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Objectives: Neuronal intranuclear inclusion disease (NIID) exhibited significant clinical heterogeneities. However, the clinical features, radiographic changes, and prognosis of patients with encephalitis-like NIID have yet to be systematically elucidated. Methods: Clinical data including medical history, physical examination, and laboratory examinations were collected and analyzed. Skin and sural nerve biopsies were conducted on the patient. Repeat-primed PCR (RP-PCR) and fluorescence amplicon length PCR (AL-PCR) were used to detect the expansion of CGG repeat. We also reviewed the clinical and genetic data of NIID patients with cortical enhancement. Results: A 54-year-old woman presented with encephalitis-like NIID, characterized by severe headache and agitative psychiatric symptoms. The brain MRI showed cortical swelling in the temporo-occipital lobes and significant enhancement of the cortical surface and dura, but without hyperintensities along the corticomedullary junction on diffusion-weighted image (DWI). A biopsy of the sural nerve revealed a demyelinating pathological change. The intranuclear inclusions were detected in nerve and skin tissues using the p62 antibody and electron microscopy. RP-PCR and AL-PCR unveiled the pathogenic expansion of CGG repeats in the NOTCH2NLC gene. A review of the literature indicated that nine out of the 16 patients with cortical lesions and linear enhancement exhibited encephalitis-like NIID. Conclusion: This study indicated that patients with encephalitis-like NIID typically exhibited headache and excitatory psychiatric symptoms, often accompanied by cortical edema and enhancement of posterior lobes, and responded well to glucocorticoid treatment. Furthermore, some patients may not exhibit hyperintensities along the corticomedullary junction on DWI, potentially leading to misdiagnosis. [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]

Introduction: Anti-N-methyl-D-aspartate receptor (NMDAr) antibody encephalitis is an autoimmune disorder characterized by synaptic NMDAr current disruption and receptor hypofunction, often affecting women during pregnancy. Clinical manifestations associated with anti-NMDAr encephalitis can occur both in the mother and fetus. Methods: We generated a systematic search of the literature to identify epidemiological, clinical, and serological data related to pregnant women with anti-NMDAr encephalitis and their children, analyzing the fetal outcomes. We examined the age and neurologic symptoms of the mothers, the presence of an underlying tumor, immunotherapies used during pregnancy, duration of the pregnancy, and type of delivery. Results: Data from 41 patients were extrapolated from the included studies. Spontaneous interruption of pregnancy, premature birth, and cesarean section were reported in pregnant women with NMDAr encephalitis. Several fetal and neonatal symptoms (e.g., movement disorders, spina bifida, poor sucking, respiratory distress, cardiac arrhythmias, infections, icterus, hypoglycemia, and low birth weight) depending on the mother's serum anti-NR1 concentration were also reported. Conclusions: We characterized the outcomes of children born from mothers with anti-NMDAr encephalitis, analyzing the pivotal risk factors related to pregnancy and maternal disorder. Neuropsychiatric involvement seems strictly related to pathogenic NMDAr antibodies detected in maternal and/or neonatal serum. These findings clarify a complex condition to manage, outlining the risks associated with pregnant women with anti-NMDAr encephalitis and also providing a concrete guide for therapeutic strategies to prevent potential harm to the fetus and the child's neurodevelopment. [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]

Background: Recognizing the predictors of poor short-term prognosis after first-line immunotherapy in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is essential for individualized treatment strategy. The objective of this study was to ascertain the factors that forecast short-term prognosis in patients with anti-NMDAR encephalitis, develop a prognostic prediction model, and authenticate its efficacy in an external validation cohort. Further, all patients were followed-up long-term to assess the factors of long-term outcome and relapses. Methods: A prospective enrollment of patients diagnosed with anti-NMDAR encephalitis was conducted across five clinical centers in China from June 2014 to Mar 2022. The enrolled patients were divided into the derivation and validation sets based on enrollment time. The short-term prognostic model was visualized using a nomogram. Further, all patients were followed-up long-term to assess the factors of long-term outcome. Results: This study found that poor short-term prognosis was a risk factor for poor long-term outcome (6-month prognosis, OR 29.792, 95%CI 6.507-136.398, p < 0.001; 12-month prognosis, OR 15.756, 95%CI 3.384–73.075, p < 0.001; 24-month prognosis, OR 5.500, 95%CI 1.045–28.955, p = 0.044). Abnormal behavior or cognitive dysfunction (OR 8.57, 95%CI 1.48–49.79, p = 0.017), consciousness impairment (OR19.32, 95%CI 3.03-123.09, p = 0.002), autonomic dysfunction or central hypoventilation (OR 5.66, 95%CI 1.25–25.75, p = 0.025), CSF pleocytosis (OR 4.33, 95%CI 1.48–12.65, p = 0.007), abnormal EEG (OR 5.48, 95% CI 1.09–27.54, p = 0.039) were independent predictors for a poor short-term prognosis after first-line immunotherapy. A nomogram that incorporated those factors showed good discrimination and calibration abilities. The area under the curve (AUC) for the prognostic model were 0.866 (95%CI: 0.798–0.934) with a sensitivity of 0.761 and specificity of 0.869. Conclusion: We established and validated a prognostic model that can provide individual prediction of short-term prognosis after first-line immunotherapy for patients with anti-NMDAR encephalitis. This practical prognostic model may help neurologists to predict the short-term prognosis early and potentially assist in adjusting appropriate treatment timely. [ABSTRACT FROM AUTHOR]

Progressive ataxia and palatal tremor (PAPT) and anti-IgLON5 disease share possible clinical presentations. Furthermore, both have been associated to a tauopathy mainly affecting the brainstem. Nonetheless, anti-IgLON5 antibodies have never been tested in PAPT. We report on two PAPT cases without evidence of anti-IgLON5 antibodies in both CSF and serum. Despite common clinical and pathological characteristics, PAPT and IgLON5 disease are two distinct entities. [ABSTRACT FROM AUTHOR]

Anti-DNER antibody is associated with paraneoplastic cerebellar degeneration (PCD) and Hodgkin's disease (HD). However, recent studies reported cases absence of HD and that non-tumor anti-DNER antibody-associated ataxia was not well characterized. We present a case of acute cerebellar ataxia and nystagmus with detected anti-DNER antibody. Brain magnetic resonance imaging (MRI) showed cerebellar atrophy. High titer of anti-DNER antibody was detected in CSF and serum. Positron emission tomography (PET) scanning was unremarkable at a 10-month follow up. The patient improved significantly after immunosuppressive therapy with intravenous steroids, immunoglobulin followed by rituximab. Our study suggest that the presence of such anti-neuronal antibodies might not come along with malignancy and that early onset non-tumor patients are more likely to have a better outcome after immunotherapy. Early diagnosis and timely immunosuppressive therapy may prove beneficial for these patients. [ABSTRACT FROM AUTHOR]

• ASCs mainly contribute to the NR1-IgGs production in NMDAR encephalitis. • Pre-germinal centres defect in B cell tolerance checkpoint in some patients. • This study reveals the pathogenesis and helps develop tailored treatments. The pathogenicity of NR1-IgGs in N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis is known, but the immunobiological mechanisms underlying their production remain unclear. For the first time, we explore the origin of NR1-IgGs and evaluate the contribution of B-cells to serum NR1-IgGs levels. Peripheral blood mononuclear cells (PBMCs) were obtained from patients and healthy controls (HCs). Naïve, unswitched memory (USM), switched memory B cells (SM), antibody-secreting cells (ASCs), and PBMC depleted of ASCs were obtained by fluorescence-activated cell sorting and cultured in vitro. For some patients, PBMCs spontaneously produced NR1-IgGs. Compared to the patients in PBMC negative group, the positive group had higher NR1-IgG titers in cerebrospinal fluid and Modified Rankin scale scores. The proportions of NR1-IgG positive wells in PBMCs cultures were correlated with NR1-IgGs titers in serum and CSF. The purified ASCs, SM, USM B cells produced NR1-IgGs in vitro. Compared to the patients in ASCs negative group, the positive group exhibited a worse response to second-line IT at 3-month follow-up. Naïve B cells also produce NR1-IgGs, implicating that NR1-IgGs originate from naïve B cells and a pre-germinal centres defect in B cell tolerance checkpoint in some patients. For HCs, no NR1-IgG from cultures was observed. PBMC depleted of ASCs almost eliminated the production of NR1-IgGs. These collective findings suggested that ASCs might mainly contribute to the production of peripheral NR1-IgG in patients with NMDAR-antibody encephalitis in the acute phase. Our study reveals the pathogenesis and helps develop tailored treatments (eg, anti-CD38) for NMDAR-antibody encephalitis. [ABSTRACT FROM AUTHOR]

Introduction: Identifying coronavirus disease 2019 (COVID-19)-related encephalitis without clear etiological evidence is clinically challenging. The distinctions between this condition and other prevalent encephalitis types remain unknown. Therefore, we aimed to explore the similarities and differences in the clinical characteristics of COVID-19-related encephalitis and other encephalitis types. Methods: Adult patients with encephalitis admitted to the neurology department at Xuanwu Hospital were enrolled and categorized into the following six groups based on the results of metagenomic next-generation sequencing and autoimmune antibody detection in cerebrospinal fluid (CSF): COVID-19-related encephalitis (n = 36), herpes simplex virus type 1 encephalitis (HSV-1 encephalitis; n = 28), human herpesvirus 3 encephalitis (HHV-3 encephalitis; n = 10), NMDAR-antibody encephalitis (n = 18), LGI1-antibody encephalitis (n = 12), and GABAB-antibody encephalitis (n = 8). Results: The predominant characteristics of COVID-19-related encephalitis include a low incidence of seizures (38.9%), cognitive defects (30.6%), and meningeal irritation signs (8.3%). Compared with HSV-1 and HHV-3 encephalitis, COVID-19-related encephalitis exhibited lower white blood cell count (2.5 count/mm3), protein (32.2 mg/dL), and immunoglobulin M, G, and A levels (0.09, 3.2, and 0.46 mg/dL, respectively) in the CSF tests. Abnormal imaging findings were present in only 36.1% of COVID-19-related encephalitis cases, mostly showing diffuse inflammation scattered in various parts, which differed from HSV-1 encephalitis. Additionally, COVID-19-related encephalitis exhibited significant differences in clinical symptoms and CSF white blood cell counts compared with NMDAR-antibody encephalitis; however, it showed limited differences compared with LGI1-antibody and GABAB-antibody encephalitis. Discussion: COVID-19-related encephalitis and herpes virus or autoimmune encephalitis differ clinically. Symptoms and auxiliary examinations can be used as distinguishing tools. [ABSTRACT FROM AUTHOR]

Leucine-rich glioma-inactivated protein 1 (LGI-1) encephalitis is a rare form of autoimmune limbic encephalitis. Although relatively well documented in adults, pediatric cases are rare and remain poorly understood. We reviewed two pediatric cases of LGI-1 encephalitis from a single tertiary care facility retrospectively. The detailed analysis included assessment of the initial presentation, clinical progression, diagnostic challenges, treatments, and outcome. To contextualize the differences between pediatric and adult manifestations of disease, we compared these findings with existing literature. Both cases illustrate the diagnostic challenges faced at initial presentation due to the rarity of this diagnosis in children and the absence of characteristic faciobrachial dystonic seizures, which is common in adults. The constellation of neuropsychiatric symptoms and refractory focal seizures led to a high clinical suspicion for autoimmune encephalitis, therefore, both cases were treated empirically with intravenous methylprednisolone. The diagnosis in both cases was confirmed with positive serum antibody testing, reinforcing that LGI-1 antibodies are more sensitive in the serum rather than the cerebrospinal fluid (CSF). Seizure control and improvement in cognitive symptoms was achieved through a combination of immunotherapy and antiseizure medications. This case series underscores the significance of considering LGI-1 encephalitis in the differential diagnosis of pediatric patients exhibiting unexplained neuropsychiatric symptoms and focal seizures and emphasizes the importance of performing both serum and CSF antibody testing. It is necessary to conduct further research to identify the full range of pediatric presentations and to determine the optimal treatment protocol. [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]

Purpose: To delineate the characteristics of probable antibody-negative pediatric autoimmune encephalitis (probable Ab-negative AE), we compared the clinical features of probable Ab-negative AE to those of major antibody-positive AE. Methods: We retrospectively reviewed the clinical features of 18 patients with probable Ab-negative AE, 13 with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE), and 13 with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Clinical characteristics, neuroimaging findings, treatments, and outcomes were analyzed. Results: The age of onset and length of hospital stay were significantly higher in the NMDARE group than in the other groups (p = 0.02 and p < 0.01). Regarding initial neurological symptoms, acute symptomatic seizures in the probable Ab-negative AE group (67%) were significantly more frequent than in the NMDARE (15%) and MOGAD (23%) groups (p<0.01). Paraclinical evidence of neuroinflammation within 1 month of disease onset revealed that single-photon emission computed tomography (SPECT) detected abnormal alterations in 14/14 (100%), cerebrospinal fluid (CSF) analysis in 15/18 (83%), and magnetic resonance imaging (MRI) in 11/18 (61%) in patients with probable Ab-negative AE. In the probable Ab-negative AE group, seven patients (39%) developed autoimmune-associated epilepsy, whereas one patient (8%) had both NMDARE and MOGAD (not statistically significant, p = 0.07). Conclusion: Patients with probable Ab-negative AE exhibited acute symptomatic seizures as initial neurological symptoms significantly more frequently. They developed autoimmune-associated epilepsy more frequently than those with NMDARE and MOGAD, which was not statistically significant. SPECT within 1 month of disease onset might be a valuable surrogate marker of ongoing neuroinflammation and neuronal dysfunction, even in patients with negative MRI findings. [ABSTRACT FROM AUTHOR]

Introduction: Schizophrenia (SCZ) and autism spectrum disorder (ASD) are neurodevelopmental diseases characterized by different psychopathological manifestations and divergent clinical trajectories. Various alterations at glutamatergic synapses have been reported in both disorders, including abnormal NMDA and metabotropic receptor signaling. Methods: We conducted a bicentric study to assess the blood serum levels of NMDA receptors-related glutamatergic amino acids and their precursors, including L-glutamate, L-glutamine, D-aspartate, L-aspartate, L-asparagine, Dserine, L-serine and glycine, in ASD, SCZ patients and their respective control subjects. Specifically, the SCZ patients were subdivided into treatment-resistant and non-treatment-resistant SCZ patients, based on their responsivity to conventional antipsychotics. Results: D-serine and D-aspartate serum reductions were found in SCZ patients compared to controls. Conversely, no significant differences between cases and controls were found in amino acid concentrations in the two ASD cohorts analyzed. Discussion: This result further encourages future research to evaluate the predictive role of selected D-amino acids as peripheral markers for SCZ pathophysiology and diagnosis. [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]

Background Methods Results Conclusion Anti‐IgLON5 encephalitis was a rare neurological and heterogeneous disorder, which was mainly found in adults. Epileptic seizures related to anti‐IgLON5 disease were rarely reported.Neural antibodies associated with autoimmune encephalitis in serum and cerebrospinal fluid (CSF) were tested using cell‐based assays (CBA) with immunofluorescence double staining. The antibodies in serum were further confirmed by tissue‐based assay (TBA) with rat brain and kidney tissue.We reported a pediatric case presented with epileptic seizures, cognitive impairments, and sleep disorders. Autoantibody screening showed anti‐IgLON5 antibody IgG (1:100+) and anti‐NMDAR antibody IgG (1:10+) in the serum. She was diagnosed as anti‐IgLON5 encephalitis. Her conditions improved rapidly by treated with intravenous immunoglobulin and high dose intravenous methylprednisolone.We described the second pediatric case with anti‐IgLON5 encephalitis, who was also the first presented with epileptic seizures as the initial presentation. Anti‐IgLON5 encephalitis might have mild manifestations. For patients with new onset seizures associated with cognitive impairments and sleep disturbances, anti‐IgLON5 antibody should be tested as early, even in children. [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested that N-methyl-D-aspartate (NMDA) receptors are involved in the cell proliferation in several tumors. However, there have been no reports demonstrating the expression of NR1 subunit of the NMDA receptor in large cell neuroendocrine carcinoma (LCNEC). Case presentation: Here, we report the first elderly case of paraneoplastic anti-NMDA receptor encephalitis associated with LCNEC of the lung with NR1 expression. Of note, NR1 subunit expression in the tumor cells of the present case was confirmed by immunohistochemistry (IHC). Radiation therapy and immunotherapies, such as corticosteroids and intravenous immunoglobulin (IVIG), shrank the tumors and improved neurological symptoms in the present case. Additionally, we also confirmed the expression of NR1 in the tumor cells obtained from three other cases with LCNEC of the lung at our hospital by IHC. Conclusion: Our IHC results indicate that LCNEC generally expresses NR1 subunit and NMDA receptor may be involved in the tumor development and growth. [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase-like protein 6 (DPPX) antibody encephalitis is a rare autoimmune encephalitis. Diagnosis and treatment of DPPX remain challenging, particularly in patients with refractory disease. Herein, we report the first case of anti-DPPX encephalitis treated with ofatumumab. The patient had a chronic insidious onset and predominantly presented with severe neuropsychiatric symptoms and the typical triad of symptoms (weight loss, central nervous system hyperexcitability, and cognitive dysfunction). Positive anti-DPPX antibodies in the serum (1:1,000) and cerebrospinal fluid (CSF) (1:100) were detected at the disease peak. The patient was unresponsive to four types of standard immunotherapies (intravenous globulin, plasma exchange, steroids, and tacrolimus), resulting in a treatment switch to ofatumumab. After five doses of injection and 12 months of follow-up, the patient improved well, with only a mild cognitive deficit. [ABSTRACT FROM AUTHOR]

Background and aims. Psychiatrists are often the first to be consulted in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Thus, they need to be aware of clinical features, differential diagnoses, and treatment options for this condition. In this study, we aimed to investigate the familiarity of Romanian psychiatrists with anti-NMDAR encephalitis. Methods. We recruited psychiatrists from Romania and conducted a crosssectional observational study by using a web-based survey. Results. The survey was completed by 111 psychiatrists, of whom 47 (42.34%) were specialists, while 64 (57.66%) were trainees. The median length of training for specialists was ten years (interquartile range - IQR 9.5), while for trainees it was 2.5 years (IQR 3). In total, 31 (27.93%) psychiatrists encountered a case of anti-NMDAR encephalitis, with no significant difference between specialists and trainees. 31 (27.93%) psychiatrists were either unaware of the disorder or only knew its name, while 77 (69.37%) had knowledge of an outline of it. Only 3 (2.7%) psychiatrists had comprehensive knowledge of the disorder. Respondents with a higher awareness level had undergone significantly longer training (p=0.014). Unsurprisingly, having encountered a case significantly influenced awareness levels (p<0.001). There were no significant differences between specialists and trainees regarding specific knowledge about anti-NMDAR encephalitis. However, higher awareness levels and having encountered a case significantly influenced answer accuracy for questions regarding psychiatric presentation and epidemiological features. Conclusions. Our study indicates that Romanian psychiatrists have suboptimal knowledge of anti-NMDAR encephalitis, highlighting the need for improved awareness of this disorder. [ABSTRACT FROM AUTHOR]

This article discusses the potential of avacopan, a medication that blocks a specific receptor, to improve the condition of patients with a type of blood vessel inflammation called ANCA-associated vasculitis. The article presents a case study of a patient who had high levels of a specific antibody despite treatment with other medications. However, when avacopan was added to their treatment, the antibody levels decreased. The authors suggest that avacopan may have the potential to lower antibody levels and improve the condition, but more research is needed. The article also provides information about conflicts of interest, funding, patient consent, and data availability. [Extracted from the article]

Key Clinical Message: This case underscores the critical importance of timely recognition and management of NMDAR encephalitis in adolescents to mitigate potential long‐term sequelae. If a pediatric patient presents with suspected viral encephalitis, autoimmune etiology must be excluded via cerebrospinal fluid antibody assay to guide appropriate immunosuppressive therapy, and improve patient outcomes. Autoimmune encephalitis particularly involving the n‐methyl‐d‐aspartate receptor (NMDAR) is recognized as a rare cause of acute encephalopathy in pediatric patients. The following case is of a 14‐year‐old female diagnosed with anti‐NMDAR encephalitis who initially presented with fever, episodic convulsions, and loss of consciousness. She subsequently developed right‐sided body weakness, expressive aphasia, and visual hallucinations. Clinical examination revealed prominent neuropsychiatric manifestations such as altered sensorium, motor deficits, hallucinations, and visual disturbances. Cerebello‐bulbar signs were not appreciable in this particular case. She was treated for viral encephalitis but showed no improvement. Laboratory investigations revealed the presence of NMDAR antibodies in the cerebrospinal fluid confirming the diagnosis of autoimmune etiology. The patient demonstrated notable improvement following immunosuppressive treatment. [ABSTRACT FROM AUTHOR]

During deployment, a 52-year-old male developed acute behavioral changes. Though initially considered to have PTSD and related agitation and confusional state, his evaluation was consistent with acute encephalopathy. Magnetic resonance imaging of the brain showed T2 hyperintensities, and CSF analysis was positive for anti-N-methyl-D-aspartate receptor antibody. A nuclear protein in testis carcinoma midline carcinoma was discovered in the lung. Immunotherapy and surgical resection led to steady improvement prior to adjuvant chemotherapy. Autoimmune encephalitis due to anti-N-methyl-D-aspartate receptor antibodies is increasingly being recognized as causal of acute behavioral change. [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]

Objectives: To report an autoimmune paraneoplastic encephalitis characterized by immunoglobulin G (IgG) antibody targeting synaptic protein calmodulin kinase‐like vesicle‐associated (CAMKV). Methods: Serum and cerebrospinal fluid (CSF) samples harboring unclassified antibodies on murine brain‐based indirect immunofluorescence assay (IFA) were screened by human protein microarray. In 5 patients with identical cerebral IFA staining, CAMKV was identified as top‐ranking candidate antigen. Western blots, confocal microscopy, immune‐absorption, and mass spectrometry were performed to substantiate CAMKV specificity. Recombinant CAMKV‐specific assays (cell‐based [fixed and live] and Western blot) provided additional confirmation. Results: Of 5 CAMKV‐IgG positive patients, 3 were women (median symptom‐onset age was 59 years; range, 53–74). Encephalitis‐onset was subacute (4) or acute (1) and manifested with: altered mental status (all), seizures (4), hyperkinetic movements (4), psychiatric features (3), memory loss (2), and insomnia (2). Paraclinical testing revealed CSF lymphocytic pleocytosis (all 4 tested), electrographic seizures (3 of 4 tested), and striking MRI abnormalities in all (mesial temporal lobe T2 hyperintensities [all patients], caudate head T2 hyperintensities [3], and cortical diffusion weighted hyperintensities [2]). None had post‐gadolinium enhancement. Cancers were uterine adenocarcinoma (3 patients: poorly differentiated or neuroendocrine‐differentiated in 2, both demonstrated CAMKV immunoreactivity), bladder urothelial carcinoma (1), and non‐Hodgkin lymphoma (1). Two patients developed encephalitis following immune checkpoint inhibitor cancer therapy (atezolizumab [1], pembrolizumab [1]). All treated patients (4) demonstrated an initial response to immunotherapy (corticosteroids [4], IVIG [2]), though 3 died from cancer. Interpretation: CAMKV‐IgG is a biomarker of immunotherapy‐responsive paraneoplastic encephalitis with temporal and extratemporal features and uterine cancer as a prominent oncologic association. ANN NEUROL 2024;96:21–33 [ABSTRACT FROM AUTHOR]

This retrospective study aimed to describe a cohort of 38 pediatric patients with MOGAD and to investigate the clinical differences between patients with CSF-negativity and CSF-positivity for MOG-abs. The clinical and laboratory characteristics of pediatric patients with MOGAD were retrospectively studied. Demographics, clinical characteristics, CSF analysis, treatments and prognosis of patients were recorded. All patients' serums and CSF were tested for MOG-IgG by live cell-based assays (CBA). The data were statistically analysed. A total of 38 pediatric MOGAD patients were enrolled in the study, including 22 (57.9 %) females and 16 male (42.1 %) with a mean age of 8.4 ± 4.0 years at disease onset. Twenty-seven (71.7 %) patients were CSF-positive for MOG-abs while 11 (28.9 %) patients were CSF-negative for MOG-abs. The median follow-up was 25.5 months (IQR 5.5–73.25). Seventeen (44.7 %) patients presented a relapsing disease course, and the majority of these patients was CSF positive with a significant difference between the two groups (p = 0.038) in terms of recurrent diseases. CSF-positive patients presented more often an increased white cell count (p = 0.043), and in this cohort clinical phenotypes with spinal involvement were more frequent while encephalitis-like phenotypes were more frequent in the CSF negative cohort (p = 0.019). CSF-status appears to identify two subgroups in this pediatric MOGAD population; thus, CSF-status requires further studies in pediatric patients with MOGAD. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 67-year-old woman with myasthenia gravis who developed symptoms of parkinsonism, visual disturbances, and stiff-limb syndrome due to anti-GlyR antibodies. The patient experienced difficulties with movement, gait, and voice, as well as unusual visual phenomena and muscle stiffness. Treatment with intravenous methylprednisolone led to significant improvement in her symptoms. The article emphasizes the need for further research on the diverse symptoms associated with anti-GlyR antibodies and highlights the importance of prompt recognition and treatment of autoimmune diseases. [Extracted from the article]

The article presents a case study of a 69-year-old man suffering from mGluR5 encephalitis, a rare autoimmune condition involving antibodies against metabotropic glutamate receptor 5. It is reported that this neurological disorder presented with a variety of symptoms, including myoclonus (involuntary muscle jerks), ataxia (loss of coordination), psychosis, and various neuropsychiatric manifestations.

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]

Germ cell tumors of childhood are tumors arising from germline cells in gonadal or extragonadal locations. Extragonadal germ cell tumors are characteristically located in the midline, arising intracranially or in the mediastinum, retroperitoneum, or pelvis. These tumors are generally easily diagnosed due to typical sites of origin, characteristic imaging findings, and laboratory markers. However, germ cell tumors can be associated with unusual clinical syndromes or imaging features that can perplex the radiologist. This review will illustrate atypical imaging/clinical manifestations and complications of abdominal germ cell tumors in childhood. These features include unusual primary tumors such as multifocal primaries; local complications such as ovarian torsion or ruptured dermoid; atypical presentations of metastatic disease associated with burned-out primary tumor, growing teratoma syndrome, and gliomatosis peritonei; endocrine manifestations such as precocious puberty and hyperthyroidism; and antibody mediated paraneoplastic syndrome such as anti-N-methyl-D-aspartate-receptor antibody-mediated encephalitis. This review aims to illustrate unusual imaging features associated with the primary tumor, metastatic disease, or distant complications of abdominal germ cell tumors of childhood. [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]

Autoimmune encephalitis (AE) is one of the paraneoplastic syndromes of ovarian teratoma. Insufficient knowledge about the evolution of the disease, as well as its manifestation in the form of non-specific clinical symptoms (such as significant deterioration of memory and cognitive functions of patients), is a common cause of a prolonged diagnostic process and delay in the introduction of targeted treatment. The aim of the study was to summarize the data available in the literature, as well as recent reports, to facilitate and accelerate the diagnosis of the syndrome and ensure better care for patients. A literature review was performed in the PubMed, Google Scholar databases and the guidelines of the Polish Society of Gynecologists and Obstetricians, by using keywords. Making a diagnosis of AE requires the cooperation of a team of specialists (including, among others, neurologists, gynecologists and oncologists). Justification for this is the manifestation of pathology comes in the form of non-specific clinical symptoms. Treatment includes surgery to remove the tumor, pharmacotherapy: corticosteroids and immunoglobulin infusions, in addition to allied modern plasmapheresis treatments – in severe cases. Sorting out the non-specific symptoms of AE would facilitate faster and more accurate diagnosis, and this improve the functioning of patients suffering from ovarian teratoma. Pertinent tests are necessary to facilitate and optimize the differential diagnosis. Education of doctors about its alarming symptoms is important, as is cooperation between doctors of different specialties. [ABSTRACT FROM AUTHOR]

Super refractory status epilepticus (SRSE) is a condition in which status epilepticus persists despite 48 hours of anesthetic treatment. Nonconvulsive status epilepticus (NCSE) is characterized by seizures lasting more than 30 min on an electroencephalogram, with accompanying changes in behavior or consciousness without convulsions. Prompt treatment of NCSE is crucial, as delayed treatment may lead to additional brain damage and progression to convulsive status epilepticus. Although vagus nerve stimulation (VNS) has been approved as an adjunct treatment for drug-resistant epilepsy, it is rarely used to treat refractory status epilepticus. To the best of our knowledge, only two cases of NCSE treated with VNS have been reported to date, and these patients were successfully treated with VNS for NCSE caused by anti-NMDAR encephalitis. We report the case of a patient with posttraumatic epilepsy who developed super refractory-NCSE after convulsive status epilepticus and was successfully treated with VNS. [ABSTRACT FROM AUTHOR]

A study conducted in Poland found that auricular vagal nerve stimulation (atVNS) using the VGuard device significantly improved cognition in patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD). The study involved 51 patients with AD and showed that the active treatment group had statistically significant cognitive improvement compared to the placebo group. However, the cognitive improvement returned to baseline values after 24 weeks of no treatment. This study suggests that atVNS may be an effective therapeutic approach in delaying the conversion of MCI into the initial stages of AD. Additionally, this document contains summaries of several other research studies in the field of neurology, including studies on protein levels in neurodegenerative diseases, CAR T cell therapy for neurological autoimmune diseases, treatment strategies for acute ischemic stroke in patients with active cancer, and a predictive model for the outcome of anti-NMDAR encephalitis. [Extracted from the article]

The "hot cross bun" sign (HCBs) is a cruciform hyperintensity on T2-weighted imaging within the pons initially found in patients diagnosed as multiple system atrophy. However, recent findings have broadened the disease spectrum presented with HCBs. Here is a case report at an academic medical center. Cerebral magnetic resonance imaging (MRI), electroneuromyography, serum, and CSF analysis were performed. Literature is comprehensively reviewed. We investigated a woman presented with blurred speech and cerebellar ataxia. Her MRI showed the vertical line of HCBs 2 weeks after disease onset and gradually enhanced, presenting as an intact HCBs in a year. Glutamic acid decarboxylase 65-kDa isoform (GAD65) antibody IgG was detected in serum and CSF. The patient was diagnosed as GAD65 associated cerebellar ataxia and treated with corticosteroid and rituximab. We found 6 previously reported autoimmune cerebellar ataxia patients with HCBs. Anti-KLHL-11, anti-Homer-3, anti-Ri, and anti-Amphiphysin were associated. All patients had cerebellar ataxia with other neurological symptoms. Five patients were diagnosed with tumor. First-line immunotherapy including corticosteroid, intravenous immunoglobulin, and plasma exchange for most patients was unsatisfied. This case highlights the importance of considering GAD65 IgG evaluation in patients with progressive cerebellar syndrome and HCBs. Early diagnosis and therapy are challenging but imperative. Further studies are required in regard to therapeutic management. [ABSTRACT FROM AUTHOR]

Antibodies against the neuronal protein Ma2 have been reported in a peculiar form of paraneoplastic encephalitis with prominent involvement of the limbic, brainstem, and diencephalic structures and usually associated with germ cell testicular, lung, or breast cancer. The diagnosis is frequently challenged by atypical clinical manifestations including parkinsonism, sleep disturbances, hypothalamic-pituitary dysfunctions, and motor neuron-like syndrome. In recent years, the advent of monoclonal antibodies targeting immune checkpoints has deeply changed the treatment of different tumors, especially melanoma and lung cancer. However, given their nature, an increasing number of neurological immune-related adverse events, including ocular motor abnormalities, have been described. Here, we report a woman with advanced non-small cell lung cancer treated with anti-PD-L1 durvalumab, presenting with an isolated pendular torsional nystagmus, in association with anti-Ma2 antibodies. This peculiar case widens our knowledge on the clinical presentation of anti-Ma2 encephalitis associated with checkpoint inhibitors. [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]

This document, published in the Journal of Neurology, explores the use of [18F]DPA-714-PET-MRI as a diagnostic tool for autoimmune limbic encephalitis (ALE) with specific autoantibodies. The study involved two patients with these autoantibodies, and the results showed increased tracer uptake in certain areas of the brain. The study suggests that [18F]DPA-714-PET-MRI could be a valuable tool for diagnosing ALE and assessing the immune response in the brain. However, further research is needed to fully understand its potential for clinical use in ALE. [Extracted from the article]

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]

The article focuses on Omas Müller's journey through profound depression and misdiagnosis, ultimately finding relief through a neuropsychiatrist's identification of autoimmune encephalitis, shedding light on a growing understanding of autoimmune conditions triggering psychosis and revolutionizing clinical psychiatry.

Introduction: Anti-IgLON5 antibody-related encephalitis is a rare autoimmune disorder of the central nervous system, predominantly occurring in middle-aged elderly individuals, with paediatric cases being exceptionally rare. This study aims to enhance the understanding of paediatric anti-IgLON5 antibody-related encephalitis by summarising its clinical and therapeutic characteristics. Method: A retrospective analysis was conducted on two paediatric patients diagnosed with anti-IgLON5 antibody-related encephalitis at Hunan Children's Hospital from August 2022 to November 2023. This involved reviewing their medical records and follow-up data, in addition to a literature review. Results: The study involved two patients, one male and one female, aged between 2.5 and 9.6 years, both presenting with an acute/subacute course of illness. Clinically, both exhibited movement disorders (including dystonia, involuntary movements, and ataxia), cognitive impairments, sleep disturbances, and psychiatric symptoms. Patient 1 experienced epileptic seizures, while Patient 2 exhibited brainstem symptoms and abnormal eye movements. Neither patient showed autonomic dysfunction. Patient 1 had normal cerebrospinal fluid (CSF) and Brain MRI findings, whereas Patient 2 showed moderate leukocytosis and mild protein elevation in the CSF, and Brain MRI revealed symmetrical lesions in the basal ganglia and cerebellum. Oligoclonal bands in the CSF were positive in both cases. Both patients tested negative for HLA-DQB*05:01 and HLADRB* 10:01. They received both first-line and second-line immunotherapies, with Patient 2 showing a poor response to treatment. Discussion: Paediatric cases of anti-IgLON5 antibody-related encephalitis similarly present sleep disturbances as a core symptom, alongside various forms of movement disorders. Immunotherapy is partially effective. Compared to adult patients, these paediatric cases tend to exhibit more pronounced psychiatric symptoms, a more rapid onset, and more evident inflammatory changes in the CSF. The condition appears to have a limited association with HLA-DQB*05:01 and HLA-DRB*10:01 polymorphisms. [ABSTRACT FROM AUTHOR]

Objective: Anti-dipeptidyl-peptidase-like protein-6 (DPPX) encephalitis is a rare autoimmune encephalitis, and clinical and experimental information regarding this disease is limited. We conducted this study to comprehensively describe the clinical characteristics, ancillary test results, neuroimaging results, and treatment response in a group of Chinese patients with anti-DPPX encephalitis for better understanding this disease. Methods: We recruited 14 patients who tested positive for anti-DPPX antibodies in the serum and/or cerebrospinal fluid from 11 medical centers between March 2021 and June 2023. This retrospective study evaluated data on symptoms, autoantibody test, auxiliary examinations, treatments, and outcomes. Results: The average age at diagnosis was 45.93 ± 4.62 years (range: 11-72 years), and 9 of the 14 patients were males. The main symptoms included cognitive impairment (50.0%, 7/14), central nervous system hyperexcitability (42.9%, 6/14), gastrointestinal dysfunction (35.7%, 5/14), and psychiatric disorders (35.7%, 5/14). Notably, we discovered specific findings on 18F-fluorodeoxyglucose positronemission tomography (PET)/magnetic resonance imaging in two patients. Co-existing autoantibodies were identified in two patients. Parainfection was identified in four patients. One patient had other autoimmune diseases, and one had tumor. Eleven patients received immunotherapy and most patients improved at discharge. Surprisingly, three male patients but no female patients relapsed during the 6 months of follow-up. Conclusion: The development and outcome of anti-DPPX encephalitis are variable. Male patients were predominant in our cohort. The most common symptoms were the classical triad of prodromal gastrointestinal dysfunction, cognitive and mental disorders, and central nervous system hyperexcitability. Infections, immune dysregulation, and tumors may be important etiologies. Long-term monitoring of disease development should be done in male patients. Overall, our results highlight novel clinical characteristics of anti-DPPX encephalitis. [ABSTRACT FROM AUTHOR]

Introduction: Anti-NMDA receptor encephalitis is an autoimmune disorder caused by autoantibodies (abs) against the conformational epitope on GluN1 subunits. GluN1-abs have been determined with cell-based assay (CBA) coexpressing GluN1/GluN2 subunits. However, commercial fixed CBA expressing only GluN1 subunit has increasingly been used in clinical practice. The ab titers can be determined with serial dilutions, but its clinical significance remains unclear. We aimed to develop an H-intensity scale (HIS) score to estimate GluN1-ab titers in cerebrospinal fluid (CSF) with one-time immunostaining using both commercial CBA and immunohistochemistry and report its usefulness. "H" is the initial of a patient with high CSF GluN1-ab titers (1:2,048). Methods: We first determined the reliability of CBA in 370 patients with suspected autoimmune encephalitis by comparing the results between commercial CBA and established assay in Dalmau's Lab. Then, we made positive control panels using the patient H's CSF diluted in a fourfold serial dilution method (1:2, 1:8, 1:32, 1:128, 1:512, and 1:2,048). Based on the panels, we scored the intensity of ab reactivity of 79 GluN1-ab-positive patients' CSF (diluted at 1:2) on a scale from 0 to 6 (with ≥1 considered positive). To assess inter-assay reliability, we performed immunostaining twice in 21 patients' CSF. We investigated an association between the score of CSF obtained at diagnosis and the clinical/paraclinical features. Results: The sensitivity and specificity of CBA were 93.7% (95% CI: 86.0-97.3) and 98.6% (95% CI: 96.5-99.5), respectively. Linear regression analysis showed a good agreement between the scores of the first and second assays. Patients with a typical spectrum, need for mechanical ventilation support, autonomic symptoms/central hypoventilation, dyskinesias, speech dysfunction, decreased level of consciousness, preceding headache, ovarian teratoma, and CSF leukocyte count >20 cells/µL had a higher median HIS score than those without, but HIS score was not associated with sex, age at onset, or seizure. HIS score at diagnosis had a significant effect on 1-year functional status. Discussion: The severity of disease and four of the six core symptoms were associated with higher GluN1-ab titers in CSF at diagnosis, which may play a role in poor 1-year functional status. An incomplete phenotype can be attributed to low CSF GluN1-ab titers. [ABSTRACT FROM AUTHOR]

Background: Autoimmune diseases have always been one of the difficult diseases of clinical concern. Because of the diversity and complexity of its causative factors, unclear occurrence and development process and difficult treatment, it has become a key disease for researchers to study. And the disease explored in this paper, anti-NMDA encephalitis, belongs to a common type of autoimmune encephalitis. However, the quality of articles and research hotspots in this field are not yet known. Therefore, in this field, we completed a bibliometric and visualization analysis from 2005 to 2023 in order to understand the research hotspots and directions of development in this field. Materials and methods: We searched the SCI-expanded databases using Web of Science's core databases on January 22, 2024 and used tools such as VOS viewer, Cite Space, and R software to visualize and analyze the authors, countries, journals, institutions, and keywords of the articles. Results: A total of 1,161 literatures were retrieved and analyzed in this study. China was the country with the most total publications, and USA and Spain were the most influential countries in the field of anti-NMDA encephalitis. University of Pennsylvania from USA was the institution with the highest number of publications. While Dalmau Josep is the most prolific, influential and contributing author who published one of the most cited articles in Lancet Neurology, which laid the foundation for anti-NMDA encephalitis research, the top three appearances of keyword analysis were: "antibodies", "diagnosis", and "autoimmune encephalitis." Conclusion: Bibliometric analysis shows that the number of studies on anti-NMDA encephalitis is generally increasing year by year, and it is a hot disease pursued by researchers. USA and Spain are leading in the field of anti-NMDA encephalitis, while China should continue to improve the quality of its own research. The suspected causes of anti-NMDA encephalitis other than ovarian teratoma and herpes simplex, the specific clinical manifestations that are not masked by psychiatric symptoms, the diagnostic modalities that are faster and more accurate than antibody tests, and the improvement of treatment modalities by evaluating prognosis of various types of patients are the hotspots for future research. [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]

Association between anti-GABAAR encephalitis and myasthenia gravis is extremely rare with few reported cases. Herein, we report a case of a female patient diagnosed with anti-GABAAR encephalitis and thymoma at the first admission. She was administered glucocorticoids for long-term immunotherapy, and thymectomy with biopsy demonstrated a type A thymoma. After 4 months, the symptoms of encephalitis were relieved, but she then developed post-thymectomy myasthenia gravis with anti-AChR and anti-titin dual positivity. Antibodies to connective tissue (anti-ANA, anti-PCNA) and those characteristics of paraneoplastic syndrome (anti-Ma2/Ta) were also positive. She received oral glucocorticoids and tacrolimus as immunosuppressive therapy, and myasthenic symptoms were stable during a 2-year follow-up. Our case revealed that anti-GABAAR encephalitis and myasthenia gravis can appear in patient with type A thymoma at different periods, which alerts physicians to take long-term follow-up for anti-GABAAR encephalitis with thymoma, even after thymectomy. Concurrent positivity for more than one antibody after thymectomy is rarely observed, and their contribution to the clinical course and treatment decision remains to be further investigated. [ABSTRACT FROM AUTHOR]

The article discusses the challenges in predicting outcomes for patients with anti- N-methyl-D-aspartate (NMDA) receptor encephalitis due to limited data on influencing factors, emphasizing the importance of evaluating cognitive and mood disorders for prognosis.

This document is a compilation of various research articles related to neuropsychiatric disorders. The articles cover a range of topics including the use of lithium for brain plasticity and neuroprotection, poststroke depression, biomarkers for migraine and cluster headache, atrophy in frontotemporal dementia, common neurobiological substrates for mental illness, neuroimaging in functional neurological disorder, autoimmune encephalitis, and the importance of cross-disciplinary education in neurology and psychiatry. The articles provide valuable insights into the diagnosis, treatment, and understanding of these disorders, and may be useful for researchers and clinicians in the field. [Extracted from the article]

Japanese Encephalitis (JE) poses a significant public health threat across Asia and the Western Pacific, leading to considerable mortality and morbidity if not promptly diagnosed and treated. This flaviviral infection, transmitted by Culex mosquitoes, primarily affects children but can impact individuals of all ages. Prompt diagnosis relies on detecting Japanese Encephalitis Virus (JEV) IgM antibodies in serum or Cerebrospinal Fluid (CSF), alongside characteristic Magnetic Resonance Imaging (MRI) findings. In this MRI case series, three confirmed cases of JE are presented, showcasing the typical neuroimaging manifestations observed in affected individuals. All cases exhibited bilateral thalamic hyperintensities on T2-weighted and Fluid Attenuated Inversion Recovery (FLAIR) images, a hallmark feature of JE. Additionally, one patient demonstrated involvement of the substantia nigra and bilateral frontal cortex. The clinical implications of present study findings underscore the importance of considering JE as a differential diagnosis in patients presenting with symptoms of encephalitis, especially when MRI reveals bi-thalamic signal alterations. Early recognition and initiation of appropriate treatment, including antiviral agents, are crucial for improving outcomes and reducing mortality. This study contributes to the existing literature by reinforcing the importance of neuroimaging in diagnosing JE and highlighting the distinct MRI patterns associated with the disease. Recognising these characteristic imaging features can aid clinicians in promptly identifying and managing JE cases, thereby mitigating the associated morbidity and mortality. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Prompt identification and management of anti‐N‐methyl‐D‐aspartate receptor encephalitis in young patients with acute psychiatric symptoms, seizures, and neurological deficits are crucial. Timely immunomodulatory therapy is essential for positive outcomes and minimizing long‐term complications. High suspicion for this rare disorder is necessary for timely diagnosis and optimal care. Anti‐N‐methyl‐D‐aspartate (NMDA) receptor encephalitis is characterized by the presence of antibodies against the NMDA receptor, a crucial component of synaptic signaling. This autoimmune disorder often manifests with psychiatric symptoms, seizures, and neurological deficits. Early diagnosis is essential, as delayed treatment can result in severe complications. In this case, the patient received corticosteroids and intravenous immunoglobulin (IVIG), leading to a successful recovery with no lingering neurological abnormalities. The prompt initiation of treatment highlights the importance of recognizing this condition early. Anti‐NMDA receptor encephalitis is a rare autoimmune disorder that presents with a range of neurological symptoms. In this case report, we highlight the significance of early recognition and treatment by discussing the emergency room visit of a 23‐year‐old woman who presented with acute‐onset agitation, disorientation, and seizures. A 23‐year‐old woman, presented to the emergency room with acute‐onset agitation, disorientation, and seizures. Magnetic resonance imaging (MRI) scans revealed temporal lobe signal alterations and electroencephalogram (EEG) showed widespread activity slowing. Importantly, anti‐NMDA receptor antibodies were detected in both serum and cerebrospinal fluid, confirming the diagnosis of anti‐NMDA receptor encephalitis. This case report underscores the significance of understanding the presentation, diagnosis, and treatment of anti‐NMDA receptor encephalitis. Timely recognition and intervention are crucial for achieving favorable outcomes in patients with this rare but clinically important autoimmune disorder. Increased awareness among healthcare professionals is essential to ensure early diagnosis and prompt initiation of appropriate treatment strategies. [ABSTRACT FROM AUTHOR]