Psychiatric Presentation of Anti-NMDA Receptor Encephalitis

Abstract

Background: Anti-N-methyl D-aspartate (NMDA) receptor encephalitis is an autoimmune condition characterized by neuropsychiatric symptoms, including epileptic seizures, movement disorders, autonomic instability, disturbances of consciousness, paranoia, delusions, and catatonia. Ovarian teratomas and viral infections, typically Herpes simplex viruses, have previously been demonstrated to precipitate anti-NMDA receptor encephalitis, but in many cases, the trigger remains unclear. The detection of anti-NMDA receptor antibodies in cerebrospinal fluid (CSF), in combination with other CSF, electroencephalography (EEG), or magnetic resonance imaging (MRI) abnormalities, typically leads to diagnostic clarification.Case Presentation: We present the case of a 22-year-old female patient who developed an acute polymorphic psychotic episode 3 days after receiving a booster vaccination against tetanus, diphtheria, pertussis, and polio (Tdap-IPV). Her psychiatric symptoms were initially diagnosed as a primary psychiatric disorder. Her MRI, EEG, and CSF results were non-specific. Anti-NMDA receptor IgG antibodies against the GluN1 subunit were detected in her serum (with a maximum titer of 1:320), but not in her CSF. [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) showed pronounced relative hypermetabolism of her association cortices and a relative hypometabolism of the primary cortices, on the basis of which an anti-NMDA receptor encephalitis diagnosis was made, and treatment with a steroid pulse was initiated. The treatment led to fast and convincing clinical improvement with normalization of neuropsychological findings, considerable improvement of FDG-PET findings, and decreasing antibody titers.Conclusion: The patient's psychiatric symptoms were most likely caused by anti-NMDA receptor encephalitis. Her polymorphic psychotic symptoms first occurred after she had received a Tdap-IPV booster vaccination. Although the vaccination cannot have caused the initial antibody formation since IgG serum antibodies were detected only 3 days after administration of the vaccine, the vaccine may have exerted immunomodulatory effects. MRI, EEG, and CSF findings were non-specific; however, FDG-PET identified brain involvement consistent with anti-NMDA receptor encephalitis. This case shows the importance of implementing a multimodal diagnostic work-up in similar situations. The negative CSF antibody finding furthermore fits to the hypothesis that the brain may act as an immunoprecipitator for anti-NMDA receptor antibodies.

Cerebrospinal fluid, antineuronal autoantibody, EEG, and MRI findings from 992 patients with schizophreniform and affective psychosis

“…Initially, these Abs were only tested in the CSF, as CSF testing was considered more sensitive for the detection of anti-NMDAR encephalitis 45 . Our own observations revealed that anti-NMDAR encephalitis can probably also occur in patients with isolated positive serum results 38 , so serum analyses were introduced later, in addition to CSF analysis. The retrospective approach of the study also meant that confirmatory test results for the positive Ab findings from other investigators or with other methods or in other laboratories were not routinely performed.…”

Autoimmune encephalitis as a differential diagnosis of schizophreniform psychosis: clinical symptomatology, pathophysiology, diagnostic approach, and therapeutic considerations

“…Five patients developed an initial encephalitis with isolated [14,15,18,22,52,70] psychotic symptoms (0.9%), and 18 patients (3.2%) had isolated psychiatric symptoms during a relapse [44]. In the meantime, cases with isolated anti-NMDA-R Ab detection in the serum and typical [ 18 F]fluorodeoxyglucose positron emission tomography (FDG-PET) alterations were published [28]. In a case collection of 46 classic psychiatric Hashimoto encephalopathy cases, 12 patients suffered from acute psychosis (26.1%), and one patient met the criteria for schizophrenia (2.2%) [59].…”

“…2 Red flags that should lead to antibody diagnostics (according to [2,5,22,36,53,55,61,67,74,76,77,85]). EEG electroencephalography, MRI magnetic resonance imaging All serum-Ab findings should be interpreted in the context of extended history data, the clinical syndrome, and the examination findings (especially including CSF Ab testing; [51,82,85] Compared to MRI, FDG-PET possibly has higher sensitivity for inflammatory changes ( [5,28,35]; Fig. 3).…”

Anti-N-Methyl-D-Aspartate-Receptor Encephalitis: A 10-Year Follow-Up

“…The long untreated course may have enhanced the ongoing dysexecutive syndrome, as it is well known that late treatment is associated with poorer prognosis (4,6). A full remission can also be achieved in patients with a short course of disease (19). In the present patient, the symptomatic psychiatric treatment with low-dose, atypical neuroleptics and psychotherapy was also started late.…”