Anti-NMDA Receptor Encephalitis Presenting as an Acute Psychotic Episode in a Young Woman: An Underdiagnosed yet Treatable Disorder

Anti-NMDA receptor (NMDAR) encephalitis is a recently identified autoimmune disorder with prominent psychiatric symptoms. Patients usually present with acute behavioral change, psychosis, catatonic symptoms, memory deficits, seizures, dyskinesias, and autonomic instability. In female patients an ovarian teratoma is often identified. We describe a 32-year-old woman who presented with acute psychosis. Shortly after admission, she developed generalized seizures and deteriorated into a catatonic state. Although ancillary tests including MRI, electroencephalogram, and cerebrospinal fluid (CSF) analysis were unremarkable, the presentation of acute psychosis in combination with recurrent seizures and a relentless course suggested autoimmune encephalitis. The patient underwent pelvic ultrasound which disclosed a dermoid cyst and which led to an urgent cystectomy. Plasmapheresis was then initiated, yielding partial response over the next two weeks. Following the detection of high titers of anti-NMDAR antibodies in the CSF, the patient ultimately received second line immunosuppressive treatment with rituximab. Over several months of cognitive rehabilitation a profound improvement was eventually noted, although minor anterograde memory deficits remained. In this report we call for attention to the inclusion of anti-NMDAR encephalitis in the differential diagnosis of acute psychosis. Prompt diagnosis is critical as early immunotherapy and tumor removal could dramatically affect outcomes.

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Frequency and temporal sequence of clinical features in adults with anti-NMDA receptor encephalitis presenting with psychiatric symptoms

Psychological Medicine ◽

10.1017/s0033291718003665 ◽

2018 ◽

Vol 49 (16) ◽

pp. 2709-2716 ◽

Cited By ~ 3

Author(s):

Ronald J. Gurrera

Keyword(s):

Nmda Receptor ◽

Clinical Features ◽

Psychiatric Symptoms ◽

Autoimmune Encephalitis ◽

Signs And Symptoms ◽

Nmda Receptor Encephalitis ◽

Nmdar Encephalitis ◽

Unexplained Fever ◽

Study Inclusion

AbstractBackgroundAnti-NMDA receptor (NMDAr) encephalitis is the most common autoimmune encephalitis in adults. It mimics psychiatric disorders so often that most patients are initially referred to a psychiatrist, and many are misdiagnosed. Without prompt and effective treatment, patients are likely to suffer a protracted course with significant residual disability, or death. This study focuses on the frequency and chronology of salient clinical features in adults with anti-NMDAr encephalitis who are likely to be first evaluated by a psychiatrist because their presentation suggests a primary psychiatric disorder.MethodsA systematic search of PubMed and EMBASE databases identified published reports of anti-NMDAr encephalitis associated with prominent behavioral or psychiatric symptoms. After eliminating redundancies, the frequencies and relative timing of clinical features were tabulated. Signs and symptoms were assigned temporal ranks based on the timing of their first appearance relative to the first appearance of other signs and symptoms in each patient; median ranks were used to compare temporal sequencing of both individual features and major symptom domains.ResultsTwo hundred thirty unique cases (185 female) met study inclusion criteria. The most common features were seizures (60.4%), disorientation/confusion (42.6%), orofacial dyskinesias (39.1%), and mutism/staring (37.4%). Seizures, fever, and cognitive dysfunction were often the earliest features to emerge, but psychiatric features predominated and sequencing varied greatly between individuals.ConclusionsClinicians should consider anti-NMDAr encephalitis when new psychiatric symptoms are accompanied by a recent viral prodrome, seizures or unexplained fever, or when the quality of the psychiatric symptoms is unusual (e.g. non-verbal auditory hallucinations).

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Anti-NMDAR Encephalitis: Higher Suspicious Needed for Earlier Diagnosis (Case Report, Literature Review and Diagnostic Criteria)

Case Reports in Neurological Medicine ◽

10.1155/2019/7476254 ◽

2019 ◽

Vol 2019 ◽

pp. 1-5

Author(s):

Chanaka Amugoda ◽

Noushin Chini Foroush ◽

Hamed Akhlaghi

Keyword(s):

Mental Health ◽

Emergency Department ◽

Nmda Receptor ◽

Psychiatric Symptoms ◽

Health Assessment ◽

Young Patients ◽

Psychotic Episode ◽

Acute Psychosis ◽

Nmda Receptor Encephalitis ◽

Immune Mediated

Background. Auto-immune mediated anti-NMDA receptor encephalitis is a very common delayed diagnosed encephalitis which predominately affecting young population. Objectives. This encephalitis is relatively unknown amongst emergency physicians and a majority of patients are admitted to psychiatric wards before their diagnosis is confirmed and appropriate treatments are commenced. We reported a case of a 22-year-old female presented to our emergency department with acute psychiatric symptoms. She was initially diagnosed with first presentation of acute psychosis and was hospitalised under mental health act. further assessment in the emergency department identified possible an organic cause for her acute psychosis and she was later admitted under medical team after her mental health assessment order was revoke. Several days later, her CSF result was positive with anti-NMDA receptor anti-bodies. Appropriate treatments were instituted leading to her full recovery. Conclusion. This case was the first confirmed anti-NMDA receptor encephalitis in our emergency department. It highlights the importance of thorough assessment of psychiatric presentations to emergency departments and consideration of auto-immune medicated encephalitis as one of the differential diagnosis in young patients presenting with first acute psychotic episode.

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Anti- NMDAR Autoimmune Encephalitis Presenting as Acute Psychosis: A Case Report

Nepal Medical Journal ◽

10.37080/nmj.87 ◽

2020 ◽

Vol 3 (1) ◽

pp. 59-61

Author(s):

Bibek Rajbhandari ◽

Minani Gurung

Keyword(s):

Behavioral Change ◽

Psychiatric Symptoms ◽

Autoimmune Encephalitis ◽

Autoimmune Disorder ◽

Clinical Findings ◽

Acute Psychosis ◽

Abnormal Movements ◽

Nmdar Encephalitis ◽

Long Time ◽

Autonomic Instability

Anti-NMDA receptor (NMDAR) encephalitis is a recently identified autoimmune disorder with prominent psychiatric symptoms. Patients usually present with acute behavioral change, psychosis, catatonic symptoms, memory deficits, seizures, dyskinesias, and autonomic instability. We present a case of a 13-year old who presented with noticeably chirpiness, excessive talking with unknown people and wandering around the neighborhood without purpose.The main symptoms of the patient and the important clinical findings were irrelevant talking which later developed into slurring of speech, abnormal movements and memory loss.This case is an example of how easily we are misled towards diagnosis based on the present symptoms. The patient suffered the unnecessary stigma of a psychiatric illness, which might stay imprinted on her for a long time. In this report we call for attention to the inclusion of anti-NMDAR encephalitis in the differential diagnosis of acute psychosis. It adds on to show that NMDAR might present in the most unexpected and unpredictable ways, sometimes misleading the patient away from medical help.Prompt diagnosis is critical as early immunotherapy and tumor removal could dramatically affect outcomes.

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N-Methyl-D-Aspartate Receptor Encephalitis with Psychiatric Symptoms and an Ovarian Teratoma Detected by MRI in a 17-Year-Old Girl

Neuropediatrics ◽

10.1055/s-0039-1692417 ◽

2019 ◽

Vol 50 (04) ◽

pp. 253-256

Author(s):

A. Barth ◽

I. Nassenstein ◽

R.B. Tröbs ◽

A. Tannapfel ◽

H. Dercks ◽

...

Keyword(s):

Magnetic Resonance ◽

Mr Imaging ◽

Ovarian Tumor ◽

Psychiatric Symptoms ◽

Autoimmune Encephalitis ◽

Adolescent Females ◽

Ovarian Teratoma ◽

Aspartate Receptor ◽

Nmdar Encephalitis

AbstractN-methyl-D-aspartate receptor (NMDAR) encephalitis is a rare antibody-mediated autoimmune encephalitis often associated with an ovarian teratoma in adolescent females. Here we present a 17-year-old girl with only and unusual psychiatric symptoms as part of her NMDAR encephalitis in combination with a very small ovarian teratoma suspected by magnetic resonance (MR) imaging and finally histologically confirmed. We further review the literature of NMDAR encephalitis in combination with an ovarian teratoma and discuss the recommended radiological workup in children with a suspected ovarian tumor.

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Anti-N-methyl-D-aspartate receptor encephalitis presenting as atypical psychosis in multiple sclerosis: a case report

BMC Psychiatry ◽

10.1186/s12888-021-03351-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Khushminder Chahal ◽

Tara Endeman ◽

Sarah Scapinello ◽

Michal Sapieha

Keyword(s):

Multiple Sclerosis ◽

Psychiatric Symptoms ◽

Neuropsychiatric Symptoms ◽

Psychiatric Inpatient ◽

Treatment Protocol ◽

Autoimmune Encephalitis ◽

Ovarian Teratoma ◽

Atypical Symptoms ◽

Aspartate Receptor ◽

Nmdar Encephalitis

Abstract Background Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder which often presents with neuropsychiatric symptoms. A large proportion of cases are associated with an identifiable tumor, most commonly ovarian teratoma. However, recent literature has also described an overlap of anti-NMDAR encephalitis and demyelinating syndromes. Cases have been reported of anti-NMDAR encephalitis in patients with ADEM, optic neuritis, myelitis and multiple sclerosis. This link is considered rare, however has important clinical implications as treatments and prognosis may differ. Case presentation A 33-year-old female with a history of multiple sclerosis presented with new-onset neuropsychiatric symptoms. After substance-induced psychosis was ruled out, she was admitted to the medical ward for work up of psychosis secondary to multiple sclerosis. However, the consultation-liaison psychiatry service noted atypical symptoms which were concerning for autoimmune encephalitis. Admission to a psychiatric inpatient ward was deferred. Anti-NMDAR encephalitis was diagnosed with CSF analysis demonstrating lymphocytic pleocytosis and anti-NMDAR antibodies. In addition to first-line treatment of encephalitis with steroids, second-line immunotherapies were also implemented given the patient’s underlining demyelinating syndrome. The patient’s neurologic and psychiatric symptoms began to improve. Conclusions There is literature to demonstrate a possible connection between anti-NMDAR encephalitis and demyelinating syndromes. As such, autoimmune encephalitis should be considered in patients with multiple sclerosis presenting with atypical symptoms. Determining the correct diagnosis is crucial to inform the appropriate treatment protocol, and to improve prognosis.

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Clinical Relevance of Cerebrospinal Fluid Antibody Titers in Anti-N-Methyl-d-Aspartate Receptor Encephalitis

Brain Sciences ◽

10.3390/brainsci12010004 ◽

2021 ◽

Vol 12 (1) ◽

pp. 4

Author(s):

Meng-Ting Cai ◽

Yang Zheng ◽

Sa Wang ◽

Qi-Lun Lai ◽

Gao-Li Fang ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Psychiatric Symptoms ◽

Autoimmune Encephalitis ◽

Memory Deficits ◽

Clinical Severity ◽

Weak Correlation ◽

Aspartate Receptor ◽

Nmdar Encephalitis ◽

Significant Difference ◽

The Relationship

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is the most common autoimmune encephalitis. To date, there has been no study on the relationship between antibody (Ab) titers and clinical phenotype. This study aims to clarify the relationship between cerebrospinal fluid Ab titers and clinical manifestations of anti-NMDAR encephalitis at onset. Seventy-six consecutive patients with a definite diagnosis were enrolled. The relationship between Ab titers and different onset symptoms including psychiatric symptoms, seizures, and memory deficits were analyzed. We further investigated the correlation between Ab titers and clinical severity as assessed by the modified Rankin scale (mRS) and the clinical assessment scale for autoimmune encephalitis (CASE), respectively. The Ab titers had a median value of 1:10 (range 1:1–1:100). There was no significant difference in titers among various clinical factors including gender and combination of tumor and other diseases (each p > 0.05). Patients presenting with psychiatric symptoms at onset had higher titers than those with seizures (p = 0.008) and memory deficits (p = 0.003). The mRS scores revealed a significant but weak correlation with Ab titers (r = 0.243, p = 0.034), while CASE scores did not correlate with the titers (p = 0.125). Our findings indicated that the Ab titers were associated with the type of onset symptoms, with a higher level of patients with psychiatric symptoms. Regarding the clinical severity, the titers showed a weak correlation with the mRS, but no correlation with the CASE.

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Clinical Characteristics and Outcome of Neuronal Surface Antibody-Mediated Autoimmune Encephalitis Patients in a National Cohort

Frontiers in Neurology ◽

10.3389/fneur.2021.611597 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zsófia Hayden ◽

Beáta Bóné ◽

Gergely Orsi ◽

Monika Szots ◽

Ferenc Nagy ◽

...

Keyword(s):

Clinical Characteristics ◽

Clinical Symptoms ◽

Psychiatric Symptoms ◽

Brain Mri ◽

Disease Onset ◽

Neuronal Cell ◽

Autoimmune Encephalitis ◽

Ovarian Teratoma ◽

Test Results ◽

Nmdar Encephalitis

Background: In our previous single-center study of autoimmune encephalitis (AE) related autoantibody test results we found positivity in 60 patients out of 1,034 with suspected AE from 2012 through 2018 as part of a Hungarian nationwide program. In our current multicenter retrospective study, we analyzed the clinical characteristics and outcome of AE patients with positive neuronal cell surface autoantibody test results.Methods: A standard online questionnaire was used to collect demographic and clinical characteristics, laboratory and imaging data, therapy and prognosis of 30 definitive AE patients in four major clinical centers of the region.Results: In our study, 19 patients were positive for anti-NMDAR (63%), 6 patients (20%) for anti-LGI1, 3 patients for anti-GABABR (10%) and 3 patients for anti-Caspr2 (10%) autoantibodies. Most common prodromal symptoms were fever or flu-like symptoms (10/30, 33%). Main clinical features included psychiatric symptoms (83%), epileptic seizures (73%) and memory loss (50%). 19 patients (63%) presented with signs of central nervous system (CNS) inflammation, which occurred more frequently in elder individuals (p = 0.024), although no significant differences were observed in sex, tumor association, time to diagnosis, prognosis and immunotherapy compared to AE patients without CNS inflammatory markers. Anti-NMDAR encephalitis patients were in more severe condition at the disease onset (p = 0.028), although no significant correlation between mRS score, age, sex and immunotherapy was found. 27% of patients (n = 8) with associated tumors had worse outcome (p = 0.045) than patients without tumor. In most cases, immunotherapy led to clinical improvement of AE patients (80%) who achieved a good outcome (mRS ≤ 2; median follow-up 33 months).Conclusion: Our study confirms previous publications describing characteristics of AE patients, however, differences were observed in anti-NMDAR encephalitis that showed no association with ovarian teratoma and occurred more frequently among young males. One-third of AE patients lacked signs of inflammation in both CSF and brain MRI, which emphasizes the importance of clinical symptoms and autoantibody testing in diagnostic workflow for early introduction of immunotherapy, which can lead to favorable outcome in AE patients.

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Psychiatric Symptoms As Onset of Anti-Nmdar Encephalitis

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.1941 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S525-S525

Author(s):

M.C. Cancino Botello ◽

A. Cercos López ◽

V. Chavarria Romero ◽

G. Sugranyes Ernest

Keyword(s):

Nmda Receptor ◽

Psychiatric Symptoms ◽

Autoimmune Encephalitis ◽

Autoimmune Disorder ◽

Psychotic Symptoms ◽

Nmdar Encephalitis ◽

Clinical Presentations ◽

Children And Young Adults ◽

Competing Interest ◽

Specific Symptoms

IntroductionEvery more often, there is evidence that shows a relationship between psychiatric symptoms and autoimmune disorders. Such is the case of anti-NMDAR encephalitis, in which it has been recently described the development of psychotic symptoms. Anti-NMDAR encephalitis is an autoimmune disorder that involves IgG autoantibodies against the NMDA receptor subunit GluN1. This last fact could support the relationship with the glutamatergic model of schizophrenia.ObjectiveTo conduct a current review to deepen the detection and management of anti-NMDAR encephalitis, due to the frequent existence of psychiatric symptoms at onset, which have contributed to the difficulty of diagnose.MethodSystematic review of the literature in English (PubMed), with the following keywords: “Autoimmune encephalitis”, “psychosis”, and “NMDA receptor”.ResultsAutoimmune encephalitis appears more frequently in children and young adults and it is characterized by a prodromal period, in which there usually are non-specific symptoms of headaches or fever. Next, it could progress to cognitive deficits, seizures, catatonic symptoms and psychosis. However, sometimes in the rarest clinical presentations, there is nothing but psychiatric symptoms at the onset of encephalitis, which leads to misdiagnose and lack of proper treatment. This fact has stimulated the curiosity of the psychiatry scientific community, since the anti-NMDAR encephalitis may mimic the glutamatergic model of schizophrenia.ConclusionsTo make an accurate and detailed diagnostic formulation in people with psychiatric symptoms as onset of any disorder is essential to determine whether it is a primary psychiatric disorder or symptoms associated to another disease.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Cotard syndrome in a young man?

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.1232 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S348-S348

Author(s):

A. Cercos López ◽

M.C. Cancino Botello ◽

V. Chavarria Romero ◽

G. Sugranyes Ernest

Keyword(s):

Differential Diagnosis ◽

Suicide Ideation ◽

Psychiatric Symptoms ◽

Past History ◽

Gastrointestinal Symptoms ◽

Autoimmune Encephalitis ◽

Psychomotor Retardation ◽

Stressful Events ◽

Psychotic Episode ◽

Degree Relative

IntroductionAnti-NMDA encephalitis normally appears as a characteristic syndrome with typical symptoms that undergoes with multiphase evolution. However, it sometimes develops atypical symptoms so we must perform a careful differential diagnosis.ObjectivesTo conduct a current review of detection and management of anti-NMDAr encephalitis, and psychiatric manifestations.MethodSystematic review of the literature in English (PubMed), with the following keywords: “Autoimmune encephalitis”, “psychosis”, and “NMDA receptor”.ResultsWe present the case of a 15-year-old boy referred to evaluation for a first psychotic episode. He had no past history of psychiatric illness or substance abuse. The only relevant antecedent is multiple sclerosis in a first degree relative. For the last months, he presented high levels of anxiety symptoms apparently related to college stressful events and fluctuating hypoesthesia of left cranial side. Days later, it appeared autolimited gastrointestinal symptoms, headache and fever. During the next days it appeared psychomotor retardation, choreic movements, suicide ideation and mood-congruent paranoid and nihilistic ideation, auditory and visual hallucinations, perplexity and catatonic symptoms so he was hospitalized. We observed cognitive functions impairment, unsteady gait, dysartria, dysphasia, clonus and left babinsky sign. EEG showed slow waves on right frontal area. CFS showed protein elevation and immunologic study revealed positive anti-NMDA antibodies. Treatment with methylprednisolone and gammaglobuline was started with partial response, needing addition of rituximab.ConclusionsIn this case, we highlight the importance of early detection and a detailed differential diagnosis, to determine whether the etiology of psychiatric symptoms in order to achieve an accurate and early treatment.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Anti-N-methyl-D-aspartate receptor encephalitis and ovarian teratomas: is there any association?

Voprosy ginekologii akušerstva i perinatologii ◽

10.20953/1726-1678-2020-5-124-131 ◽

2020 ◽

Vol 19 (5) ◽

pp. 124-131

Author(s):

N.M. Podzolkova ◽

◽

V.V. Korennaya ◽

O.S. Levin ◽

E.E. Vasenina ◽

...

Keyword(s):

Pathological Condition ◽

Rare Complication ◽

Autoimmune Encephalitis ◽

Neurological Deficits ◽

Ovarian Teratoma ◽

Aspartate Receptor ◽

Nmdar Encephalitis ◽

Life Threatening ◽

Causal Treatment ◽

Ovarian Teratomas

This article aims to explore the problem of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis and also describes our own experience in treating anti-NMDAR encephalitis in patients with ovarian teratomas. This pathological condition is a rare complication of cancer. Practicing gynecologists are often unfamiliar with it, although its consequences can be life-threatening. Early diagnosis and causal treatment, particularly teratoma removal, are critical for the outcome and can prevent death or the development of neurological deficits in patients. Key words: anti-NMDAR, autoimmune encephalitis, ovarian cysts, complications, ovarian teratoma, encephalitis, encephalitis in women

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