Receptor Autoimmune Encephalitis Research Articles

Contribution of cerebrospinal fluid antibody titers and sex to acute cerebral blood flow in patients with anti-NMDAR autoimmune encephalitis.

The objective of this study was to elucidate the contribution of cerebrospinal fluid (CSF) antibody titers (AT) and sex to acute cerebral blood flow (CBF) in patients diagnosed with anti-N-methyl-d-aspartate receptor autoimmune encephalitis (NMDAR AE). Forty-five patients diagnosed with NMDAR AE were recruited from December 2016 to January 2023. The acute CBF in patients with NMDAR AE at the early stage of the disease was analyzed using arterial spin labeling. The groups were compared based on CSF AT and sex. The connectivity of the CBF in the region of interest was also compared between groups. The patients with different CSF AT exhibited varied brain regions with CBF abnormalities compared to the healthy subjects (p = 0.001, cluster-level FWE corrected). High antibody titers (HAT) in CSF contributed to more brain regions with CBF alterations in female patients than in female patients with low antibody titers (LAT) in CSF (p = 0.001, cluster-level FWE corrected). Female patients with HAT in CSF displayed more decreased CBF in the left post cingulum gyrus, left precuneus, left calcarine, and left middle cingulum gyrus than the male patients with the same AT in CSF (p = 0.001, cluster-level FWE corrected). All patients with NMDAR AE showed increased CBF in the left putamen (Putamen_L) and left amygdala (Amygdala_L) and decreased CBF in the right precuneus (Precuneus_R), which suggests that these are diagnostic CBF markers for NMDAR AE. CSF AT and sex contributed to CBF abnormalities in the patients diagnosed with NMDAR AE. Altered CBF might potentially serve as the diagnostic marker for NMDAR AE.

Anti-N-methyl-D-aspartate Receptor Encephalitis after Herpes Simplex Virus Encephalitis

Abstract Encephalitis due to herpes simplex virus 1 (HSV1) has been described as a potential trigger for the development of anti-N-methyl-D-aspartate receptor (NMDAR) autoimmune encephalitis within few days to months. Here, we report one such case of anti-NMDAR encephalitis which was triggered by preceding HSV encephalitis. The patient had a history of headache and fever of 1–2-week duration, and cerebrospinal fluid and magnetic resonance imaging picture suggestive of HSV encephalitis. After 2 weeks of completion of 14-day course of acyclovir, he had symptoms of altered behavior, headache, and vomiting. The possibility of anti-N-methyl-D-aspartate (NMDA) encephalitis occurring after HSV encephalitis was considered. Serum for anti-NMDA antibody came positive, and he improved with treatment. A high index of suspicion and awareness of such a possibility can help in making the diagnosis and initiate early therapy.

Anti-NMDAR Encephalitis Clinical Practice Guideline: Improving Time to Diagnosis, Treatment, and Hospital Length of Stay.

A clinical practice guideline (CPG) was created to standardize evaluation and treatment for patients with suspected anti-methyl-d-aspartate receptor (NMDAR) autoimmune encephalitis (AE), the most common AE in children. The objective of this study was to evaluate the CPG effect on time to diagnosis, treatment, and hospital length of stay (LOS). Patients with an inpatient consult to pediatric rheumatology for AE during a 4-year period (period 2) after CPG implementation were identified. Data were extracted and compared with data over the preceding 4-year period (period 1). During period 1, fewer patients underwent diagnostic testing than during period 2 (34 vs 80). Number of patients diagnosed with AE did not differ from period 1 to that from period 2 (NMDAR AE 9 vs 8; seronegative AE 4 vs 5). The average time to diagnostic evaluation with lumbar puncture decreased from 5.4 to 1.5 days (p = 0.0082), and time to treatment decreased from 7.6 to 3.9 days (p = 0.018). LOS showed a trend toward improvement (40.4-29.2 days (p = 0.23)). Creation of a CPG for patients with suspected AE was associated with an improved time to diagnostic evaluation and treatment. With the CPG, more patients underwent AE testing, though total diagnoses remained the same.

Pediatric neuroimaging findings and clinical presentations of COVID-19: A systematic review

ObjectivesSymptoms from SARS-CoV-2 infection can involve multiple organ systems. Several reviews discussed the neurologic involvement and neuroimaging findings in adults but research on children is lacking. This study aimed to analyze the incidence of neurologic involvement in patients diagnosed with pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C); and also to summarize current literature on possible neuroimaging findings in SARS-CoV-2 infected children. MethodsA literature search in six electronic databases was performed to retrieve case series, cohort studies, and cross-sectional studies on neurologic involvement in COVID-19 patients younger than 21 years of age published between December 2019 to September 2023, including COVID-19 patients. ResultsA total of 2224 patients with MIS-C from 10 cohorts and cross-sectional studies suggested that neurologic involvement in these subsets ranges from 8.5% to 32.1%. Symptoms included acute encephalitis, seizures, stroke, cranial nerve palsy, nausea/vomiting, and intracranial hypertension. Neuroradiology findings of 114 children from 50 case reports included splenial or acute disseminated encephalomyelitis (ADEM)-like lesions, cytotoxic brain edema, autoimmune demyelinating diseases, ischemic stroke and arteritis, venous thrombosis, intracranial hemorrhage, meningitis, posterior reversible encephalopathy syndrome, anti-N-methyl-D-aspartate receptor autoimmune encephalitis, acute hemorrhagic leukoencephalitis, hydrocephalus, olfactory bulb atrophy, cerebellitis, and acute necrotizing encephalitis. ConclusionRadiologic findings of SARS-CoV-2 infection in the pediatric population are diverse. Neuroimaging studies should be considered in critically ill patients to rule out neurologic involvement and facilitate early interventions.

Neuronal pathomechanisms of anti-AMPA receptor autoimmune encephalitis

Neuronal pathomechanisms of anti-AMPA receptor autoimmune encephalitis

Infectious profiles in pediatric anti-N-methyl-d-aspartate receptor encephalitis

Anti-N-methyl-d-aspartate receptor autoimmune encephalitis (NMDAR AE) is an antibody-mediated neurological disorder that may be caused by post-herpes simplex virus-1 meningoencephalitis (HSV ME) and ovarian teratomas, although most pediatric cases are idiopathic. We sought to evaluate if other infections precede NMDAR AE by conducting a single-center, retrospective, case-control study of 86 pediatric cases presenting to Texas Children's Hospital between 2006 and 2022. HSV ME (HSV-1 and HSV-2) was a significantly more common preceding infection in the experimental group compared to control patients with idiopathic intracranial hypertension, while there was no difference in remote HSV infection between the two groups. Recent Epstein-Barr virus infection was evident in 8/42 (19%) tested experimental patients in comparison to 1/25 (4%) tested control patients which provided evidence for a genuine measure of effect but was not statistically significant due to small sample size (p = 0.07). The other 25 infectious etiologies were not different among the two groups and not all variables were clinically indicated or obtained in every subject, highlighting the need for future standardized, multi-institutional studies on underlying infectious precursors of autoimmune encephalitis.

Arterial Spin Labeling Changes Parallel Asymmetric Perisylvian and Perirolandic Symptoms in 3 Pediatric Cases of Anti-NMDAR Encephalitis.

Anti-NMDA receptor autoimmune encephalitis (NMDAR AE) is an autoantibody-mediated disorder characterized by seizures, neuropsychiatric symptoms, movement disorder, and focal neurologic deficits. Conventionally defined broadly as an inflammatory brain disease, the heterotopic localization is rarely discussed in children. Imaging findings are often nonspecific, and there are no early biomarkers of disease other than the presence of anti-NMDAR antibodies. We conducted a retrospective analysis of our pediatric NMDAR AE cases (as determined by either positive serum or CSF antibodies or both) at Texas Children's Hospital between 2020-2021 and extracted medical record data of those patients who had arterial spin labeling (ASL) as part of their imaging workup for encephalitis. The ASL findings were described in the context of their symptoms and disease courses. We identified 3 children on our inpatient floor, intensive care unit (ICU), and emergency department (ED) settings who were diagnosed with NMDAR AE and had ASL performed as part of their focal neurologic symptom workup. All 3 patients presented with focal neurologic deficits, expressive aphasia, and focal seizures before the onset of other well-characterized NMDAR AE symptoms. Their initial MRI revealed no diffusion abnormalities but uncovered asymmetric and predominantly unilateral multifocal hyperperfusion of perisylvian/perirolandic regions on ASL that correlated with focal EEG abnormalities and their focal examination findings. All 3 patients were treated with first-line and second-line therapies, and their symptoms improved. We found that ASL may be a suitable early imaging biomarker to highlight perfusion changes corresponding to the functional localization of NMDAR AE in pediatric patients. We briefly highlight the neuroanatomic parallels between working models of schizophrenia, chronic NMDAR antagonist administration (ketamine abuse), and NMDAR AE affecting primarily language centers. The regional specificity seen in NMDAR hypofunction may make ASL a reasonable early and specific biomarker of NMDAR AE disease activity. Future studies are necessary to evaluate regional changes in those patients who present with primarily psychiatric phenotypes rather than classical focal neurologic deficits.

Assessment of cognitive status in pediatric anti-NMDA receptor encephalitis during inpatient rehabilitation: A retrospective cohort

ObjectivesAnti-NMDA receptor autoimmune encephalitis (NMDARE) is a common pediatric encephalitis, resulting in neuropsychiatric symptoms. Predicting severity and course is challenging, with objective cognitive assessments lacking in NMDARE, especially in children. The CASE (Clinical Assessment Scale in Autoimmune Encephalitis) measures severity in autoimmune encephalitis. The CALS (Cognitive and Linguistic Scale) assesses cognitive-linguistic recovery in children with acquired brain injury. This study examines severity and cognitive status in pediatric NMDARE by comparing objectives measures: modified Rankin score (mRS), CASE, and CALS. MethodsTwenty-one patients were identified via retrospective chart review with a confirmed NMDARE diagnosis (ages of 3–18 years) who required inpatient rehabilitation. The mRS, CASE, and CALS were assessed at admission and discharge. ResultsScores demonstrated improvement from admission to discharge, with variability in individual recovery trajectories. CALS identified three clusters of patients with differential rates of early recovery. CALS <30 was associated with minimal improvement and poor outcomes. CALS ≥30 had a likelihood ratio score of 12.0 to predict improvement. CASE and CALS were moderately correlated, but neither correlated with mRS. DiscussionCALS and CASE appear to be complementary measures for assessing severity and cognitive status in pediatric NMDARE, including those with low responsiveness, with implications for treatment and outcomes.

Pediatric Anti-NMDA Receptor Autoimmune Encephalitis Masquerading as Depression: A Case Report From a Tertiary Care Center in South India

Abstract Autoimmune disorders are now widely recognized as playing a larger role in encephalitis than previously thought. The most common disorder appears to be anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. Psychological symptoms, memory difficulties, and autonomic instability are all part of the complicated presentation and are being considered an important differential diagnosis for children presenting with acute behavioral disturbances. We present the case of a 17-year-old girl, who presented with a 1.5-year history of psychiatric symptoms such as pervasive low mood, decreased ability to concentrate on her studies, academic decline, memory disturbances along with poor social interaction, decreased self-esteem, and ideas of guilt. This was accompanied by altered biological functions. Within a week, the symptoms changed dramatically, with labile mood, over familiarity, over identification, déjà vu, auditory hallucinations and anxiety symptoms, nonspecific somatic symptoms such as fever, vomiting, and neurological symptoms including seizures and dyskinesia. Diagnosis of anti-NMDAR encephalitis was made by electroencephalography and serum antibody testing. Symptom improvement was noted with five cycles of plasmapheresis and injection of rituximab. Psychiatric manifestations are common, and child and adolescent psychiatrists are frequently the first to be contacted for patients with anti-NMDAR encephalitis. There is, therefore, an increasing need for them to become aware of the disorder and consider it in their differential diagnosis. A better prognosis can be achieved with appropriate evaluation by a multi-disciplinary team.

Late-Onset Anti-NMDA Receptor Auto-Immune Encephalitis in a Patient with a Double Lung Transplant—a Case Report

Late-Onset Anti-NMDA Receptor Auto-Immune Encephalitis in a Patient with a Double Lung Transplant—a Case Report

Association between COVID-19 and catatonia manifestation in two adolescents in Central Asia: Incidental findings or cause for alarm?

Catatonia is a rare neuropsychiatric syndrome that can accompany various medical conditions, including schizophrenia, autoimmune encephalitis, and infectious diseases. We present two cases of catatonia in males aged 12 and 17 years from Central Asia who tested positive for SARS-Cov-2 antibodies. Detailed medical assessments declined other potential precipitating factors, including schizophrenia or anti-NMDA receptor autoimmune encephalitis. FDG-PET in the younger patient demonstrated focal hypometabolism in left frontotemporal and right associative visual cortex, matching patterns previously seen in adults with catatonia. These isolated findings raise concerns about a possible causal relationship between COVID-19 infection and risk of catatonia manifestation in adolescents.

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

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.

Ovarian Teratoma and N-Methyl-D-Aspartate Receptor Autoimmune Encephalitis: Insights Into Imaging Diagnosis of Teratoma and Timing of Surgery

Mature ovarian teratoma is the most common type of germ cell tumor and mostly detected incidentally in women in second or third decade. Recent researches have provided strong evidence between mature ovarian teratoma and encephalitis, which is caused due to the presence of anti-N-methyl-D-aspartate (NMDA) antibodies. We would like to report four patients who had typical neuropsychiatric manifestations, such as abnormal behavior, speech disorder, seizures, movement disorders, loss of consciousness, and autonomic dysfunction. All the patients had prolonged course of disease before the diagnosis of NMDA encephalitis had been made. The importance of timely evaluation of symptomatic young women with serum and cerebrospinal fluid (CSF) NMDA receptor (NMDAR) antibodies is emphasized. Imaging ranging from transvaginal ultrasound to positron emission tomography-computed tomography (PET-CT) will help in arriving at a probable diagnosis. Surgical treatment is the cornerstone of management, and patients responded well post surgery with almost full recovery, with addition of immunotherapy, physiotherapy, rehabilitation providing a vital role. There is significant variation in clinical presentation of encephalitis and thus in time to diagnosis for those with non-specific symptoms, particularly psychiatric ones. The index of suspicion of anti-NMDA encephalitis should be high in young females and involvement of a gynecology team needs to be done. Surgical removal of the teratoma is the key and the gynecology team should not be deterred by the acute symptoms and debilitating nature of the symptoms J Clin Gynecol Obstet. 2021;10(1):22-27 doi: https://doi.org/10.14740/jcgo715

Ovarian Teratoma and N-Methyl-D-Aspartate Receptor Autoimmune Encephalitis: Insights Into Imaging Diagnosis of Teratoma and Timing of Surgery

Ovarian Teratoma and N-Methyl-D-Aspartate Receptor Autoimmune Encephalitis: Insights Into Imaging Diagnosis of Teratoma and Timing of Surgery

Nonparaneoplastic anti-NMDA receptor autoimmune encephalitis presenting as psychosis: A case report.

Nonparaneoplastic anti-NMDA receptor autoimmune encephalitis presenting as psychosis: A case report.

Case Report: Refractory Hypotension of GABA B Receptor Autoimmune Encephalitis

Introduction: With the development of antibody detection technology, Gamma-Aminobutyric Acid (GABA) B receptor encephalitis is a known autoimmune disease. This paper describes a patient with refractory hypotension who suffered GABA B receptor autoimmune encephalitis.Case Report: We describe a 63-year-old man with GABA B receptor autoimmune encephalitis who had hypotension on day 17 of the disease onset. Despite two rounds of immunoglobulin administration, high-dose intravenous steroid injections and immunosuppressive therapy on day 35 of hospitalization, psychiatric symptoms and seizures were significantly improved; however, the patient's blood pressure remained low.Conclusion: This case study and literature review investigated the impairment of autonomic nerve function and its subsequent management in patients with GABA B receptor autoimmune encephalitis.

Early Diagnosis and Treatment of N-Methyl D-Aspartate Receptor Autoimmune Encephalitis in Children

Background: Acute pediatric encephalitis is a debilitating neurological disorder that develops as a rapidly progressive encephalopathy (usually in less than 6 weeks) due to brain inflammation, autoimmune encephalitis (AE) is a heterogeneous group of recently identified disorders. Despite severe and even prolonged neurologic deficits, dramatic improvements may occur with proper immunotherapy in some patients with AE. Anti-neuronal antibodies have been discovered in cerebrospinal fluid (CSF) of patients, Aim and Objectives: The aim of the current study was to test the relation of early diagnosis with treatment of N-methyl D- Aspartate Receptor autoimmune encephalitis. Patients and Methods: This is Prospective observational cohort study that was carried out at pediatric department, Faculty of Medicine, Zagazig University, the study was conducted on 36 cases, Results: There was no statistical significant difference between the studied groups with and without autoimmune encephalitis regarding results of CSF analysis (larger percentage without autoimmune encephalitis had abnormal CSF analysis). There is a statistical significant difference between the studied groups with and without autoimmune encephalitis regarding prognosis. Conclusion: CSF NMDAR antibodies are highly sensitive biomarker in prediction of mortality and poor prognosis of encephalitis in children.

Differential Diagnosis of Autoimmune Encephalitis from Infectious Lymphocytic Encephalitis by Analysing the Lymphocyte Subsets of Cerebrospinal Fluid.

This study is aimed at investigating the lymphocyte subsets of cerebrospinal fluid (CSF) to provide possible differential diagnostic values and better understand the pathophysiological mechanism underlying autoimmune encephalitis (AE) and infectious lymphocytic encephalitis. A series of CD markers, including CD3/4/8/20 representing different types and developmental stages of lymphocytes, were used to count the corresponding subpopulations of CSF from clinical and laboratory confirmed cases of anti-N-methyl-D-aspartate receptor AE (NMDAR-AE), herpes simplex virus encephalitis (HSVE), and tuberculous meningitis (TBM). The percentages of lymphocytes observed and the CD4 : CD8 ratios were compared between the three groups. There were no significant differences of the percentage of total lymphocytes, CD3 cells, and CD4 cells of CSF among each group. However, there were strongly statistical differences of the CD4 : CD8 ratio in CSF of each group with 0.6 : 1 in NMDAR-AE, 0.9 : 1 in HSVE, and 3.2 : 1 in TBM. The percentage of CD20 B lymphocytes in NMDAR-AE was statistically higher than that of other groups. The distinct percentages of lymphocyte subpopulations of CSF appeared to be characteristic and could potentially serve as diagnostic indicators. Further verification and research will be necessary to clarify the significance and nature of CD4 : CD8 ratios and B lymphocytes in CSF between AE and the infectious lymphocytic encephalitis.

Two Case Reports of Neuropsychological Outcomes following Pediatric anti-N-methyl D-aspartate Receptor Autoimmune Encephalitis

ABSTRACTAnti-NMDAR autoimmune encephalitis is a rare neurological condition. Limited existing pediatric case studies have shown mild, but persisting, neuropsychological impairments. This report described neuropsychological functioning in two patients treated for anti-NMDAR autoimmune encephalitis. Patient A is a 16-year-old male (10 months after symptom onset) and Patient B is a 5-year-old female (45 months after symptom onset). Contrary to expectations, their cognitive profiles were largely intact, raising the possibility of minimal cognitive implications for some pediatric patients with this condition. Additional research is needed to identify factors that contribute to better cognitive outcomes in children with anti-NMDAR autoimmune encephalitis.

A Simple Cell-based Immunofluorescence Assay to Detect Autoantibody Against the N-Methyl-D-Aspartate (NMDA) Receptor in Blood.

The presence of anti-NMDA receptor autoantibody can cause various neuropsychiatric symptoms in the affected patients, termed anti-NMDA receptor autoimmune encephalitis. Detection of the specific autoantibody against the NMDA receptor in the blood or cerebrospinal fluid (CSF) is essential for the accurate diagnosis of this condition. The NMDA receptor is an ion channel protein complex that contains four subunits, including two mandatory NMDA receptor subunit 1 (NR1) and one or two NMDA receptor subunit 2A (NR2A), NMDA receptor subunit 2B (NR2B), NMDA receptor subunit 2C (NR2C), or NMDA receptor subunit 2D (NR2D). The epitope of anti-NMDA receptor autoantibody was reported to be present at the extracellular N-terminal domain of the NR1 subunit of the NMDA receptor. The goal of this study is to develop a simple cell-based immunofluorescence assay that can be used as a screening test to detect the presence of autoantibodies against NR1 subunit of the NMDA receptor in the blood to facilitate the clinical and basic research of anti-NMDA receptor autoimmune encephalitis.