scholarly journals Differential expression of antibodies to NMDA receptor in anti-NMDA receptor encephalitis and in neuropsychiatric systemic lupus erythematosus

2019 ◽  
Vol 6 (1) ◽  
pp. e000359 ◽  
Author(s):  
Shunsei Hirohata ◽  
Keiko Tanaka
Keyword(s):  
Nmda Receptor ◽  
Lupus Erythematosus ◽  
Healthy Subjects ◽  
Autoimmune Encephalitis ◽  
Cross Reactivity ◽  
Nmda Receptor Encephalitis ◽  
A Value ◽  
Neuropsychiatric Sle ◽  
Transmembrane Channels ◽  
Nr2 Subunits

ObjectiveAnti-NMDA receptor encephalitis is the most prevalent autoimmune encephalitis having characteristic clinical features with autoantibodies against tetrameric transmembrane channels composed of combinations of NR1 subunits of NMDA receptors with NR2 subunits, which are detected by cell-based assay (anti-NR1/NR2). On the other hand, antibodies against the linear epitope in NR2 subunit (anti-NR2) have been shown to be expressed in patients with diffuse psychiatric/neuropsychological syndromes of neuropsychiatric SLE (diffuse NPSLE). However, it has not been explored whether anti-NR1/NR2 might be detected in NPSLE, nor has it been clear whether anti-NR2 might have cross-reactivity with anti-NR1/NR2. The current study was therefore performed to explore the prevalence of anti-NR1/NR2 in NPSLE.MethodsSerum specimens were obtained from 31 patients with NPSLE (22 with diffuse NPSLE and 9 with neurological syndromes or polyneuropathy) and from 18 normal healthy subjects. Anti-NR2 and anti-NR1/NR2 were measured by ELISA and cell-based assay, respectively. The positivity for anti-NR2 was defined by a value exceeding mean+2 SD of normal healthy subjects.ResultsAnti-NR2 was positive in the sera of 19 of 31 patients with NPSLE (in 15 of 22 patients with diffuse NPSLE). By contrast, anti-NR1/NR2 was positive only in 2 of 31 patients with NPSLE (in 2 of 22 patients with diffuse SLE). The positivity for anti-NR1/NR2 was not correlated with anti-NR2 values.ConclusionsThese results demonstrate that the prevalence of anti-NR1/NR2 is extremely low in NPSLE. Moreover, the data also confirm that anti-NR2 antibodies do not have cross-reactivity with anti-NR1/NR2.

scholarly journals Clinical case of encephalitis with antibodies to NMDA receptors

2019 ◽  
Vol 18 (4) ◽  
pp. 67-69
Author(s):  
L. U. Ulukhanova ◽  
N. S. Karnayeva ◽  
M. M. Yaraliev ◽  
A. G. Gadzhimirzaevа ◽  
S. G. Agaevа
Keyword(s):  
Nmda Receptor ◽  
Clinical Observation ◽  
Neuropsychiatric Symptoms ◽  
Fatal Outcome ◽  
Autoimmune Encephalitis ◽  
Final Diagnosis ◽  
Nmda Receptor Encephalitis ◽  
General Weakness ◽  
The Central Nervous System ◽  
Nr2 Subunits

Anti-NMDA receptor encephalitis is an autoimmune disease of the central nervous system caused by autoantibodies to the NR1 and NR2 subunits of the glutamate NMDA receptor, with the possibility of both death and rapid remission. The binding of these antibodies blocks receptors and causes slowly developing psychiatric disorders, motor disorders and seizures.Presented clinical observation in a 9-year-old patient. The disease debuted with prodromal flu-like symptoms, fever, headache and general weakness, after which neuropsychiatric symptoms, impaired memory and speech developed, further progression of the disease, convulsive status, and coma with a fatal outcome were noted. The final diagnosis of autoimmune encephalitis was made after identification of antibodies to the N-methyl-D-aspartate (NMDA) receptor in the blood.

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 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.

scholarly journals Decreased occipital lobe metabolism by FDG-PET/CT

2017 ◽  
Vol 5 (1) ◽  
pp. e413 ◽  
Author(s):  
John C. Probasco ◽  
Lilja Solnes ◽  
Abhinav Nalluri ◽  
Jesse Cohen ◽  
Krystyna M. Jones ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Fdg Pet ◽  
Medical Center ◽  
Academic Medical Center ◽  
Autoimmune Encephalitis ◽  
Occipital Lobe ◽  
Nmda Receptor Encephalitis ◽  
Pet Ct ◽  
Fdg Pet Ct ◽  
Occipital Lobes

Objective:To compare brain metabolism patterns on fluorodeoxyglucose (FDG)-PET/CT in anti–NMDA receptor and other definite autoimmune encephalitis (AE) and to assess how these patterns differ between anti–NMDA receptor neurologic disability groups.Methods:Retrospective review of clinical data and initial dedicated brain FDG-PET/CT studies for neurology inpatients with definite AE, per published consensus criteria, treated at a single academic medical center over a 10-year period. Z-score maps of FDG-PET/CT were made using 3-dimensional stereotactic surface projections in comparison to age group–matched controls. Brain region mean Z scores with magnitudes ≥2.00 were interpreted as significant. Comparisons were made between anti–NMDA receptor and other definite AE patients as well as among patients with anti–NMDA receptor based on modified Rankin Scale (mRS) scores at the time of FDG-PET/CT.Results:The medial occipital lobes were markedly hypometabolic in 6 of 8 patients with anti–NMDA receptor encephalitis and as a group (Z = −4.02, interquartile range [IQR] 2.14) relative to those with definite AE (Z = −2.32, 1.46; p = 0.004). Among patients with anti–NMDA receptor encephalitis, the lateral and medial occipital lobes were markedly hypometabolic for patients with mRS 4–5 (lateral occipital lobe Z = −3.69, IQR 1; medial occipital lobe Z = −4.08, 1) compared with those with mRS 0–3 (lateral occipital lobe Z = −0.83, 2; p < 0.0005; medial occipital lobe Z = −1.07, 2; p = 0.001).Conclusions:Marked medial occipital lobe hypometabolism by dedicated brain FDG-PET/CT may serve as an early biomarker for discriminating anti–NMDA receptor encephalitis from other AE. Resolution of lateral and medial occipital hypometabolism may correlate with improved neurologic status in anti–NMDA receptor encephalitis.

scholarly journals Anti-N-methyl-d-aspartate receptor encephalitis: review of clinical presentation, diagnosis and treatment

2015 ◽  
Vol 39 (1) ◽  
pp. 19-23 ◽  
Author(s):  
Helen Barry ◽  
Susan Byrne ◽  
Elizabeth Barrett ◽  
Kieran C. Murphy ◽  
David R. Cotter
Keyword(s):  
Nmda Receptor ◽  
Clinical Presentation ◽  
Behavioural Change ◽  
Review Of The Literature ◽  
Impaired Consciousness ◽  
Motor Disturbance ◽  
Nmda Receptor Encephalitis ◽  
Aspartate Receptor ◽  
Nr2 Subunits ◽  
Symptoms And Signs

SummaryAnti-N-methyl-d-aspartate (NMDA) receptor encephalitis is a form of encephalitis occurring primarily in women and associated with antibodies against NR1 or NR2 subunits of the NMDA receptor. As a potentially treatable differential for symptoms and signs seen in neurology and psychiatric clinics, clinicians practising across the lifespan should be aware of this form of encephalitis. Common clinical features include auditory and visual hallucinations, delusions, behavioural change (frequently with agitation), impaired consciousness, motor disturbance (ranging from dyskinesia to catatonia), seizures, and autonomic dysfunction. We present a review of the literature on the disorder, including its clinical presentation, differential diagnosis, epidemiology, treatment and prognosis.

scholarly journals ENSEFALITIS ANTIRESEPTOR NMDA: ENSEFALITIS DENGAN GEJALA AWAL PSIKOSIS

2020 ◽  
Vol 35 (1) ◽  
Author(s):  
Riwanti Estiasari ◽  
Darma Imran ◽  
Kartika Maharani ◽  
David Pangeran ◽  
Fitri Octaviana ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Nmda Receptor ◽  
Psychiatric Symptom ◽  
Autoimmune Encephalitis ◽  
Antibody Test ◽  
The Other ◽  
Receptor Antibody ◽  
The Third ◽  
Nmda Receptor Encephalitis ◽  
Cognitive Disturbance

     ANTI-NMDA RECEPTOR ENCEPHALITIS: ENCEPHALITIS PRESENTING WITH EARLY PSYCHOSIS SYMPTOMSABSTRACTAnti N-methyl-D-aspartate (NMDA) receptor encephalitis is seldom found in Indonesia. The atypical initial presentation of psychosis and cognitive disturbance results in underdiagnosed, or even undiagnosed case. This report described a 12-year-old girl presenting with initial psychiatric symptom followed by seizure and oropharyngeal dystonia. Anti-NMDA receptor antibody test carried out on both serum and  cerebrospinal  fluid (CSF) were positive and  no other pathogen was detected in the CSF. Clinical improvement was seen following the third day of methylprednisolone administration. This case demonstrates the importance of considering anti-NMDA receptor encephalitis or the other autoimmune encephalitis as the differential of infective encephalitis. Anti-NMDA receptor antibody test, which can already be performed in Indonesia, will greatly guide to the definitive diagnosis.Keywords: Encephalitis, NMDA, oropharyngeal dystonia, psychiatricABSTRAKEnsefalitis antireseptor N-metil-D-aspartat (NMDA) masih jarang ditemukan di Indonesia. Gejala awal yang tidak khas berupa psikosis dan gangguan kognitif menyebabkan keterlambatan diagnosis, atau bahkan tidak terdiagnosis, ensefalitis jenis ini. Berikut dilaporkan kasus seorang perempuan 12 tahun dengan gejala awal berupa gejala psikiatrik yang diikuti dengan kejang dan munculnya distonia orofaring. Pemeriksaan antibodi antireseptor NMDA pada serum dan cairan serebrospinal (CSS) positif dan tidak ditemukan patogen lain pada pemerikaan CSS. Perbaikan klinis terlihat setelah pemberian metilprednisolon selama 3 hari. Kasus ini memperlihatkan pentingnya mempertimbangkan diagnosis ensefalitis antireseptor NMDA atau ensefalitis autoimun lainnya sebagai diagnosis banding pada kasus ensefalitis infeksi. Oleh karena itu, pemeriksaan antibodi antireseptor NMDA yang telah dapat dilakukan di Indonesia akan sangat membantu proses penegakan diagnosis.Kata kunci: Distonia orofaring, ensefalitis, NMDA, psikiatrik

scholarly journals Efficacy of tacrolimus as long-term immunotherapy for neuronal surface antibody-mediated autoimmune encephalitis

2022 ◽  
Vol 13 ◽  
pp. 204062232110630
Author(s):  
Chenchen Liu ◽  
Suqiong Ji ◽  
Huajie Gao ◽  
Zhuajin Bi ◽  
Qin Zhang ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Autoimmune Encephalitis ◽  
Efficacy And Safety ◽  
Nmda Receptor Encephalitis ◽  
Significant Difference ◽  
Observational Cohort ◽  
Surface Antibody ◽  
Retrospective Observational Cohort Study

Aims: We aimed to verify the efficacy and safety of tacrolimus as long-term immunotherapy for the treatment of neuronal surface antibody-mediated autoimmune encephalitis (AE) during the first attack. Methods: In this retrospective observational cohort study, patients with neuronal surface antibody-mediated AE who experienced the first attack were enrolled. We compared the outcomes of 17 patients who received tacrolimus with those of 47 patients treated without tacrolimus. Patients were assessed at onset and 3, 6, and 12 months, as well as at the last follow-up, by using the modified Rankin scale (mRS) and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The efficacy of tacrolimus was also compared in a subgroup of patients with anti-NMDA receptor encephalitis. Results: Among all patients with neuronal surface antibody-mediated AE, those receiving tacrolimus had lower median mRS scores [1 (IQR = 0–1) versus 2 (IQR = 1–3) in controls, p = 0.001)], CASE scores [2 (IQR = 1–3) versus 3 (IQR = 2–7), p = 0.006], and more favorable mRS scores (94.1% versus 68.1%, p = 0.03) at the 3-month follow-up. No difference was found at the last follow-up. There was no significant difference in the occurrence of relapse and adverse events between the two groups (11.8% versus 14.9%, p = 0.75). In the subgroup of patients with anti-NMDA receptor encephalitis, patients treated with tacrolimus had a lower median mRS score at the 3-month follow-up [1 (IQR = 0–2) versus 2 (IQR = 1–3), p = 0.03]; however, no difference in the outcome was detected at the last follow-up. Conclusion: Tacrolimus can be used as long-term immunotherapy in patients with neuronal surface antibody-mediated AE during the first attack. Treatment with tacrolimus appears to accelerate the clinical improvement of neuronal surface antibody-mediated AE.

scholarly journals Relatedness of Antibodies to Peptides Containing Homocitrulline or Citrulline in Patients with Rheumatoid Arthritis

2017 ◽  
Vol 45 (3) ◽  
pp. 302-309 ◽  
Author(s):  
Patrick Lac ◽  
Maud Racapé ◽  
Lillian Barra ◽  
David A. Bell ◽  
Ewa Cairns
Keyword(s):  
Rheumatoid Arthritis ◽  
Lupus Erythematosus ◽  
Healthy Subjects ◽  
Cross Reactivity ◽  
Strongly Correlated ◽  
Spearman Correlation ◽  
Peptide Backbone ◽  
The Relationship ◽  
Citrullinated Protein ◽  
Homologous Peptide

Objective.Antibodies that target citrullinated protein/peptide (ACPA) and homocitrullinated/carbamylated protein/peptide (AHCPA) are associated with rheumatoid arthritis (RA). The relationship between ACPA and AHCPA remains unclear. We examined the expression and cross-reactivity of these antibodies using citrulline- and homocitrulline-containing synthetic peptides, CitJED and HomoCitJED, respectively, which have equal numbers of citrulline or homocitrulline residues on the same peptide backbone.Methods.Serum from healthy subjects (n = 51) and patients with RA (n = 137), systemic lupus erythematosus (SLE; n = 37), and psoriatic arthritis (PsA; n = 37) were screened for IgG anti-CitJED and anti-HomoCitJED antibodies by ELISA. Cross-reactivity of these antibodies was examined by inhibition with various concentrations of CitJED and HomoCitJED.Results.Out of 137 patients with RA, antibodies to CitJED and HomoCitJED were detected in 69 (50%) and 78 (57%), respectively. Anti-CitJED and HomoCitJED antibodies were 77% concordant and their levels were strongly correlated [Spearman correlation coefficient (rs) = 0.6676]. Sera from 25/27 patients (93%) with RA were inhibited by both CitJED and HomoCitJED with equal or higher affinity for the cognate (homologous) peptide.Conclusion.Antibodies to CitJED and HomoCitJED frequently occurred in RA, but were not found in SLE or PsA, suggesting that these antibodies are specific to RA. Cross-reactivity between anti-HomoCitJED and anti-CitJED antibodies suggests that ACPA and AHCPA are derived from the same B cell population and both may contribute to the pathogenesis of RA.

scholarly journals Anti NMDA receptor encephalitis: a potentially treatable encephalitis

2020 ◽  
Vol 7 (7) ◽  
pp. 1624
Author(s):  
Archana K. M. ◽  
Sushma Save ◽  
Koppikar Rahul Gautam
Keyword(s):  
Nmda Receptor ◽  
Neuropsychiatric Symptoms ◽  
Autoimmune Encephalitis ◽  
Ivig Therapy ◽  
Receptor Subunit ◽  
Nmda Receptor Subunit ◽  
Nmda Receptor Encephalitis ◽  
Autonomic Instability ◽  
High Index Of Suspicion ◽  
Age Range

Anti NMDA receptor encephalitis is autoimmune encephalitis where antibodies are directed against NMDA receptor subunit. It represents a new category of immune-mediated disorder that is often paraneoplastic, presenting with neuropsychiatric symptoms, which is treatable and can be diagnosed serologically affecting both children and adults. Patient can have variable clinical presentation ranging from prodromal illness, neuropsychiatric symptoms, seizures, autonomic instability, hyperkinesias, catatonia, hypoventilation and with or without an associated teratoma. A positive serum or CSF sample screening for antibodies to the NMDA receptor subunit is confirmative. Supportive findings include CSF study, EEG and MRI Brain. The first-line therapies includes IVIG, corticosteroids or plasma exchange. Second line immunotherapy is rituximab or cyclophosphamide or both. Given the high mortality rate (up to 25%), the likelihood of presentation across the age range and the potential for treatment, a high index of suspicion is warranted by clinicians. Authors report a case of a 5 year old child with anti NMDA receptor encephalitis who responded well to IVIG therapy.

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