scholarly journals Case Report: Daratumumab in a Patient With Severe Refractory Anti-NMDA Receptor Encephalitis

2020 ◽  
Vol 11 ◽  
Author(s):  
Dominica Ratuszny ◽  
Thomas Skripuletz ◽  
Florian Wegner ◽  
Matthias Groß ◽  
Christine Falk ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Neuropsychiatric Symptoms ◽  
Clinical Status ◽  
Disease Onset ◽  
Autoimmune Encephalitis ◽  
Intravenous Immunoglobulins ◽  
Nmda Receptor Encephalitis ◽  
Life Threatening ◽  
Therapy Strategies

Anti-NMDA receptor encephalitis is the most common type of antibody mediated autoimmune encephalitis (AIE). Patients often develop neuropsychiatric symptoms and seizures, women are affected about four times more than men, and in about 50% the disease is associated with a neoplasia, especially teratomas of the ovary. We describe the case of a 20-year-old woman suffering from a severe therapy refractory course of anti-NMDA receptor encephalitis. Treatment included glucocorticoids, plasma exchange, intravenous immunoglobulins, rituximab, and bortezomib without clinical improvement. Due to a therapy refractive course 28 weeks after disease onset, the patient received 10 cycles of daratumumab. Therapy escalation was performed with the anti-CD38 monoclonal antibody daratumumab as off label treatment, based on the therapy of refractory myeloma and led to an improvement of her clinical status. She spent about 200 days on the intensive care unit, followed by several weeks on the intermediate care unit with close follow ups every 4–6 weeks afterward. During follow-up, the patient was able to resume everyday and self-care activities, reflected by the modified Rankin scale (mRS) and Barthel index. Because this disease is potentially life threatening and can lead to irreversible brain atrophy, development of further therapy strategies are of great importance. Our case describes a successful treatment for therapy refractory anti-NMDA receptor encephalitis using the anti-CD38 antibody daratumumab.

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 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.

scholarly journals 133 Toxic Psychosis: Follow-up After One Year of Treatment

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 284-284
Author(s):  
Glen Oriaifo
Keyword(s):  
Nmda Receptor ◽  
Psychotic Symptoms ◽  
Psychiatric Facility ◽  
Nmda Receptor Encephalitis ◽  
Life Threatening ◽  
One Year ◽  
Work Up ◽  
Prompt Diagnosis ◽  
Probable Diagnosis

Abstract:Introduction:Anti-NMDA (N-methyl-D-aspartate) receptor encephalitis often presents itself in psychiatric settings as first-break psychosis. I present a case of a 31-year-old female who returned to the clinic one year after being treated for NMDA receptor antibody encephalitis.CASE REPORT:Ms. C is a 31 y/o female who returned to the clinic after one year of being discharged from the hospital for NMDA-receptor encephalitis with positive serological NR1 antibodies. She was initially admitted to our inpatient psychiatric facility for an unspecified psychotic disorder complicated with seizure-like episodes. She was given various psychotropic medications without any improvement. She was moderately responsive to olanzapine and lorazepam. Her condition gradually worsened; she stopped communicating and became mute. Neurology consultation prompted work-up for encephalitis and the probable diagnosis of NMDA receptor encephalitis. She was subsequently treated with steroids, IVIG and then intrathecal rituximab and bortezomib. In addition to these aforementioned medications, she underwent a prophylactic oophorectomy and 10 ECT treatments for life threatening catatonia. After three weeks of this regimen, Ms. C recovered completely and was discharged home.DISCUSSION:This case adds to literature that suggests prompt diagnosis and management of NMDA receptor encephalitis significantly improves prognosis. Treatment should be initiated if the patient meets probable diagnostic criteria for NMDA receptor encephalitis. Similar to other cases in the literature, our patient’s symptom of catatonia improved with ECT administration. During Ms. C one year follow-up, no evidence of psychotic symptoms were appreciated. Family members reported that she had returned to her baseline cognitive function.

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

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.

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.

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.

scholarly journals Complete cognitive recovery in a severe case of anti-N-methyl-d-aspartate receptor encephalitis treated with electroconvulsive therapy

2020 ◽  
Vol 13 (2) ◽  
pp. e233772
Author(s):  
Cæcilie Leding ◽  
Lisbet Marstrand ◽  
Anders Jorgensen
Keyword(s):  
Nmda Receptor ◽  
Electroconvulsive Therapy ◽  
Neuropsychiatric Symptoms ◽  
Behavioural Change ◽  
Severe Case ◽  
Cognitive Outcome ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Cognitive Domains ◽  
Nmda Receptor Encephalitis

Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis usually presents with prominent neuropsychiatric symptoms and many patients experience cognitive sequelae. Electroconvulsive therapy (ECT) has been suggested as a part of the treatment, particularly for catatonia, but concerns that ECT may worsen the cognitive function and long-term outcome may limit its use. We present a case of anti-NMDA receptor encephalitis with severe neuropsychiatric manifestations including refractory catatonia and behavioural change. A pre-ECT neuropsychological assessment revealed dysfunction in multiple cognitive domains in spite of intensive pharmacological treatment. Twenty days after the ninth and last ECT treatment, the patient underwent the same neuropsychological tests, which showed normalised test results within all cognitive domains and no need of rehabilitation. The case demonstrates that the use of ECT in anti-NMDA receptor encephalitis with severe pretreatment cognitive dysfunction can be associated with a highly favourable cognitive outcome.

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 005 Electroclinical characteristics of autoimmune encephalitis as outcome biomarkers

2019 ◽  
Vol 90 (e7) ◽  
pp. A2.2-A2
Author(s):  
Robb Wesselingh ◽  
James Broadley ◽  
Chris Kyndt ◽  
Katherine Buzzard ◽  
Terence O’Brien ◽  
...  
Keyword(s):  
Epileptiform Activity ◽  
Autoimmune Encephalitis ◽  
List Type ◽  
Predictive Values ◽  
Nmda Receptor Encephalitis ◽  
Prolonged Duration ◽  
Eeg Changes ◽  
Drug Resistant Epilepsy ◽  
Objective Description

IntroductionSeizures are a common characteristic of Autoimmune encephalitis (AIE). The use of the electroclinical characteristics to assist in the diagnosis of AIE has been explored1 however use of specific electroencephalogram (EEG) changes has not been examined with regards to outcome prediction.MethodsPatients with AIE were recruited retrospectively across 4 hospitals in Victoria. Clinical Data was collected during admission and at final follow-up. EEGs of patients were reviewed using an objective proforma. Associations between EEG biomarkers and clinical outcomes were demonstrated using logistic regression modelling.ResultsWe recruited 88 patients with AIE and available EEGs. Presence of rhythmic delta, superimposed fast activity and an abnormal background were significantly more common in N-methyl-D-aspartame receptor (NMDAR) antibody associated AIE patients (p<0.05). ICU admission was associated with rhythmic delta epileptiform activity (OR 3.25, p=0.046), sharp elements in the EEG abnormality (OR 3.55, p=0.05), and an abnormal background rhythm (OR 3.56, p=0.03). Development of drug resistant epilepsy was associated with prolonged duration of abnormality on EEG (OR 11.99, p=0.013), and sharp elements in the EEG abnormality (OR 7.29, p=0.02).ConclusionWe have identified EEG biomarkers that differentiate NMDAR AIE from other subtypes, and likely represents an objective description of extreme delta brush which has previously been described in NMDAR AIE.2 We have also demonstrated biomarkers associated with important outcomes that can be used to help guide treatment and prognosis.ReferencesLimotai C, Denlertchaikul C, Saraya AW, Jirasakuldej S. Predictive values and specificity of electroencephalographic findings in autoimmune encephalitis diagnosis. Epilepsy Behav 2018;84:29–36.Veciana M, Becerra JL, Fossas P, Muriana D, Sansa G, Santamarina E, et al. EEG extreme delta brush: An ictal pattern in patients with anti-NMDA receptor encephalitis. Epilepsy Behav 2015;49:280–5.

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