiate prompt treatment without wait-
ing for antibody testing results which are often
delayed and may be negative in the context of
possible or probable AE (see Table 1) [12].
Rapid differentiation between infectious ence-
phalitis and AE is of utmost importance in patients
presenting to the ICU, as it can prompt earlier
initiation of appropriately targeted therapies and
could spare patients unnecessarily prolonged empir-
ical antimicrobial management. A retrospective
analysis aimed at comparing viral with AE found
that patients with AE were more likely to have
subacute to chronic presentations, psychiatric and
memory complaints, and less inflammation in the
CSF (<50 white blood cells) [14]. Another study
evaluated clinical criteria for AE and acute infectious
encephalitis, and found that presentation with
fever, CSF protein 75 mg/dl, and CSF WBC
50 cells/ml, an AE diagnosis was found to be highly
unlikely (negative predictive value 95%, and posi-
tive predictive value 64%) [15] (see Table 2).
Table 1. Diagnostic criteria for possible autoimmune
All three criteria are required
1 Subacute progression (within 3 months) of memory deficits,
altered mental status or psychiatric symptoms
2 One or more of the indicated features:

New focus central nervous system deficits

Unexplained seizures

CSF pleocytosis

MRI findings suggesting encephalitis
3 Exclusion of a specific list of alternative disorders
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 Acute neurological problems
Table 2. Patients characteristics found in autoimmune or infectious encephalitis
Charlson comorbidity index < 2
Subacute (6--30 days) to chronic (>30 days) onset
Psychiatric and/ or memory complaints
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Presence of fever
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Inflammation in CSF
CSF White blood cell > 50/mm3
CSF protein >75 mg/dl
GENERAL DIAGNOSTIC APPROACH
The preliminary diagnosis and decision for initiat-
ing treatment of AE cases are often not dependent
on antibody status. A thorough laboratory evalua-
tion including blood tests to evaluate systemic
inflammatory changes including consideration of
primary rheumatological etiologies is important, as
well as other common AE mimics. Cancer screening
is typically recommended in adults presenting with
presumed AE. CSF lymphocytic pleocytosis and CSF
elevated protein supports the diagnosis though is
not uniformly present. Workup for alternative eti-
ologies including infections varies dependent on
patient history as well as local epidemiology includ-
ing risk factors for an immunocompromised state.
In addition to standard infectious etiology testing,
more novel unbiased platforms are being increas-
ingly used especially in critically ill populations.
Recent studies have evaluated newer modalities to
rapidly evaluate for pathogens, including meningi-
tis/encephalitis multiplex PCR panels and unbiased
sequencing methods. The FilmArray Meningitis/
Encephalitis (ME) multiplex polymerase chain reac-
tion (PCR) panel targets 14 bacteria, viruses, and
fungi including common etiologies of community-
acquired bacterial meningitis (CABM) pathogens
and the most common viral causes of encephalitis,
including HSV-1 and HSV-2. Prior studies show an
overall agreement of 93–99% between the ME panel
and conventional diagnostic testing with notable
exceptions of human herpes virus 6 (HHV-6) and
Cryptococcal species [16]. Sensitivities for L. mono-
cytogenes, H. influenzae, E. coli, and HSV-1 have also
been identified to be suboptimal, suggesting that
this panel may not be appropriate to definitively
rule out infection in a context of a high clinical
suspicion [17].
Sequencing methods are another promising
modality that could help improve the identification
of infectious pathogens in the CSF. Sequencing
methods performed on CSF samples have shown
variable performance in detecting pathogens in
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Autoimmune encephalitis Infectious encephalitis
Likely Unlikely
Very likely Unlikely
Very likely Unlikely
Unlikely Very likely
Unlikely Very likely
Unlikely Very likely
CNS infections. In a multicenter study, NGS allowed
identification of pathogens in 22% of cases, which
&&
were not diagnosed by conventional tests [18 ].
Current generalizability is limited because of cost,
current turnaround time, and limited centers with
expertise in laboratory and bioinformatics.
Autoimmune tests
Antibody testing should be performed in both CSF
and serum samples to avoid misinterpretation of
serological only results. Careful interpretation of
criteria should be done by clinicians including
familiarity with clinical syndromes rather than
being overly reliant on antibody testing and results,
the importance of relying more on CSF testing for
autoantibodies rather than serological testing alone,
and the importance of increasing awareness that a
&&
positive test result may be insignificant [19 ,20,21].
Interpretation of testing results should carefully
consider clinical presentation especially in the con-
text of low positive titers, only serological positivity,
and multiple positive autoantibodies. Specifically,
voltage-gated potassium channel complex without
binding to LGI1 or CASPR2 has limited clinical
significance. In the ICU, status epilepticus is com-
monly seen and frequently identified in anti-
NMDAR encephalitis as well as GABA-B and
GABA-A receptor encephalitis.
Electroencephalogram
AE is often associated with seizures including as a
common cause of new-onset refractory status epi-
lepticus (NORSE) [22]. In addition to NORSE, delta
activity is noted frequently with a recent study
showing that 63% had periodic or rhythmic pat-
terns, with generalized rhythmic delta activity iden-
tified in 33% of patients [23]. Delta activity is more
commonly identified in anti-NMDA receptor ence-
phalitis, and extreme delta brush is associated with
worse outcomes [24].
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 Autoimmune and inflammatory neurological disorders in the intensive care unit Legouy et al.

Basic neuroimaging study of 382 patients with NMDARE showing that

MRI is the gold standard for evaluation of parenchy- 70% had a normal brain MRI [26].
mal inflammation and patterns of contrast-enhance-
ment [12]. Other MRI sequences may be of
importance as a study evaluating the differences seen ADVANCED NEUROIMAGING
in diffusion-weighted imaging (DWI) between an Fluorodeoxyglucose – positron emission tomogra-
HSV and an AE cohort with similar lesion topography phy (FDG-PET) has taken a significant role in diag-
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showed that restricted diffusion was seen in only nosis and management of AE (Fig. 1) [27]. FDG-PET
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4.8% of patients from the AE cohort as opposed to
83.3% of the HSV cohort, and thus may discriminate
between the two early in the disease course [25].
Though importantly, normal neuroimaging does
not rule out the possibility of AE and is often depend-
ent on timing from disease onset, with a retrospective
studies should be considered for patients who can-
not obtain MRI or for cases of diagnostic uncertainty
following MRI. Specific patterns of hypermetabo-
lism and hypometabolism may support a specific
subtype of autoantibody associated illness or Ras-
&&
mussen’s encephalitis [28 ].

Step 1: confirm focal or multifocal brain pathology suggestive of autoimmune encephalitis

Brain MRI EEG*
(if encephalopathy or
seizures)
Brain PET if MRI negative and diagnosis
remains uncertain after initial testing
Step 2: confirm inflammatory etiology and rule out competing possibilities
Lumbar puncture** Blood tests including
including CSF serum neuronal
neuronal autoantibodies
autoantibodies
Brain biopsy if diagnostic remains uncertain
Step 3: screen for associated neoplasm***
CT chest, abdomen, Mammogram, breast Pelvic or testicular
and pelvis MRI ultrasound
Body PET if initial
screen negative
*EEG can confirm focalization and rule out non-convulsive seizures
**In addition to neuronal antibodies, CSF should be tested for infections, inflammatory markers
(IgG index and oligoclonal bands), and cytology.

*In most cases, general neoplasm screening starts with CT and then other modalities are
added until a neoplasm is found or ruled out.

FIGURE 1. Diagnostic algorithm for autoimmune encephalitis, adapted from [27]. EEG can confirm focalization and rule out
nonconvulsive seizures. In addition to neuronal antibodies, CSF should be tested for infections, inflammatory markers (IgG
index and oligoclonal bands), and cytology. In most cases, general neoplasm screening starts with CT and then other
modalities are added until a neoplasm is found or ruled out.

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Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

 Acute neurological problems
In some cases, FDG-PET may also be employed
to monitor therapeutic response to immunomodu-
lators both qualitatively and quantitatively and may
be superior to MRI [29]. A recent study suggests a
clever role for the use of FDG-PET in critically ill
patients with status epilepticus. FDG-PET performed
under burst suppression allowed differentiation of
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ictal versus nonictal aspects of the disease. This was
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not only useful in guiding management (antiepilep-
tic medications versus immunosuppression) but
also helped with identification of an autoimmune
etiology of status epilepticus in some cases [30].
MULTIMODALITY MONITORING
While raised intracranial pressure (ICP) is not fre-
quently discussed in the management of encepha-
litis, it is likely underrecognized. Amongst critical ill
patients with viral and postviral encephalitis, up to
69%% of patients were found to have ICP greater
than 15 mmHg [31]. The pathophysiology of raised
ICP in encephalitis is multifactorial and may be due
to a combination of cerebral edema, inflammatory
response, cerebrovascular injury – either through
vasospasm, thrombosis, or impaired autoregulation.
Recent literature supports the beneficial use of
ICP monitors in viral infection related AE (SARS-
CoV-2 and influenza) [32–34]. Limited data might
also be extrapolated from the growing use of ICP
monitors in infectious meningoencephalitis [35],
especially amongst children [36]. There are no
guidelines-based recommendations for ICP monitor
placement outside of TBI but a recent scoring system
was proposed for meningoencephalitis [37]. Brain
tissue oxygenation monitoring and microdialysis
catheters have been infrequently used in the man-
agement cerebral edema in meningoencephalitis
and surgical decision making and warrant further
investigation [38,39].
Table 3. Diagnosis of MOGAD [46 ] &&
Diagnosis of MOGAD requires fulfilment of A, B and C
(A) Core clinical demyelinating event Optic neuritis
Myelitis
Acute disseminated encephalomyelitis (ADEM)
Cerebral focal deficit
Brainstem or cerebellar deficit
Cerebral cortical encephalitis often with seizures
(B) Positive MOG-IgG test in serum Clear positive
Low positive / Positive without reported titre /
Negative but CSF positive
(C) Exclusion of better diagnoses including multiple sclerosis
MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease.
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Growing research into noninvasive monitors
hold promise for the identification and manage-
ment of elevated ICP in encephalitis [40]. Optical
nerve sheath diameter ultrasound has been used as a
proxy for ICP monitoring in brain infections [41]
while pupillometry may assist with early detection
of worsening edema [42]. Noninvasive monitors
such as brain4care have developed noninvasive
ICP waveform analysis device which may inform
clinicians to impairment in intracranial compliance
and can used continuously to evaluate treatment
response [43].
Noninvasive cerebral blood flow may be eval-
uated with near-infrared spectroscopy or via trans-
cranial Doppler ultrasound (TCD). TCD-derived
pulsatility index may help identify possible focal
elevations in ICP as well as vasospasm in encepha-
litis [44]. TCD has also been helpful at identification
of ictal vasodilation in autoimmune encephalitis
related seizures [45].
SPECIFIC INFLAMMATORY CONDITIONS
Myelin oligodendrocyte glycoprotein
antibody-associated disease
Neuromyelitis optica spectrum disorder (NMOSD)
had been categorized in two different disorders
due to the discovery of two immunoglobulin G
(IgG) antibodies [against aquaporin 4 (anti-AQP4)
and myelin oligodendrocyte glycoprotein (anti-
MOG)]. A recent international panel of specialists
&&
proposed diagnostic criteria for MOGAD [46 ] (see
Table 3). Key findings should raise concern for a
diagnosis of MOGAD including neurological
impairment in the absence of recurrent attack
and a lack of improvement following treatment
with high-dose corticosteroids for an acute
attack [47].
No additional supporting features required
þ AQP4-IgG seronegative
AND
 1 supporting clinical or MRI feature
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 Autoimmune and inflammatory neurological disorders in the intensive care unit Legouy et al.

Neuronal surface autoantibody-mediated Autoimmune encephalitis with anti-a-

encephalitis syndromes
Excluding the distinct neurological pattern of well
known AE (see Table 4) such as NMDARE, the diag-
nosis of AE can be challenging for neurologists and
intensivists. A panel of experts recently proposed
practice recommendations covering the clinical pre-
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amino-3-hydroxy-5-methyl-4-isoxazole
propionic acid receptor antibodies
a-Amino-3-hydroxy-5-methyl-4-isoxazole propionic
acid receptors (AMPAR) belong to glutamate receptors
(mediate the excitatory synaptic transmission) and
their antibodies are directed against the extracellular

sentation, diagnostic workup, and acute manage- epitopes of the GLuA1 or GluA2 subunits of the
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ment of AE summarized in 13 points [27]. receptor leading to a decreased surface synaptic

Anti-NMDA receptor encephalitis
Anti-NMDA receptor encephalitis (NMDARE) is an
immune-mediated disease characterized by the pres-
ence of CSF antibodies against the GluN1 subunit of
the NMDAR causing an impairment via internal-
ization. The NMDAR network dysfunction lead to
psychiatric symptoms within the first weeks fol-
lowed by neurological complications (movement
abnormalities, dysautonomia, central hypoventila-
tion, seizures, decreased level of consciousness) fre-
quently resulting to intensive care admission [11]
and prolonged deficits if not treated. Diagnosis may
be challenging for atypical syndromes although,
definite and probable diagnosis criteria have been
defined several years ago [12].
AMPAR clusters and their internalization. In a review
of 66 patients, most had an acute or subacute onset
with a median age of 57 years and a male to female
ratio of about 1 : 2. Most common clinical manifesta-
tions were cognitive impairment (82%) (short-term
memory loss, disorientation), psychiatric disorder
(80%) (abnormal behavior, agitation, mood disor-
ders), altered state of consciousness (77%), dyskinesia
(38%), seizure (29%) and more rarely speech disorders
(15%), insomnia (11%), autonomic dysfunction (9%)
[48]. In another cohort, 75% patients with AMPAR
antibodies had associated tumor (with a majority of
thymoma, small cell lung cancer, breast cancer, ovar-
ian cancer) [49,50], classifying AMPAR-IgG as a ‘high-
risk’ antibody (>70% associated with cancer) in a
new diagnostic criteria for paraneoplastic neurologic

Table 4. Presentation of specific autoimmune encephalitis

Specific autoimmune
encephalitis Diagnostic criteria Differential diagnosis

Limbic encephalitis
Acute disseminated
encephalomyelitis
Bickerstaff’s brainstem
encephalitis
Clinical presentation: subacute onset (<3 months) of cognitive, HSV, VZV, HHV6
psychiatric and/or epileptic presentation
CSF: mild to moderate lymphocytic pleocytosis (<100 cells/mm3) in
60--80%, elevated IgG index or oligoclonal bands (50%)
Possible associated antibodies: Hu, CRMP5/CV2, Ma2, NMDAR,
AMPAR, LGI1, CASPR2, GAD65, GABABR, DPPX, mGluR5, AK5,
Neurexin-3a antibodies
Radiology: Bilateral brain abnormalities on T2-weighted fluid attenuated
inversion recovery MRI highly restricted to the medial temporal lobes
EEG: Epileptic or slow-wave activity involving temporal lobes
Clinical presentation: A first multifocal, clinical CNS event of presumed Susac’s syndrome
inflammatory demyelinating cause.
Possible associated antibodies: MOG antibodies
Radiology:

Diffuse, poorly demarcated, large (>1--2 cm) lesions predominantly
involving the cerebral white matter

T1-hypointense lesions in the white matter in rare cases

Deep grey matter abnormalities (e.g., thalamus or basal ganglia)
can be present
Evolution: No new clinical or MRI findings after 3 months of symptom
onset
Clinical presentation: subacute onset (<4 weeks) of: Listeria rhombencephalitis,

Decreased level of consciousness, neurosarcoidosis, Behcet,

Bilateral external ophthalmoplegia lymphoma, progressive

Ataxia multifocal leukoencephalopathy,
Possible associated antibodies: IgG anti-GQ1b antibodies central pontine myelinolysis,
Whipple

AE, autoimmune encephalitis; CNS, central nervous system; AMPAR, a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors; IgG, immunoglobulin G;
MOG, myelin oligodendrocyte glycoprotein; NMDARE, including anti-NMDA receptor encephalitis.

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 Acute neurological problems
&&
syndromes [51 ] and were associated with co-existing
antibodies in 60% of patients with other neurological
syndromes such as myasthenia gravis.
Central nervous system vasculitis
The diagnostic criteria of Primary angiitis of the
Central Nervous System (PACNS) include a neuro-
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logic or psychiatric deficit with the presence of
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either classic angiographic or histopathologic fea-
tures of angiitis after exclusion of any differential
diagnosis including systemic vasculitis [52,53]. A
systematic review and meta-analysis reported that
CSF analysis had a moderate sensitivity and a low
specificity for the diagnosis of PACNS but remained
interesting for exclusion of malignant or infectious
disease [54].
PRACTICAL APPROACH FOR
IMMUNOMODULATION AND SUPPORTIVE
CARE
Admission to the ICU should be proposed for every
patient with suspected/confirmed AE presenting
with severe alteration of mental status, seizures,
and/or extra-neurologic organ failure. Patients with
autonomic dysfunction, presenting with elevated
heart rate, blood pressure and/or fever also require
continuous monitoring of vital signs. A practical
approach is presented in Fig. 2.
Immunomodulation strategies play a crucial
role in the management of severe AE. Frist-line
FIGURE 2. Practical approach for immunomodulation and supportive care.
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approaches include high-dose corticosteroids to sup-
press inflammation (i.e., IV methylprednisolone
1000 mg for 3–5 days), intravenous immunoglobulin
(IVIG, 2 g/kg over 5 days), and/or plasmapheresis
(i.e., 5–7 sessions over 10–14 days) to remove circu-
lating autoantibodies. Immunosuppressive agents
such as rituximab or cyclophosphamide are consid-
ered to target specific immune cells and are usually
used as second-line therapies [11]. Additionally,
emerging therapies, like monoclonal antibodies tar-
geting specific immune pathways or immunothera-
pies that harness the body’s own regulatory T cells,
show promise in fine-tuning the immune response.
The choice of immunomodulation strategy often
depends on the patient’s clinical presentation, under-
lying autoantibody profile, and individual response
to treatment, underscoring the importance of per-
sonalized medicine in managing AE.
Antiepileptic drugs are essential for seizure con-
trol, and the selection of drugs is tailored to the
individual’s specific seizure type and overall medical
condition. Close monitoring of treatment response
and potential adverse effects is paramount, neces-
sitating collaboration between intensivists, neurol-
ogists, and other healthcare providers to achieve
seizure control.
The management of autonomic dysregulation
requires prompt recognition and intervention to
prevent further complications. Sympathetic storm-
ing often presents with elevated heart rate, blood
pressure, and fever. The primary goal is to reduce
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 Autoimmune and inflammatory neurological disorders in the intensive care unit Legouy et al.
excessive sympathetic activity and manage associ-
ated symptoms. In a hospital setting, continuous
monitoring of vital signs is crucial. Treatment may
include sedation and the administration of medi-
cations to modulate sympathetic activity. Medica-
tions such as benzodiazepines (e.g., midazolam) and
propofol may be used to provide sedation and con-
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trol autonomic hyperactivity. Other medications,
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including alpha-2 agonists (clonidine, dexmedeto-
midine) and beta-blockers, may be employed to
attenuate the effects of excessive catecholamine
release in selected cases.
OUTCOMES AND PROGNOSTICATION
Outcomes and prognostication scores in AE are
essential tools for assessing the severity of the con-
dition and predicting a patient’s long-term progno-
sis. Several factors, such as the type of autoimmune
antibody involved, the timing of diagnosis, and
the prompt initiation of immunotherapy, can sig-
nificantly influence outcomes. Other prognostic
indicators include brain MRI findings, CSF inflam-
mation, and response to first-line therapies. One
example is the ‘NMDAR Encephalitis One-Year
Functional Status (NEOS) Score,’ which predicts
patient’s functional outcome at 1-year postonset
[55]. This score was externally validated in an inde-
pendent cohort [56]. However, it is important to
note that individual responses to therapy can vary,
and that prognostic scores, while useful, should not
be used alone and should be best integrated in a
multimodal approach. Despite prolonged ICU stays,
many patients can still achieve favorable outcomes
with proper and timely management.
CONCLUSION
AE and related disorders are increasingly recognized
in the ICU population. Once suspected, timely eval-
uation and prompt initiation of immunotherapy is
required, after exclusion of common infectious
causes. Critical care physicians should be aware of
these conditions and consider them early in the
differential diagnosis of acute encephalopathy. Mul-
tidisciplinary approach is mandatory for accurate
diagnosis, ICU management, specific therapy,
and prognostication.
Acknowledgements
None.
Financial support and sponsorship
R.S. received grants from the French Ministry of Health,
anf LFB. K.T. National Institutes of Health (NIH)
1070-5295 Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
1K23NS105935-01, Centers for Disease Control and
Prevention funding support.
Conflicts of interest
Consultant Delve Bio. A.A. and C.L. no conflicts of
interest Funding statement: R.S. received grants from
the French Ministry of Health, anf LFB. K.T. National
Institutes of Health (NIH) 1K23NS105935-01, Centers
for Disease Control and Prevention funding support.
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Volume 30
Number 2
April 2024