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Objective: In adult anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis, corticosteroids are commonly used as first‐line treatment. However, the optimal oral prednisone tapering (OPT) following intravenous methylprednisolone pulse therapy remains unclear. We aim to compare the efficacy and safety of different OPT courses in anti‐NMDAR encephalitis. Methods: The CHASE study, a multicenter prospective observational cohort study, enrolled patients with autoimmune encephalitis from October 2011 to March 2023. Patients were grouped based on oral prednisone tapering course: ≤3 months (Group ≤3 month), 3–6 months (Group 3–6 months, including 3 months), and >6 months (Group > 6 months). Kaplan–Meier plots were used to analyze time to relapse and time to total recovery within 2 years. Results: Among 666 screened patients, 171 (median [IQR] age 27 [21.0–36.5] years, 55.0% female) met selection criteria. Responders at 3 months were prevalent in Group ≤3 months (OR 7.251 [95% CI 2.252 to 23.344] and Group 3–6 months (OR, 3.857 [95% CI 1.107 to 13.440] than in Group >6 months. Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores at 12 months were higher in Group >6 months than in Group ≤3 months and Group 3–6 months (β, −2.329 [95% CI −3.784 to −.875]; β, −2.871 [95% CI −4.490, −1.253]). CASE seizures subscore was higher in Group >6 months than in Group 3–6 months (β, −.452 [95% CI −.788 to −.116]). No significant difference in seizure freedom rates among the groups. Adverse events were higher in Group 3–6 months and Group >6 months than in Group ≤3 months (OR 6.045 [95% CI 2.352 to 15.538]; OR 6.782 [95% CI 1.911 to 24.073]). Significance: Longer oral prednisone courses for adult patients with anti‐NMDAR encephalitis did not show superior effects compared to shorter courses in improving modified Rankin Scale (mRS) scores and CASE scores, reducing the risk of relapse within 2 years, or achieving seizure freedom. Instead, extended prednisone courses may lead to more side effects— particularly weight gain. This outcome recommends evaluating the possibility of shortening the duration of oral prednisone after a thorough patient assessment. [ABSTRACT FROM AUTHOR]

Anti‐N‐methyl‐D‐aspartate receptor (anti‐NMDAR) encephalitis is the most commonly identified cause of autoimmune encephalitis. Therapeutic plasma exchange has been increasingly employed to treat this disease. This expansion is a consequence of improved techniques and apheresis instruments, as well as the recognition of its applicability in neurological diseases. However, several aspects of treatment remain incompletely clarified, and treatment strategies are still heterogeneous, especially with regard to therapeutic plasma exchange in anti‐NMDAR encephalitis. This review provides an overview of the use of therapeutic plasma exchange including the principle and mechanisms, the evidence, initial time, efficiency and complications in anti‐NMDAR encephalitis. [ABSTRACT FROM AUTHOR]

Background and purpose: Anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis is characterized by a range of cognitive impairments, especially in executive function. Our study aims to identify the abnormal regional homogeneity (ReHo) in anti‐NMDAR encephalitis patients and its relationship with the executive function. Methods: Forty patients and 42 healthy volunteers undertook an Attention Network Test and a resting‐state functional magnetic resonance imaging scan. ReHo analysis was performed to investigate the neuronal activity synchronization in all subjects. Based on ReHo analysis, a multivariate pattern analysis (MVPA) was carried out to identify the brain regions that differed the most between the two groups. Results: Compared to controls, the patients had higher executive control scores (p < 0.05). The patients presented reduced ReHo values in the bilateral posterior cerebellar lobe, anterior cerebellar lobe, midbrain, bilateral caudate nucleus, right superior frontal gyrus, right middle temporal gyrus, bilateral inferior parietal lobule and the left middle frontal gyrus. The ReHo values of the bilateral inferior parietal lobule in patients were found to be negatively associated with executive control scores. The classification of patients and controls using MVPA had an accuracy of 76.83%, a sensitivity of 82.50%, a specificity of 71.43% and the area under the curve was 0.83. Conclusions: Our study provides evidence of abnormal cerebral function in anti‐NMDAR encephalitis patients, which may contribute to unveiling the neuropathological mechanisms of anti‐NMDAR encephalitis and their influences on executive dysfunction. The MVPA classifier, based on ReHo, is helpful in identifying anti‐NMDAR encephalitis patients from healthy controls. [ABSTRACT FROM AUTHOR]

Aim: Anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis is one of the autoimmune encephalitis, which often occurs in children and young adults, especially in young women. In addition to viral infection, teratoma is an important causative factor. Anti‐NMDAR encephalitis is well known to neurologist. However, this is less well known to gynecologists, who may have a decisive role in etiological management. Therefore, from the perspective of gynecologists, we provide an overview of the relationship between the encephalitis and ovarian teratoma, the clinical features and treatment of this disease, and prognosis of pregnant women with this encephalitis. Methods: We searched the PubMed database using the search terms in various combinations "teratoma," "dermoid cyst," "ovary," "ovarian," "anti‐NMDAR encephalitis," and "N‐methyl‐D‐aspartate receptor." Results: According to the current literature, the mechanism of anti‐NMDAR encephalitis is probably due to the ectopic expression of the NMDAR in the teratomas tissue. The disease has a high mortality rate if not treated promptly and effectively. An important way to improve patients' outcome is to remove the ovarian tumor in time. Pregnant women are also at risk of developing anti‐NMDAR encephalitis during pregnancy. The fetal outcome is usually better in patients with mid‐ to late‐pregnancy onset than in early pregnancy, and patients are often able to maintain their pregnancies into late pregnancy. Conclusion: Young women with sudden onset of abnormal psychiatric behavior should be actively screened for ovarian tumors and, if confirmed to be teratoma‐associated anti‐NMDAR encephalitis, should undergo gynecologic surgery as early as possible, which can help improve their prognosis. [ABSTRACT FROM AUTHOR]

Aims: To explore large‐scale brain network alterations and examine their clinical and neuropsychological relevance in patients with anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis. Methods: Twenty‐four patients with anti‐NMDAR encephalitis and 26 matched healthy controls (HCs) were enrolled in our study. Based on the multimodal MRI dataset, individual morphological, structural, and functional brain networks were constructed and compared between the two groups at multiple levels. The associations with clinical/neuropsychological variables and the discriminant ability of significant alterations were further studied. Results: Multimodal network analysis revealed that anti‐NMDAR encephalitis mainly affected morphological and structural networks, but subtle alterations were observed in functional networks. Intriguingly, decreased network local efficiency was observed for both morphological and structural networks and increased nodal centrality in the lateral orbital gyrus was convergently observed among the three types of networks in the patients. Moreover, the alterations, particularly those from structural networks, accounted largely for cognitive deficits of the patients and could distinguish the diseased individuals from the HCs with excellent performance (area under the curve =0.933). Conclusions: The current study provides a comprehensive view of characteristic multimodal network dysfunction in anti‐NMDAR encephalitis, which is crucial to establish new diagnostic biomarkers and promising therapeutic targets for the disease. [ABSTRACT FROM AUTHOR]

Background and purpose: Autoantibodies targeting the GluN1(NR1) subunit of the anti‐N‐methyl‐D‐aspartate receptor (NMDAR) cause encephalitis. Although it has been shown that anti‐NMDAR encephalitis is associated with human leukocyte antigen (HLA) loci, susceptibility genes for the disease outside the HLA loci remain unidentified. In this study, we aimed to explore the association of anti‐NMDAR encephalitis with non‐HLA genes. Methods: Two Chinese anti‐NMDAR encephalitis cohorts from Han populations were recruited for this study. The North Chinese case–control set consisted of 98 patients and 460 controls, while the South Chinese case–control set included 78 patients and 541 controls. All participants were genotyped for 28 single nucleotide polymorphisms that are associated with autoimmune disorders or infectious diseases. Results: In two independent case–control sets, we identified significant associations of anti‐NMDAR encephalitis with IRF7 rs1131665 (odds ratio [OR] 3.34, 95% confidence interval [CI] 1.99–5.63; P < 0.000001, Padjusted = 0.00004), BANK1 rs4522865 (OR 1.44, 95% CI 1.15–1.82; P = 0.0017, Padjusted = 0.0149), and TBX21 rs17244587 (OR 2.03, 95% CI 1.35–3.05; P = 0.00051, Padjusted = 0.0066). Furthermore, analysis of the three polymorphisms with clinical features of the disease revealed that the IRF7 rs1131665 was associated with tumor status. Conclusion: The present study has for the first time identified non‐HLA susceptibility genes for anti‐NMDAR encephalitis. The association of IRF7, BANK1 and TBX21 with anti‐NMDAR encephalitis suggests that B‐cell activation, Th1 responses, virus infection and the type I interferon signaling pathway are involved in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Objective: We reviewed the psychotic symptoms of anti‐NMDA receptor encephalitis (NMDARE) to differentiate its presentation from those found in a primary psychiatric disorder. We hypothesized that the cycloid psychosis (CP) phenotype would be a frequent clinical presentation in the psychiatric phase of NMDARE. Method: A systematic literature review in PubMed of all case reports published on NMDARE was performed from database inception to March 2020. We included all cases where psychotic symptoms were reported and whose diagnoses were confirmed by the presence of anti‐NMDAR antibodies in the cerebrospinal fluid (CSF). An email including a short test (CP phenotype, Perris and Brockington's criteria) was sent to all case report authors asking them to describe the psychotic symptoms. Results: We identified 335 case reports fulfilling our criteria, and the authors of 200 replied. Our analyses were based exclusively on those answers and data extracted from the articles. Median patient age was 25 years (+‐11.4), 81% were female, and 39% had an ovarian teratoma. A complete CP phenotype was identified in 175 patients (87%). These were acute psychotic episodes with a sudden onset and a fluctuating clinical pattern mostly characterized by confusion (97%), delusions (75%), hallucinations (69%), motility disturbances (87%), and mood oscillations (80%). Conclusion: The complete CP phenotype was frequently the expression of psychotic symptoms in NMDARE. We suggest that patients with a first psychotic episode who initially exhibit the CP phenotype should undergo CSF analysis to determine whether antibodies against neuronal cell surface or synaptic receptors are present to rule out a possible diagnosis of autoimmune encephalitis. [ABSTRACT FROM AUTHOR]

Background: Acute encephalitis refers to inflammation of the brain that develops as a rapidly progressive encephalopathy. It usually has an infectious origin, but an increasing number of autoimmune etiologies have been identified recently. Keeping a high index of suspicion is of great importance, because delayed diagnosis and delayed initiation of appropriate therapy may lead to poor outcome. Case presentation: This paper describes a case of anti‐N‐methyl‐D‐aspartate receptor (anti‐NMDAR) encephalitis in a young female who presented with a short prodrome; had a rapidly progressive illness; and could not be saved even after early, optimal, and aggressive immunomodulatory therapy. Conclusions: Despite early diagnosis, and prompt therapy, anti‐NMDAR encephalitis may progress and remain refractory to treatment. More studies are needed for further therapeutic avenues in treatment‐refractory cases of anti‐NMDAR encephalitis not responding even to cyclophosphamide as highlighted by our case. [ABSTRACT FROM AUTHOR]

Objectives: Seizures are a prominent feature of anti–N‐methyl‐d‐aspartate receptor (anti‐NMDAR) encephalitis. Nearly half of brain magnetic resonance image (MRI) results are abnormal. The aim of our study was to evaluate the associations between seizures and brain MRI results in patients with anti‐NMDAR encephalitis. Methods: Patients with anti‐NMDAR encephalitis were enrolled between January 2015 and December 2018. The patients included were divided into normal and abnormal MRI groups. Seizure outcomes and modified Rankin Scale scores at the 1‐year follow‐up were assessed. Seizure characteristics and outcomes were compared between groups. Results: Of 35 patients with anti‐NMDAR encephalitis, 28 patients (80%) had reported seizures in the acute phase. Patients with abnormal MRI findings more frequently had focal seizures than patients with normal MRI findings (72.7% vs 17.6%, P <.01). The incidence of patients treated with 2 or more antiepileptic drugs was higher in the normal MRI group than in the abnormal MRI group (100% vs 45.4%, P <.01). The onset‐immunotherapy time was shorter in the abnormal MRI group than in the normal MRI group (P <.05). There were no statistically significant differences in seizure outcomes between the normal and abnormal MRI groups (P >.05). Conclusions: Focal seizures were most common in patients with abnormal MRI lesions. In the acute stage of the disease, the abnormal MRI group was more likely than the normal MRI group to achieve seizure control. Abnormal MRI findings did not affect the overall good prognosis of patients with anti‐NMDAR encephalitis with seizures. [ABSTRACT FROM AUTHOR]

Seizure is one of the main symptoms of anti‐NMDAR encephalitis, but data of ictal electroencephalogram (EEG) patterns remain limited. In this study, we aimed to introduce a unique ictal pattern. This delta brush variant (DBV) was characterized as generalized delta rhythm with fast spike activity riding on it. We retrospectively evaluated the ictal pattern from six patients with anti‐NMDAR encephalitis, and patients were grouped based on the presence of DBV. DBV was found in two patients who were in the florid phase of the disease: (a) A 17‐year‐old girl experienced rhythmical jerking of bilateral limbs. Corresponding EEG patterns showed generalized DBV. Seizure terminated after intravenous injection of midazolam, but oral‐facial dyskinesia reappeared; and (b) a 24‐year‐old man suffered stiffening of the right limbs and oral‐facial dyskinesia. The EEG pattern showed frontal DBV with left prominence. Seizure was controlled, but oral‐facial dyskinesia remained after intravenous injection of midazolam. Compared with patients without DBV, patients in this group were more likely to have prolonged excessive delta brush (100% vs 25%) and hyperpyrexia (39.7℃ vs 38.2℃). Duration in ICU (36 days vs 18 days) and hospital (52 days vs 36 days) was relatively longer in DBV group, and no significant difference was found in terms of the mRS score (1 vs 0.5) and seizure relapse rate (0% vs 25%) during 3‐month follow‐up. DBV is a peculiar pattern in anti‐NMDAR encephalitis. An EEG‐based monitoring should be considered to avoid misleading this ictal EEG pattern to the electromyographic artifact. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the long‐term cognitive or neuropsychiatric outcomes and potential risk factors associated with prolonged cognitive deficits or neuropsychiatric symptoms in patients with anti‐N‐methyl‐D‐aspartate receptor (anti‐NMDAR) encephalitis. Methods: In this cohort follow‐up study, patients with a definitive diagnosis of anti‐NMDAR encephalitis from the inpatient of West China Hospital between June 2012 and December 2017 were included and underwent a prospective cognitive and neuropsychiatric assessment every 3 months by cognitive impairment rating scale, Neuropsychiatric Inventory (NPI) and/or Montreal Cognitive Assessment. Results: Up to 97.5% patients had severe cognitive deficits and neuropsychiatric symptoms in acute phase. Decreasing proportion of patients with prolonged cognitive deficits was observed and time dependent. At 2 years' follow‐up, 7.8% of patients with cognitive deficits were unable to complete some previous activities or return to work. The risk factors associated with persistent cognitive deficits included age of disease onset over 40 years old (HR, 1.77; 95% CI, 1.11‐2.82; P = .01) and with clinical relapses (HR, 2.22; 95% CI, 1.21‐4.09; P = .02). The predictors of prolonged neuropsychiatric symptoms included clinical relapses (HR, 2.79; 95% CI, 1.21‐6.43; P = .02). Among the 12 neuropsychiatric symptoms of NPI, irritability was shown as the most prevalent and persistent. Conclusions: Combined cognitive and neuropsychiatric assessment and intervention are essential elements of comprehensive care of anti‐NMDAR encephalitis. [ABSTRACT FROM AUTHOR]

The article presents case study of 12-year-old girl with anti-N-methyl-D-aspartate encephalitis. Topics include The patient had not exhibited any immunodeficiency signs, so the reason why she had such protracted methicillin-susceptible Staphylococcus epidermis's., an attenuated bacterium, infection remains unclear. The pre-existing tubulointerstitial changes were attributable her remaining urine abnormalities.

Background: Anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system (CNS). Interleukin (IL)‐6 and IL‐17A may play important roles in the pathogenesis of this disease. High‐mobility group box protein 1 (HMGB1), a small but highly conserved ubiquitous protein, is recognized to be a potent innate inflammatory mediator that can activate the nuclear factor light chain enhancer of activated B cells and release cytokines such as IL‐6 and IL‐17A when released extracellularly. However, whether cerebrospinal fluid (CSF) HMGB1 levels are altered in anti‐NMDAR encephalitis is still unclear. Objective: The aim of this study was to determine whether a correlation exists between the CSF concentrations of HMGB1 and IL‐6 and IL‐17A in anti‐NMDAR encephalitis patients. We also sought to assess whether HMGB1 influences the clinical outcomes in anti‐NMDAR encephalitis patients. Methods: Thirty‐three patients with anti‐NMDAR antibodies and 38 controls were recruited. CSF HMGB1 was measured using an enzyme‐linked immunosorbent assay. The main clinical outcomes were evaluated using the modified Rankin scale (mRS). The data were extracted using microarray analysis software. Results and Conclusion: Our results showed significant increases in CSF HMGB1, IL‐6, and IL‐17A (P < .05) in anti‐NMDAR encephalitis patients. But between 3 months’ mRS scores in anti‐NMDAR encephalitis patients and CSF data, there was no correlation. Our study suggests that HMGB1 CSF levels are increased in patients with anti‐NMDAR encephalitis and reflect the underlying neuroinflammatory process. [ABSTRACT FROM AUTHOR]

Objective To evaluate the long-term seizure outcome and potential factors associated with seizure outcome in patients with anti- N-methyl- d-aspartate receptor (anti- NMDAR) encephalitis. Methods In the setting of a prospective, single-center, longitudinal cohort study, 109 patients were evaluated with ongoing follow-up. Patients underwent clinical evaluation every 3 months. Seizure outcomes and the potential risk factors were assessed with a median follow-up of 24 months (6-60 months). Results Of 109 patients (47 men; 62 women) with anti- NMDAR encephalitis, 88 patients (80.7%) had reported seizures at acute phase, including single seizure (17/88, 19.3%), repetitive seizures (27/88, 30.7%), nonrefractory status epilepticus (22/88, 25%), refractory status epilepticus (SE; 13/88, 14.8%), and super refractory status epilepticus (9/88, 10.2%). Seizure was more likely to recur in patients with tumor presence, status epilepticus ( SE) development, coma, or intensive care unit (ICU) admission in the acute phase (p < 0.05). Seizure freedom was achieved within 2 years in all patients. More than 80% of the whole cohort with acute seizures had their last seizure within 6 months of disease onset. Significance Seizure is a common feature in the acute stage of anti- NMDAR encephalitis but not thereafter. The presence of tumor, SE, coma, and/or ICU admission in the acute phase predicts early seizure occurrence after the acute phase. Seizure freedom was typically achieved in our follow-up, and long-term use of antiepileptic drugs may not be necessary. [ABSTRACT FROM AUTHOR]

In recent years, autoantibodies to proteins or receptors expressed on the surface of neurons have been detected in movement and psychiatric disorders. These autoantibodies can assist in better recognition of clinical syndromes and offer novel treatment opportunities via immunotherapies, potentially leading to improved patient outcome. In this review, we describe several autoimmune syndromes associated with movement and psychiatric disorders, including anti- N-methyl- d-aspartate receptor encephalitis, basal ganglia encephalitis, Sydenham chorea, and autoantibody-associated psychosis and schizophrenia. However, rather than focusing on clinical aspects of these diseases, as they have been reviewed in detail elsewhere, we mainly focus on the scientific aspects of the different methodologies for detecting antibodies, with an emphasis on the current gold standard in the field, the cell-based assay, and on issues related to the use of live versus permeabilized cells. We also reflect on the implications associated with the choice of patient serum and cerebrospinal fluid for antibody testing, on the mechanism of antibody entry into the central nervous system through the blood-brain barrier, and the essential issue of antibody pathogenicity. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Movement disorders are frequent but difficult to characterize in patients with anti- N-methyl- d-aspartate receptor ( NMDAR) encephalitis. Methods The phenomenology of movement disorders was characterized after a detailed examination of children with anti- NMDAR-encephalitis. Results We studied 9 children (5 females), ages 3-14 years, with confirmed anti- NMDAR-encephalitis. All patients presented with at least 1 movement disorder, including chorea (n=4), stereotypic movements (n=4), ataxia (n=3), limb dystonia (n=2), limb myorhythmia (n=2), oromandibular dystonia (n=2), facial myorhythmia, blepharospasm, opisthotonus, athetosis, and tremor (n=1, each). More than a single movement disorder was observed in 6 of these patients. Resolution of the abnormal movements was observed in all patients with immunotherapy; 1 patient improved with tetrabenazine. Conclusions A wide variety of movement disorders, often in combination, can be observed in children with anti- NMDAR encephalitis. Patients commonly present with more than a single movement disorder. © 2013 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background: Neurofilaments (Nf) are a series of highly specific scaffolding proteins of neurons. Neurofilament light chains (Nf‐L) and the heavy one (Nf‐H) are subunits of Nf, and they are recognized as potent productions of neural damage. The concentrations of Nf aggrandized significantly in neurological disease including neuromyelitis optica, multiple sclerosis, and Alzheimer's disease. However, whether Nf in cerebrospinal fluid (CSF) elevated in anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis is unclear. Here, we aimed to detect whether CSF Nf is altered in NMDAR and whether changes in CSF Nf can serve as an objective and effective biomarker to evaluate disease severity and prognosis. Methods: We collected 24 anti‐NMDAR encephalitis patients, 11 viral meningoencephalitis/encephalitis (VM) patients, and 21 controls in this study. CSF Nf‐L, Nf‐H, and cytokine levels (IL‐1β, IL‐6, and IL‐17A) were determined by enzyme‐linked immunosorbent assay (ELISA) and compared between groups. We evaluated patients' clinical outcomes or prognosis according to modified Rankin scale (mRS) score. Results: Compared with controls, both CSF Nf‐L and Nf‐H levels were significantly increased in anti‐NMDAR encephalitis patients. While compared with VM patients, only Nf‐L were increased in anti‐NMDAR encephalitis patients. Moreover, CSF Nf‐L were positively correlated with concentration of cytokines (IL‐1β, IL‐17A) and mRS scores in anti‐NMDAR encephalitis patients. After treatment, both CSF Nf‐L and Nf‐H levels decreased. Furthermore, the Nf‐L during follow‐up positively correlated with 3‐month mRS scores, and ΔNf‐L positively correlated with ΔmRS. Conclusions: Briefly, CSF Nf‐L levels notably increased in anti‐NMDAR encephalitis patients in acute phase and positively correlated with disease severity. It could be considered as a useful indicator for clinical outcomes and prognosis. [ABSTRACT FROM AUTHOR]