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

2018 ◽  
Vol 49 (16) ◽  
pp. 2709-2716 ◽  
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).

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

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Shikma Keller ◽  
Pablo Roitman ◽  
Tamir Ben-Hur ◽  
Omer Bonne ◽  
Amit Lotan
Keyword(s):  
Nmda Receptor ◽  
Cognitive Rehabilitation ◽  
Psychiatric Symptoms ◽  
Immunosuppressive Treatment ◽  
Autoimmune Encephalitis ◽  
Memory Deficits ◽  
Ovarian Teratoma ◽  
Psychotic Episode ◽  
Acute Psychosis ◽  
Nmdar Encephalitis

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.

Management And Psychiatric Manifestations Of Anti-NMDA Receptor Encephalitis, A Case Report

2016 ◽  
Vol 33 (S1) ◽  
pp. S525-S526
Author(s):  
R. Gallego ◽  
A. Flores
Keyword(s):  
Case Report ◽  
Nmda Receptor ◽  
Psychiatric Symptoms ◽  
Multidisciplinary Treatment ◽  
Autoimmune Disorder ◽  
Clonic Seizure ◽  
Nmda Receptor Encephalitis ◽  
Abnormal Movements ◽  
Nmdar Encephalitis ◽  
Psychiatric Manifestations

IntroductionAnti-NMDA receptor (NMDAR) encephalitis, formally recognized in 2007 by Dalmau et al, is an autoimmune disorder with a complex presentation that includes psychiatric symptoms, memory deficits, and autonomic instability. The exact incidence is unknown but age, gender, and ethnicity may all play a role. Presence of antibodies against the GluN1 subunit of the NMDAR in the CSF and serum confirm the diagnosis of NMDAR encephalitis.Case reportWe report the case of a previously healthy, 19-year-old woman, 6 weeks pregnant. She had a generalized tonic-clonic seizure followed by psychiatric symptoms, including insomnia, emotional lability, delusions, and disorganized behavior. During the course of the disease, she demonstrated speech impairments and catatonic features associated with abnormal movements.She was provided lorazepam 1 mg twice a day to treat her catatonic symptoms, her insomnia and her speech improved. Olanzapine was introduced, reaching a dose of 20 mg/day for managing psychosis and agitation.DiscussionNMDA-R encephalitis is a novel disorder with prominent psychiatric manifestations that is widely underdiagnosed. Neuroleptics may be helpful for managing psychosis and agitation, but may exacerbate movement abnormalities. Benzodiazepines are helpful for agitation, insomnia and catatonia associated with this condition.ConclusionEarlier recognition of this illness is crucial as prompt diagnosis and multidisciplinary treatment, can potentially improve prognosis. There is an increasing need for psychiatrists to become aware of the disorder and consider it in their differential diagnosis, specially in patients with new onset psychosis, history of encephalitis or subtle neurological symptoms. Careful selection of psychopharmacological interventions may reduce suffering.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Clinical features of seronegative, but CSF antibody-positive, anti-NMDA receptor encephalitis

2020 ◽  
Vol 7 (2) ◽  
pp. e659 ◽  
Author(s):  
Mar Guasp ◽  
Yasmina Módena ◽  
Thaís Armangue ◽  
Josep Dalmau ◽  
Francesc Graus
Keyword(s):  
Nmda Receptor ◽  
Clinical Features ◽  
Serum Antibody ◽  
Independent Variables ◽  
Nmda Receptor Encephalitis ◽  
Retrospective Assessment ◽  
Nmdar Encephalitis ◽  
Paired Serum ◽  
Detectable Serum ◽  
Hospital Clinic

ObjectiveTo determine the frequency of anti-NMDA receptor encephalitis without detectable serum NMDAR antibodies and to compare the clinical features of these patients with those with NMDAR antibodies in serum and CSF.MethodsThis is a retrospective assessment of serum antibody status and clinical features of 489 patients with anti-NMDAR encephalitis, defined by the presence of NMDAR antibodies in the CSF, and available paired serum/CSF samples examined at Hospital Clínic-Institut d’Investigacions Biomèdiques August Pi I Sunyer, Barcelona, between January 2007 and December 2017. NMDAR antibodies were determined with rat brain immunostaining, in-house cell-based assay (CBA), and a commercial CBA. Patients were considered seronegative if NMDAR antibodies were undetectable with the 3 indicated techniques.ResultsSerum NMDAR antibodies were not detected in 75 of 489 (15%) patients. Compared with the 414 seropositive patients, the seronegative were older (23.5 years [interquartile range (IQR): 17–43] vs 20.5 [IQR: 14–31]; p < 0.0001) and less frequently women (39 [52%] vs 313 [76%]; p < 0.001) and had less tumors (6 [9%] vs 128 [32%]; p < 0.001). In multivariate analysis, older age at diagnosis (odds ratio [OR]: 1.35 [per decade]; 95% confidence interval [CI]: 1.10–1.67), absence of tumor (OR: 0.14; 95% CI: 0.05–0.43), and less need for intensive care unit admission (OR: 0.35; 95% CI: 0.18–0.69) were independent variables associated with the absence of serum NMDAR antibodies. Time to diagnosis, treatment with immunotherapy, relapses, and outcome were similar in seronegative and seropositive patients.ConclusionsNMDAR antibodies are not detected in the serum of 15% of the patients with anti-NMDAR encephalitis. These patients appear to be older and have milder neurologic symptoms with less frequency of tumors.

scholarly journals A patient with a long history of relapsing psychosis and mania presenting with anti-NMDA receptor encephalitis ten years after first episode

2015 ◽  
Vol 9 (3) ◽  
pp. 311-314 ◽  
Author(s):  
Mateus Mistieri Simabukuro ◽  
Christian Henrique de Andrade Freitas ◽  
Luiz Henrique Martins Castro
Keyword(s):  
Psychiatric Disorders ◽  
Psychiatric Symptoms ◽  
Bipolar Affective Disorder ◽  
Autoimmune Encephalitis ◽  
Autoimmune Disorder ◽  
First Episode ◽  
Nmda Receptor Encephalitis ◽  
Nmdar Encephalitis ◽  
Lack Of Information ◽  
History Of

Anti-N-methyl- D-aspartate receptor (NMDAR) encephalitis is a recently discovered autoimmune disorder, in which antibodies target NMDARs in the brain, leading to their removal from synapses. Early in the disease course, patients often present with marked psychosis and mood disturbances (i.e. mania, depression), explaining why most of these patients are first seen by psychiatrists. Hence, autoimmune encephalitis is receiving growing attention from psychiatry, mainly owing to concerns over misdiagnosing immunomediated and potentially curable disorders as primary psychiatric disorders, such as schizophrenia or major depressive disorder. Although anti-NMDAR encephalitis occurs in the context of new-onset psychiatric symptoms, there is a lack of information on differential diagnosis and treatment of this disorder after a long-term diagnostic history of functional psychiatric disorders. We report a case of a patient with a long history of bipolar affective disorder evolving with anti-NMDAR encephalitis, initially misdiagnosed as non-organic psychosis.

scholarly journals Molecular mimicry of NMDA receptors may contribute to neuropsychiatric symptoms in severe COVID-19 cases

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Veronika Vasilevska ◽  
Paul C. Guest ◽  
Hans-Gert Bernstein ◽  
Matthias L. Schroeter ◽  
Christian Geis ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Molecular Mimicry ◽  
Psychiatric Symptoms ◽  
Auditory Hallucination ◽  
Neuropsychiatric Symptoms ◽  
Autoimmune Encephalitis ◽  
Altered Mental Status ◽  
Warning Signs ◽  
High Dose ◽  
Nmda Receptor Encephalitis

AbstractApproximately 30% of individuals with severe SARS-CoV-2 infections also develop neurological and psychiatric complaints. In rare cases, the occurrence of autoimmune encephalitis has been reported after SARS-CoV-2 infection. In this systematic review, we have identified eight SARS-CoV-2-associated cases of anti-NMDA receptor encephalitis. All had cerebrospinal fluid antibodies against the NMDA receptor and a recent onset of working memory deficits, altered mental status, or psychiatric symptoms, such as confusion, agitation, auditory hallucination, catatonia and speech dysfunction. All patients received high-dose steroid and immunoglobulin therapeutics and conditions improved in each case. These findings suggest that clinical attention should be paid to warning signs of autoimmune encephalitis in severe COVID-19 cases. If characteristic features of autoimmune encephalitis are present, autoantibody diagnostics should be performed and confirmed cases should be treated with immunotherapy to minimize neurological impairments.

Psychiatric Symptoms As Onset of Anti-Nmdar Encephalitis

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.

scholarly journals Decreased inflammatory cytokine production of antigen-specific CD4+ T cells in NMDA receptor encephalitis

2021 ◽  
Author(s):  
Le-Minh Dao ◽  
Marie-Luise Machule ◽  
Petra Bacher ◽  
Julius Hoffmann ◽  
Lam-Thanh Ly ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Ex Vivo ◽  
Autoimmune Encephalitis ◽  
Active Immunization ◽  
Inflammatory Cytokine Production ◽  
T Cell Infiltration ◽  
Nmda Receptor Encephalitis ◽  
Nmdar Encephalitis ◽  
Disease Specific

AbstractAnti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis is the most common autoimmune encephalitis with psychosis, amnesia, seizures and dyskinesias. The disease is mediated by pathogenic autoantibodies against the NR1 subunit that disrupt NMDAR function. Antibody infusion into mouse brains can recapitulate encephalitis symptoms, while active immunization resulted also in strong T cell infiltration into the hippocampus. However, whether T cells react against NMDAR and their specific contribution to disease development are poorly understood. Here we characterized the ex vivo frequency and phenotype of circulating CD4+ T helper (TH) cells reactive to NR1 protein using antigen-reactive T cell enrichment (ARTE) in 24 patients with NMDAR encephalitis, 13 patients with LGI1 encephalitis and 51 matched controls. Unexpectedly, patients with NMDAR encephalitis had lower frequencies of CD154-expressing NR1-reactive TH cells than healthy controls and produced significantly less inflammatory cytokines. No difference was seen in T cells reactive to the synaptic target LGI1 (Leucine-rich glioma-inactivated 1), ubiquitous Candida antigens or neoantigens, suggesting that the findings are disease-specific and not related to therapeutic immunosuppression. Also, patients with LGI1 encephalitis showed unaltered numbers of LGI1 antigen-reactive T cells. The data reveal disease-specific functional alterations of circulating NMDAR-reactive TH cells in patients with NMDAR encephalitis and challenge the idea that increased pro-inflammatory NMDAR-reactive T cells contribute to disease pathogenesis.

scholarly journals Phylogenetic Analysis to Explore the Association Between Anti-NMDA Receptor Encephalitis and Tumors Based on microRNA Biomarkers

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 572 ◽  
Author(s):  
Wang
Keyword(s):  
Phylogenetic Analysis ◽  
Nmda Receptor ◽  
Phylogenetic Trees ◽  
Tumor Resection ◽  
Autoimmune Disorder ◽  
Control Of Gene Expression ◽  
Nmda Receptor Encephalitis ◽  
Nmdar Encephalitis ◽  
Non Coding Rna ◽  
The Relationship

MicroRNA (miRNA) is a small non-coding RNA that functions in the epigenetics control of gene expression, which can be used as a useful biomarker for diseases. Anti-NMDA receptor (anti-NMDAR) encephalitis is an acute autoimmune disorder. Some patients have been found to have tumors, specifically teratomas. This disease occurs more often in females than in males. Most of them have a significant recovery after tumor resection, which shows that the tumor may induce anti-NMDAR encephalitis. In this study, I review microRNA (miRNA) biomarkers that are associated with anti-NMDAR encephalitis and related tumors, respectively. To the best of my knowledge, there has not been any research in the literature investigating the relationship between anti-NMDAR encephalitis and tumors through their miRNA biomarkers. I adopt a phylogenetic analysis to plot the phylogenetic trees of their miRNA biomarkers. From the analyzed results, it may be concluded that (i) there is a relationship between these tumors and anti-NMDAR encephalitis, and (ii) this disease occurs more often in females than in males. This sheds light on this issue through miRNA intervention.

scholarly journals RARE-36. BORTEZOMIB WOKE UP A PATIENT WITH ANTI-NMDA RECEPTOR ENCEPHALITIS REFRACTORY TO STANDARD THERAPY AND LONG TERM FOLLOW-UP

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi229-vi229
Author(s):  
Kong Xiao-Tang ◽  
Leonid Groysman ◽  
Cyrus Dastur ◽  
Beverly Fu ◽  
Daniela Bota
Keyword(s):  
Nmda Receptor ◽  
Standard Therapy ◽  
Autoimmune Encephalitis ◽  
Ivig Therapy ◽  
Term Care ◽  
Good Communication ◽  
Nmda Receptor Encephalitis ◽  
Long Term Follow Up ◽  
One Year

Abstract OBJECTIVE To report a case with refractory NMDA encephalitis in comatose for 18 months, who was treated successfully with bortezomib. BACKGROUND Anti-NMDA encephalitis is a rare autoimmune encephalitis. Standard therapy include corticosteroid, IVIG or plasma exchange, cyclophosphamide, rituximab, and tumor removal. Refractory cases are very severe and often stay in ICU on ventilation for several months to years. Bortezomib for the treatment of refractory anti-NMDA receptor encephalitis was reported. We have applied the treatment to our refractory case and successfully woke up the patient. And we have followed up the patient for 3 years. METHODS Case report. RESULTS A 40 yo male was diagnosed as anti-NMDA encephalitis. Standard therapy was applied. After stabilization, the patient was eventually discharged to ICU at a long term care subacute hospital. The patient was brought back for more Rituxan or steroid or IVIG therapy. The condition had not improved at all. Eighteen months in comatose, the patient had worsening NMDA titer in CSF to 1:640. Decision was made to start bortezumib as reported with modification: 1.3 mg/m2 bortezomib were administered on days 1, 8, 11 and 14 and allowed two weeks off therapy. After first cycle, the patent started to talk first word “hurt.” After 6 cycles, the patient sat up and started riding bicycles for physical therapy. The NMDA titer in CSF was reduced to 1:40 at the end of 6 cycles. One year later, the patent stood up and ambulated with a walker. One and half year later, the patient walks without assistance and his speech and cognition have significantly improved with good communication with family members and staff. CONCLUSIONS Proteasome inhibitor bortezomib might be considered to be the third line therapy as early as possible if the first line and second line are ineffective to treat anti-NMDA receptor encephalitis.

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