Treatment Of anti-NMDAR Encephalitis Research Articles

Characteristics and Treatment of anti-NMDAR Encephalitis in People Living with HIV: A Case Report and Literature Review (P5-5.005)

<h3>Objective:</h3> To describe the risk factors, symptoms, treatment, and outcomes of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis occurring in people living with HIV (PLWH). <h3>Background:</h3> Herpes simplex virus encephalitis is a known trigger of anti-NMDAR encephalitis. In recent years, multiple case reports also document anti-NMDAR encephalitis in PLWH, especially those who develop cerebrospinal fluid (CSF) escape, defined by an elevated CSF viral load in the setting of plasma viral suppression. Although the relationship between HIV and other viruses with anti-NMDAR encephalitis has not been fully elucidated, possible mechanisms include molecular mimicry or viral-induced release of NMDAR and other proteins as a result of neurotoxicity. HIV-induced functional dysregulation of CD4+ cell subtypes is another plausible contributor. <h3>Design/Methods:</h3> We conducted a literature search for published cases of autoimmune encephalitis in PLWH. We added an unpublished case from our center and described the clinical features of this unique cohort. <h3>Results:</h3> Eight published cases of anti-NMDAR encephalitis among PLWH were identified, as well as one unpublished case from our center. Common trends in these 9 cases include elevated CSF HIV viral load, T2 hyperintense lesions on MRI, and clinical improvement with immunomodulation. Our patient was a 51-year-old woman who presented off of antiretroviral therapy (recent CD4 range 199–252 cells/mm3) with status epilepticus and was found to have an elevated CSF HIV viral load and multiple non-enhancing T2-hyperintense lesions on brain MRI. Anti-NMDAR antibodies were positive in the serum and CSF. She did not respond to steroids or intravenous immunoglobulins, but began to improve after plasma exchange and was subsequently treated with rituximab. <h3>Conclusions:</h3> Anti-NMDAR encephalitis is an important, treatable consideration in PLWH who present with altered mental status or new seizures. Patients with an elevated CSF viral load may be at higher risk for this syndrome, and immunomodulation may be indicated even in patients who are immunosuppressed. <b>Disclosure:</b> Dr. White has nothing to disclose. Dr. Vila has nothing to disclose. The institution of Dr. Bissonnette has received research support from Michael J Fox Foundation. The institution of Dr. Bissonnette has received research support from Cogan Family Foundation. Dr. Martinez-Ramirez has nothing to disclose. Dr. Anand has nothing to disclose. Dr. Cervantes-Arslanian has nothing to disclose.

Elevated ApoB/ApoA-I ratio is associated with acute anti-N-Methyl-D-aspartate receptor encephalitis, but not disease outcomes.

ObjectiveThe purpose of the present study is to clarify the relationship between the apolipoprotein B100/apolipoprotein A-I (ApoB/ApoA-I) ratio and anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis.MethodsA total of 71 patients with anti-NMDAR encephalitis were included in this study, and their ApoB/ApoA-I ratios in baseline and follow-up were retrospectively analyzed.ResultsThe ApoB/ApoA-I ratio was closely correlated with the baseline-modified Rankin scale (mRS) score of >3 in patients with anti-NMDAR encephalitis. A subgroup analysis showed obvious differences between the high and low ApoB/ApoA-I ratio groups. The ApoB/ApoA-I ratio was positively correlated with intensive care unit (ICU) treatment, length of hospital stay, baseline mRS score, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The ratios of the high and low ApoB/ApoA-I groups both improved in the follow-up.ConclusionThe increased ApoB/ApoA-I ratio is associated with acute anti-NMDAR encephalitis, but not disease outcomes. Serum ApoB/ApoA-I ratio was related to inflammation and immunity in peripheral blood. The findings might provide a new idea for further exploration of the pathogenesis and treatment of anti-NMDAR encephalitis.

Anti-NMDAR Encephalitis: Multidisciplinary Development of a Clinical Practice Guideline.

Anti-NMDAR Encephalitis: Multidisciplinary Development of a Clinical Practice Guideline.

Thyroid Function and Anti-thyroid Antibodies in Pediatric Anti-NMDAR Encephalitis.

Objective: Recent studies found that changes of thyroid antibodies (ATAbs), thyroid hormone, and non-thyroidal illness syndrome (NTIS) characterized by thyroid hormone inactivation with low triiodothyronine and high reverse triiodothyronine followed by suppressed thyroid-stimulating hormone (TSH) in adult anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis were associated with disease severity. This study aimed to explore thyroid function and ATAbs in pediatric anti-NMDAR encephalitis and their clinical association.Methods: We retrospectively analyzed the clinical data of 51 pediatric cases with anti-NMDAR encephalitis hospitalized in Guangzhou Women and Children's Medical Center from August 2016 to 2019.Results: A percentage of 52.9% of patients belonged to the ATAb (+) group, with 26 cases both positive for anti-thyroid peroxidase antibodies (TPOAb) and anti-thyroglobulin antibodies (TGAb), and one patient only positive for TPOAb. A percentage of 62.7% of patients had at least one abnormality in terms of FT3, free thyroxin (FT4), or TSH levels. Meanwhile, 45.1% of patients were diagnosed with NTIS. Among 25 cases retested for thyroid function 2 months after the initial test, the respectively decreased FT3 and FT4 in 13 and 11 cases on admission returned to normal or closer normal than before; TPOAb in eight cases and TGAb in 12 cases were changed from positivity to negativity. Compared with onset, the level of TPOAb and TGAb at relapse remained stable or significantly decreased, respectively. Compared with the ATAb (–) group, the ATAb (+) group had an older onset age, a higher ratio of movement disorders, elevated rate of sleep disorders, increased anti-nuclear antibody positivity rate, and higher ratio of more than one course of intravenous immunoglobulin treatment. There were no significant differences between the NTIS and non-NTIS groups in clinical characteristics.Conclusion: Anti-thyroid antibody positivity, abnormality of FT3, FT4, or TSH levels and NTIS are frequent in pediatric anti-NMDAR encephalitis. Thyroid antibody and thyroid hormone abnormalities could be improved through the course of treatment of anti-NMDAR encephalitis. Cases with ATAbs (+) are at older onset ages and more likely to be treated by intravenous immunoglobulin therapy more than once. Unlike adult anti-NMDAR encephalitis, NTIS might not be associated with the clinical characteristics of anti-NMDAR encephalitis in pediatric patients.

Electroencephalographic Findings in Pediatric Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis: The San Diego Experience

AbstractDiagnosing anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis clinically can be challenging. There is a growing interest in identifying specific electroencephalographic features to help guide early management. A retrospective chart review was conducted of pediatric patients admitted to Rady Children's Hospital between January 1, 2010 and April 1, 2017. We included patients with the diagnosis of encephalitis who underwent continuous video electroencephalogram (VEEG) for at least 12 hours, and presented with less than 14 days of symptoms. We compared the electroencephalographic features of non-rapid eye movement (NREM) sleep between patients with antibody confirmed anti-NMDAR encephalitis and patients with encephalitis from other etiologies. We identified seven patients who met our inclusion criteria, five of whom were diagnosed with anti-NMDAR encephalitis. Four of the five patients had a significant reduction in NREM sleep, while one patient had increased NREM sleep associated with clinical catatonia and hypersomnolence. Sleep was preserved in the two cases of nonimmune mediated encephalitis. Our results suggest that a prolonged VEEG to capture sleep coupled with clinical features can aid in early diagnosis and treatment of anti-NMDAR encephalitis, often before confirmatory antibody testing is available.

P62 Cyclophosphamide and maintenance mycophenolate mofetil for the treatment of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis in a paediatric patient

BackgroundAnti-NMDAR encephalitis is one of the commonest known types of autoimmune encephalitis with an increasing recognition in the paediatric population.1 2 It is characterised by abnormal behavioural and cognitive symptoms, seizures and movement disorders where treatment failure or failure to treat can result in long term disabilities or mortality.1A 4-year-old patient with a background of autism was admitted to the paediatric intensive care unit (PICU) due to encephalitis with convulsive status epilepticus where he remained intubated for 22 days and was later diagnosed with anti-NMDAR encephalitis. The patient had persistent abnormal choreoathetoid movements and intermittent seizures despite multiple anti-epileptics, two courses of corticosteroids, two courses of intravenous immunoglobulin, two cycles (10 sessions per cycle) of plasmapheresis and a course of weekly rituximab. Due to the lack of response from these initial pharmacological interventions, the use of cyclophosphamide and mycophenolate mofetil was considered. Cyclophosphamide and mycophenolate mofetil inhibits the proliferations of B- and T-lymphocytes3 4 which acts as the basis of its immunosuppressive actions. However, available evidence on the dosing and monitoring information in the paediatric population for this unlicensed indication is limited.Pharmacy ContributionsAfter discussion with the multi-disciplinary team (MDT) with extensive input from the paediatric neurologist, a literature search was conducted to determine an appropriate dosing regimen. As this was an off-label use, the paediatric neurologist and the attending consultant took clinical responsibility. Intravenous cyclophosphamide was started at 750 mg/m2 once a month for three cycles and oral mycophenolate mofetil was started at 600 mg/m2 twice a day as maintenance therapy a week after. The specialist pharmacist explained the individualised treatment plan for the patient to the MDT and ensured measures (hydration and mesna) for the prevention of cyclophosphamide-induced haemorrhagic cystitis were appropriately prescribed on the electronic prescribing system with the appropriate timings of administration. Monitoring parameters to determine adverse effects were closely observed. A local guideline was developed during the treatment cycles to ensure all members of the MDT were following the correct procedures.OutcomeThe patient responded to cyclophosphamide and clinically improved after the completion of three cycles of monthly treatment. Maintenance mycophenolate mofetil was subsequently stopped a month after the last cycle of cyclophosphamide due to neutropenia. A review of the patient one year after first presentation shows the patient is almost back to their baseline.Lessons LearnedAlthough there are potentially serious side effects, cyclophosphamide and mycophenolate mofetil has been successful in the treatment of anti-NMDAR encephalitis. The recovery of this patient required extensive support from the entire MDT.ReferencesNHS England. Clinical Commissioning Policy: Rituximab for second line treatment for anti-NMDAR autoimmune encephalitis (all ages). March 2018.Salvucci A, Devine IM, Hammond D, et al. Pediatric anti-NMDA (N-methyl D-Aspartate) receptor encephalitis. Pediatric Neurology 2014;50:507–510.Summary of Product Characteristics. Cyclophosphamide 1000 mg Powder for Solution for Injection or Infusion. Last updated on eMC on 27-Jun-2017. Available at https://www.medicines.org.uk/emc/product/3525/smpc# [Accessed 04 July 2019]Summary of Product Characteristics. CellCept 1 g/5 mL powder for oral suspension. Last updated on eMC on 16-Mar-2018. Available at https://www.medicines.org.uk/emc/product/1569/smpc [Accessed 04 July 2019]

A case of NMDAR encephalitis treated in the third trimester - novel arterial spin labeling findings and a review of literature

Diagnosis and treatment of anti-NMDAR encephalitis during pregnancy are challenging. We report a case of anti-NMDAR encephalitis in a 28-year-old, 24 weeks pregnant woman. Her brain magnetic resonance imaging was normal, but arterial spin labeling (ASL) showed increased cerebral blood flow in the right insula and temporal area. She was successfully treated with emergent cesarean section and immunotherapies including intravenous immunoglobulin, steroids, and rituximab. The newborn was healthy and she recovered fully. Early suspicion and proper management is important in treatment of anti-NMDAR encephalitis during pregnancy. ASL can help diagnosing anti-NMDAR encephalitis during pregnancy.

1941 Ovarian Dermoid Cyst as the Cause of Anti-Nmda Receptor Encephalitis: A Case Series

Study Objective Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune condition often presenting in the form of a neuropsychiatric disorder. Ovarian dermoid cyst has been described as a possible instigator of this state with surgical therapy often leading to substantial clinical improvement. We aim to describe our hospital's experience and highlight the importance of ultra sound in the diagnosis and treatment of Anti-NMDAR encephalitis. Design A case series. Setting All women were treated at the gynecology department of a tertiary teaching hospital between January 2013 and December 2018. Patients or Participants We describe 3 cases of anti-NMDAR encephalitis. In the first case a 33 y/o woman presented with headaches, dizziness, and seizures for the first time in her life and later, developed aphasia. In the second case, a 37 y/o woman was referred to the emergency room with acute confusion, delusions and hallucinations and in the third case, a 32 y/o woman appeared with psychosis and seizures. All three were diagnosed with ANTI NMDA antibodies and an ultrasound examination revealed a dermoid cyst ranging from 1 to 4 cm, and in one case the cyst was not detected by CT-scan. Interventions All women underwent ovarian resection and continued immunosuppressive medical therapy with gradual improvement in their condition. Measurements and Main Results We show that even small dermoid cysts may evoke antibody titer rise emphasizing the importance of performing early gynecologic ultrasound for women with new-onset encephalitis. Conclusion ANTI-NMDAR encephalitis caused by dermoid cyst is an important entity which can easily go misdiagnosed. Early cystectomy or ovarian resection and immunosuppressive treatment are key elements in the management of such cases.

Effect of Clozapine on Anti-N-Methyl-D-Aspartate Receptor Encephalitis With Psychiatric Symptoms: A Series of Three Cases.

The main clinical manifestations of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis are acute or subacute seizures, cognition impairment, and psychiatric symptoms. Nowadays, the scheme of antipsychotic therapy for this disease has not been established. This study reports three cases of anti-NMDAR encephalitis with psychiatric symptoms. The anti-NMDAR antibodies in cerebrospinal fluid (CSF) and serum were positive. The psychiatric symptoms still existed after intravenous immunoglobulin (IVIG) treatment; thus, clozapine was used for antipsychotic therapy. Case 1 was a 37-year-old man who suffered from bad mood and suicide behaviors for 1 month. Hallucination and delusion still existed after IVIG treatment and hormone therapy, and the symptoms were relieved when given clozapine for 12 months. Case 2 was a 28-year-old man who was admitted to our hospital due to injuring other people and destructive behaviors for 2 days. He showed irritability, bad temper, declined cognition, and severe delusion of persecution after IVIG treatment and hormone therapy, but the psychiatric symptoms disappeared when given clozapine for 3 months. Case 3 was a 23-year-old man who suffered from headache and babbing for 7 days. Symptoms such as irritability, bad temper, babbing, and injuring other people still existed after IVIG treatment and hormone therapy, but they disappeared when given clozapine for 2 months. Therefore, we suggest that during the treatment of anti-NMDAR encephalitis with psychiatric symptoms, if the anti-NMDAR antibodies in CSF and serum were positive, and psychiatric symptoms could not be controlled after IVIG and hormone therapy, clozapine may work.

A Case of Teratoma-Associated Anti-NMDAR Encephalitis

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune encephalitis that is associated with the NMDA receptor and has a good response to treatment. However, only a small number of cases related teratoma has been reported in literature. Here we report a case of teratoma-associated anti-NMDAR encephalitis. A 25-year-old woman with the presentation of fever for 20 days and psychiatric symptoms for 9 days was admitted to the hospital. This patient progressed to a minimally conscious state consistent with encephalitis. Considering the possibility of autoantibody-mediated encephalitis, laboratory tests were undertaken to observe the anti-NMDAR antibodies in cerebrospinal fluid (CSF) and serum, which confirmed the diagnosis of anti-NMDAR encephalitis. Furthermore, gynecological ultrasound investigation detected teratoma in the left ovary. After resection of the teratoma with Laparoscopic adnexectom and treatment with immunosuppressive therapy, the patient recovered gradually and was discharged one month after the operation. Due to the lack of clinical practice guidelines for the prevention and treatment of anti-NMDAR encephalitis, the disease is still difficult to diagnose because of its vague manifestations. For the further study, the clinic data of one case of teratoma-related anti-NMDAR encephalitis was analyzed and the relevant literatures were reviewed.

Clinical characteristics and pathogen screening of 38 children with anti-N-methyl-D-aspartate receptor encephalitis

Objective To analyze the clinical characteristics and screen pathogens and prognosis of anti-N-methyl-D-aspartate receptor(NMDAR) encephalitis in children and so as to improve the diagnosis and treatment of anti-NMDAR encephalitis in children. Methods A retrospective and follow-up analysis of 38 cases of pediatric anti-NMDAR encephalitis was performed, who were admitted to the West China Second University Hospital, Sichuan University from May 2012 to June 2016, and their clinical features, associated pathogen screening, treatment and prognosis were reviewed. Results Those 38 cases included 14 males and 24 females.The age ranged from 1 year and 10 months to 17 years and 6 months.The most common symptoms were psychiatric symptoms (33 cases), and dyskinesias and movement disorders (33 cases), speech disturbances (31 cases). Twenty-four cases (63.2%) received positive pathogenic screening and only one case had right ovarian mature cystic teratoma.Among them, 11 cases had positive mycoplasma pneumonia immunoglobulin M(IgM) antibodies, 10 cases had positive virus screening, and 1 case had toxoplasma gondii IgM antibodies positive, and 2 cases had mix infection.Symptoms of one case were relieved after anti-toxoplasma treatment without immunosuppression treatment, and another case had partial symptom relief after mycoplasma pneumonia treatment.Thirty-seven cases received immunosuppressant therapy(4 cases were treated with glucocorticoid, 12 cases were treated with glucocorticoid combined with immune globulin, 2 cases were treated with glucocorticoid combined with plasma exchange, still 19 cases were treated with glucocorticoid combined with immune globulin and plasma exchange). After follow-up for median 12 months, 3 cases relapsed, 29 cases were fully recovered, 5 cases had mild language impairment, 2 cases had mild memory impairment, and 2 cases had involuntary movement. Conclusions The most common symptoms of the patients were psychiatric symptoms, dyskinesias and movement disorders, and speech disturbances.Children with anti-NMDAR encephalitis had a low incidence of tumors, while various pathogen infections including mycoplasma pneumonia, virus and toxoplasma gondii, which may trigger abnormal immune response of anti-NMDAR encephalitis.Pathogen screening needs to be done for pediatric anti-NMDAR encephalitis and anti-pathogenic treatment may be helpful for disease remission. Key words: Anti-N-methyl-D-aspartate receptor encephalitis; Pathogen; Child

Anti-N-Methyl-D-Aspartate Receptor Encephalitis and Ovarian Teratoma: A Case Report

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is often associated with ovarian teratomas in young women. However, children are less likely to develop this condition. We herein report a very rare case of anti-NMDAR encephalitis and an ovarian teratoma in a young girl. A previously healthy 9-year-old girl presented with convulsions and unconsciousness. Her cerebral spinal fluid was positive for anti-NMDAR antibody. She underwent immunotherapy, and although her clinical course improved, she did not fully recover. A right ovarian teratoma was then found and removed, and she became negative for anti-NMDAR antibody. She exhibited almost full recovery and no relapse. Tumor resection is recommended in the treatment of anti-NMDAR encephalitis. A tumor search should be actively carried out in patients aged < 12 years. Int J Clin Pediatr. 2017;6(1-2):20-23 doi: https://doi.org/10.14740/ijcp260w

Catatonic schizophrenia vs anti-NMDA receptor encephalitis – A video case report

IntroductionAnti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a treatable autoimmune disease of the CNS with prominent neuropsychiatric features that primarily affects young adults and children.ObjectiveTo present the diagnosis course of a case of anti-NMDAR encephalitis in a patient with previous diagnosis of Schizophrenia.MethodsAnalysis of the patient's clinical records and of a PubMed database review, using “anti-NMDAR encephalitis” as keywords.ResultsWe report a single case of a 33-year-old man diagnosed with Paranoid Schizophrenia in 2009 that after 1 year of treatment abandoned follow-up. Six years later, the patient presented to the psychiatric emergency department with persistent headaches, abnormal behavior and loss of motor skill. He was admitted to the psychiatric ward with a presumptive diagnosis of “Catatonic Schizophrenia” and began to manifest fluctuating catatonic symptoms (captured in video). Neuroleptics and benzodiazepines were tried without success. There was a clinical deterioration with autonomic dysfunction, breathing instability and seizures. Complementary exams revealed: EEG with slow base activity; brain MRI with right temporal pole and right frontobasal lesions compatible with head trauma; CSF with pleocytosis; and positive anti-NMDAR antibodies. Occult neoplasm was excluded. Treatment with high-dose steroids, intravenous immunoglobulins, followed by cyclophosphamide resulted in relevant clinical improvement.ConclusionsAs early detection of antibodies may allow for earlier treatment of anti-NMDAR encephalitis, which is associated with better outcomes, we believe the present case underscores the importance of clinicians maintaining vigilance for neuropsychiatric symptoms that have not adequately responded to therapy.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Extreme Delta Brushes in Pediatric Anti-N-Methyl-DAspartate Receptor Encephalitis

Anti-N-Methyl-D-Aspartate receptor (NMDAR) encephalitis is probably the most common paraneoplastic encephalitis. In children, seizures, behavioral disturbances and abnormal movements are the most frequent symptoms. Electroencephalogram is abnormal in most patients. We report a child with anti- NMDAR encephalitis presenting extreme delta brushes in the EEG. This new EEG feature is described in patients with anti-NMDAR encephalitis, mostly adults. The identification of this EEG pattern may guide to an early diagnosis and treatment of anti-NMDAR encephalitis.

Anti-NMDAR-encephalitis in children

Anti-N-methyl-D-aspartate receptor encephalitis (Anti-NMDAR-encephalitis) in children is a type of autoimmune encephalitis associated with NMDA receptor.Its etiology and clinical manifestations are specific in children.This disease is associated with teratoma more in adult than in children.However,its etiology is more associated with infection and heredity in children.The pathogenesis is that the anti-NMDAR-antibody can combine with NMDAR of neurons selectively and reversibly.The clinical manifestations include psychiatric syndrome,language,motor,sleep and autonomic nervous disorders.Tumor resection and immtmotherapy are chief treatments.This disorder is often misdiagnosed as it is rarely reported in children.It is valuable to make early diagnosis and treatment.This paper reviews the mechanism,clinical features,diagnosis and treatment of antiNMDAR-encephalitis of children. Key words: Anti-NMDAR-encephalitis; Children; Clinical manifestation; Treatment

1352 – Anti-NMDA-receptor encephalitis: a new differential diagnosis to first psychotic break

Introduction First psychotic break represents a challenging differential diagnosis for psychiatrists as the clinical outcome depends on an aetiology-directed approach. There is growing focus on detection of treatable causes of psychosis because treatment can alter the natural history of disease. Anti-NMDA-receptor encephalitis is a recently described treatable neuropsychiatric disease presenting with psychiatric symptoms. Objectives Review of epidemiology, clinical presentation, diagnostic tests and differential diagnosis, treatment and prognosis of anti-NMDAr encephalitis. Methods Case report of a patient diagnosed with anti-NMDAr encephalitis. Review of relevant literature collected from medical internet databases. Results Male 15 year-old patient with a previous episode of involuntary movements of the limbs and loss of conscience, presented with distonic contact, behaviour disturbances, sexual stereotypies, agitation and disturbed speech, that evolved with generalized tonic-clonic seizures, global aphasia and sinking of consciousness. A diagnose of anti-NMDAr encephalitis was made and partial recovery was obtained after treatment. Discussion Anti-NMDAr encephalitis is an auto-immune process against synaptic receptors, paraneoplasic or not, detectable by anti-body mesurement in CSF. Most patients develop a multistage illness initially presenting with psychiatric manifestations, progressing to seizures, language disintegration and catatonic states associated with abnormal movements. As patients are frequently treated with antipsychotics, motor abnormalities and catatonia are often interpreted as extrapyramidal effects or neuroleptic malignant syndrome, confounding the diagnosis. Conclusion Early recognition and treatment of anti-NMDAr encephalitis improve the outcome. Psychiatrists working in emergency departments and first psychotic break units should be aware of this severe disorder in order to start adequate treatment and prevent negative outcomes