Background

Anti-NMDAR encephalitis is a relatively rare diagnosis with just a few hundred cases reported in medical literature, but its true prevalence especially in individuals with purely psychiatric manifestations is yet to be determined as a large majority present to a psychiatrist first. Herein, we report a case that presented with hyperreligiosity and proved to have autoimmune encephalitis.

We found only one case of the hyper-religious theme in the context of delirium after extensive web search (PubMed, Medline, Google).

Case presentation

A 21-year-old female, student, previously healthy with no past medical history and no past psychiatric illness or drug abuse presented to our emergency department in Embaba Fever Hospital with a fever and altered mental status (Tables 1, 2, 3, and 4).

Table 1 Biochemical, immunologic, metabolic, and serological investigations
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Table 2 CSF analysis, oligoclonal bands, and NMDA receptor antibodies
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Table 3 Meningitis/encephalitis panel by Biofire Film Array (Multiplex PCR)
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Table 4 Patient management
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The history dated back 2 weeks before admission when she started to suffer from fever and headache followed by prominent psychiatric changes in the form of anxiety, delusions, hallucinations, and hyperreligiosity. She had developed abnormal behavior in the form of talking excessively about religious matters as no God except Allah. She had also expressed her desire to die in Ramadan while she is fasting; she got easily confused and even paranoid; she could not focus, could not sleep, and could not sit still. During the same time period, there was a fluctuation in the level of orientation to time, place, and person.

This acute confusional state was initially diagnosed by psychiatrists as acute psychosis and received antipsychotic medications; as the symptoms worsened, she received one session of electroconvulsive therapy; the fever persisted, and the consciousness level deteriorated more; she was referred to the fever hospital as suspected encephalitis.

On examination

The patient was febrile with generalized spasticity; pupils were rounded, regular, and reactive 10/15 (E5V1M4). There was unilateral abnormal slow movement on the right hand and right side of the face mimicking focal fits. Systemic examination was within normal.

CBC: mild normocytic normochromic anemia.

CRP: 2 mg/l, normal metabolic panel, and normal ANA.

Urine analysis: normal.

CSF analysis shows lymphocytic pleocytosis: 15 cells/cu mm, no pathogen seen by gram stain, no acid-fast bacilli by Ziehl–Neelsen stain, sugar: 58 mg%, protein: 30 mg%, negative CSF culture.

CSF viral meningitis panel (Biofire Film Array®) was negative.

CSF and serum electrophoresis (by isoelectric focusing): oligoclonal band.

Normal abdominopelvic ultrasound examination.

EEG: diffuse slowing with no epileptiform activities (diffuse encephalopathy).

Brain CT examination without contrast was normal.

Brain MRI with gadolinium and MRV: normal.

A thorough workup for neoplasms was negative including a body PET CT scan.

Given the concern for viral encephalitis, acyclovir was started empirically, but after the meningitis panel, the viral causes were excluded, and we had to think about non-infectious causes of encephalitis, so as regards initial presentation and the neuropsychiatric manifestations, and the MRI result, anti-NMDA antibodies in CSF was requested. She had started intravenous immunoglobulins (IVIG) for presumed autoimmune encephalitis.

CSF result was positive for anti-NMDA antibodies (1/100), and then, the diagnosis was confirmed as anti-NMDA receptor encephalitis.

Intravenous immunoglobulins IV Ig and methylprednisolone were started together with the antiepileptics to control the abnormal movements that mimic the fits.

After a few days, the patient started to show clinical improvement, and their consciousness level improved. Although her recovery was slow, follow-up of the patient was excellent; there were no anxiety or panic attacks, and no hallucinations or paranoid thoughts after 1 month; she was referred for plasmapheresis. After 5 sessions of plasmapheresis, the patient improved more and was discharged home for follow-up.

Discussion

Anti-NMDAR encephalitis patients are usually picked up by psychiatrists [1] since anti-NMDARs play a central role in synaptic transmission helping to modulate human memory and cognition and explain common psychiatric signs and symptoms in this disease including decreased cognition and personality changes [2]. The psychiatric manifestations of anti-NMDAR encephalitis syndrome is preceded by a non-specific prodromal stage that can include headaches, low-grade fevers, diarrhea, or upper respiratory infection symptoms [1,2,3,4,5,6,7].

About half of the cases are associated with tumors, most commonly teratomas of the ovaries [3,4,5].

Another established trigger is herpes viral encephalitis, while the cause in other cases is unclear [1,2,3].

The focus issue in this patient is the clinical presentation of delirium caused by autoimmune encephalitis where hyperreligiosity and increased flow of speech leading to excessive talkativeness were the presenting features before she had gone into the state of stupor.

Getting a hyper-religious theme in the context of delirium may not have an impact on the outcome or management, but it may nurture diagnostic confusion as delirious mania, and acute manic episodes with psychiatric symptoms may also have a similar presentation [8, 9].

Diagnosis is typically based on finding specific antibodies in the cerebral spinal fluid [1], MRI of the brain is often normal [2], and misdiagnosis is common [7]. The current diagnosis is based on finding anti-NMDAR antibodies in the CSF or serum. CSF studies show lymphocytic pleocytosis and normal to a mild elevation of protein. The oligoclonal band may be present in 60% of patients [10].

Differential diagnosis

The differential diagnosis often includes a primary psychiatric disorder, drug abuse, neuroleptic malignant syndrome, or infectious encephalitis [11].

In some instances, the diagnosis of rabies has been considered due to the presence of extreme agitation, prominent sialorrhea, and abnormal movements. In contrast to anti-NMDAR encephalitis in which the brain MRI is frequently normal [12], the MRI of patients with rabies often shows symmetric involvement of the gray matter of dorsal brainstem, thalamus, basal ganglia, or central region of the spinal cord [13].

Prognosis is as follows: the recovery process from anti-NMDAR encephalitis can take many months, the symptoms may reappear in reverse order, and the patient may experience psychosis again leading many people to falsely believe the patient is not recovering. As the recovery process continues, the psychosis fades. Lastly, the person’s social behavior and executive functions begin to improve.

Conclusion

Autoimmune encephalitis is an important consideration in patients presenting with new onset of the altered mental status of unknown etiology. Emergency physicians are not familiar with this disease.

It can be assumed that hyper-religious thought content can be a part of excited delirium; the presence of hyper-religious thinking does not rule out delirium.

In case of a patient with a suggestive clinical picture of anti-NMDAR encephalitis presenting to the emergency room, lumbar puncture should be performed as soon as possible to look for CSF pleocytosis, oligoclonal bands, and anti-NMDAR in the CSF. Identification of AE is important because it facilitates prompt use of immunotherapy, and triggering malignancy screening as well as detection of any occult neoplasm is critical.