Genome-Wide Association Study Identifies IFIH1 and HLA-DQB1*05:02 Loci Associated With Anti-NMDAR Encephalitis.

BACKGROUND AND OBJECTIVES: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a rare autoimmune neurologic disorder, the genetic etiology of which remains poorly understood. Our study aims to investigate the genetic basis of this disease in the Chinese Han population. METHODS: We performed a genome-wide association study and fine-mapping study within the major histocompatibility complex (MHC) region of 413 Chinese patients with anti-NMDAR encephalitis recruited from 6 large tertiary hospitals and 7,127 healthy controls. RESULTS: Our genome-wide association analysis identified a strong association at the IFIH1 locus on chromosome 2q24.2 (rs3747517, p = 1.06 × 10-8, OR = 1.55, 95% CI, 1.34-1.80), outside of the human leukocyte antigen (HLA) region. Furthermore, through a fine-mapping study of the MHC region, we discovered associations for 3 specific HLA class I and II alleles. Notably, HLA-DQB1*05:02 (p = 1.43 × 10-12; OR, 2.10; 95% CI 1.70-2.59) demonstrates the strongest association among classical HLA alleles, closely followed by HLA-A*11:01 (p = 4.36 × 10-7; OR, 1.52; 95% CI 1.29-1.79) and HLA-A*02:07 (p = 1.28 × 10-8; OR, 1.87; 95% CI 1.50-2.31). In addition, we uncovered 2 main HLA amino acid variation associated with anti-NMDAR encephalitis including HLA-DQß1-126H (p = 1.43 × 10-12; OR, 2.10; 95% CI 1.70-2.59), exhibiting a predisposing effect, and HLA-B-97R (p = 3.40 × 10-8; OR, 0.63; 95% CI 0.53-0.74), conferring a protective effect. Computational docking analysis suggested a close relationship between the NR1 subunit of NMDAR and DQB1*05:02. DISCUSSION: Our findings indicate that genetic variation in IFIH1, involved in the type I interferon signaling pathway and innate immunity, along with variations in the HLA class I and class II genes, has substantial implications for the susceptibility to anti-NMDAR encephalitis in the Chinese Han population.

Advances in using ultrasound to regulate the nervous system.

Ultrasound is a mechanical vibration with a frequency greater than 20 kHz. Due to its high spatial resolution, good directionality, and convenient operation in neural regulation, it has recently received increasing attention from scientists. However, the mechanism by which ultrasound regulates the nervous system is still unclear. This article mainly explores the possible mechanisms of ultrasound's mechanical effects, cavitation effects, thermal effects, and the rise of sonogenetics. In addition, the essence of action potential and its relationship with ultrasound were also discussed. Traditional theory treats nerve impulses as pure electrical signals, similar to cable theory. However, this theory cannot explain the phenomenon of inductance and cell membrane bulging out during the propagation of action potential. Therefore, the flexoelectric effect of cell membrane and soliton model reveal that action potential may also be a mechanical wave. Finally, we also elaborated the therapeutic effect of ultrasound on nervous system disease such as epilepsy, Parkinson's disease, and Alzheimer's disease.

The cerebral lymphatic drainage system and its implications in epilepsy.

The central nervous system has long been thought to lack a clearance system similar to the peripheral lymphatic system. Therefore, the clearance of metabolic waste in the central nervous system has been a subject of great interest in neuroscience. Recently, the cerebral lymphatic drainage system, including the parenchymal clearance system and the meningeal lymphatic network, has attracted considerable attention. It has been extensively studied in various neurological disorders. Solute accumulation and neuroinflammation after epilepsy impair the blood-brain barrier, affecting the exchange and clearance between cerebrospinal fluid and interstitial fluid. Restoring their normal function may improve the prognosis of epilepsy. However, few studies have focused on providing a comprehensive overview of the brain clearance system and its significance in epilepsy. Therefore, this review addressed the structural composition, functions, and methods used to assess the cerebral lymphatic system, as well as the neglected association with epilepsy, and provided a theoretical basis for therapeutic approaches in epilepsy.

Effect and Mechanism of LIN28 on Ferroptosis in Mg2+-free Rat Hippocampal Neuron Model of Epilepsy.

Studies have demonstrated that LIN28 is expressed in the CNS and may exert protective effects on neurons. However, it remains unknown whether LIN28 regulates ferroptosis in the context of epilepsy. In this study, we established an epilepsy model by culturing hippocampal neurons from rats in a magnesium-free (Mg2+-free) medium. In Mg2+-depleted conditions, hippocampal neurons exhibited reduced LIN28 expression, heightened miR-142-5p expression, decreased glutathione peroxidase (GPX) activity and expression, elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA), resulting in a significant decline in cell viability and an increase in ferroptosis. Conversely, overexpression of LIN28 reversed these trends in the mentioned indices. Altogether, this study reveals that LIN28 may exert neuroprotective effects by inhibiting the miR-142-5p expression and suppressing ferroptosis in hippocampal neurons induced by Mg2+-free via increasing GPX4 expression.

ATF5-regulated Mitochondrial Unfolded Protein Response Attenuates Neuronal Damage in Epileptic Rat by Reducing Endoplasmic Reticulum Stress Through Mitochondrial ROS.

Endoplasmic reticulum (ER) dysfunction caused by excessive ER stress is a crucial mechanism underlying seizures-induced neuronal injury. Studies have shown that mitochondrial reactive oxygen species (ROS) are closely related to ER stress, and our previous study showed that activating transcription factor 5 (ATF5)-regulated mitochondrial unfolded protein response (mtUPR) modulated mitochondrial ROS generation in a hippocampal neuronal culture model of seizures. However, the effects of ATF5-regulated mtUPR on ER stress and the underlying mechanisms remain uncertain in epilepsy. In this study, ATF5 upregulation by lentivirus infection attenuated seizures-induced neuronal damage and apoptosis in a rat model of pilocarpine-induced epilepsy, whereas ATF5 downregulation by lentivirus infection had the opposite effects. ATF5 upregulation potentiated mtUPR by increasing the expression of mitochondrial chaperone heat shock protein 60 (HSP60) and caseinolytic protease proteolytic subunit (ClpP) and reducing mitochondrial ROS generation in pilocarpine-induced seizures in rats. Additionally, upregulation of ATF5 reduced the expression of glucose-regulated protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), suggesting suppression of ER stress; Moreover, ATF5 upregulation attenuated apoptosis-related proteins such as B-cell lymphoma-2 (BCL2) downregulation, BCL2-associated X (BAX) and cleaved-caspase-3 upregulation. However, ATF5 downregulation exerted the opposite effects. Furthermore, pretreatment with the mitochondria-targeted antioxidant mito-TEMPO attenuated the harmful effects of ATF5 downregulation on ER stress and neuronal apoptosis by reducing mitochondrial ROS generation. Overall, our study suggested that ATF5-regulated mtUPR exerted neuroprotective effects against pilocarpine-induced seizures in rats and the underlying mechanisms might involve mitochondrial ROS-mediated ER stress.

Similarities and differences of dynamic and static spontaneous brain activity between left and right temporal lobe epilepsy.

To comprehensively investigate the potential temporal dynamic and static abnormalities of spontaneous brain activity (SBA) in left temporal lobe epilepsy (LTLE) and right temporal lobe epilepsy (RTLE) and to detect whether these alterations correlate with cognition. Twelve SBA metrics, including ALFF, dALFF, fALFF, dfALFF, ReHo, dReHo, DC, dDC, GSCorr, dGSCorr, VMHC, and dVMHC, in 46 LTLE patients, 43 RTLE patients, and 53 healthy volunteers were compared in the voxel-wise analysis. Correlation analyses between metrics in regions showing statistic differences and epilepsy duration, epilepsy severity, and cognition scores were also performed. Compared with the healthy volunteers, the alteration of SBA was identified both in LTLE and RTLE patients. The ALFF, fALFF, and dALFF values in LTLE, as well as the fALFF values in RTLE, increased in the bilateral thalamus, basal ganglia, mesial temporal lobe, cerebellum, and vermis. Increased dfALFF in the bilateral basal ganglia, increased ReHo and dReHo in the bilateral thalamus in the LTLE group, increased ALFF and dALFF in the pons, and increased ReHo and dReHo in the right hippocampus in the RTLE group were also detected. However, the majority of deactivation clusters were in the ipsilateral lateral temporal lobe. For LTLE, the fALFF, DC, dDC, and GSCorr values in the left lateral temporal lobe and the ReHo and VMHC values in the bilateral lateral temporal lobe all decreased. For RTLE, the ALFF, fALFF, dfALFF, ReHo, dReHo, and DC values in the right lateral temporal lobe and the VMHC values in the bilateral lateral temporal lobe all decreased. Moreover, for both the LTLE and RTLE groups, the dVMHC values decreased in the calcarine cortex. The most significant difference between LTLE and RTLE was the higher activation in the cerebellum of the LTLE group. The alterations of many SBA metrics were correlated with cognition and epilepsy duration. The patterns of change in SBA abnormalities in the LTLE and RTLE patients were generally similar. The integrated application of temporal dynamic and static SBA metrics might aid in the investigation of the propagation and suppression pathways of seizure activity as well as the cognitive impairment mechanisms in TLE.

Oral microbiome alterations in epilepsy and after seizure control.

Background: The existing diagnostic methods of epilepsy such as history collection and electroencephalogram have great limitations in practice, so more reliable and less difficult diagnostic methods are needed. Methods: By characterizing oral microbiota in patients diagnosed with epilepsy (EPs) and patients whose seizures were under control (EPRs), we sought to discover biomarkers for different disease states. 16S rRNA gene sequencing was performed on 480 tongue swabs [157 EPs, 22 EPRs, and 301 healthy controls (HCs)]. Results: Compared with normal individuals, patients with epilepsy exhibit increased alpha diversity in their oral microbiota, and the oral microbial communities of the two groups demonstrate significant beta diversity differences. EPs exhibit a significant increase in the abundance of 26 genera, including Streptococcus, Granulicatella, and Kluyvera, while the abundance of 14 genera, including Peptostreptococcus, Neisseria, and Schaalia, is significantly reduced. The area under the receiver operating characteristic curve (AUC) of oral microbial markers in the training cohort and validation cohort was 98.85% and 97.23%, respectively. Importantly, the AUC of the biomarker set achieved 92.44% of additional independent validation sets. In addition, EPRs also have their own unique oral community. Conclusion: This study describes the characterization of the oral microbiome in EP and EPR and demonstrates the potential of the specific microbiome as a non-invasive diagnostic tool for epilepsy.

Acute Symptomatic Seizures and Risk of Seizure Recurrence in Patients with Anti-NMDAR, Anti-LGI1, and Anti-GABABR Encephalitis.

AIMS: To analyze the clinical characteristics of acute symptomatic seizures and predict the risk factors for seizure recurrence in patients with anti-N-methyl-D-aspartate receptor (NMDAR), anti-leucine-rich glioma-inactivated 1 (LGI1), and anti-gamma-aminobutyric acid B receptor (GABABR) encephalitis. METHODS: In this retrospective study, we included hospitalized patients who had been diagnosed with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis between November 2014 and April 2021. Binary logistic regression analysis was performed to identify the potential risk factors for seizure recurrence. RESULTS: In total, 262 patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis were included, 197 (75.2%) of whom presented with acute symptomatic seizures. During follow-up, 42 patients exhibited seizure recurrence. In anti-NMDAR encephalitis, frontal lobe abnormality on brain magnetic resonance imaging, delayed immunotherapy, early seizures, and focal motor onset were associated with seizure recurrence. CONCLUSIONS: Acute symptomatic seizure is a common clinical feature observed in patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis, with 50% of patients presenting with seizures as an initial symptom. The prognosis of patients with acute symptomatic seizures can be improved after receiving immunotherapy. Nevertheless, a minority of patients will experience seizure recurrence; therefore, restarting immunotherapy is recommended.

Abdominal obesity and digestive system cancer: a systematic review and meta-analysis of prospective studies.

BACKGROUND: The diagnostic criteria for abdominal obesity are usually waist circumference or waist-to-hip ratio. The magnitude of the risks for cancers of the digestive system and abdominal obesity is unknown. To assess whether abdominal obesity increases the risk of digestive cancer, we conducted a systematic review and meta-analysis of prospective cohort studies in a database. METHODS: PubMed, Embase, and Web of Science databases were searched from their inception to December 2022. The 9-star Newcastle Ottawa Scale was used to assess  study quality. Pooled relative risks and 95% confidence intervals were calculated using fixed or random effect models respectively. The stability of the results was explored by one-by-one exclusion. Subgroup analysis was conducted to explore sources of heterogeneity. Publication bias was evaluated by Begg's and Egger's tests. RESULTS: A total of 43 cohort studies were included. There were 42 and 31 studies in the meta-analysis of waist circumference and waist-to-hip ratio on digestive system cancer, respectively. The results of the meta-analysis revealed that the greater waist circumference and waist-to-hip ratio were correlated with increased incidence of digestive system cancers: waist circumference: RR 1.48, 95% CI 1.38-1.59, p < 0.001; waist-to-hip ratio: RR 1.33, 95% CI 1.28-1.38, p = 0.001. Subgroup analysis by cancer type showed that higher WC and WHR would increase the prevalence of LC, PC, GC, EC, and CRC. The sensitivity analysis was conducted by a one-by-one elimination method, and the results of the meta-analysis remained stable. It is proved that the results were robust by the trim-and-fill method. CONCLUSIONS: There was evidence to suggest that abdominal obesity increased the incidence of digestive cancer, it is necessary to take appropriate measures to reduce abdominal obesity. Waist circumference and waist-to-hip ratio may be better predictors of digestive system cancers. However, the association between waist circumference and digestive system cancer was greater, so more attention should be paid to measuring abdominal obesity with waist circumference.

Knowledge and coping style about depression in medical students: A cross-sectional study in China.

OBJECTIVES: The current study aimed at ascertaining the depression levels of medical students and their knowledge levels of depression, and exploring the relationship between the level of knowledge and coping styles of the medical students on depression. METHODS: An online-based survey was developed in Changzhi Medical College. The questionnaire included demographic and socioeconomic data, questions about depression knowledge and copying styles of depression, and the Zung Self-Rating Depression Scale (SDS). A total of 1931 questionnaires were returned by respondents. RESULTS: The medical students produced a mean SDS score of 44.29 (SD = 11.67). The prevalence of depression was 29.7%. Sophomore, female, and poor family relationships were parameters associated with a higher SDS score. The total correct rate for knowledge of depression was 64.14%. There were statistical differences between with depression students and non-depression students on the rate of the correct answers in the following questions:"Female has more probability", "Depression can be adjusted by oneself", "Associated with one's character", "Know cure method of depression", "Know drug use of depression", "Know depression influence for health", and "Know prevention method of depression". Depression students were more likely to have a lower rate of correct answer for above questions. Asking for help from psychological consultation was the primary coping mechanism among the medical students. The logistic regression analysis results found that depressed students who chose the coping way of no ways of coping were more likely to be females OR = 1.470 (1.078, 2.005), residents in rural area OR = 1.496 (1.038, 2.156), in poor family relationships OR = 2.428 (1.790, 3.293), and have lower cognitive level of depression knowledge OR = 1.920 (1.426, 3.226). CONCLUSIONS: It is necessary to focus on mental health of medical students, especially in female, residents in rural area, in poor family relationships, and having lower cognitive level of depression knowledge. Medical students were insufficient on depression knowledge and coping styles, and efforts that train students know risk of impaired mental health could also improve diagnosis and treatment.

Novel mutations in ATP7B in Chinese patients with Wilson's disease and identification of kidney disorder of thinning of the glomerular basement membrane.

Introduction: Wilson's disease is an autosomal recessive disorder caused by ATP7B pathogenic mutations. The hallmark of this disorder mainly consists of liver involvement, neurologic dysfunction and psychiatric features. In addition, the kidneys can also be affected by excessive copper deposition. Methods: A total of 34 patients clinically diagnosed with WD were recruited. They underwent ATP7B gene sequencing and clinical data of symptoms, examination, and treatment were collected. Moreover, renal pathology information was also investigated. Results: We identified 25 potentially pathogenic ATP7B variants (16 missense, 5 frameshift, 3 splicing variants and 1 large deletion mutation) in these 34 WD patients, 5 of which were novel. In our cases, the most frequent variant was c.2333G>T (R778L, 39.06%, exon 8), followed by c.2621C>T (A874V, 10.94%, exon 11) and c.3316G>A (V1106I, 7.81%, exon 11). Furthermore, we described the thinning of the glomerular basement membrane as a rare pathologically damaging feature of Wilson's disease for the first time. Additionally, two patients who received liver transplant were observed with good prognosis in present study. Discussion: Our work expanded the spectrum of ATP7B variants and presented rare renal pathological feature in WD patients, which may facilitate the development of early diagnosis, counseling, treatment regimens of WD.

Impact of blood-brain barrier disruption on clinical features and treatment response in patients with newly diagnosed autoimmune encephalitis.

AIMS: Blood-brain barrier (BBB) breakdown is an essential mechanism in inflammatory diseases of the central nervous system. However, the association between BBB integrity and autoimmune encephalitis (AE) has not been investigated. Our study aimed to analyze this relationship in patients with AE between BBB integrity with clinical manifestations and therapeutic responses. METHODS: Our study enrolled 147 patients with AE who were newly diagnosed at the First Affiliated Hospital of Zhengzhou University between August 2015 and December 2021. Patients were classified into normal or damaged BBB groups based on cerebrospinal fluid (CSF) albumin/serum albumin (QAlb). To evaluate the severity of the illness, we used the modified Rankin Scale (mRS) and the Clinical Assessment Scale for Autoimmune Encephalitis (CASE). RESULTS: We found a higher proportion of males, higher CSF protein, immunoglobulin IgG, and 24-h intrathecal IgG synthesis rate in the damaged BBB group. The improvement rate was lower in the damaged BBB group, but we found that double- or triple-combination immunotherapy had better clinical outcomes than single immunotherapy. In addition, there was a positive correlation between the CASE score and mRS score, and a positive correlation between the CASE score or mRS score and QAlb on admission. CONCLUSIONS: BBB integrity is closely related to the clinical features and treatment responses of newly diagnosed AE. Patients with AE and a damaged BBB may benefit from combination immunotherapy.

Alterations in static and dynamic regional homogeneity in mesial temporal lobe epilepsy with and without initial precipitating injury.

Objectives: Initial precipitating injury (IPI) such as febrile convulsion and intracranial infection will increase the susceptibility to epilepsy. It is still unknown if the functional deficits differ between mesial temporal lobe epilepsy with IPI (mTLE-IPI) and without IPI (mTLE-NO). Methods: We recruited 25 mTLE-IPI patients, 35 mTLE-NO patients and 33 healthy controls (HC). Static regional homogeneity (sReHo) and dynamic regional homogeneity (dReHo) were then adopted to estimate the alterations of local neuronal activity. One-way analysis of variance was used to analyze the differences between the three groups in sReHo and dReHo. Then the results were utilized as masks for further between-group comparisons. Besides, correlation analyses were carried out to detect the potential relationships between abnormal regional homogeneity indicators and clinical characteristics. Results: When compared with HC, the bilateral thalamus and the visual cortex in mTLE-IPI patients showed an increase in both sReHo and variability of dReHo. Besides, mTLE-IPI patients exhibited decreased sReHo in the right cerebellum crus1/crus2, inferior parietal lobule and temporal neocortex. mTLE-NO patients showed decreased sReHo and variability of dReHo in the bilateral temporal neocortex compared with HC. Increased sReHo and variability of dReHo were found in the bilateral visual cortex when mTLE-IPI patients was compared with mTLE-NO patients, as well as increased variability of dReHo in the left thalamus and decreased sReHo in the right dorsolateral prefrontal cortex. Additionally, we discovered a negative correlation between the national hospital seizure severity scale testing score and sReHo in the right cerebellum crus1 in mTLE-IPI patients. Conclusion: According to the aforementioned findings, both mTLE-IPI and mTLE-NO patients had significant anomalies in local neuronal activity, although the functional deficits were much severer in mTLE-IPI patients. The use of sReHo and dReHo may provide a novel insight into the impact of the presence of IPI on the development of mTLE.

COVID-19 vaccination for patients with epilepsy: A Chinese expert consensus.

Coronavirus disease-2019 (COVID-19) first emerged in late 2019 and has since spread worldwide. More than 600 million people have been diagnosed with COVID-19, and over 6 million have died. Vaccination against COVID-19 is one of the best ways to protect humans. Epilepsy is a common disease, and there are approximately 10 million patients with epilepsy (PWE) in China. However, China has listed "uncontrolled epilepsy" as a contraindication for COVID-19 vaccination, which makes many PWE reluctant to get COVID-19 vaccination, greatly affecting the health of these patients in the COVID-19 epidemic. However, recent clinical practice has shown that although a small percentage of PWE may experience an increased frequency of seizures after COVID-19 vaccination, the benefits of COVID-19 vaccination for PWE far outweigh the risks, suggesting that COVID-19 vaccination is safe and recommended for PWE. Nonetheless, vaccination strategies vary for different PWE, and this consensus provides specific recommendations for PWE to be vaccinated against COVID-19.

Clinical study of autonomic dysfunction in patients with autoimmune encephalitis.

BACKGROUND: Autoimmune encephalitis (AE) is a collective name, covering an emerging spectrum of autoimmune-mediated neurological diseases related to antibodies and synaptic or intracellular proteins. Anti-NMDAR, anti-LGI1, and anti-GABABR are three types of neuronal cell surface antibodies. Autonomic dysfunction represents a frequently occurring clinical manifestation. This observational study purposes to investigate comparisons between two groups with or without autonomic dysfunction and detect the autonomic dysfunction and other indexes in anti-NMDAR, anti-LGI1, and anti-GABABR cohorts. METHODS: Patients with anti-NMDAR, anti-LGI1 and anti-GABABR encephalitis were recruited from the May 2017 to the April 2022. The following information was recorded: age, age at onset, tumor presence, gender, prodromal symptoms, clinical manifestations, cranial magnetic resonance imaging, cerebrospinal fluid and blood examinations, and immunotherapy. RESULTS: There were totally 161 patients enrolled in this study. Among these participants, 104 individuals (64.6%) presented autonomic dysfunction and the remaining 57 (35.4%) were free of autonomic dysfunction. Sinus tachycardia was the most common autonomic dysfunction, followed by pollakiuria/uroclepsia, feverscence, central hypoventilation, sinus bradycardia, constipation, uroschesis, hyperhidrosis, hypersalivation, hypotension, and early satiety/emesis. Compared to patients without autonomic dysfunction, those with autonomic dysfunction had a higher incidence of central hypoventilation and ICU admissions. Meanwhile, in both groups with or without autonomic dysfunction, meatal behavior disorder, cognitive impairment, and epileptic seizure were three most common clinical manifestations. There were no significant differences in cranial magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) examination, antibody titers and number of immunotherapy types. Further analysis of AE mediated by distinct neuronal surface antibodies demonstrated that there were 85 anti-NMDAR, 56 anti-LGI1, and 20 anti-GABABR encephalitis patients. The significant differences between these three cohorts appeared in age, tumor presence, fervescence presence and antibody titers. CONCLUSION: This study demonstrated the comparisons between autonomic dysfunction group and autonomic dysfunction-free group and provided insights into better diagnosis and treatment.

NEXMIF variants are associated with epilepsy with or without intellectual disability.

OBJECTIVES: Variants in NEXMIF had been reported associated with intellectual disability (ID) without epilepsy or developmental epileptic encephalopathy (DEE). It is unkown whether NEXMIF variants are associated with epilepsy without ID. This study aims to explore the phenotypic spectrum of NEXMIF and the genotype-phenotype correlations. MATERIALS AND METHODS: Trio-based whole-exome sequencing was performed in patients with epilepsy. Previously reported NEXMIF variants were systematically reviewed to analyze the genotype-phenotype correlations. RESULTS: Six variants were identified in seven unrelated cases with epilepsy, including two de novo null variants and four hemizygous missense variants. The two de novo variants were absent in all populations of gnomAD and four hemizygous missense variants were absent in male controls of gnomAD. The two patients with de novo null variants exhibited severe developmental epileptic encephalopathy. While, the patients with hemizygous missense variants had mild focal epilepsy with favorable outcome. Analysis of previously reported cases revealed that males with missense variants presented significantly higher percentage of normal intellectual development and later onset age of seizure than those with null variants, indicating a genotype-phenotype correlation. CONCLUSION: This study suggested that NEXMIF variants were potentially associated with pure epilepsy with or without intellectual disability. The spectrum of epileptic phenotypes ranged from the mild epilepsy to severe developmental epileptic encephalopathy, where the epileptic phenotypes variability are potentially associated with patients' gender and variant type.

Clinical features and brain MRI volumetric changes in anti-mGluR5 encephalitis.

BACKGROUND: Anti-metabotropic glutamate receptor 5 (mGluR5) encephalitis is a rare and under-recognized autoimmune encephalitis. This study is conducted to characterize its clinical and neuroimaging features. METHODS: Twenty-nine patients with anti-mGluR5 encephalitis (15 new cases identified in this study and 14 previously reported cases) were included in this study and their clinical features were characterized. Brain MRI volumetric analysis using FreeSurfer software was performed in 9 new patients and compared with 25 healthy controls at both early (≤6 months of onset) and chronic (>1 year of onset) disease stages. RESULTS: The common clinical manifestations of anti-mGluR5 encephalitis included cognitive deficits (n = 21, 72.4%), behavioral and mood disturbances (n = 20, 69%), seizures (n = 16, 55.2%), and sleep disorder (n = 13, 44.8%). Tumors were observed in 7 patients. Brain MRI T2/FLAIR signal hyperintensities were observed predominantly in mesiotemporal and subcortical regions in 75.9% patients. MRI volumetric analysis demonstrated significant amygdala enlargement in both early and chronic disease stages compared to healthy controls (P < 0.001). Twenty-six patients had complete or partial recovery, one remained stable, one died and one was lost to follow-up. CONCLUSION: Our findings demonstrated that cognitive impairment, behavioral disturbance, seizures, and sleep disorder are the prominent clinical manifestations of anti-mGluR5 encephalitis. Most patients showed a good prognosis with full recovery, even in the paraneoplastic disease variants. The amygdala enlargement in the early and chronic disease stages is a distinct MRI feature, which exploratively offer a valuable perspective for the study of the disease processes.

Clinical characteristics and prognostic factors for short-term outcomes of autoimmune glial fibrillary acidic protein astrocytopathy: a retrospective analysis of 33 patients.

Background: Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a recently discovered inflammatory central nervous system (CNS) disease, whose clinical characteristics and prognostic factors for short-term outcomes have not been defined yet. We aimed to assess the symptoms, laboratory tests, imaging findings, treatment, and short-term prognosis of GFAP-A. Methods: A double-center retrospective cohort study was performed between May 2018 and July 2022. The clinical characteristics and prognostic factors for short-term outcomes were determined. Results: We enrolled 33 patients with a median age of 28 years (range: 2-68 years), 15 of whom were children (<18 years). The clinical spectrum is dominated by meningoencephalomyelitis. Besides, we also found nausea, vomiting, poor appetite, and neuropathic pain in some GFAP-A patients, which were not mentioned in previous reports. And adults were more prone to limb numbness than children. Magnetic resonance imaging revealed lesions involving the brain parenchyma, meninges, and spinal cord, exhibiting patchy, linear, punctate, and strip T2 hyperintensities. First-line immunotherapy, including corticosteroid and gamma globulin, was effective in most patients in the acute phase (P = 0.02). However, patients with overlapping AQP4 antibodies did not respond well to first-line immunotherapy and coexisting neural autoantibodies were more common in women. Additionally, the short-term prognosis was significantly better in children than in adults (P = 0.04). Positive non-neural autoantibodies and proven viral infection were independent factors associated with poor outcomes (P = 0.03, 0.02, respectively). Conclusion: We expanded the spectrum of clinical symptoms of autoimmune GFAP-A. The clinical symptoms and short-term prognosis differed between children and adults. Positive non-neural autoantibodies and proven viral infection at admission suggest a poor short-term prognosis.

Exosomal circRNAs as promising liquid biopsy biomarkers for glioma.

Liquid biopsy strategies enable the noninvasive detection of changes in the levels of circulating biomarkers in body fluid samples, providing an opportunity to diagnose, dynamically monitor, and treat a range of diseases, including cancers. Glioma is among the most common forms of intracranial malignancy, and affected patients exhibit poor prognostic outcomes. As such, diagnosing and treating this disease in its early stages is critical for optimal patient outcomes. Exosomal circular RNAs (circRNAs) are involved in both the onset and progression of glioma. Both the roles of exosomes and methods for their detection have received much attention in recent years and the detection of exosomal circRNAs by liquid biopsy has significant potential for monitoring dynamic changes in glioma. The present review provides an overview of the circulating liquid biopsy biomarkers associated with this cancer type and the potential application of exosomal circRNAs as tools to guide the diagnosis, treatment, and prognostic evaluation of glioma patients during disease progression.

Static and temporal dynamic alteration of intrinsic brain activity in MRI-negative temporal lobe epilepsy.

PURPOSE: To comprehensively explore the potential brain activity abnormalities affected by MRI-negative temporal lobe epilepsy (TLE) and to detect whether the changes were associated with cognition and help in the diagnosis or lateralization. METHOD: Six static intrinsic brain activity (IBA) indicators (ALFF, fALFF, ReHo, DC, GSCorr, VMHC) and their corresponding six temporal dynamic indicators in 39 unilateral MRI-negative TLE patients and 42 healthy volunteers were compared. Correlation analyses were performed between these indicators in areas displaying group differences, cognitive function, and epilepsy duration. ROC analyses were performed to test the diagnostic and lateralization ability of the IBA parameters. RESULTS: Considerable overlap was present among the abnormal brain regions detected by different static and dynamic indicators, including (1) alteration of fALFF, Reho, DC, VMHC, dfALFF, dReHo, and dDC in the temporal neocortex (predominately ipsilateral to the epileptogenic foci); (2) decreased dGSCorr and dVMHC in the occipital lobe. Meanwhile, the ReHo and VMHC values in the temporal neocortex correlated with the cognition scores or epilepsy duration (P < 0.01). The ROC analysis results revealed moderate diagnosis or lateralization efficiency of several IBA indicators (fALFF, dfALFF, ReHo, DC, dDC, and VMHC). CONCLUSION: The abnormal condition of neuronal activity in the temporal neocortex, predominately lateralized to the epileptic side, was a crucial feature in patients with MRI-negative TLE and might offer diagnosis or lateralization information. The application of dynamic intrinsic brain activity indicators played a complementary role, further revealing the temporal variability decline of the occipital lobe in MRI-negative TLE patients.