Journal Pre-proof

Anti-NMDAR Encephalitis: A Multidisciplinary Approach to Identification of the

Disorder and Management of Psychiatric Symptoms

Anique Forrester, MD, Samantha Latorre, MD, Pamela K. O’Dea, MD, Charles
Robinson, MD, Eric Luria Goldwaser, DO, PhD, Adam Trenton, DO, Anthony Tobia,
MD, Rehan Aziz, MD, Survandita Dhawan, MS-4 (anticipated MD in May 2020),
Andrew Brennan, MS-4 (anticipated MD in May 2020), Mohan Kurukumbi, MD, Yu
Dong, MD, David R. Benavides, MD, PhD (DR Benavides), Ada Ibe Offurum, MD

PII: S0033-3182(20)30130-4
DOI: https://doi.org/10.1016/j.psym.2020.04.017
Reference: PSYM 1098

To appear in: Psychosomatics

Received Date: 11 March 2020

Revised Date: 21 April 2020
Accepted Date: 21 April 2020

Please cite this article as: Forrester A, Latorre S, O’Dea PK, Robinson C, Goldwaser EL, Trenton
A, Tobia A, Aziz R, Dhawan S, Brennan A, Kurukumbi M, Dong Y, Benavides DR, Offurum AI, Anti-
NMDAR Encephalitis: A Multidisciplinary Approach to Identification of the Disorder and Management of
Psychiatric Symptoms, Psychosomatics (2020), doi: https://doi.org/10.1016/j.psym.2020.04.017.

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 Word Count – 2880

Title
Anti-NMDAR Encephalitis: A Multidisciplinary Approach to Identification of the Disorder and

Management of Psychiatric Symptoms

Anique Forrester, MD1

Samantha Latorre, MD1
Pamela K. O’Dea, MD2
Charles Robinson, MD1
Eric Luria Goldwaser, DO, PhD1
Adam Trenton, DO4
Anthony Tobia, MD4
Rehan Aziz, MD4
Survandita Dhawan, MS-4 (anticipated MD in May 2020)4
Andrew Brennan, MS-4 (anticipated MD in May 2020)4
Mohan Kurukumbi, MD5
Yu Dong, MD1
David R. Benavides, MD, PhD2 (DR Benavides)
Ada Ibe Offurum, MD3

University of Maryland School of Medicine, Department of Psychiatry Baltimore, MD 21201

University of Maryland School of Medicine, Department of Neurology, Baltimore, MD 21201
University of Maryland School of Medicine, Department of Medicine, Baltimore, MD 21201
Rutgers Robert Wood Johnson Medical School, Department of Psychiatry, New Brunswick, NJ
08901
Virginia Commonwealth University/INOVA Fairfax Hospital, Department of Neurology,
Fairfax, VA 22031
Anti-NMDAR Multidisciplinary

Author Note
Correspondence concerning this article should be sent to: Anique Forrester, MD at the
University of Maryland School of Medicine at aforrest@som.umaryland.edu

Acknowledgements
None of the above authors have any conflicts of interest to disclose EXCEPT Dr. David
Benavides.

Dr. Benavides author contributions: Acquisition, analysis or interpretation of data; drafting of

manuscript; critical revision of the manuscript for important intellectual content.

Disclosures: Dr. Benavides reported research grants from NIH/NINDS (1K08NS114039) and
University of Maryland School of Medicine (seed grant) during the conduct of the study and
outside the submitted work.

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Anti-NMDAR Multidisciplinary

Abstract

The novelty of anti-NMDA receptor encephalitis, for which somatic treatments have only

recently been developed, has led to a lack of information on assessment and treatment of its

variable behavioral manifestations. In this article, we discuss four challenging cases of anti-

NMDAR encephalitis, focusing on the importance of a multidisciplinary approach to

identification and management of the disorder and the necessity of close collaboration in the

acute hospital setting for management of the behavioral symptoms. The cases we discuss

highlight some of the medication and non-pharmacologic treatment strategies which may

facilitate management of psychiatric symptoms, both while the medical work-up is ongoing and

after the diagnosis has been confirmed.

Keywords: Ant-NMDAR, Encephalitis, Collaborative, Psychiatric, Multidisciplinary

Anti-NMDAR Encephalitis: A Multidisciplinary Approach to Identification of the Disorder and
Management of Psychiatric Symptoms

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Anti-NMDAR Multidisciplinary

Introduction

Anti-NMDAR (Anti-NMDA receptor) encephalitis was first described as a paraneoplastic

condition associated with ovarian teratoma, marked by prominent memory deficits, psychiatric

symptoms, and decreased consciousness1. In 2011, anti-NMDAR encephalitis was found not to

be exclusively a paraneoplastic syndrome but also the first identified autoimmune synaptic

encephalitis2. Unlike paraneoplastic NMDAR encephalitis, the autoimmune synaptic variant

often responds to immunomodulatory therapies. More than 1500 patients have been reported

with the condition3. A multicenter study of causes of encephalitis showed that 4% of patients had

anti-NMDAR antibodies, second only to acute disseminated encephalomyelitis4.

The initial symptoms of anti-NMDAR encephalitis are frequently nonspecific. Unless there are

definitive signs, such as extreme delta brush pattern on EEG or an ovarian teratoma, the

differential diagnosis perforce includes all autoimmune and infectious causes of encephalitis.

Many of its features overlap with those of limbic encephalitides, including anti-Hu, anti-Ma2,

anti-GAD, anti-AMPA, anti-GABA-B, and anti-LGI15. Up to 20-30% of patients with Herpes

simplex virus encephalitis have been reported to develop anti-NMDAR antibodies, which may

lead to symptomatic recurrence after resolution of acute HSV encephalitis. Such patients may not

respond to treatment unless the syndrome is correctly identified6.

Psychiatric symptoms are usually the first alarming and prominent findings, especially in

patients without prior psychiatric illness. In a series of 100 anti-NMDAR encephalitis patients,

77 initially presented to psychiatric services3. For the first 1-3 weeks, patients may exhibit a wide

variety of mood, anxiety and psychotic symptoms; disorganized behaviors; and personality

change. Changes in language and speech are common, including alogia, echolalia,

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Anti-NMDAR Multidisciplinary

perseveration, mumbling, and mutism2. These alterations often persist or progress through later

stages of the illness. The most common psychiatric symptoms include agitation (59% of cases),

psychosis (54%), catatonia (42%), and mood lability (30%)8. Unfortunately, case reports have

revealed a trial-and-error method of treating psychiatric symptoms.

The diagnosis is usually one of exclusion, unless the patient exhibits the classic signs described

above, or the treating physicians have had significant experience with the disorder. Confirmatory

laboratory testing is quite limited in its availability. There is no standardized diagnostic and

treatment algorithm for acute care physicians. Unfortunately, treatment is often delayed because

many patients are initially thought to have a primary psychiatric illness.

If the syndrome is left unrecognized and untreated, neurological symptoms will emerge, mostly

movement abnormalities (e.g. catatonia, dystonia, dyskinesia, or chorea). Patients may quickly

progress to decreased responsiveness, dysautonomia, and hypoventilation, often requiring

intensive care. Seizure may occur in nearly 80% of cases3. The mortality rate is 4%, primarily

due to respiratory, cardiac, and infectious problems that usually occur during intensive care

support7.

In each case, clinical suspicion of this diagnosis and time to confirmatory diagnostic testing

depended upon multidisciplinary collaboration.

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Anti-NMDAR Multidisciplinary

Clinical Cases

Case 1
A 32-year-old female with well-controlled epilepsy (seizure-free for 10 years) presented with

breakthrough seizures and two weeks of mania-like personality change. Brain MRI was

unremarkable. Video EEG showed subclinical seizures, with intermittent electrographic seizures

originating from the right temporal region (Fig. 1). A previous EEG had shown left temporal

lobe seizure activity. Seizure control was re-established with valproic acid 2500 mg, lacosamide

200mg, and clobazam 20mg. However, the patient continued to have labile mood and crying

outbursts, which did not improve with olanzapine 15mg daily. She became lethargic and slept

more than 20 hours a day, becoming combative when she awoke. She developed echolalia,

prominent retrograde and anterograde amnesia, increased muscle tone, and fine hand tremor.

Olanzapine was discontinued. Haloperidol and lorazepam were used as needed for agitation. At

this point the patient’s unusual clinical progression led to the consideration of autoimmune

encephalitis. Empiric treatment with intravenous immunoglobulin (IVIG) for 5 days led to some

lucid periods, but most symptoms persisted. On hospital day 16, CSF serology returned positive

for the NMDA receptor antibody, and IV corticosteroid treatment was begun. After subsequent

discovery and removal of an ovarian teratoma, lacosamide and clobazam were tapered off. The

patient was discharged on day 26, with resolution of psychiatric symptoms.

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Anti-NMDAR Multidisciplinary

Case 2

A 34-year-old woman with no significant medical or psychiatric history presented to a local

emergency department with aggressive and disorganized behavior. She was paranoid, delusional,

and hypervigilant. Routine evaluation, including CBC; CMP; acetaminophen, alcohol, and

salicylate levels; and EKG, was unremarkable. Inpatient psychiatric treatment was

recommended. On the psychiatric unit the patient was found to respond to internal stimuli and to

be alternately agitated and catatonic. Int the first two weeks of admission, she required multiple

medications, including lorazepam 36.5mg total daily dose, olanzapine 65mg total over 14 days,

ziprasidone 60mg daily, risperidone 6mg daily, diphenhydramine 625mg total over 14 days, and

haloperidol 70mg, as well as intermittent restraints and locked-door seclusion.

After two weeks she had a generalized tonic-clonic seizure, which was treated with lorazepam

2mg and fosphenytoin 1125mg (19.8 mg/kg). She required intubation and sedation and was

transferred to the neurology service. Lumbar puncture and brain MRI, with and without

gadolinium, revealed no significant abnormalities. Given concern for her unusual presentation

(age 34 with new onset psychiatric sx) and lack of response to standard treatments prior to the

seizure, there was increasing suspicion for anti-NMDAR encephalitis. Patient later tested

positive for serum anti-NMDAR receptor antibody. CT of her abdomen and pelvis showed a

large mass and bilateral ovarian cysts. Intravenous methylprednisolone 1g daily for 5 days was

administered, followed by a prednisone taper, along with plasmapheresis. After four more days,

the adnexal mass, left ovary, and right ovarian cyst were excised: pathology confirmed mature

teratoma. When the patient still did not improve, rituximab (600mg, 375mg/m2) weekly was

started. Four cycles of this therapy produced only minor improvement, and cyclophosphamide

1280mg/day was started.

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Anti-NMDAR Multidisciplinary

She continued to be agitated and confused, receiving intermittent haloperidol 5mg daily.

Quetiapine was begun and titrated from 50mg to 100mg, and behavior improved. Haloperidol

was discontinued and quetiapine was then tapered to 25mg twice daily. Autonomic instability

developed and was treated with clonidine until it resolved, whereupon the patient was discharged

to an acute rehabilitation facility. She continued to improve after discharge, she scored 20/30 on

the Montreal Cognitive Assessment (MoCA), indicating mild cognitive impairment. EEG

showed periods of frontal intermittent rhythmic delta activity (FIRDA), with a delta brush

pattern (Fig. 2). An outpatient EEG two months later showed no evidence of seizures or

epileptiform discharges.

Case 3

A 59-year-old African American woman with schizoaffective disorder was brought to the ED by

her daughter after three days of slurred speech and right sided weakness. The patient appeared

anxious and continuously repeated, “Kay, Kay”. Home psychiatric medications consisted of

citalopram, olanzapine, and zolpidem. She had not kept outpatient appointments for five months

prior to this presentation. Her outpatient psychiatrist reported that she had been inconsistently

compliant with medications for several years. Her family reported that she had no psychiatric

symptoms for the previous three years.

Brain MRI showed FLAIR hyperintensities in the left temporal region and insula (Fig 3). EEG

showed left-sided slowing but no epileptiform activity. Intravenous acyclovir was empirically

started for viral encephalitis. Infectious disease consultants recommended evaluation of CSF for

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Anti-NMDAR Multidisciplinary

other causes of encephalitis. However, because the patient’s serum was positive for HSV IgG,

the patient was continued on IV acyclovir for 16 days.

By hospital day 7, the patient had begun to refuse medications and she became increasingly

agitated. Psychiatric consultation noted impaired speech, continued perseveration on the syllable

“Kay,” and repetitive hitting of her bed. Due to concern for catatonia, lorazepam 1mg IV was

given and titrated to 1mg three times daily. The patient became able to say, “Things have been

wrong in my head for 4 months.” IV lorazepam was continued. At the same time, neurology

consultants suggested evaluation for autoimmune encephalitis given the constellation of clinical

symptoms.

Over the next several days the patient became physically assaultive. Olanzapine was changed to

risperidone 0.5mg twice daily with minor improvement. On day 22, preliminary results of the

CSF autoimmune panel were positive for NMDAR antibodies. The patient underwent five

rounds of plasma exchange and treatment with IV methylprednisolone 1000mg, as well as four

days of IVIG, dosed at 500mg/kg.

PET CT and transvaginal ultrasound showed no evidence of ovarian teratoma or other

malignancy. By day 27 the patient’s speech had improved so much that she was able to speak in

full, comprehensible sentences, though she continued to have occasional word-finding errors. On

day 35, she was discharged home with 24-hour supervision continuing with outpatient IV

rituximab 375mg/m2 per week for 4-8 weeks. Two weeks after her hospitalization she had

continued to improve and reportedly had become able to perform all ADLs independently.

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Anti-NMDAR Multidisciplinary

Case 4
A 40-year-old Hispanic woman presented to the ED after three days of fever, left temporal

headache, and mental status changes. Four months prior to admission, she had suffered a

ruptured left posterior communicating artery aneurysm which had been treated with open

craniotomy and aneurysm clipping. Though recovery had been further complicated by cerebral

edema and subsequent hemicraniectomy, she had displayed no significant behavioral or

cognitive changes at a follow-up visit 2 months afterward. She otherwise had no significant

psychiatric, medical, or substance use history.

Head CT showed increased anterior left temporal lobe encephalomalacia and left temporal horn

dilation, along with new small areas of encephalomalacia in the left frontal lobe and external

capsule. CSF findings, serum white blood cell count, basic metabolic panel, urinalysis, urine

drug screen, TSH, vitamin B12, RPR, and HIV assay were unremarkable. She was treated

empirically for meningitis with vancomycin and ceftazidime.

Neurology consultation was obtained on hospital day 2 due to an episode of staring and urinary

incontinence. Brain MRI with contrast revealed a 1.3 cm enhancement in the left temporal

anteromedial region (Fig. 4). EEG showed intermittent, polymorphic left temporal activity and

continuous, semi-rhythmic right temporal 1.5 Hz delta slowing. A second seizure-like event

occurred on day 5.

Psychiatric consultation was obtained for evaluation of suspected catatonia due to dyskinetic

movements. On evaluation, the patient was stuporous. She had autonomic instability, intermittent

agitation, and gross memory deficits. The psychiatrist recommended testing CSF for anti-

NMDAR receptor antibodies. Empiric treatment for autoimmune encephalitis with

methylprednisolone 1000 mg IV daily for five days yielded no improvement.

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Anti-NMDAR Multidisciplinary

On day 23, CSF results confirmed the anti-NMDAR antibody. Symptoms were resistant to

treatment with corticosteroids (IV methylprednisolone 1000 mg/day on days 9-13 and 24-25),

intravenous immunoglobulin (IVIG 10% 25 g/day), plasma exchange, rituximab (1 g/day) for

three months, and cyclophosphamide (1240 mg) given monthly. High doses of benzodiazepines

(equivalent to IV lorazepam 30.5 mg/day) were necessary to manage agitation and dyskinetic

movements during months 2-4. These were augmented with quetiapine 75 mg/day on days 49-

139. Symptoms eventually improved with monthly IV infusions of bortezomib, which was

started on day 98.

By discharge on day 185, the patient was moving and eating with little assistance, more

consistently following commands, and no longer requiring benzodiazepines or quetiapine.

However, she still had mild residual oral dyskinesia and left arm tremors. At her first follow-up

appointment, 231 days after admission, motor and cognitive symptoms were further improved,

but she had not returned to her previous baseline.

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Anti-NMDAR Multidisciplinary

Discussion

Behavioral and Psychiatric Symptom Management

Psychiatric symptoms were prominent in the initial presentations of all four cases. In no case did

routine psychiatric symptom management yield a satisfactory response. In all four cases,

antipsychotics were used to manage agitation and psychotic symptoms, with mixed results.

Though case reports and analyses have suggested using atypical antipsychotics as first line

agents, these cases do not suggest superiority of one agent over others9,10. Route of

administration can be a limiting factor and guide to agent selection: haloperidol (IV, IM),

olanzapine (IM), and ziprasidone (IM) are available parenterally; olanzapine and risperidone are

available in an orally soluble tablet; however, other second-generation agents are available only

in tablets or capsules.

Table 1 shows the various medications, dosages, and responses obtained. Unfortunately,

response rates to psychotropic medication are lower in autoimmune encephalitis than in primary

psychiatric disorders11.

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Table 1. Neuropsychiatric symptoms, management trials, outcomes, and management considerations.

Case Demographics Neuropsychiatric symptoms Management trials – Outcomes

daily dosing

1 32F Stable epilepsy with new onset mania, seizures, VPA 2,500mg PO Seizure control, no
and mood lability. Progressed to change in mania
hypersomnolence and intermittent
combativeness, echolalia, retro-/anterograde Lacosamide 200mg PO Seizure control
amnesia, hypertonicity, and fine hand tremor
Clobazam 20mg PO Seizure control

Olanzapine 15mg PO No change in labile

mood, agitation

Haloperidol 1-2mg IV Agitation improved,

sedated with 2mg

Lorazepam 1mg IV Agitation improved

2 34F New onset paranoia, hypervigilance, psychosis, Clonidine 0.1mg PO Dysautonomia

and seizures, with suspicion of catatonia. BID resolved.

Risperidone 6mg PO No improvement in

agitation

Lorazepam 36.5mg IV No change in behavior

Zolpidem 10mg TID No change in catatonia

PO

Fosphenytoin 1,125mg Loading dose for GTC

IV seizure

Phenytoin 100mg IV Seizure control

TID

Ketamine 86.3mg IV Worsened seizures on

EEG

Levetiracetam 2,000mg Status epilepticus

BID IV control

Lacosamide 100mg Status epilepticus

BID PO control

Quetiapine 100mg PO Modest improvement

in agitation
Haloperidol 5mg IV

3 59F Slurred speech and right-sided weakness, Olanzapine 5mg PO Home med, ineffective
verbigeration. Dysautonomia. FLAIR
hyperintensities in left temporal region. Lorazepam 1mg BID- Improved catatonia
TID IV

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 Anti-NMDAR Multidisciplinary

Haloperidol 5mg IV Worsened agitation

Risperidone 0.5mg Minor improvement in

BID-TID PO confusion

4 40F Fever, headache, dysautonomia, altered mental Lorazepam 30.5mg/day Dyskinesia and
status, and seizure, which progressed to IV agitation
catatonia with dyskinesias, staring, mutism, and improvements
stupor. Quetiapine 75mg PO

General Management Considerations of Psychiatric Symptoms in anti-NMDAR encephalitis

- High potency antipsychotics (e.g. haloperidol) can cause EPS and mimic dyskinesia which result from the
encephalitis12.

- Atypical antipsychotics can still be sedating but cause less EPS and are recommended for agitation.

- Mood stabilizing antiepileptics and benzodiazepines are recommended for agitation as the encephalitis itself is
associated with seizures which can present at any stage13.

- Catatonia is seen is 1/3 of anti-NMDAR encephalitis cases and can be exacerbated by antipsychotic treatment12.

Factors Affecting Diagnosis and Recovery

Patients 1 (epilepsy) and 3 (schizoaffective disorder) had pre-existing, confounding conditions

that impeded diagnosis and treatment. In both cases, the symptoms of NMDAR encephalitis

bore some resemblance to those of their established diagnoses, but in both cases there were

distinguishing features. The patient in case 1 had breakthrough seizures accompanied by

personality changes and manic symptoms, which arose from the right temporal region rather than

from the left, as they had before. Though patients with temporal lobe seizures on one side of the

brain may develop seizure activity in the contralateral temporal lobe15, it is rare to develop new

personality changes and manic features as well. In case 3, the patient had MRI changes, focal

EEG findings, and new-onset focal weakness on exam. None of these symptoms occur in

schizoaffective disorder. In case 2, the patient presented with paranoid delusions and catatonia,

with no previous psychiatric history, and responded poorly to antipsychotic medications.

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Anti-NMDAR Multidisciplinary

Atypical features, changing seizure or symptoms, and poor treatment response should prompt

diagnostic re-evaluation.

Table 2 displays the course of disease, time to diagnosis, and diagnostic considerations,

immunologic treatment, and treatment outcomes.

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 Anti-NMDAR Multidisciplinary

Table 2. Disease course and immunologic considerations.

Case Days to Initial Length MRI / EEG Cancer Treatment for encephalitis Outcomes of
diagnosis diagnosis of hosp. workup screenings, treatment
(days) confounds

1 16 Auto- 26 MRI neg. Ovarian Tumor excision; IVIG x 5d Baseline mental

immune teratoma empirically prior to CSF results. status on
encephalitis EEG: right IV corticosteroids. discharge
temporal seizure
(previously left
temporal seizure)

2 14 Index 46 MRI neg. Ovarian Tumor excision; Resolution of

psychotic teratoma; methylprednisolone 1g IV daily seizure activity at
episode EEG: FIRDA, Status and PLEX; rituximab 600mg, two-months post-
delta brush epilepticus 375mg/m2 weekly, then discharge. MoCA
cyclophosphamide 1280mg/day 20/30

3 22 Viral 35 MRI: FLAIR Negative PLEX x5 rounds, IV Completing all

encephalitis hyperintensities malignancy on methylprednisolone 1g, IVIG ADLs; functional
in left temporal TVUS and 0.5mg/kg x 4 days. Discharged on improvement
region and insula PET-CT; rituximab 375mg/m2 weekly for 4-
Schizoaffective 8 weeks outpatient.
cEEG: left-sided disorder
slowing

4 23 Meningitis 185 MRI: 1.3cm left Posterior IV methylprednisolone 1000mg Improved on

anteromedial circulation daily x 5 days; IVIG, PLEX, discharge, with
enhancement aneurysm rituximab x 3 months, residual
rupture and cyclophosphamide. Intractable to motor/cognitive
EEG: left subarachnoid all immunomodulators except symptoms
temporal hemorrhage bortezomib.
polymorphic
activity and right
temporal delta
slowing

FIRDA: Frontal intermittent rhythmic delta activity; PLEX: Plasma exchange; MoCA: Montreal Cognitive
Assessment; IVIG: intravenous immunoglobulin

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Anti-NMDAR Multidisciplinary

Catatonia Management
Catatonic symptoms occur in the course of 1/3 of cases of anti-NMDAR encephalitis.

Benzodiazepines are still considered the first-line treatment, since antipsychotics can worsen

catatonic behaviors and even precipitate autonomic instability8,12.

When the patient in case 3 was given haloperidol for acute agitation, she became significantly

more agitated and physically assaulted a staff member. Intravenous lorazepam improved verbal

expression and physical restlessness. However, atypical antipsychotics were still required for

agitation.

In cases 1 and 3 lorazepam reduced catatonic symptoms but caused excessive sedation. In case 4

high-dose benzodiazepines were partially effective in managing catatonic symptoms, though

these did not fully resolve without immunotherapy. Although the benzodiazepines are more

effective for catatonia than neuroleptics, the benefits clearly are not uniform. Electroconvulsive

therapy is a potential alternative in refractory cases or when sedation is a problem14.

Seizure Management
Although seizure control is not a part of behavioral management per se, it warrants mention here

for several reasons: Inadequate seizure control may lead to postictal psychosis, which may

present as treatment refractory behavioral problems. Seizure control is a consideration in

choosing medications (e.g. valproic acid) that may also be of use in behavioral management.

Seizure medications present a risk of pharmacologic interactions, or in some cases (e.g.

levetiracetam) may have adverse effects on behavior themselves16. For these reasons,

collaboration between those directing seizure control and those managing behavioral syndromes

is essential.

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Anti-NMDAR Multidisciplinary

Multidisciplinary Approach to Care

In all of these cases, clinicians from different specialties collaborated closely. Each patient was

primarily managed by a different medical specialty, and input from other specialties was

necessary to arrive at the correct diagnosis and course of treatment. Anti-NMDAR encephalitis

was suspected because of poor response to standardized treatments, unusual presentations, and/or

unusual combinations of symptoms. In each of these cases, clinicians from different specialties

made key observations leading to the elucidation of the clinical problem. Such collaboration

leads to not only improved patient outcomes but also time to swifter, more accurate diagnosis. It

remains unclear if any single specialty has ultimate authority to request specific antibody testing

if this diagnosis is suspected. Ultimately, attention to the details of the clinical scenario along

with individual clinical experiences in identifying and treating anti-NMDAR encephalitis will be

the eventual deciding factors.

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Anti-NMDAR Multidisciplinary

Limitations
Limitations in this report are intrinsic to small case series. The few cases here are obviously not

representative of the full range of NMDAR cases or of a typical case: in fact, they illustrate the

remarkable variability of cases and the dangers of seeking a typical pattern. Also, a few details

including results of initial and follow-up cognitive testing for some cases, medication dosing,

and timing were not recoverable in retrospective review.

Conclusion
Anti-NMDAR encephalitis mimics symptoms of other disorders. Psychiatric management is

often a key aspect of care, both before and after definitive diagnosis. In cases where the

presenting symptoms are more consistent with seizure and/or mania, mood stabilizers and

benzodiazepines have demonstrated some effectiveness. When features of catatonia

predominate, benzodiazepines seem to have the greatest clinical benefit. Atypical antipsychotics

have also shown some promise for treatment of symptoms of psychosis, though their effect on

agitation is highly variable. In general, attention to an individual patient’s response has far more

benefit than reliance upon a particular medication or class of medications. Accordingly, no

specific treatment algorithms currently exist, and we can propose none. Future research is

needed.

Atypical presentations, unusual responses to standard medications, and clinical histories

consistent with encephalitis should prompt clinicians to consult colleagues and to initiate testing

as part of the diagnostic work-up. Multispecialty collaboration is vital to increase awareness,

facilitate more rapid diagnosis and treatment, and improve patient outcomes.

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Anti-NMDAR Multidisciplinary

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Stimulation 2019; 12: 329-334.

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15. Chen, Hai, and Mohamad Z. Koubeissi. Electroencephalography in Epilepsy

Evaluation. CONTINUUM: Lifelong Learning in Neurology, vol. 25, no. 2, 2019, pp.

431–453., doi:10.1212/con.0000000000000705.

16. Vitaliani, R. et al. Paraneoplastic encephalitis, psychiatric symptoms, and

hypoventilation in ovarian teratoma. Annals of Neurology, vol. 58, no. 4, 2005, pp.

594-604. doi: 10.1002/ana.20614

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Fig.1 – EEG Tracings Case #1

A. Continuous EEG showing rhythmic delta activity originating from right temporal onset with
secondary spread to right frontocentral and right frontal region

B. Continuous EEG showing accentuation of rhythmic delta activity and secondary spread to left
frontal region

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Anti-NMDAR Multidisciplinary

Fig. 2 EEG Tracings Case #2

A. Extreme delta brush pattern

B. Right fronto-cortical subclinical seizure

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C. Rhythmic delta and delta brush pattern

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Anti-NMDAR Multidisciplinary

Fig 3. Brain MRI Case #3

Abnormal FLAIR signal within the sulci of the left cerebral hemisphere with associated cortical
restricted diffusion and edema

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Anti-NMDAR Multidisciplinary

Fig. 4 Brain MRI Case #4

A. Abnormal T2 weighted FLAIR 1.3 cm enhancement in the left temporal anteromedial region

B. Alternate view of abnormal FLAIR signal in left temporal anteromedial region

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