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

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.

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

Biomolecules ◽

10.3390/biom9100572 ◽

2019 ◽

Vol 9 (10) ◽

pp. 572 ◽

Cited By ~ 2

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.

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Persistent seropositivity in oophorectomy-resistant anti-NMDA receptor encephalitis

BMJ Case Reports ◽

10.1136/bcr-2021-241878 ◽

2021 ◽

Vol 14 (9) ◽

pp. e241878

Author(s):

Susmit Tripathi ◽

Nara M Michaelson ◽

Alan Segal

Keyword(s):

Clinical Decision Making ◽

Serum Antibody ◽

Disease Patient ◽

Clinical Decision ◽

High Serum ◽

Nmda Receptor Encephalitis ◽

Resistant Disease ◽

Nmdar Encephalitis ◽

Antibody Titres ◽

Case Basis

To discuss (1) the significance of seropositivity in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and (2) clinical decision making in oophorectomy resistant disease. Patient A (a 35-year-old woman) had high CSF and serum anti-NMDA antibody titres, a complicated hospital course, little improvement with first and second-line therapies, and remained with high CSF and serum antibody titres despite unilateral oophorectomy, requiring a nearly 13-month long hospitalisation. Conversely, patient B (a 29-year-old woman) had low CSF titres, seronegative disease and quickly recovered to her baseline with first line therapies and oophorectomy. Anti-NMDAR antibodies are themselves pathological, causing signalling dysfunction and internalisation of the NMDAR. Seropositivity with anti-NMDAR antibodies likely reflects leakage from the blood–brain barrier, with high serum titres being a downstream effect of high CSF titres. Empiric bilateral oophorectomies is controversial but appropriate on a case-by-case basis in extremely treatment-resistant NMDAR encephalitis given the possibility of antigenic microteratomas, which may not be detected on imaging or even bilateral ovarian biopsies.

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F68. Presenting Clinical Features of Anti-NMDA Receptor Encephalitis in Children and Adolescents

Biological Psychiatry ◽

10.1016/j.biopsych.2019.03.605 ◽

2019 ◽

Vol 85 (10) ◽

pp. S239

Author(s):

Ronald Gurrera

Keyword(s):

Nmda Receptor ◽

Children And Adolescents ◽

Clinical Features ◽

Nmda Receptor Encephalitis

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Clinical Features, Treatment, and Outcome of 500 Patients with Anti-NMDA Receptor Encephalitis (PL01.001)

Neurology ◽

10.1212/wnl.78.1_meetingabstracts.pl01.001 ◽

2012 ◽

Vol 78 (Meeting Abstracts 1) ◽

pp. PL01.001-PL01.001 ◽

Cited By ~ 9

Author(s):

M. Titulaer ◽

L. McCracken ◽

I. Gabilondo Cuellar ◽

E. Martinez-Hernandez ◽

F. Graus ◽

...

Keyword(s):

Nmda Receptor ◽

Clinical Features ◽

Nmda Receptor Encephalitis

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Pregnancy outcomes in anti-NMDA receptor encephalitis

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000668 ◽

2020 ◽

Vol 7 (3) ◽

pp. e668 ◽

Cited By ~ 4

Author(s):

Bastien Joubert ◽

Anna García-Serra ◽

Jesús Planagumà ◽

Eugenia Martínez-Hernandez ◽

Andrea Kraft ◽

...

Keyword(s):

Nmda Receptor ◽

Pregnancy Outcomes ◽

Normal Development ◽

English Literature ◽

Cortical Dysplasia ◽

Obstetrical Complications ◽

Nmda Receptor Encephalitis ◽

Nmdar Encephalitis ◽

And Behavior

ObjectiveTo report the effects of anti-NMDA receptor (NMDAR) encephalitis in pregnant patients and their babies.MethodsWe studied a retrospective cohort of patients who developed anti-NMDAR encephalitis during pregnancy or became pregnant while recovering from the encephalitis. In addition, we reviewed the English literature between 2010 and 2019 related to this topic.ResultsWe studied 11 patients; 6 developed anti-NMDAR encephalitis during pregnancy, and 5 became pregnant while recovering. There were no obstetrical complications, but 6 (55%) babies were premature. Ten newborns were healthy, and 1 (9%) developed transient respiratory distress. Nine infants had assessable follow-up (median 18 months; range, 7–96 months), and all showed normal development. We identified 21 cases in the English literature. Obstetrical complications occurred in 7 (33%) pregnancies. Two patients died of septic shock (1 baby successfully delivered), another 2 had miscarriages, and in 2, the pregnancy was terminated. Sixteen babies (76%) were delivered, 9 (56%) premature. At birth, 13/16 (81%) newborns were healthy, 2/16 (13%) had transient neurologic or respiratory symptoms, and 1 (6%) died of brain edema. Follow-up (median 12 months; range, 6–36 months) was reported for 8 children: 7 (88%) showed normal development and behavior, and 1 (13%) cortical dysplasia. Immunotherapy was used during pregnancy in 7 (64%) of our patients and 18 (86%) of the reported cases, including rituximab in 4 cases, without adverse effects.ConclusionsPatients who develop anti-NMDAR encephalitis during pregnancy or become pregnant during recovery often have obstetrical complications, but most of the newborns are healthy and appear to have normal development.

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

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.1946 ◽

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.

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