ANTI-NMDA RECEPTOR ENCEPHALITIS 1

Anti-NMDA Receptor Encephalitis

Amy Barley

Pennsylvania College of Health Sciences

ANTI-NMDA RECEPTOR ENCEPHALITIS 2

Anti-NMDA Receptor Encephalitis

The purpose of this paper is to present a case study that exemplifies a challenge that

confronts both patients and providers working in the field of mental health. The challenge will

be introduced according to its relevance to mental health. The details of the challenge will then

be broken down into stages. As each of the stages is presented, a case study of a patient will be

utilized as an example of the different stages. In addition, the information presented will be

discussed as it relates to the field of mental health nursing. Finally ideas will be offered for what

still can be explored concerning this challenge.

Introduction

Despite the numerous advances in medicine over the last century, there remains just as

much, if not more opportunity to advance even further in understanding how poor health is

repaired and good health is maintained. Mental health is one of the fields of medicine that has

gone through the most dramatic changes from ancient ideas of etiology being demon possession

to novel ideas about etiology that include diet and trauma. Whatever the cause, the result has

always been behavior that has resulted in patients being either a danger to themselves, others, or

both. Treatment at one time was limited to custodial care that aimed mainly to protect the

mentally healthy from the mentally ill and the mentally ill from themselves. Now treatment is

focused on a collaboration of psychology and psychiatry to understand and treat symptoms of

mental illness and to improve the quality of life for those that it afflicts. Psychology is the

component that considers the environmental origins of presenting symptoms and how best to

help a patient confront their circumstances. Examples include all types of talk therapy,

psychoanalysis, and non-pharmacological interventions. Psychiatry is the component that

considers the organic origins of presenting symptoms and how to best manipulate that biology.
ANTI-NMDA RECEPTOR ENCEPHALITIS 3

Examples include numerous pharmacotherapies, surgeries, and consideration of medical

comorbidities as underlying causes. Identifying the origin of symptoms is certainly critical in

order to implement effective treatment. Ascertaining the causes of mental pathology has been

especially difficult for psychologists and psychiatrists. The intricacies of the brain have been the

last frontier which researchers have been working to harness. Considering the overlap of causes

of mental health symptoms, it is clear that mental health care providers need to be familiar with

the presentations of primarily organic conditions as a means to ensure patients receive the

treatment they need as early in their illness as possible.

Anti-NMDA (N -methyl-D-aspartate) receptor encephalitis is an organic condition that

will trick the unknowledgeable practitioner into diagnosing its victim as someone who is

primarily suffering from a mental health disorder, all the while delaying the treatment that is

necessary to avoid long-lasting detrimental effects and/or death. Anti-NMDA-receptor

encephalitis is an autoimmune disorder that is “basically the presence of pathological

autoantibodies adhering to the NMDA receptors found in the brain” (Celik, et al, 2019, p. 133)

and this “state of hypofunction by the autoantibodies [that]…can explain some of the prominent

psychiatric manifestations of anti-NMDA receptor encephalitis” [CITATION Man14 \p 39 \l 1033 ].

The disorder follows a fairly consistent pattern of development consisting of a prodromal stage

that does not always present but can last about two weeks, an initial stage that has a duration of

around three months or longer during which “patients develop severe symptoms” [CITATION Dal19

\p 1050 \l 1033 ], and a recovery stage that can last for six months or longer during which “the

indicated symptoms have largely resolved but patients still have alterations of behavior, memory,

cognition, and executive functions” [CITATION Dal19 \p 1050 \l 1033 ].

ANTI-NMDA RECEPTOR ENCEPHALITIS 4

The case study follows a 26-year-old female who was admitted to an acute care facility as

an involuntarily committed psychiatric patient. Details of this case study will be discussed

throughout as they pertain to the course and stages of anti-NMDA-receptor encephalitis.

Prodromal Stage

Many times, the onset of anti-NMDA-receptor encephalitis is preceded by a flu-like

upper respiratory infection and is otherwise of no remarkable interest. “A key factor in

recognizing this disorder is that it often follows a pattern of syndrome development. In about

70% of cases, prodromal symptoms develop, including headache, fever, and gastrointestinal and

upper respiratory tract symptoms” [CITATION Bro17 \p 30 \l 1033 ]. The patient in the case study

reported not having had experienced any of these prodromal symptoms. She is representative of

the 30% of cases that first present with the symptoms characteristic of stage one. An

implication for mental health nursing practice pertaining to this stage would be to consider and

document any recent illness, even mild illness, when assessing a patient with new and

unexplained psychiatric symptoms.

Initial Stage

The case study patient was did not seek care until she exhibited catatonic behavior

including being nonverbal with an inability to engage in an assessment interview or conversation

with her husband. She needed assistance with her activities of daily living (ADLs) at home and

had to be fed. Her husband had reported that for the past month he had been noticing that she

was staring for long periods of time and not responding, and was appearing confused and making

nonsensical statements including that her husband looks like an alien. Her husband also reported

that she had lost a sense of reality and memory of where she was and who people were. At the
ANTI-NMDA RECEPTOR ENCEPHALITIS 5

slightest touch, she shivered and appeared to be more distressed. At that time, she was given

lorazepam by mouth for catatonia. In addition, extensive lab work and imaging all came back

with unremarkable results. The patient received a diagnosis of de-realization syndrome, anxiety,

and major depressive disorder single episode severe with psychosis and catatonia. The patient

was approved for transfer to an inpatient psychiatric facility. The patient’s presentation,

subsequent diagnoses, and psychiatric admission is classic of the initial stage of anti-NMDA

receptor encephalitis. It is at this point that “increased vigilance from the clinicians for this

particular entity” [ CITATION Cha17 \l 1033 ] will result in early and “successful treatment with

immune-suppression therapy” [ CITATION Cha17 \l 1033 ]. Treatment was delayed another day,

however, as the patient was continued on lorazepam for catatonia and initiated on the anti-

psychotic olanzapine zydis for her psychotic symptoms. Unfortunately, in the case of anti-

NMDA receptor encephalitis, “using anti-psychotics have been associated with exacerbation of

dystonic and catatonic symptoms and can produce a complex clinical picture that resembles

neuroleptic malignant syndrome” [CITATION Man14 \p 39 \l 1033 ]. The implications for nursing

practice here are that possessing a solid base of knowledge about medical conditions that can be

masked due to psychiatric symptoms will enable a nurse to recognize the possibility of these

medical conditions and offer recommendations based on their knowledge. It is paramount that

mental health nurses resist the temptation to become less concerned with the medical needs of

their patients and to become complacent about the maintenance of their knowledge of

pathophysiology.

Fortunately, the very next day, the primary nurse providing care for the patient noticed

that her symptoms were worsening even with medication, and that she appeared to be

experiencing seizures. The patient was still needing total assistance with her ADLs and she was
ANTI-NMDA RECEPTOR ENCEPHALITIS 6

observed gagging on her own saliva. She also had an episode of severe agitation during which

she was flailing her extremities, pushing and pulling at staff, grabbing at their clothing. In

addition, the patient vomited her medications. At this time she was given an injection of

lorazepam. She was also transferred to the local emergency department for possible seizure. An

electroencephalogram did show seizure activity. Her catatonia was thought to be due to

psychiatric disease, which had resulted in cessation of oral intake and dehydration. The patient

was provided with supportive care including tube feeds and intravenous (IV) fluids. As other

reversible causes of catatonia had not been fully explored, the possibilities were broadened to

include anti-NMDA receptor encephalitis. In the meantime, the patient continued to decline

significantly and was experiencing continuous seizures. She was started on levetiracetam and

lacosamide and was airlifted to a larger, more equipped facility to receive treatment for probable

anti-NMDA receptor encephalitis. A day later by results of an antibody test that detected

abnormal levels of anti-NR1 antibodies in serum and cerebrospinal fluid (CSF) confirmed a

diagnosis of anti-NMDA receptor encephalitis. NR1 is a subunit of the NMDA receptor.

Recovery Stage

Recovery can only begin after appropriate treatment has been implemented and disease

succumbs to the treatment. For someone with anti-NMDA receptor encephalitis, treatment “is

focused on tumor resection [if tumor is present] and first-line immunotherapy (corticosteroids,

plasma exchange, and intravenous immunoglobulin [and] in non-responders, second-line

immunotherapy (rituximab or cyclophosphamide or combined) is required” [CITATION Kup14 \p

388 \l 1033 ]. The patient in the case study received both first-line and second-line

immunotherapy. During this time, the patient was mechanically ventilated, received nutrition

through a tube feedings and IV fluids, and was totally assisted in all ADLs. As a result of the
ANTI-NMDA RECEPTOR ENCEPHALITIS 7

intense life support that she was receiving in addition to the immunosuppressive therapy, she

suffered multiple infections including several urinary tract infections, methicillin-sensitive

staphylococcus aureus pneumonia (MSSA PNA), tracheobronchitis with pseudomonas

colonization, ileus, hypotension, tachycardia, tremors, pneumatosis, and intussusception during

her recovery. She completed numerous rounds of antibiotics to combat the infections. She also

endured focal status epilepticus, autonomic storming, orofacial dyskinesia, and persistent

fluctuating catatonia and agitation. Her recovery lasted eight months and left her weakened and

frail but in remission from all psychiatric and neurological symptoms. She was discharged to an

acute rehab facility where she continued her occupational, physical, and speech therapy to

further recover from the damage caused by anti-NMDA receptor encephalitis.

Conclusion

Anti-NMDA receptor encephalitis is a potentially fatal and always serious diagnosis that

is often at first mistaken for mental illness due to its initial presentation of psychiatric symptoms.

According to Brown (2017), “because of the significant morbidity and mortality associated with

anti-NMDA receptor encephalitis, it is essential that psychiatrists in all settings but especially in

inpatient, emergency, and consultation-liason roles be acquainted with the presentation and

diagnosis of the condition” (p. 29). Nurses who are also acquainted with the condition will know

to document accordingly, will know when to notify the physician of concerning symptoms, and

will know what recommendations to make. As knowledge of how biology is connected to

psychiatric symptoms increases, mental illness may eventually be considered a medical

condition. As “Future research on anti-NMDA receptor encephalitis will contribute to our

knowledge of psychosis, autoimmunity, and glutamatergic function; although the extent to which

the condition applies to specific conditions such as schizophrenia remains unknown” [CITATION
ANTI-NMDA RECEPTOR ENCEPHALITIS 8

Bro17 \p 31 \l 1033 ]. Understanding the chemistry involved in this condition is helping to solve

the mystery of the relationship between biology and schizophrenia.

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References
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psychiatrists. Psychiatric Times, 34(8), pp. 29-31.

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presenting features of anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis.

Asian Journal of Psychiatry, 112. doi:10.1016/j,ajp.2017.02.017.

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