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Background: Combined first-line therapies have been frequently adopted for patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Plasma exchange (PE) or immunoadsorption (IA) was used as an add-on option following initial immunotherapies, including high-dose steroids and intravenous immunoglobulin (IVIG). However, whether a shorter delay of PE or IA can improve the early recovery prognosis of patients with anti-NMDAR encephalitis remains largely unknown. Objective: To compare short-term clinical improvement between patients with early and late initiation of PE or IA in anti-NMDAR encephalitis. Design: A retrospective study was conducted for patients admitted with anti-NMDAR encephalitis between January 2015 and December 2023 (n = 29), including 21 patients who received PE or IA as synergistic therapies. Methods: The clinical prognosis was compared between the early PE/IA group and the late PE/IA group in the research. Primary outcome included changes in the Clinical Assessment Scale for Autoimmune Encephalitis (∆CASE) at 90 and 120 days after encephalitis onset. Secondary outcomes included changes in the modified Rankin scale (∆mRS) after 90 and 120 days from encephalitis onset, and the length of intensive care unit (ICU) stay for patients with severe anti-NMDAR encephalitis. Results: The ∆CASE scores after 90 and 120 days from encephalitis onset revealed a significant difference between patients with early and late initiation of PE or IA (p ⩽ 0.05). A significant difference in the ∆mRS was also found between patients with early and late initiation of PE or IA in severe encephalitis (p ⩽ 0.05). No significant difference was found in the length of ICU admission (p = 0.101). Conclusion: Our findings emphasize the importance of considering PE or IA as early as feasible for patients with anti-NMDAR encephalitis, even when steroids and IVIG are in use. [ABSTRACT FROM AUTHOR]

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]

Background: Encephalitis associated with antibodies against the N-methyl-Daspartate receptor (NMDAR) results in a distinctive neuro-psychiatric syndrome. It has been reported that the serum phenylalanine-tyrosine (Phe/Tyr) ratio increases during infection. However, the connection between phenylalaninetyrosine metabolism and psychiatric symptoms remains unclear. Methods: We enrolled 24 individuals with anti-NMDAR encephalitis and 18 individuals with non-inflammatory neurological diseases (OND). Chromatography was used to measure serum levels of phenylalanine and tyrosine. Serum and cerebrospinal fluid (CSF) TNF-a levels were obtained from the clinical database. The modified Rankin Scale (mRS) score and Glasgow Coma Scale (GCS) score were recorded during the acute phase. The area under the curve (AUC) of the receiver operating characteristic curve was used to assess prediction efficacy. Results: In NMDAR patients, levels of serum Phe and the ratio of serum Phe/Tyr were higher compared to OND patients. The serum Phe/Tyr ratio was also elevated in NMDAR patients with psychiatric syndrome. Furthermore, serum Phe and Tyr levels were correlated with inflammatory indexes. Conclusion: The serum Phe/Tyr ratio is elevated in NMDAR patients with psychiatric syndrome and is associated with severity. Therefore, the serum Phe/Tyr ratio may serve as a potential prognostic biomarker. [ABSTRACT FROM AUTHOR]

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder with a variety of clinical manifestations. It has been established that anti-NMDAR encephalitis may be related to ovarian teratoma in female patients. However, a considerable number of patients have no obvious evidence of ovarian teratoma during the onset of the disease. Case: A 25-year-old previously-healthy female experienced a series of acute symptoms within two days, including confusion, disorientation, short-term memory loss, auditory hallucinations, abnormal behavior, refractory status epilepticus, etc. Her brain MRI and abdominal imaging showed no definite abnormality while her electroencephalogram exhibited the presence of low to moderate amplitude sharp, spike, and multi-spike waves. Serum and cerebrospinal fluid tests yielded positive results for anti-NMDAR antibodies. However, an ultrasound scan failed to identify an ovarian teratoma. Consequently, the diagnosis of anti-NMDAR encephalitis without teratoma was made after 4 days onset. After the plasma exchange and immunoglobulin therapy, her neurological symptoms improved and obtained a clinical cure. In the next eight months of follow-up, the patient accidentally touched a lump in the lower abdomen without any symptoms, and abdominal ultrasound and CT scan revealed a left ovarian tumor. Then she underwent left ovarian teratoma resection surgery and histopathology showed a mature cystic teratoma with neural components. The patient continued to receive five years of follow-up, and her condition remained stable without any recurrence, except that there had been a low titer of anti-NMDAR antibody in her serum. Conclusion: Our case demonstrated the importance of long-term follow-up for female patients with anti-NMDAR encephalitis, since anti-NMDAR encephalitis-associated ovarian teratomas may develop in a delayed manner, even without any symptoms. [ABSTRACT FROM AUTHOR]

Introduction: This study was designed to analyze clinical and radiographic features of adult patients coexisting with NMDAR-IgG and MOG-IgG. Methods: Eleven adult patients coexisting with NMDAR-IgG and MOG-IgG were collected from Xiangya Hospital, Central South University, between June 2017 and December 2021. Fifty-five patients with anti-NMDAR encephalitis and 49 with MOG-AD were served as controls. Results: Onset age was 27 (IQR 20–34) years old. Seizures and psychotic symptoms were prominent symptoms. Ten of eleven patients presented abnormal T2/FLAIR hyperintensity, mainly involving the cortex, brainstem, and optic nerve. Compared with the NMDAR IgG (+)/MOG IgG (−) group, the NMDAR IgG (+)/MOG IgG (+) group showed more ataxia symptoms (27.3% vs. 3.6%, P = 0.037), while more T2/FLAIR hyperintensity lesions were found in the brainstem (54.5% vs. 7.3%, P < 0.001) and optic nerve (27.3% vs. 1.8%, P = 0.011) with more abnormal MRI patterns (90.9% vs. 41.8%, P = 0.003). In comparison with the NMDAR IgG (−)/MOG IgG (+) group, the NMDAR IgG (+)/MOG IgG (+) group had more seizures (72.7% vs. 24.5%, P = 0.007) and mental symptoms (45.5% vs. 0, P < 0.001). The NMDAR IgG (+)/MOG IgG (+) group tended to be treated with corticosteroids alone (63.6% vs. 20.0%, P = 0.009), more prone to recur (36.5% vs. 7.3%, P = 0.028) and lower mRS score (P = 0.036) at the last follow-up than pure anti-NMDAR encephalitis. Conclusion: The symptoms of the NMDAR IgG (+)/MOG IgG (+) group were more similar to anti-NMDAR encephalitis, while MRI patterns overlapped more with MOG-AD. Detecting both NMDAR-IgG and MOG-IgG maybe warranted in patients with atypical encephalitis symptoms and demyelinating lesions in infratentorial regions. [ABSTRACT FROM AUTHOR]

Objective: The alterations of the functional network (FN) in anti-N-methyl-Daspartate receptor (NMDAR) encephalitis have been recognized by functional magnetic resonance imaging studies. However, few studies using the electroencephalogram (EEG) have been performed to explore the possible FN changes in anti-NMDAR encephalitis. In this study, the aim was to explore any FN changes in patients with anti-NMDAR encephalitis. Methods: Twenty-nine anti-NMDAR encephalitis patients and 29 age- and gender-matched healthy controls (HC) were assessed using 19-channel EEG examination. For each participant, five 10-second epochs of resting state EEG with eyes closed were extracted. The cortical source signals of 84 Brodmann areas were calculated using the exact low resolution brain electromagnetic tomography (eLORETA) inverse solution by LORETA-KEY. Phase Lag Index (PLI) matrices were then obtained and graph and relative band power (RBP) analyses were performed. Results: Compared with healthy controls, functional connectivity (FC) in the delta, theta, beta 1 and beta 2 bands significantly increased within the 84 cortical source signals of anti-NMDAR encephalitis patients (p < 0.05) and scalp FC in the alpha band decreased within the 19 electrodes. Additionally, the anti-NMDAR encephalitis group exhibited higher local efficiency and clustering coefficient compared to the healthy control group in the four bands. The slowing band RBP increased while the fast band RBP decreased in multiple-lobes and some of these changes in RBP were correlated with the modified Rankin Scale (mRS) and Mini-mental State Examination (MMSE) in anti-NMDAR encephalitis patients. Conclusions: This study further deepens the understanding of related changes in the abnormal brain network and power spectrum of anti-NMDA receptor encephalitis. The decreased scalp alpha FC may indicate brain dysfunction, while the increased source beta FC may indicate a compensatory mechanism for brain function in anti-NMDAR encephalitis patients. These findings extend understanding of how the brain FN changes from a cortical source perspective. Further studies are needed to detect correlations between altered FNs and clinical features and characterize their potential value for the management of anti-NMDAR encephalitis. [ABSTRACT FROM AUTHOR]

Patients with autoimmune encephalitis (AE) often developed psychiatric features during the disease course. Many studies focused on the psychiatric characteristic in anti-NMDAR encephalitis (NMDAR-E), but anti-LGI1 encephalitis (LGI1-E) had received less attention regarding the analysis of psychiatric features, and no study compared psychiatric characteristic between these two groups. The clinical data of AE patients (62 NMDAR-E and 20 LGI1-E) who developed psychiatric symptoms were analyzed in this study. In NMDAR-E, the most common higher-level feature was "behavior changes" (60/62, 96.8%) and the lower-level feature "incoherent speech" was observed in 33 patients (33/62, 53.2%), followed by "agitation" (29/62, 46.8%) and "incongruent laughter/crying" (20/62, 32.3%). Similar to NMDAR-E, "behavior changes" was most common in LGI1-E (17/20, 85.0%), but the features of suicidality, eating, and obsessive–compulsive were not reported. The top three lower-level features were visual hallucinations (9/20, 45.0%), incoherent speech (8/20, 40.0%), and mood instability (7/20, 35.0%). The comparative study found that "incongruent laughter/crying", in lower-level features, was more frequently observed in NMDAR-E (32.3% vs. 0%, p = 0.002). Moreover, the Bush Francis Catatonia Rating Scale (BFCRS) assessing the catatonic symptoms in NMDAR-E were higher than LGI1-E, but the 18 item-Brief Psychiatric Rating Scale (BPRS-18) showed no difference in the two groups. In summary, both NMDAR-E and LGI1-E often developed psychiatric symptoms. In contrast with LGI1-E, the psychiatric feature "incongruent laughter/crying" was more frequently associated with NMDAR-E, and catatonic symptoms were more severe in NMDAR-E. [ABSTRACT FROM AUTHOR]

Introduction: Genetic predisposition to autoimmune encephalitis with antibodies against N-methyl-D-aspartate receptor (NMDAR) is poorly understood. Given the diversity of associated environmental factors (tumors, infections), we hypothesized that human leukocyte antigen (HLA) and killer-cell immunoglobulin-like receptors (KIR), two extremely polymorphic gene complexes key to the immune system, might be relevant for the genetic predisposition to anti-NMDAR encephalitis. Notably, KIR are chiefly expressed by Natural Killer (NK) cells, recognize distinct HLA class I allotypes and play a major role in anti-tumor and anti-infection responses. Methods: We conducted a Genome Wide Association Study (GWAS) with subsequent control-matching using Principal Component Analysis (PCA) and HLA imputation, in a multi-ethnic cohort of anti-NMDAR encephalitis (n=479); KIR and HLA were further sequenced in a large subsample (n=323). PCAcontrolled logistic regression was then conducted for carrier frequencies (HLA and KIR) and copy number variation (KIR). HLA-KIR interaction associations were also modeled. Additionally, single cell sequencing was conducted in peripheral blood mononuclear cells from 16 cases and 16 controls, NK cells were sorted and phenotyped. Results: Anti-NMDAR encephalitis showed a weak HLA association with DRB1*01:01~DQA1*01:01~DQB1*05:01 (OR=1.57, 1.51, 1.45; respectively), and DRB1*11:01 (OR=1.60); these effects were stronger in European descendants and in patients without an underlying ovarian teratoma. More interestingly, we found increased copy number variation of KIR2DL5B (OR=1.72), principally due to an overrepresentation of KIR2DL5B*00201. Further, we identified two allele associations in framework genes, KIR2DL4*00103 (25.4% vs. 12.5% in controls, OR=1.98) and KIR3DL3*00302 (5.3% vs. 1.3%, OR=4.44). Notably, the ligands of these KIR2DL4 and KIR3DL3, respectively, HLA-G and HHLA2, are known to act as immune checkpoint with immunosuppressive functions. However, we did not find differences in specific KIR-HLA ligand interactions or HLA-G polymorphisms between cases and controls. Similarly, gene expression of CD56dim or CD56bright NK cells did not differ between cases and controls. Discussion: Our observations for the first time suggest that the HLA-KIR axis might be involved in anti-NMDAR encephalitis. While the genetic risk conferred by the identified polymorphisms appears small, a role of this axis in the pathophysiology of this disease appears highly plausible and should be analyzed in future studies. [ABSTRACT FROM AUTHOR]

Introduction: Neuroinfection is associated with the deposition of amyloid-beta (Aβ) peptides, and subsequent decrease in cerebrospinal fluid (CSF) amyloid levels. However, whether autoimmune encephalitis involves extracellular deposition of Aβ peptides in the brain is unreported. Methods: We examined CSF amyloid and tau values in adults with anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E). Forty-two patients with NMDAR-E, 35 patients with viral and bacterial neuroinfections, and 16 controls were included. We measured CSF Aβ1–42 (cAβ1–42), Aβ1–40 (cAβ1–40), t-Tau (ct-Tau), and p-Tau181 (cp-Tau181) levels and assessed their efficacies regarding differential diagnosis and predicting prognosis. Results: NMDAR-E patients had lower cAβ1–42 levels; however, they were higher than those of patients with bacterial meningitis. ct-Tau levels in NMDAR-E patients were lower than those in patients with neuroinfections. No changes were observed in controls. cAβ1–42 and ct-Tau were combined as an excellent marker to distinguish NMDAR-E from neuroinfections. cAβ1–42 levels in NMDAR-E patients were positively correlated with Montreal Cognitive Assessment scores. We observed an inverse relationship between cAβ1–42 levels and modified Rankin Scale scores. Patients with poor outcomes exhibited low cAβ1–42 levels and high levels of several blood parameters. cAβ1–42 was the highest quality biomarker for assessing NMDAR-E prognosis. Correlations were found between cAβ1–42 and some inflammatory indicators. Conclusion: cAβ1–42 was decreased in NMDAR-E patients. cAβ1–42 levels indicated NMDAR-E severity and acted as a biomarker for its prognosis. Combining cAβ1–42 and ct-Tau levels could serve as a novel differential diagnostic marker for NMDAR-E. [ABSTRACT FROM AUTHOR]

Anti-N-methyl D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder characterized by IgG antibodies targeting NMDAR. The prevalence is remarkably higher in women and some develop the condition during pregnancy. While immunotherapies have shown good outcomes for pregnant mothers and their infants, the impact on early neurodevelopment remains elusive. This study investigates the effects of anti-NMDAR antibody on the development of primary cortical cultures. Anti-NMDAR antibody was administered to the cultures at day in vitro 5 for the following 5 days to assess dendritic branching and arbor complexity, and at day in vitro 14 for measuring the expression of brain-derived neurotrophic factor (BDNF) and synaptic proteins. Immature cultured neurons treated with anti-NMDAR antibody exhibited impaired dendritic branching and arbor complexity. Interestingly, BDNF expression was unaffected in mature neurons. Additionally, GluN1 expression, a mandatory NMDAR subunit, was significantly reduced, while no significant alterations were observed in PSD-95, gephyrin and synaptophysin expression. These findings shed light on the structural and synaptic impacts of anti-NMDAR antibody on immature neurons, providing evidence for their consequences in early neuronal development. [ABSTRACT FROM AUTHOR]

Background: Recently, cases of overlapping encephalitis caused by anti-N-methyl-D-aspartate receptor (anti-NMDAR) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies have been reported, and their clinical characteristics are gradually becoming clear. Acute-phase treatment typically involves the use of steroids, and although some studies have suggested that steroids can be effective, the extent of their efficacy has not yet been fully explored. Case presentation: We present the case of a 25-year-old man with anti-NMDAR and anti-MOG antibody overlapping encephalitis who showed considerable improvement after steroid treatment. To gain a deeper understanding of the efficacy of steroids in managing this condition, we conducted a literature review of cases of anti-NMDAR and anti-MOG antibody double-positive encephalitis that were treated with steroids during the acute phase. Thirteen cases were analyzed, including a new case diagnosed at our hospital. All patients showed improvement after receiving steroid treatment in the acute phase. Ten patients did not have any sequelae, and nine of them showed a rapid or major response during the acute phase. In contrast, three patients experienced sequelae (mild cognitive decline, visual impairment, and memory impairment, respectively), with their response to steroids in the acute phase being slow or limited. Relapses occurred in five patients, in one patient during steroid tapering, and in another two patients after cessation of steroids. Conclusion: Steroid therapy can be effective in the acute stage of anti-NMDAR and anti-MOG antibody overlapping encephalitis. A positive prognosis may be expected in patients who experience substantial improvement with steroid therapy during the acute phase. [ABSTRACT FROM AUTHOR]

We described a challenging case of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in a young girl. Despite enduring months of reduced consciousness with ongoing antibody presence, she ultimately exhibited remarkable improvement within a 5-year follow-up period. Additionally, we conducted a concise review of relevant literature on anti-NMDAR encephalitis, with a specific focus on anti-NMDAR antibodies. Our findings enhance the clinical comprehension of anti-NMDAR encephalitis and offer valuable insights to clinicians for its management. [ABSTRACT FROM AUTHOR]

With the increase in the number of cases of autoimmune encephalitis (AE), the cerebrospinal fluid (CSF) of people living with HIV (PLWH) showing abnormal behavior, cognitive impairment or abnormal movements should be actively screened for the antibody panel of AE. Early recognition and treatment can prevent severe seizures or coma and markedly improve the prognosis of patients. The first-line immunotherapy for AE includes intravenous methylprednisolone and immunoglobulin. However, whether long-time immunosuppressive maintenance therapy is needed is debated. For PLWH, immunosuppressive therapy and even steroids could be more challenging. Here, we review and summarize the clinical characteristics often reported cases and report one case from our center to improve the diagnosis and treatment of anti-N-methyl-d-aspartate receptor encephalitis in PLWH. [ABSTRACT FROM AUTHOR]

Cerebellar ataxia is an uncommon and atypical manifestation of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, often accompanied by seizures, psychiatric symptoms, and cognitive deficits. Previous cases of isolated brainstem-cerebellar symptoms in patients with anti-NMDAR encephalitis have not been documented. This report presents a case of anti-NMDAR encephalitis in which the patient exhibited cerebellar ataxia, nystagmus, diplopia, positive bilateral pathological signs, and hemiparesthesia with no other accompanying symptoms or signs. The presence of positive CSF anti-NMDAR antibodies further supports the diagnosis. Other autoantibodies were excluded through the use of cell-based assays. Immunotherapy was subsequently administered, leading to a gradual recovery of the patient. [ABSTRACT FROM AUTHOR]

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune encephalitis due to immune production of anti-NMDAR antibodies against the NR1 subunit of the NMDA receptor which is present throughout the central nervous system. This condition had been reported to be prevalent in patients with certain medical conditions; however so far, there have been limited systematic reviews and meta-analyses on the prevalence and factors associated. Objective: This study was to determine the prevalence and factors associated with anti-NMDAR encephalitis among affected patients. Material and Methods: The protocol of this study has been registered (2019: CRD42019142002) with the International Prospective Register of Systematic Reviews (PROSPERO). The primary outcome was the incidence or prevalence of anti-NMDAR encephalitis and secondary outcomes were factors associated with anti-NMDAR encephalitis. Results: There were 11 studies and a total of 873 million patients taken from high-risk populations across 11 countries that were included in the primary analysis. The overall pooled prevalence of anti-NMDAR encephalitis among patients with medical conditions was 7.0% (95% CI = 4.4, 9.6). Those with first episode of psychosis or schizophrenia were at a higher risk of developing anti-NMDAR encephalitis with an odds ratio of 5.976 (95% CI = 1.122, 31.825). Conclusion: We found that almost one-tenth of patients with medical conditions had anti-NMDAR encephalitis; particularly those with first episode of psychosis or schizophrenia were among the high-risk medical conditions. [ABSTRACT FROM AUTHOR]

Background: Persistent somatoform pain disorder (PSPD) is often the initial diagnosis in patients seeking treatment in psychiatric departments, making it challenging to consider organic nervous system diseases. However, autoimmune encephalitis can present with atypical initial symptoms, leading to misdiagnosis or missed diagnosis. Lumbar puncture, with antibody support, plays a crucial role in diagnosing autoimmune encephalitis. Case presentation: This report describes a 40-year-old male adult patient who was initially diagnosed with persistent somatoform pain disorder in 2022. The patient reported a reduction in pain while resting on his back. There were no fever or relevant medical history. Despite 8 months of symptomatic treatment, the symptoms did not improve. Moreover, the patient developed confusion, gibberish speech, non-cooperation during questioning, and increased frequency and amplitude of upper limb convulsions. Lumbar puncture revealed elevated protein levels and protein-cell dissociation. The autoimmune encephalitis antibody NMDAR (+) was detected, leading to a diagnosis of autoimmune encephalitis (NMDAR). Conclusion: Autoimmune encephalitis (NMDAR), starting with persistent somatoform pain (PSPD), often presents with atypical symptoms and can be easily misdiagnosed. Therefore, it is important to consider the possibility of organic nervous system disease in time, and to test serum or cerebrospinal fluid antibodies to rule out organic nervous system disease after symptomatic treatment of mental disorders is ineffective. This approach facilitates the early diagnosis of autoimmune encephalitis and other underlying organic neurological disorders. [ABSTRACT FROM AUTHOR]

Objective: Movement disorders (MDs) are common in anti-N-methyl-Daspartate receptor (NMDAR) encephalitis but are poorly studied. This study aimed to investigate the clinical characteristics of MDs and the clinical differences between patients with and without MDs in anti-NMDAR encephalitis. Methods: A retrospective study was conducted on patients with anti-NMDAR encephalitis who were first diagnosed and treated in the First People's Hospital of Yunnan Province from January 2017 to September 2022. According to the presence or absence of MDs, all patients were divided into two groups, and the clinical manifestations, auxiliary examinations, and prognosis of the two groups were compared. Patients in the MDs group were further subgrouped by different ages (<12 years, 12-17 years, and ≥ 18 years) and genders, and the prevalence of each MD was compared in different age and gender groups. Results: (1) In our study there were 64 patients, of whom 76.6% (49/64) presented with MDs; the median age of onset in patients with MDs was 21 (15,35) years and 65.3% (32/49) were female. The three most common MDs were orofacial dyskinesia (OFLD) (67.3%), dystonia (55.1%), and stereotypies (34.7%). Patients <12 years were more likely to experience chorea than patients in other age groups (p = 0.003). (2) Compared with the non-MDs group, patients in the MDs group showed higher rates of prodromal manifestations, autonomic dysfunction, consciousness disorders, as well as pulmonary infection and gastrointestinal dysfunction (all p < 0.05). Peripheral blood neutrophil to lymphocyte ratio (NLR) (p = 0.014), the proportion of cerebrospinal fluid (CSF) NMDAR antibody titers ≥1:32 (p = 0.047), ICU admission rate (p = 0.04), length of stay (p = 0.007), maximum mRS score in the course of disease (p = 0.001) and mRS score at discharge (p = 0.006) in the MDs group were significantly higher than the non-MDs group. Conclusion: MDs associated with anti-NMDAR encephalitis were predominantly hyperkinetic. Chorea occurred more commonly in patients aged <12 years. Patients with MDs were prone to autonomic dysfunction, consciousness disorders, pulmonary infection, and gastrointestinal dysfunction; they had more intense inflammation, more severe disease, and a poorer short-term prognosis. [ABSTRACT FROM AUTHOR]

Introduction: The cases of MOG-AD (MOG antibody-associated disorder) and anti-NMDAR encephalitis overlapping syndrome (MNOS) are rare, especially among pediatric patients, and their clinical understanding is limited. This study aimed to investigate the clinical manifestations, imaging findings, treatments, and prognosis of Chinese pediatric patients who tested positive for anti-NMDAR and MOG antibodies. Methods: This retrospective study enrolled 10 MNOS pediatric patients, 50 MOGAD (anti-NMDAR antibody-negative), and 81 anti-NMDAR encephalitis (MOG antibody-negative) pediatric patients who were admitted from July 2016 to June 2022 and used their clinical data for comparison. Results: The MNOS patients had a significantly lower incidence of psychobehavioral abnormalities and involuntary movements than anti-NMDAR antibody (+)/MOG antibody (-) patients and had a significantly higher incidence of sleep disorders, seizures, and psycho-behavioral abnormalities than MOG antibody (+)/anti-NMDAR antibody (-) patients. The MNOS patients had a significantly higher incidence of MRI abnormalities than the anti-NMDAR antibody (+)/MOG antibody (-) patients, while there was no significant difference in the incidence between the MNOS patients and the MOG antibody (+)/anti-NMDAR antibody (-) patients. No significant difference was seen in the initial mRS score between the three groups of patients. The anti-NMDAR antibody (+)/MOG antibody (-) patients had a higher rate of admission to the ICU, a longer length of in-hospital stay, and a higher rate of introduction to second-line treatment than the other two groups of patients. No significant difference was seen in the mRS score at the last follow-up and in the disease recurrence rate between the three groups. All these patients respond well to immunosuppressive therapy. Discussion: In the presence of psycho-behavioral abnormalities, sleep disorders, and frequent seizures in MOG-AD patients or demyelinating symptoms of the central nervous system or demyelinating lesions on head MRI in anti-NMDAR encephalitis patients, the coexistence of MOG and anti-NMDAR antibodies should be considered and would suggest a diagnosis of MNOS for these patients. Immunotherapy is effective among these patients and should be given possibly earlier. [ABSTRACT FROM AUTHOR]

Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is a complex neuropsychiatric syndrome known for its diverse neurological manifestations, often involving psychiatric symptoms and seizures that elevate the risk of suicidal ideation and behavior. We present a case illustrating the potentially lethal nature of anti-NMDARE, wherein an unexpected suicide attempt occurred 10 days after the onset of seizures in a 21-year-old man. Upon arrival at the emergency room, immediate interventions addressed hypovolemic shock, followed by subsequent neurosurgical and orthopedic procedures. Six days after cessation of sedation, the patient exhibited atypical focal seizures, behavioral arrest, psychotic responses, and delusions. Despite normal brain magnetic resonance imaging and cerebrospinal fluid (CSF) analysis results, a high CSF immunoglobulin G index and posterior hypometabolism on brain F-fluorodeoxyglucose positron emission tomography raised suspicion of autoimmune encephalitis. Steroids and intravenous immunoglobulins were administered. A comprehensive evaluation ruled out other conditions. Serum and CSF tests confirmed the presence of anti-NMDAR antibodies. This case highlights the potential lethality of the acute stage of anti-NMDARE, emphasizing the absence of apparent psychiatric symptoms before a suicide attempt. Further studies on suicidality associated with anti-NMDARE are crucial, underscoring the importance of vigilance in cases involving newly diagnosed seizures or psychoses. [ABSTRACT FROM AUTHOR]

Introduction: Mature cystic teratoma (MCT) is a common type of ovarian tumors that can, in rare cases, undergo malignant transformation. It has been discovered that MCT patients may experience psychiatric symptoms due to the presence of anti-N-methyl-D-aspartate receptor (NMDAR) antibodies, which is the underlying cause of autoimmune encephalitis. Here, we present the first documented case of a patient with anti-NMDAR encephalitis who also had a morphology of low-grade glioma within MCT. Case Report: A 45-year-old woman presented with seizures, altered consciousness, abnormal NMDAR antibody IgG titers, and abnormal brain MRI findings confirm the diagnosis of anti-NMDAR encephalitis. Physical examination revealed an oval mixed echo mass measuring 54 × 37 mm in the left adnexal area on ultrasound of the uterine appendage. The patient underwent laparoscopic left ovarian and fallopian tube resection. The pathological gross examination revealed a pile of grayish-red cystic and solid fragmented tissue measuring 7 × 6 × 2.2 cm. Histological examination revealed characteristic components of MCT. Furthermore, the solid component of the gross tissue showed proliferative and densely arranged astrocytes with cellular atypia, which were positive for GFAP and Olig-2, negative for IDH1 and EMA. And the Ki67 index was approximately 10%, suggesting the presence of low-grade glioma lesions. The patient was diagnosed with malignant transformation of MCT into a morphology of low-grade glioma, not otherwise specified. After the removal of the ovarian tumor, the patient's psychiatric symptoms improved. Conclusions: Low-grade glioma within MCT is a rare occurrence, and the presence of this malignant transformation in patients with anti-NMDAR encephalitis is even more uncommon. [ABSTRACT FROM AUTHOR]

Anti N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disease that often presents with various neurological and neuropsychiatric symptoms. Although most reported cases occur in children, only a limited number of studies on children are available. The subject of this case report is an 8-month-old female who presented with fever, vomiting, and seizure. She was diagnosed with encephalitis and treated with acyclovir. After 21 days, she showed irritability, seizure, orolingual-facial dyskinesias, choreodystonic movements, hemiparesis, dysphagia, strabismus, lack of interest in light and objects. Clinical signs, neuroimaging findings, and serum analysis of anti-NMDAR antibodies confirmed the diagnosis of anti-NMDAR encephalitis. After the first line of treatment, she showed full recovery. We update the infants with anti-NMDAR encephalitis in the literature. Clinical outcomes suggest that patients with anti-NMDAR encephalitis are mostly poor in the infants, excluding our case. We propose that early and appropriate treatments are critical for timely diagnosis and rapid improvement. [ABSTRACT FROM AUTHOR]

Anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis caused by antibodies (Ab) against the GluN1 subunit of the NMDAR. The disease typically presents with a combination of psychiatric and neurological symptoms. Presentation solely with psychiatric symptoms is rare, especially in childhood. After treatment substantial recovery with mild or no residual symptoms is seen in most cases in both children and adults. Relapse occurs in 10%–25% of patients, with recurrent episodes presenting less severe than initial presentation in most cases. We herein describe a child with a pure psychiatric presentation of anti-NMDAR encephalitis. Diagnosis and treatment was delayed because of the atypical presentation. The child relapsed several times and severe residual psychiatric symptoms persisted after recovery. This case illuminates the need to consider the diagnosis of anti-NMDAR encephalitis in both adults and children with an atypical psychiatric presentation. It also demonstrates the need for a multidisciplinary approach and brings attention to the possible severe impact of the disease on long-term psychosocial functioning. [ABSTRACT FROM AUTHOR]

The disruption of the blood–brain barrier (BBB) is hypothesized to be involved in the progression of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, but its mechanism is still unclear. Recently, the phosphatidylinositol 3-kinase (PI3K)/threonine kinase (Akt) pathway is involved in the regulation of the BBB in various diseases. This study is aimed to investigate the mechanism of BBB damage and neurobehavior changes in anti-NMDAR encephalitis mice. Female C57BL/6J mice were actively immunized to establish an anti-NMDAR encephalitis mouse model and evaluate the neurobehavior changes of mice. To study its potential mechanism, LY294002 (PI3K inhibitor, 8 mg/kg) and Recilisib (PI3K agonist, 10 mg/kg) were treated by intraperitoneal injection, respectively. Anti-NMDAR encephalitis mice showed neurological deficits, increased BBB permeability, open endothelial tight junctions (TJs), and decreased expression of TJ-related proteins zonula occludens (ZO)-1 and Claudin-5. However, administration of PI3K inhibitor significantly reduced the expression of p-PI3K and p-Akt, improved neurobehavior function, decreased BBB permeability, and upregulated the expressions of ZO-1 and Claudin-5. Furthermore, PI3K inhibition reversed the decline of NMDAR NR1 in the membranes of hippocampal neurons, which reduced the loss of neuron-specific nucleoprotein (NeuN) and microtubule-associated protein 2 (MAP2). In contrast, administration of the PI3K agonist Recilisib showed a tendency to exacerbate BBB breakdown and neurological deficits. Our results showed that the activation of PI3K/Akt, along with the changes in TJ-related proteins ZO-1 and Claudin-5, may be closely related to BBB damage and neurobehavior changes in anti-NMDAR encephalitis mice. PI3K inhibition attenuates BBB disruption and neuronal damage in mice, thereby improving neurobehavior. [ABSTRACT FROM AUTHOR]

Introduction: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a common autoimmune encephalitis, and it is associated with psychosis, dyskinesia, and seizures. Anti-NMDAR encephalitis (NMDARE) in juveniles and adults presents different clinical charactreistics. However, the pathogenesis of juvenile anti-NMDAR encephalitis remains unclear, partly because of a lack of suitable animal models. Methods: We developed amodel of juvenile anti-NMDAR encephalitis using active immunization with an amino terminal domain peptide from the GluN1 subunit (GluN1356-385) against NMDARs in 3-week-old female C57BL/6J mice. Results: Immunofluorescence staining suggested that autoantibody levels in the hippocampus increased, and HEK-293T cells staining identified the target of the autoantibodies as GluN1, suggesting that GluN1-specific immunoglobulin G was successfully induced. Behavior assessment showed that the mice suffered significant cognition impairment and sociability reduction, which is similar to what is observed in patients affected by anti-NMDAR encephalitis. The mice also exhibited impaired long-term potentiation in hippocampal CA1. Pilocarpine-induced epilepsy was more severe and had a longer duration, while no spontaneous seizures were observed. Conclusion: The juvenile mouse model for anti-NMDAR encephalitis is of great importance to investigate the pathological mechanism and therapeutic strategies for the disease, and could accelerate the study of autoimmune encephalitis. [ABSTRACT FROM AUTHOR]

Objective: Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is autoimmune encephalitis with a characteristic neuropsychiatric syndrome and persistent cognition deficits even after clinical remission. The objective of this study was to uncover the potential noninvasive and quantified biomarkers related to residual brain distortions in convalescent anti-NMDARE patients. Methods: Based on resting-state electroencephalograms (EEG), both power spectral density (PSD) and brain network analysis were performed to disclose the persistent distortions of brain rhythms in these patients. Potential biomarkers were then established to distinguish convalescent patients from healthy controls. Results: Oppositely configured spatial patterns in PSD and network architecture within specific rhythms were identified, as the hyperactivated PSD spanning the middle and posterior regions obstructs the inter-regional information interactions in patients and thereby leads to attenuated frontoparietal and frontotemporal connectivity. Additionally, the EEG indexes within delta and theta rhythms were further clarified to be objective biomarkers that facilitated the noninvasive recognition of convalescent anti-NMDARE patients from healthy populations. Conclusion: Current findings contributed to understanding the persistent and residual pathological states in convalescent anti-NMDARE patients, as well as informing clinical decisions of prognosis evaluation. [ABSTRACT FROM AUTHOR]

Background: Patients with anti- N -methyl-d-aspartate (NMDA) receptor encephalitis (ANMDARE) show a wide range of behavioral abnormalities and are often mistaken for primary psychiatric presentations. We aimed to determine the behavioral hallmarks of ANMDARE with the use of systematic neuropsychiatric and cognitive assessments. Methods: A prospective study was conducted, with 160 patients admitted to the National Institute of Neurology and Neurosurgery of Mexico, who fulfilled criteria for possible autoimmune encephalitis and/or red flags along a time window of seven years. Cerebrospinal fluid (CSF) antibodies against the NR1 subunit of the NMDAR were processed with rat brain immunohistochemistry and cell-based assays with NMDA expressing cells. Systematic cognitive, neuropsychiatric, and functional assessments were conducted before knowing NMDAR antibodies results. A multivariate analysis was used to compare patients with and without definite ANMDARE according to antibodies in CSF. Results: After obtaining the CSF antibodies results in 160 consecutive cases, 100 patients were positive and classified as having definite ANMDARE. The most frequent neuropsychiatric patterns were psychosis (81%), delirium (75%), catatonia (69%), anxiety-depression (65%), and mania (27%). Cognition was significantly impaired. A total of 34% of the patients had a predominantly neuropsychiatric presentation without seizures. After multivariate analysis, the clinical hallmarks of ANMDARE consisted of a catatonia–delirium comorbidity, tonic-clonic seizures, and orolingual dyskinesia. Conclusions: Our study supports the notion of a neurobehavioral phenotype of ANMDARE characterized by a fluctuating course with psychotic and affective symptoms, catatonic signs, and global cognitive dysfunction, often accompanied by seizures and dyskinesia. The catatonia–delirium comorbidity could be a distinctive neurobehavioral phenotype of ANMDARE. [ABSTRACT FROM AUTHOR]

Background: Anti-N-methyl-d-aspartate receptor encephalitis is a neuroautoimmune syndrome typically presenting with seizures, psychiatric symptoms, and autonomic dysfunction. Human herpesvirus-7 is often found with human herpesvirus-6 and infects leukocytes such as T-cells, monocytes–macrophages, epithelial cells, and central nervous system cells. The pathogenicity of human herpesvirus-7 is unclear. Cases of anti-N-methyl-d-aspartate receptor encephalitis with human herpesvirus-7 present in cerebrospinal fluid have been documented, but the clinical significance of this finding remains unclear. Case presentation: An 11-year-old Caucasian boy was admitted to hospital after a generalized tonic–clonic seizure. Generalized tonic seizures repeated three more times during the day of hospitalization. Blood tests showed minor ongoing inflammation, while brain computed tomography yielded normal results. Brain magnetic resonance imaging showed hyperintense focal alterations in both temporal lobes, hippocampi, and at the base of the right frontal lobe. Positive anti-N-methyl-d-aspartate receptor antibodies were found in both serum and cerebrospinal fluid. Positive novel coronavirus 2 (severe acute respiratory syndrome coronavirus 2) immunoglobulin G antibodies were found in serum. Polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 was negative. Furthermore, positive human herpesvirus-7 deoxyribonucleic acid was found in cerebrospinal fluid. The patient was treated with acyclovir, human immunoglobulin, and methylprednisolone. The seizures did not repeat, and no psychiatric symptoms were present. The patient made a full recovery. Conclusions: We present a pediatric case of anti-N-methyl-d-aspartate receptor encephalitis with atypical clinical presentation. The role of human herpesvirus-7 in neurological disorders remains unclear in immunocompetent patients. [ABSTRACT FROM AUTHOR]

Background: Sleep disturbances are intertwined with the progression and pathophysiology of psychotic symptoms in schizophrenia. Reductions in sleep spindles, amajor electrophysiological oscillation during non-rapid eyemovement sleep, have been identified in patients with schizophrenia as a potential biomarker representing the impaired integrity of the thalamocortical network. Altered glutamatergic neurotransmission within this network via a hypofunction of the N-methyl-D-aspartate receptor (NMDAR) is one of the hypotheses at the heart of schizophrenia. This pathomechanism and the symptomatology are shared by anti-NMDAR encephalitis (NMDARE), where antibodies specific to the NMDAR induce a reduction of functional NMDAR. However, sleep spindle parameters have yet to be investigated in NMDARE and a comparison of these rare patients with young individuals with schizophrenia and healthy controls (HC) is lacking. This study aims to assess and compare sleep spindles across young patients affected by Childhood-Onset Schizophrenia (COS), Early-Onset Schizophrenia, (EOS), or NMDARE and HC. Further, the potential relationship between sleep spindle parameters in COS and EOS and the duration of the disease is examined. Methods: Sleep EEG data of patients with COS (N = 17), EOS (N = 11), NMDARE (N = 8) aged 7-21 years old, and age- and sex-matched HC (N = 36) were assessed in 17 (COS, EOS) or 5 (NMDARE) electrodes. Sleep spindle parameters (sleep spindle density, maximum amplitude, and sigma power) were analyzed. Results: Central sleep spindle density, maximum amplitude, and sigma power were reduced when comparing all patients with psychosis to all HC. Between patient group comparisons showed no differences in central spindle density but lower central maximum amplitude and sigma power in patients with COS compared to patients with EOS or NMDARE. Assessing the topography of spindle density, it was significantly reduced over 15/17 electrodes in COS, 3/17 in EOS, and 0/5 in NMDARE compared to HC. In the pooled sample of COS and EOS, a longer duration of illness was associated with lower central sigma power. Conclusions: Patients with COS demonstratedmore pronounced impairments of sleep spindles compared to patients with EOS and NMDARE. In this sample, there is no strong evidence that changes in NMDAR activity are related to spindle deficits. [ABSTRACT FROM AUTHOR]

Anti-NMDAR encephalitis has been associated with multiple antigenic triggers (i.e., ovarian teratomas, prodromal viral infections) but whether geographic, climatic, and environmental factors might influence disease risk has not been explored yet. We performed a systematic review and a meta-analysis of all published papers reporting the incidence of anti-NMDAR encephalitis in a definite country or region. We performed several multivariate spatial autocorrelation analyses to analyze the spatial variations in the incidence of anti-NMDA encephalitis depending on its geographical localization and temperature. Finally, we performed seasonal analyses in two original datasets from France and Greece and assessed the impact of temperature using an exposure-lag-response model in the French dataset. The reported incidence of anti-NMDAR encephalitis varied considerably among studies and countries, being higher in Oceania and South America (0.2 and 0.16 per 100,000 persons-year, respectively) compared to Europe and North America (0.06 per 100,000 persons-year) (p < 0.01). Different regression models confirmed a strong negative correlation with latitude (Pearson's R = −0.88, p < 0.00001), with higher incidence in southern hemisphere countries far from the equator. Seasonal analyses showed a peak of cases during warm months. Exposure-lag-response models confirmed a positive correlation between extreme hot temperatures and the incidence of anti-NMDAR encephalitis in France (p = 0.03). Temperature analyses showed a significant association with higher mean temperatures and positive correlation with higher ultraviolet exposure worldwide. This study provides the first evidence that geographic and climatic factors including latitude, mean annual temperature, and ultraviolet exposure, might modify disease risk. [ABSTRACT FROM AUTHOR]

Seizures are the main manifestation of the acute phase of autoimmune encephalitis (AE). Anti-seizure medications (ASMs) play an important role in controlling seizures in AE patients, but there is currently a lack of consensus regarding the selection, application, and discontinuation of ASMs. This narrative review focuses on the use of ASMs in patients with AE driven by different antibodies. The PubMed, Embase, and MEDLINE databases were searched up until 30 October 2022 using prespecified search terms. We identified 2,580 studies; 23 retrospective studies, 2 prospective studies and 9 case reports were evaluated based on our inclusion criteria. Anti-N-methyl-D-aspartic-acid-receptor (anti-NMDAR) encephalitis is the type of AE that responds best to ASMs, and long-term or combined use of ASMs may be not required in most patients with seizures; these results apply to both adults and children. Sodium channel blockers may be the best option for seizures in anti-leucine-rich-glioma-inactivated-1 (anti-LGI1) encephalitis, but patients with anti-LGI1 encephalitis are prone to side effects when using ASMs. Cell surface antibody-mediated AE patients are more likely to use ASMs for a long period than patients with intracellular antibody-mediated AE. Clinicians can score AE patients' clinical characteristics on a scale to identify those who may require long-or shortterm use of ASMs in the early stage. This review provides some recommendations for the rational use of ASMs in encephalitis mediated by different antibodies with the aim of controlling seizures and avoiding overtreatment. [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]

Ofatumumab (OFA), a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B-cells. The purpose of this study was to report the therapeutic effect and safety of OFA in two refractory anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis cases which were nonresponsive to first-line immunotherapies. Two severely affected anti-NMDAR encephalitis patients (mRS score: 5) with resistance to standard immunotherapies (corticosteroids, IV immunoglobulins) were treated with OFA (3 subcutaneous injections of 20 mg on days 1, 7, 14). The patients' guardians declined plasma exchange (PE) and RTX. The clinical outcome of the patients was followed up for 6 months after the administration of OFA. Treatment with OFA led to rapid clinical improvement accompanied by the enhancement of neuropsychiatric function, disappearance of brain MRI lesions, and decline in partial NMDAR antibody titer. The CD20-positive B-cells were completely depleted in both patients. Moreover, the therapy was well tolerated with no adverse effects. The patients were discharged without clinical deficits and with significantly improved cognition. OFA appeared to be highly effective in the two presented cases despite the limited first-line therapy without PE, which suggests good potential for the application of OFA in this field. However, the lingering effects of previously administered corticosteroids and IV immunoglobulins cannot be excluded. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to evaluate the prognostic factors in a single-center pediatric cohort with autoimmune encephalitis. Materials and Methods: The study group consisted of 23 pediatric autoimmune encephalitis patients (seropositive autoimmune encephalitis: 15, seronegative autoimmune encephalitis: 8). Five group prognostic parameters were evaluated: clinical manifestations, electroenc ephalography features, magnetic resonance imaging characteristics, biomarkers, and treatment modalities. Three scoring models were applied: the Antibody Prevalence in Epilepsy and Response to Immunotherapy in Epilepsy for predicting autoimmune-related epilepsy in the whole cohort and the anti-N-methyl-d-aspartate receptor Encephalitis 1-Year Functional Status score for overall outcome in patients with anti-N-methyl-d-aspartate receptor encephalitis. Results: The initial clinical spectrum of the disease was similar in the seronegative and seropositive groups. Almost half of the patients (48%) recovered without any complications with first-line immunotherapy. The patients with movement disorders in the acute phase of the disease needed more likely second-line immunotherapy (P = .039). The presence of status epilepticus at admission was significantly associated with adverse outcomes and the development of autoimmune-related epilepsy (P = .019). Autoimmune-related epilepsy was defined in an equal proportion of patients (91.5%) with 2 immune epilepsy scores (Antibody Prevalence in Epilepsy and Response to Immunotherapy in Epilepsy). The N-methyl-d-aspartate receptor Encephalitis 1-Year Functional Status score and the modified Rankin score assessed for the first-year prognosis were strongly correlated among the patients with anti-N-methyl-d-aspartate receptor encephalitis (P = .03, Spearmen's rho = 0.751). Conclusions: The presence of status epilepticus was the most important prognostic factor in the patients with the adverse outcome. The studied scoring models (Anti-N-methyl-d-aspartate receptor Encephalitis 1-Year Functional Status, Antibody Prevalence in Epilepsy, and Response to Immunotherapy in Epilepsy) have also been proven to be applicable to the pediatric age group for predicting overall outcome and autoimmune-related epilepsy. [ABSTRACT FROM AUTHOR]

Background: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis secondary to central nervous system (CNS) infection is a unique subtype of the autoimmune-mediated disease, of which the imaging features are unclear. Purpose: To compare the brain magnetic resonance imaging (MRI) features between the anti-NMDAR encephalitis secondary to CNS infection and that without initial infection. Material and Methods: A total of 70 adult patients with anti-NMDAR encephalitis were retrospectively enrolled (24 in the post-infection group, 46 in the non-infection-related group). Their clinical and imaging features (lesion distribution, lesion shape, enhancement pattern, brain atrophy) were reviewed and summarized. Lesion distributions were compared between the two groups on lesion probability maps. Results: The patients with normal brain MRI scans in the post-infection group were less than those in the non-infection related group (29% vs. 63%; P = 0.0113). Among the 24 patients in the post-infection group, visible lesions were shown at the anti-NMDAR encephalitis onset in 17 patients; lesion distribution was more diffuse than the non-infection-related group, showing higher lesion peak probabilities in the bilateral hippocampus, frontal lobe, temporal lobe, insula, and cingulate. The lesions with contrast enhancement were also more common in the post-infection group than the non-infection-related group (7/13 vs. 2/10). Brain atrophy was observed in eight patients in the post-infection group and three in the non-infection-related group. Conclusion: Anti-NMDAR encephalitis secondary to CNS infection has its imaging features—extensive lesion distribution, leptomeningeal enhancement, early atrophy, and necrosis—that could deepen the understanding of the pathophysiology and manifestation of the autoimmune encephalitis besides the classic type. [ABSTRACT FROM AUTHOR]

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune-mediated disease characterized by complicated neuropsychiatric symptoms and the detection of cerebrospinal fluid antibodies against the GluN1 subunit of the NMDAR. With the proposed clinical method, more anti-NMDAR encephalitis patients have been discovered since its first report. However, anti-NMDAR encephalitis overlapping with multiple sclerosis (MS) is rare. Herein we report a male patient with anti-NMDAR encephalitis who developed MS in mainland China. Furthermore, we summarized the characteristics of patients who were diagnosed with overlapping MS and anti-NMDAR encephalitis in previous studies. Additionally, we pioneered the use of mycophenolate mofetil in immunosuppressive therapy, providing a novel therapeutic alternative for overlapping anti-NMDAR encephalitis and MS. [ABSTRACT FROM AUTHOR]

New-onset refractory status epilepticus (NORSE) is rare but intractable. Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and cryptogenic etiologies are the two major causes of NORSE with distinct clinical features. To elucidate the underlying mechanisms, 6 patients with anti-NMDAR encephalitis NORSE and 5 with cryptogenic NORSE (C-NORSE) were enrolled. Five patients of cerebrovascular disorders were used as controls. Quantitative proteomic analysis of the cerebrospinal fluid (CSF) samples of the patients revealed 101 and 56 proteins were changed, respectively. The average fold-change of the upregulated proteins, namely up-proteomic score in this study, was positively correlated with the severity and prognosis of the diseases, including ICU stay (r = 0.9308, P = 0.0035 in NMDAR group; r = 0.8977, P = 0.0193 in C-NORSE group), mRS score at discharge (r = 0.9710, P = 0.0111 in NMDAR group; r = 0.7071, P = 0.2000 in C-NORSE group), and time taken for patients awaking from a coma (r = 0.8823, P = 0.0100 in NMDAR group; r = 0.7906, P = 0.2000 in C-NORSE group). Pathways involved in humoral immune response, wound healing, and epigenetic regulation of transcription were upregulated in anti-NMDAR encephalitis NORSE. Pathways of innate and lymphocyte mediated immune response, synaptic functions, ubiquitination, and cell apoptosis were up-regulated in C-NORSE, which was consistent with a mouse model of status epilepticus. Fc receptor and B cell mediated immunity signaling pathways were downregulated in C-NORSE. Immunome microarray analysis demonstrated high autoantibody targeting 48 proteins in CSF samples of anti-NMDAR encephalitis NORSE. While the reaction was kept at a very low level in C-NORSE. There is no significant difference in inflammatory cytokine level between each group. The level of IL-4 (r = 0.7435, P = 0.0451), IL-13 (r = 0.7643, P = 0.0384), IFN-γ (r = 0.7973, P = 0.0287) and TNF-α (r = 0.8598, P = 0.0141) in NMDAR group, and IL-6 (r = 0.8479, P = 0.0348), IL-8 (r = 0.9076, P = 0.0166) in C-NORSE group were positively correlated with the up-proteomic score. The present study suggests that the up-proteomic score of CSF could be a promising indicator for assessment of the severity of anti-NMDAR encephalitis NORSE and C-NORSE. The distinct CSF proteomes imply different pathogenic mechanisms of the two diseases, and immunotherapy strategies as well. [ABSTRACT FROM AUTHOR]

Ofatumumab (OFA), a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B-cells. The purpose of this study was to report the therapeutic effect and safety of OFA in two refractory anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis cases which were nonresponsive to first-line immunotherapies. Two severely affected anti- NMDAR encephalitis patients (mRS score: 5) with resistance to standard immunotherapies (corticosteroids, IV immunoglobulins) were treated with OFA (3 subcutaneous injections of 20 mg on days 1, 7, 14). The patients' guardians declined plasma exchange (PE) and RTX. The clinical outcome of the patients was followed up for 6 months after the administration of OFA. Treatment with OFA led to rapid clinical improvement accompanied by the enhancement of neuropsychiatric function, disappearance of brain MRI lesions, and decline in partial NMDAR antibody titer. The CD20-positive B-cells were completely depleted in both patients. Moreover, the therapy was well tolerated with no adverse effects. The patients were discharged without clinical deficits and with significantly improved cognition. OFA appeared to be highly effective in the two presented cases despite the limited first-line therapy without PE, which suggests good potential for the application of OFA in this field. However, the lingering effects of previously administered corticosteroids and IV immunoglobulins cannot be excluded. [ABSTRACT FROM AUTHOR]

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most recognized form of autoimmune encephalitis. It is characterized by a constellation of neurologic and psychiatric features along with positive NMDAR antibody, which is more sensitive and specific in CSF than serum. All patients should be screened at least once for neoplasm, with ovarian teratoma being found in most tumor-related cases. In the acute phase, first-line immunotherapy, often a combination of high-dose steroids, immunoglobulins, and/or plasma exchange, is strongly recommended. When first-line therapy fails, escalation to second-line immunotherapy, particularly rituximab, can further improve outcomes and prevent relapses. In refractory cases, additional complementary immunotherapies, such as cyclophosphamide, bortezomib and/or tocilizumab may be considered. Relapses occur in 10– 30% of cases, mostly within the first two years from onset. Individuals should be followed up to determine if chronic maintenance therapy is required. [ABSTRACT FROM AUTHOR]

Background: In recent years, there have been an increasing number of reports on overlapping antibodies in autoimmune encephalitis (AE). There are various types of overlapping antibodies, but the clinical significance of each type is not yet clear. Glial antibodies, such as MOG, AQP4, and especially NMDAR, can be detected in patients with AE. However, little is known about the overlapping antibodies of anti-glial fibrillary acidic protein (GFAP), and only a few case reports have described this overlap. Case presentation The patient was a 7-year-old girl with recurrent intermittent fever and seizures, and viral encephalitis was diagnosed at the beginning of the disease. She was discharged after treatment with acyclovir, high-dose immunoglobulins, and valproic acid as an antiseizure medication. Subsequently, the patient still had occasional seizures and abnormal behavior, and the anti-NMDAR antibody test was positive (1:3.2). She was treated with high-dose methylprednisolone and antiseizure therapy. Approximately half a year later, the patient experienced fever and seizures again, serum GFAP IgG was 1:100, and a head MRI indicated new lesions. Improvement was achieved after repeated high-dose methylprednisolone and continuous prednisone anti-inflammatory therapy.Conclusions: Anti-NMDAR encephalitis combined with GFAP-IgG is uncommon, and repeated tests for AE-associated antibodies may be required in patients with recurrent encephalitis. Compared with cerebrospinal fluid antibody-positive children, serum GFAP IgG-positive children should be comprehensively diagnosed according to their clinical manifestations. It is worth considering whether overlapping antibody syndrome can still be an issue for patients with AE who recover and have negative antibodies after a few months if disease recurrence and new antibodies are detected. [ABSTRACT FROM AUTHOR]

Background: We investigated the potential use of SPECT quantification in addition to qualitative brain perfusion analysis for the detection of anti-NMDAR encephalitis. The question is how to normalize brain activity to be able to quantitatively detect perfusion patterns. Usually, brain activity is normalized to a structure considered unaffected by the disease. Methods: Brain [99mTc]-HMPAO SPECT was performed as a method to detect brain perfusion patterns. The patterns of abnormal brain perfusion cannot always be reliably and qualitatively assessed when dealing with rare diseases. Recent advances in SPECT quantification using commercial software have enabled more objective and detailed analysis of brain perfusion. The cerebellum and whole brain were used as the normalization structures and were compared with visual analysis. Results: The quantification analysis performed with whole brain normalization confirmed right parietal lobe hypoperfusion while also detecting statistically significant left-to-right perfusion differences between the temporal lobe and thalamus. Whole brain normalization further described bilateral frontal lobe hyperperfusion, predominantly of the left lobe, and was in accordance with visual analysis. Conclusion: SPECT quantitative brain perfusion analysis, using the whole brain as the normalization structure rather than the cerebellum, in this case, improved confidence in the visual detection of anti-NMDAR encephalitis and provided unexpected solutions to atypical psychiatric dilemmas. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies have discovered different neuroimaging features in anti-NMDAR encephalitis associated with cognitive dysfunction. However, it is unknown whether there is a correlation between abnormal homotopic connectivity and cognitive impairment in anti-NMDAR encephalitis. We aim to explore the homotopic connectivity patterns of patients with anti-NMDAR encephalitis and their associations with clinical characteristics. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was performed on 29 patients with anti-NMDAR encephalitis and 26 healthy controls (HCs). Voxel-mirrored homotopic connectivity (VMHC) and multivariate pattern analysis (MVPA) were applied to analyze the imaging data. A correlation was also performed between aberrant brain regions and clinical parameters. Results: Compared to HCs, the performance of alertness in the patient group was typically worse (p < 0.05). A significant decrease in VMHC was observed in many regions of the patients in comparison to HCs, including the cerebellar 6, para-hippocampal gyrus, insula, precuneus, and middle frontal gyrus (p < 0.001). The insula and middle frontal gyrus were found to show positive correlations with alertness. The MVPA method achieved a classification accuracy of 74.55% with a sensitivity of 82.76% and a specificity of 65.38% in discriminating patients from HCs. Conclusion: Our findings indicate that interhemispheric functional imbalance may play a significant role in the pathophysiology of cognitive dysfunction in anti-NMDAR encephalitis. The MVPA results suggest that abnormal VMHC may play a crucial role in the identification of patients with anti-NMDAR encephalitis from HCs. [ABSTRACT FROM AUTHOR]

Introduction: Autoimmune encephalitis (AE) is caused by the antibodies that target receptors and intracellular or surface proteins. To achieve the appropriate therapeutic results, early and proper diagnosis is still the most important issue. In this review, we provide an overview of FDG-PET imaging findings in AE patients and possible relation to different subtypes and clinical features.Methods: PubMed, Web of Science, and Scopus were searched in August 2021 using a predefined search strategy.Results: After two-step reviewing, 22 studies with a total of 332 participants were entered into our qualitative synthesis. In anti-NMDAR encephalitis, decreased activity in the occipital lobe was present, in addition, to an increase in frontal, parietal, and specifically medial temporal activity. Anti-VGKC patients showed altered metabolism in cortical and subcortical regions such as striata and cerebellum. Abnormal metabolism in patients with anti-LGI1 has been reported in diverse areas of the brain including medial temporal, hippocampus, cerebellum, and basal ganglia all of which had hypermetabolism. Hypometabolism in parietal, frontal, occipital lobes, temporal, frontal, and hippocampus was observed in AE patients with anti-GAD antibodies.Conclusion: Our results indicate huge diversity in metabolic patterns among different AE subtypes and it is hard to draw a firm conclusion. Moreover, the timing of imaging, seizures, and acute treatments can alter the PET patterns strongly. Further prospective investigations with specific inclusion and exclusion criteria should be carried out to identify the metabolic defect in different AE subtypes. [ABSTRACT FROM AUTHOR]

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis predominantly presents with psychiatric symptoms. Psychiatrists need to be alert to this diagnostic possibility, especially in female adolescents and young adults, as exemplified by the real (de-identified) case outlined below. Earlier diagnosis and immunotherapy improves long-term outcomes. Collaboration with neurology colleagues is essential for optimal care. 'Red flags' for autoimmune encephalitis and 'diagnostic clues' act as helpful aide memoires for this uncommon condition. The gold standard for testing is the detection of NMDAR antibodies in cerebrospinal fluid, but serum can be tested as a more accessible (but less reliable) preliminary step. The results of routine blood tests, magnetic resonance imaging of the head and electroencephalograms can be normal or show non-specific changes. Diagnostic criteria exist to define probable and definite cases. Immunotherapy for anti-NMDAR encephalitis is effective for many patients, but recovery is prolonged and relapses can occur. [ABSTRACT FROM AUTHOR]

This editorial expands on a Praxis article published by Beattie and colleagues in the trainees' section of this journal. The authors describe an interesting case of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, outline the clinical presentation and make suggestions on ways to approach this rare disorder. Here we provide an overview of autoimmune conditions that result in the production of autoantibodies targeting central nervous system proteins mediating autoimmune encephalitis and offer a perspective on approaches to diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Autoimmune encephalitis (AE) represents a group of diseases with a core inflammatory pattern of the central nervous system (CNS), with a rather low frequency, but which is becoming more and more recognized in children and adolescents. These conditions are associated with the presence of antibodies against neuronal cell surface proteins, receptors and ion channels. However, in some forms of encephalitis, the presence of antibodies could not be identified. It is a condition known to have a significant morbidity and mortality rate. The specialized literature stipulates that the classic clinical presentation of AE consists of both neurological and psychiatric manifestations, with a wide range of symptoms including confusion, agitation, psychotic disorders, mood swings, and cognitive decline, along with neurological manifestations like seizures, movement disorders, and neurological deficits. Encephalitis with anti-NMDA receptors (NMDAR) is currently the most common and best described subtype of autoimmune encephalitis. The diagnosis of AE is often neglected in the early stages of the disease, and in some cases the onset of AE can manifest itself in the form of a psychiatric disorder. Early diagnosis as well as the initiation of treatment are vital, and the role of the psychiatrist in the multidisciplinary team is important for the diagnostic approach and the approved expertise in the use of psychotropic drugs. The objective of the article is to highlight/identify the psychiatric picture in the clinical evolution of AE as well as its therapeutic management in the pediatric population. The presentation of patients in a psychiatric ward is characterized by an acute or subacute polysymptomatic onset. The treatment of AE is specific to the autoimmune mechanism involved, the therapeutic choices being divided between first-line treatment: corticosteroids, plasmapheresis and/or immunoglobulins; and second-line treatment with molecules such as rituximab, cyclophosphamide and mycophenolate mofetil. [ABSTRACT FROM AUTHOR]

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis results in severe neuropsychiatric symptoms and persistent cognitive impairment; however, the underlying mechanism is still not fully understood. The present study utilized the degree centrality (DC), functional connectivity (FC) and multivariate pattern analysis (MVPA) to further explore neurofunctional symptoms in patients with anti-NMDAR encephalitis. A total of 29 patients with anti-NMDAR encephalitis and 26 healthy controls (HCs) were enrolled for neuropsychological assessment and resting-state functional MRI (rs-fMRI) scans. DC, FC and MVPA were examined to investigate cerebral functional activity and distinguish neuroimaging characteristics between the patient and HC groups based on the rs-fMRI data. Compared with the HCs, the patients exhibited cognitive deficits, anxiety and depression. In the DC analysis, the patients exhibited significantly decreased DC strength in the left rectus gyrus, left caudate nucleus (LCN) and bilateral superior medial frontal gyrus, as well as increased DC strength in the cerebellar anterior lobe, compared with the HCs. In the subsequent FC analysis, the LCN showed decreased FC strength in the bilateral middle frontal gyrus and right precuneus. Furthermore, correlation analysis indicated that disrupted cerebral functional activity was significantly correlated with the alerting effect and Hamilton Depression Scale score. Using DC maps and receiver operating characteristic curve analysis, the MVPA classifier exhibited an area under curve of 0.79, and the accuracy classification rate was 76.36%, with a sensitivity of 79.31% and a specificity of 78.18%. The present study revealed that the disrupted functional activity of hub and related networks in the cerebellum, including the default mode network and executive control network, contributed to deficits in cognition and emotion in patients with anti-NMDAR encephalitis. In conclusion, the present study provided imaging evidence and primary diagnostic markers for pathological and compensatory mechanisms of anti-NMDAR encephalitis, with the aim of improving the understanding of this disease. [ABSTRACT FROM AUTHOR]

Objective: to assess the performance of the Anti-N-Methyl-D-Aspartate Receptor encephalitis (NMDAR) One-Year Functional Status (NEOS) score in predicting one-year functional outcome in Chinese children with anti-NMDAR encephalitis. Methods: children with anti-NMDAR encephalitis at the Children's Hospital of Chongqing Medical University were retrospectively enrolled from January 2014 to December 2020. Patients were categorized into two groups based on the modified Rankin Scale (mRS) at one-year follow-up. Discrimination of the NEOS score was assessed by the area under curve (AUC) of the receiver operating characteristic curve. Calibration of the NEOS score was assessed by comparing predicted probabilities with observed probabilities using a calibration curve and the Hosmer-Lemeshow test. The clinical practicability of the NEOS score was evaluated by performing a decision curve analysis. Results: one hundred seventy-five children (101 females and 74 males) with anti-NMDAR encephalitis and a median age of 7.7 years were enrolled. Of those, 149 (85.1%) had a good outcome at 1 year (mRS ≤ 2), and the remaining 26 (14.9%) had a poor outcome (mRS > 2). Patients with a higher NEOS score had a significantly higher mRS at one-year follow-up [Spearman r = 0.3878, 95% confidence interval (CI): 0.2500-0.5103, P < 0.001]. The AUC of the NEOS score was 0.870 (95% CI: 0.801-0.938, P < 0.001). The observed probability and predicted probability showed moderate consistency in the calibration curve and the Hosmer-Lemeshow test (P = 0.912). The decision curve analysis showed that using the NEOS score to predict one-year outcomes could provide additional net benefit during clinical practice. Conclusions: the NEOS score is a potentially reliable model to predict the one-year functional outcome in Chinese children with anti-NMDAR encephalitis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relapse rate and study the factors that may predict the subsequent relapse in anti-NMDAR, anti-GABABR and anti-LGI1 encephalitis in Northeast China. Methods: In the retrospective cohort study, we consecutively enrolled patients with anti-N1MDAR, anti-GABABR and anti-LGI1 encephalitis between March 2015 and November 2021. The patients were followed up for at least 6 months. The outcome variable was a binary variable of relapse or not. Predictors of relapse were identified. Results: A total of 100 patients were enrolled. Relapse occurred in 26 (26%) patients after a median follow-up of 18 months since the first event. The relapse rates of anti - NMDAR, anti - GABABR and anti - LGI1 encephalitis were 25%, 33.3%, and 28.6%, respectively. The multivariable analysis results suggested that immunotherapy delay at the acute phase was independently associated with an increased risk of relapse in total patients (HR = 2.447, 95% CI = 1.027 - 5.832; P = 0.043). Subgroup analysis results showed that antibody titer was associated with the likelihood of relapse in anti-LGI1 encephalitis. The higher the concentration, the more likely it was for patients to have relapse (p=0.019). Conclusion: The general relapse rate of anti-NMDAR, anti-GABABR and anti-LGI1 encephalitis was 26%. The risk of subsequent relapse was elevated in those with delayed immunotherapy in the first episode. In subgroup of anti-LGI1 encephalitis, higher antibody titer was the risk factors of relapse. Thus, timely and aggressive immunotherapy may be beneficial for patients to prevent subsequent relapse. [ABSTRACT FROM AUTHOR]

Background: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis can coexist with neuromyelitis optica spectrum disorder (NMOSD). Patients with overlapping anti-NMDAR encephalitis with positive NMDAR antibodies and aquaporin 4 immunoglobulin G (AQP4-IgG)-seropositive NMOSD are rare but should not be ignored. Case presentation: This report describes a unique case of anti-NMDAR encephalitis coexisting with NMOSD. A 27-year-old male presented with blurred vision, cognitive impairment, psychosis, dysphagia, gait instability and urinary incontinence. Brain magnetic resonance imaging (MRI) showed abnormal signals in the right cerebellar hemisphere, temporal lobe, and corpus callosum. NMDAR antibodies were positive in the CSF. AQP4-IgG antibodies were positive in the serum. The patient's condition was stable following intravenous gamma globulin, corticosteroids, immunosuppressants and symptomatic treatments. Conclusions: This case provides further evidence for the occurrence of anti-NMDAR encephalitis overlapping NMOSD with AQP4-IgG-seropositive in a Chinese patient. However, the mechanisms underlying the occurrence of double-positive antibodies remain elusive. [ABSTRACT FROM AUTHOR]

We analyzed the clinical features and outcomes of children with anti-N-methyl-D–aspartate receptor (anti-NMDAR) encephalitis in Northwestern China. We retrospectively recruited 33 pediatric patients with anti-NMDAR encephalitis in Northwestern China from December 2013 to April 2020. The demographics, clinical features, treatments, and outcomes were reviewed. 33 patients with anti-NMDAR encephalitis were enrolled in this study (a median age of 6.8 years, 20 females and 13 males). The initial symptoms included seizures (42.4%), psychiatric symptoms (39.4%), speech dysfunction (12.1%), and paralysis (6.1%). During the course of the disease, 31 patients (93.9%) presented with psychiatric symptoms, 29 patients (87.9%) presented with speech dysfunction, 25 patients (75.8%) presented with movement disorders and 24 patients (72.7%) presented with sleep disorders followed by seizures, consciousness disturbance, autonomic nervous dysfunction, paralysis, and hypoventilation. 12 patients (36.4%) had abnormal cerebrospinal fluid (CSF) findings, 10 patients (30.3%) exhibited abnormal brain magnetic resonance imaging (MRI) results, and 29 patients (87.9%) showed abnormal Electroencephalography (EEG) findings. None of the patients had tumors. All patients received first-line immunotherapy and 8 patients both received first and second-line immunotherapy. 30 of the 33 patients achieved good outcomes (score on the modified Rankin Scale [mRS] of 0–2), whilst the other 3 patients had poor outcomes (mRS score of 3–6). Patients with higher CSF anti-NMDAR body titer were more likely to develop sleep disorders, consciousness disturbances and more severe disease states. [ABSTRACT FROM AUTHOR]