Dear Editor,
Anti-N-methyl D-aspartate (NMDA) receptor (anti-NMDAr) encephalitis is a synaptic autoimmune disorder, in which IgG auto-antibodies recognize the GluN1 subunit of NMDARs leading to their removal from the synapse.[1] The clinical presentation typically progresses in four stages: Prodromal phase, Psychotic phase, Unresponsive phase and Hyperkinetic phase.[2] Frequently half of anti-NMDAr encephalitis patients are misdiagnosed predominantly due to the psychotic features.[3] It is found to have a general mortality rate of 15%.[4]
A case of a young male presenting with psychotic features with a rapidly progressive deteriorating course, who was diagnosed with anti-NMDAr encephalitis is presented.
A 22 years old graduate, unmarried male was brought to psychiatry emergency with behavioral disturbances of abrupt onset for 4 days characterized by muttering and smiling to self, episodes of unprovoked screaming, mood lability, decreased sleep and appetite, and multiple episodes of non-projectile vomiting. He regularly consumed cannabis and tobacco in a dependent pattern. In the past he used to inject opioids but had been abstinent. His physical examination was unremarkable. On mental status, he had increased psychomotor activity and appeared perplexed. His gaze was evasive. His speech was spontaneous with an increased rate, tone and volume but was incomprehensible. A provisional diagnosis of Mental and Behavioral disorder due to use of Cannabinoids; Psychotic disorder (F12.5) was kept. Patient was started on tablet risperidone 3 mg and clonazepam 6 mg in divided doses. His initial blood investigations revealed hepatitis C reactive status though viral load was negligible. Urine drug screen was positive for tetrahydrocannabinol and benzodiazepines. Over the next week, he developed fluctuating orientation, a fixated stare and stopped taking food orally. He had picking movements, micrographic, perseveration, posturing, mutism and hypersalivation. On the 7th day, developed fever (101.5 F) and had rigidity in all four limbs with plantar reflexes being mute. He became non-responsive to verbal commands and had tachycardia, labored breathing (spO2 = 87% on room air) and stopped passing urine. He was shifted to the intensive care unit (ICU). Brain imaging, electroencephalography, blood, and urine parameters were all within normal limits. cerebrospinal fluid (CSF) examination showed lymphocytic pleocytosis and tested positive for NMDA NR1 Ig G Antibodies. Final diagnosis was revised to anti-NMDAr encephalitis and he was started on intravenous immunoglobulins on the 10th day of admission, along with corticosteroids and antiepileptics. Plasmapheresis could not be conducted due to hemodynamic instability. He also developed aspiration pneumonitis after an episode of status epilepticus and passed away with in a month due to ventilator acquired sepsis. He passed away with in a month due to ventilator acquired sepsis.
Our patient presented with first episode of psychosis. Anti-NMDAr encephalitis in its psychotic phase is characterized by change of behavior that includes agitation, insomnia, aggression, hallucinations, and catatonia, which were present in our patient.[2] The patient’s clinical picture was complicated with concomitant drug use, Hepatitis C Virus (HCV) reactive status, and being given antipsychotics on admission. These factors created a diagnostic dilemma as the differentials to anti NMDAR encephalitis are exposure to drugs, neuroleptic malignant syndrome (NMS) and infective encephalitis.[5] The course of illness was rapidly progressive and delayed initiation of immunotherapy, along with presence of number of complications and ICU admission had been considered an indicator for poor outcome in our patient.[5,6] The patient developing aspiration pneumonitis further led to hemodynamic instability that prevented use of interventions like plasmapheresis in our patient. Non-survivors in autoimmune encephalitis have a longer ICU stay, higher need for mechanical ventilation, higher comorbidity, and disease severity scores that were present in our patient.[7] Our case highlights the need for early recognition and high index of suspicion for anti NMDAR encephalitis in patients with first episode psychosis.
Author contributions
Concept, design, definition of intellectual content, literature search: SJ; Data acquisition, Akshita; Manuscript preparation, manuscript editing: Akshita, AK, SJ; Guarantor: SJ.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest
There are no conflicts of interest.
Acknowledgment
Dr Dinesh Dutt Sharma, Dr Devesh Sharma and Dr Abhilaksh Kango for their guidance and support.
Funding Statement
Nil.
REFERENCES
- 1.Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15:391–404. doi: 10.1016/S1474-4422(15)00401-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Kayser MS, Dalmau J. Anti-NMDA Receptor encephalitis in psychiatry. Curr Psychiatry Rev. 2011;7:189–93. doi: 10.2174/157340011797183184. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Shimoyama Y, Umegaki O, Agui T, Kadono N, Minami T. Anti-NMDA receptor encephalitis presenting as an acute psychotic episode misdiagnosed as dissociative disorder: A case report. JA Clin Rep. 2016;2:22. doi: 10.1186/s40981-016-0048-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Zhong R, Chen Q, Zhang X, Zhang H, Lin W. risk factors for mortality in anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis. Front Immunol. 2022;13:845365. doi: 10.3389/fimmu.2022.845365. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Samanta D, Lui F. StatPearls. Treasure Island (FL): StatPearls Publishing; 2025. Anti-NMDAR encephalitis. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551672 . [PubMed] [Google Scholar]
- 6.Chi X, Wang W, Huang C, Wu M, Zhang L, Li J, et al. Risk factors for mortality in patients with anti-NMDA receptor encephalitis. Acta Neurol Scand. 2016;136:298–304. doi: 10.1111/ane.12723. [DOI] [PubMed] [Google Scholar]
- 7.Harutyunyan G, Hauer L, Dünser MW, Karamyan A, Moser T, Pikija S, et al. Autoimmune encephalitis at the neurological intensive care unit: Etiologies, reasons for admission and survival. Neurocrit Care. 2017;27:82–9. doi: 10.1007/s12028-016-0370-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
