Autoimmune Encephalitis: NMDA Receptor Encephalitis as an Example of Translational Neuroscience

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

Neuro-Oncology ◽

10.1093/neuonc/noz175.959 ◽

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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Decreased occipital lobe metabolism by FDG-PET/CT

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000413 ◽

2017 ◽

Vol 5 (1) ◽

pp. e413 ◽

Cited By ~ 25

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.

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ENSEFALITIS ANTIRESEPTOR NMDA: ENSEFALITIS DENGAN GEJALA AWAL PSIKOSIS

Majalah Kedokteran Neurosains Perhimpunan Dokter Spesialis Saraf Indonesia ◽

10.52386/neurona.v35i1.35 ◽

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

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

Therapeutic Advances in Chronic Disease ◽

10.1177/20406223211063055 ◽

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.

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Anti NMDA receptor encephalitis: a potentially treatable encephalitis

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20202628 ◽

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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Anti-NMDA receptor encephalitis and overlapping demyelinating disorder in a 20-year old female with borderline personality disorder: proposal of a diagnostic and therapeutic algorithm for autoimmune encephalitis in psychiatric patients “case report”

BMC Psychiatry ◽

10.1186/s12888-021-03269-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

David Weiss ◽

Lisa Kertzscher ◽

Magdalena Degering ◽

David Wozniak ◽

Michael Kluge

Keyword(s):

Borderline Personality Disorder ◽

Nmda Receptor ◽

Personality Disorder ◽

Depressed Mood ◽

Psychiatric Illness ◽

Autoimmune Encephalitis ◽

Borderline Personality ◽

Nmda Receptor Encephalitis ◽

Demyelinating Disorder ◽

Therapeutic Algorithm

Abstract Background Anti-NMDA receptor encephalitis (NMDAR-E) is an autoimmune encephalitis (AE) mainly affecting young females. It typically presents with isolated psychiatric symptoms (e.g. depressed mood) at first and neurological abnormalities (e.g. seizures, movement disorders) only develop later. Thus, there is a high risk of overlooking NMDAR-E in patients with preexisting psychiatric illness due to symptom overlap in the prodromal period of the disease when treatment is most effective. Although rare, concomitant or sequential development of a demyelinating disorder is increasingly recognized as an associated disease entity (overlap syndrome), with immediate diagnostic and therapeutic implications. Case presentation We report a patient with a borderline personality disorder (BPD), which developed NMDAR-E and an overlapping demyelinating disorder with anti-Myelin oligodendrocyte glycoprotein (MOG) -IgG positivity. The initial clinical presentation with predominantly affective symptoms (e.g. mood lability, anxiety, depressed mood) lead us to suspect an exacerbation of the BPD at first. However, acute changes in premorbid behavior, newly developed psychotic symptoms and memory deficits lead us to the correct diagnosis of an AE, which was further complicated by the development of a demyelinating disorder. As a result of impaired illness awareness and psychosis, diagnostic and treatment was difficult to carry out. The symptoms completely remitted after treatment with methylprednisolone 1 g daily for 5 days and 5 cycles of plasma exchange. Conclusions Continuous awareness for neuropsychiatric clinical warning signs in patients with a pre-diagnosed psychiatric disorder is important for a timely diagnosis. Therefore, we believe that the diagnostic and therapeutic algorithm provided here, for the first time specifically addressing patients with preexisting psychiatric illness and integrating overlap syndromes, can be a useful tool. Moreover, in order to timely perform diagnostics and treatment, judicial approval should be obtained rapidly.

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A narrative review of pharmacologic approaches to symptom management of pediatric patients diagnosed with anti-NMDA receptor encephalitis

Journal of Pediatric Rehabilitation Medicine ◽

10.3233/prm-200677 ◽

2021 ◽

pp. 1-11

Author(s):

Joshua A. Vova

Keyword(s):

Nmda Receptor ◽

Symptom Management ◽

Pediatric Patients ◽

Pediatric Population ◽

Neuropsychiatric Symptoms ◽

Disease Process ◽

Autoimmune Encephalitis ◽

Nmda Receptor Encephalitis ◽

Aspartate Receptor ◽

Autonomic Instability

Anti-N-Methyl-D-Aspartate Receptor Encephalitis (ANMDARE) is one of the most common autoimmune encephalitis in the pediatric population. Patients with ANMDARE initially present with a prodrome of neuropsychiatric symptoms followed by progressively worsening seizures, agitation, and movement disorders. Complications can include problems such as aggression, insomnia, catatonia, and autonomic instability. Due to the complexity of this disease process, symptom management can be complex and may lead to significant polypharmacy. The goal of this review is to educate clinicians about the challenges of managing this disorder and providing guidance in symptom management.

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Clinical case of encephalitis with antibodies to NMDA receptors

CHILDREN INFECTIONS ◽

10.22627/2072-8107-2019-18-4-67-69 ◽

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.

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Anti-NMDA Receptor Encephalitis Presented with Acute Psychotic Symptoms: A Case Report

Iranian Journal of Psychiatry and Behavioral Sciences ◽

10.5812/ijpbs.95532 ◽

2021 ◽

Vol In Press (In Press) ◽

Author(s):

Shabnam Asadi ◽

Fahimeh Hajiakhundi ◽

Fatemeh Sadat Mirfazeli ◽

Homa Mohammadsadeghi

Keyword(s):

Nmda Receptor ◽

Psychiatric Hospital ◽

Autoimmune Encephalitis ◽

Female Adolescent ◽

Psychotic Symptoms ◽

Brain Images ◽

Nmda Receptor Encephalitis ◽

History Of ◽

One Year ◽

Perceptual Changes

Introduction: Anti-N-methyl-d-aspartic acid receptor (NMDAR) autoimmune encephalitis is one of the most challenging disorders with both psychiatric and neurologic presentations. Approximately three-fourth of patients with anti-NMDA receptor encephalitis (anti-NMDARE) first referred to psychiatrists. Case Presentation: A 15-year-old female adolescent was admitted to a psychiatric hospital. She presented a history of behavior changes, including aggression, the symptoms mimicking depression, and suicidal ideation, for one year. Then she showed more severe disinhibited behaviors, stupor, and generalized tonic-colonic seizure, so she was hospitalized in a general hospital. After neurological assessments, she was referred to a psychiatric hospital due to her uncontrollable aggressive behaviors in addition to sleep disturbance, rapid mood swings, restlessness, stereotypic behaviors, fluctuating attention and concentration, misidentification delusion, and perceptual changes. All lab tests and brain images were normal. Electroencephalograms showed generalized sharp and slow waves. The autoimmune panel tests were requested. When anti-glutamate receptor antibody was finally reported in her CSF, anti-NMDARE was finally diagnosed. Her symptoms improved by receiving five corticosteroid pulses. Conclusions: In patients with first and acute psychotic symptoms, especially in young individuals with seizures, the possibility of autoimmune disorders should be kept in mind, and complementary tests must be done for autoantibody detection.

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