Long-term Efficacy of Bilateral Globus Pallidus Stimulation in the Treatment of Meige Syndrome.

OBJECTIVE: This study aimed to investigate the long-term efficacy and prognosis of bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) in patients with benign essential blepharospasm (BEB) and complete Meige syndrome, and to search for the best therapeutic subregion within the GPi. MATERIALS AND METHODS: Data were collected for 36 patients with Meige syndrome who underwent bilateral GPi-DBS surgery at our hospital between March 2014 and February 2022. Using the Burk-Fahn-Marsden Dystonia Rating Scale (BFMDRS)-Movement (BFMDRS-M) and BFMDRS-Disability (BFMDRS-D), the severity of the symptoms of patients with complete Meige syndrome was evaluated before surgery and at specific time points after surgery. Patients with BEB were clinically evaluated for the severity of blepharospasm using BFMDRS-M, the Blepharospasm Disability Index (BDI), and Jankovic Rating Scale (JRS). Three-dimensional reconstruction of the GPi-electrode was performed in some patients using the lead-DBS software, and the correlation between GPi subregion volume of tissue activated (VTA) and symptom improvement was analyzed in patients six months after surgery. The follow-up duration ranged from six to 99 months. RESULTS: Compared with preoperative scores, the results of all patients at six months after surgery and final follow-up showed a significant decrease (p < 0.05) in the mean BFMDRS-M score. Among them, the average BFMDRS-M improvement rates in patients with BEB at six months after surgery and final follow-up were 60.3% and 69.7%, respectively, whereas those in patients with complete Meige syndrome were 54.5% and 58.3%, respectively. The average JRS and BDI scores of patients with BEB also decreased significantly (p < 0.05) at six months after surgery and at the final follow-up (JRS improvement: 38.6% and 49.1%, respectively; BDI improvement: 42.6% and 57.4%, respectively). We were unable to identify significantly correlated prognostic factors. There was a significant correlation between GPi occipital VTA and symptom improvement in patients at six months after surgery (r = 0.34, p = 0.025). CONCLUSIONS: Our study suggests that bilateral GPi-DBS is an effective treatment for Meige syndrome, with no serious postoperative complications. The VTA in the GPi subregion may be related to the movement score improvement. In addition, further research is needed to predict patients with poor surgical outcomes.

Clinicopathological characteristics of secondary trigeminal neuralgia due to cerebellopontine angle tumors. / æ¡¥å°è„‘è§’è‚¿ç˜¤ç»§å‘æ€§ä¸‰å‰ç¥žç»ç—›çš„ä¸´åºŠç— ç†ç‰¹å¾.

OBJECTIVES: Cerebellopontine angle (CPA) tumors are a common cause of secondary trigeminal neuralgia (TN), characterized by their concealed location, slow progression, and difficulty in early detection. This study aims to explore the clinicopathological characteristics of patients with secondary TN due to CPA tumors to enhance understanding and management of secondary TN. METHODS: A retrospective analysis was conducted on clinical data and pathological results of 116 patients with CPA tumor-related TN treated at Xiangya Hospital of Central South University from January 1, 2017 to December 31, 2022. The study analyzed the relationship of tumor pathological types with clinical manifestations, tumor location, surgical methods, and treatment outcomes. RESULTS: Among the cases, 95.7% (111/116) were benign tumors, 3.4% (4/116) were malignant tumors, and 0.9% (1/116) were borderline tumors. Benign tumors were predominantly acoustic neuromas, meningiomas, and schwannomas. Among the patients, 46.6% (54/116) presented with isolated TN, while 53.4% (62/116) exhibited other associated symptoms depending on factors such as tumor growth location and rate. The complete resection rate in this group was over 90%, with 41.4% (48/116) of patients undergoing concurrent microvascular decompression after tumor resection, predominantly for schwannomas. The overall effective rate of surgical treatment reached 93.9%, with schwannomas showing higher efficacy rates compared with acoustic neuromas and meningiomas (P<0.05). The recurrence rate of acoustic neuromas was significantly higher than that of meningiomas and schwannomas (P<0.05). CONCLUSIONS: CPA tumors are a major cause of secondary TN, predominantly benign, with occasional underdiagnosed malignant tumors. Early diagnosis and treatment significantly impact prognosis. Different tumor types vary in clinical symptoms, surgical approaches, and treatment efficacy. Surgical strategies should balance tumor resection extent and neural function preservation, with microvascular decompression as necessary.

Integrative analysis of expression profile indicates the ECM receptor and LTP dysfunction in the glioma-related epilepsy.

BACKGROUND: Seizures are a common symptom in glioma patients, and they can cause brain dysfunction. However, the mechanism by which glioma-related epilepsy (GRE) causes alterations in brain networks remains elusive. OBJECTIVE: To investigate the potential pathogenic mechanism of GRE by analyzing the dynamic expression profiles of microRNA/ mRNA/ lncRNA in brain tissues of glioma patients. METHODS: Brain tissues of 16 patients with GRE and 9 patients with glioma without epilepsy (GNE) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60 K. The cDNA was labeled and hybridized to the Agilent LncRNA + mRNA Human Gene Expression Microarray V3.0, 4 × 180 K. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P-value < 0.05 and absolute fold change > 2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor. RESULTS: We found that 3 differentially expressed miRNAs (miR-10a-5p, miR-10b-5p, miR-629-3p), 6 differentially expressed lncRNAs (TTN-AS1, LINC00641, SNHG14, LINC00894, SNHG1, OIP5-AS1), and 49 differentially expressed mRNAs play a vitally critical role in developing GRE. The expression of GABARAPL1, GRAMD1B, and IQSEC3 were validated more than twofold higher in the GRE group than in the GNE group in the validation cohort. Pathways including ECM receptor interaction and long-term potentiation (LTP) may contribute to the disease's progression. Meanwhile, We built a lncRNA-microRNA-Gene regulatory network with structural and functional significance. CONCLUSION: These findings can offer a fresh perspective on GRE-induced brain network changes.

Expansion of Human-Specific GGC Repeat in Neuronal Intranuclear Inclusion Disease-Related Disorders.

Neuronal intranuclear inclusion disease (NIID) is a slowly progressing neurodegenerative disease characterized by eosinophilic intranuclear inclusions in the nervous system and multiple visceral organs. The clinical manifestation of NIID varies widely, and both familial and sporadic cases have been reported. Here we have performed genetic linkage analysis and mapped the disease locus to 1p13.3-q23.1; however, whole-exome sequencing revealed no potential disease-causing mutations. We then performed long-read genome sequencing and identified a large GGC repeat expansion within human-specific NOTCH2NLC. Expanded GGC repeats as the cause of NIID was further confirmed in an additional three NIID-affected families as well as five sporadic NIID-affected case subjects. Moreover, given the clinical heterogeneity of NIID, we examined the size of the GGC repeat among 456 families with a variety of neurological conditions with the known pathogenic genes excluded. Surprisingly, GGC repeat expansion was observed in two Alzheimer disease (AD)-affected families and three parkinsonism-affected families, implicating that the GGC repeat expansions in NOTCH2NLC could also contribute to the pathogenesis of both AD and PD. Therefore, we suggest defining a term NIID-related disorders (NIIDRD), which will include NIID and other related neurodegenerative diseases caused by the expanded GGC repeat within human-specific NOTCH2NLC.

The Role of Hippocampal Neurogenesis in ANT-DBS for LiCl-Pilocarpine-Induced Epileptic Rats.

PURPOSE: Abnormal neurogenesis in the hippocampus after status epilepticus (SE) has been suggested as a key pathogeny of temporal lobe epilepsy. This study aimed to investigate the effect of deep brain stimulation of the anterior thalamic nucleus (ANT-DBS) on hippocampal neurogenesis in LiCl-pilocarpine-induced epileptic rats and to analyze its relationship with postoperative spontaneous recurrent seizures (SRS) and anxiety. METHOD: SE was induced by a systemic LiCl-pilocarpine injection in adult male rats. Rats in the DBS group underwent ANT-DBS immediately after successful SE induction. SRS was only recorded during the chronic stage. An elevated plus maze was used to evaluate the level of anxiety in rats 7, 28, and 60 days after SE onset. After the elevated plus-maze experiment, rats were sacrificed under anesthesia in order to evaluate hippocampal neurogenesis. Doublecortin (DCX) was used as a marker for neurogenesis. RESULTS: During the chronic stage, SRS in rats in the DBS group were significantly decreased. The level of anxiety was increased significantly in rats in the DBS group 28 days after SE, while no significant differences in anxiety levels were found 7 and 60 days after SE. The number of DCX-positive cells in the hippocampus was significantly increased 7 days after SE and was significantly decreased 60 days after SE in all rats in which SE was induced. However, the number of DCX-positive cells in the DBS group was significantly lower than that in the other groups 28 days after SE. CONCLUSIONS: ANT-DBS may suppress SRS and increase the postoperative anxiety of epileptic rats by influencing hippocampal neurogenesis.

Factors associated with prognosis of dysembryoplastic neuroepithelial tumors patients after surgical resection: a retrospective observational study.

OBJECTIVE: To explore factors that might be associated with prognosis of dysembryoplastic neuroepithelial tumors (DNTs). METHODS: DNTs patients who were admitted to the Department of Neurosurgery of Xiangya Hospital between 1 January 2010 and 31 December 2018 and underwent surgical resection were retrospectively analyzed. Clinical, neuroimaging, and pathological features of DNTs were compared among patients with different outcomes and analyzed using the Kaplan-Meier curves and univariable Cox regression analysis. RESULTS: Thirty-three DNTs patients were included finally, of which the average age at seizure onset was 11.59 ± 7.46 years old and the average duration of seizures prior to surgical resection was 3.00 ± 4.68 years. After surgical resection, the patients were followed up for 2.39 ± 1.97 years, and 28 patients (84.85%) were seizure-free (class I of the Engel Outcome Scale) while five patients (15.15%) were seizure-continuous (class II or III of the Engel Outcome Scale). When compared with seizure-free patients, seizure-continuous patients had greater age at seizure onset and longer duration of seizures before surgical resection (p < .05). No variables were found to be statistically significantly associated with prognosis in univariable Cox regression analysis, but patients with extra-temporal DNTs were found to have better prognosis than those with temporal DNTs (log-rank test p = .048). CONCLUSIONS: Elder seizure onset age, longer duration of seizures prior to surgical resection, and a temporal location may be risk factors of poor prognosis for DNTs patients after surgical resection.

Efficacy and safety of vagus nerve stimulation in the treatment of refractory epilepsy. / è¿·èµ°ç¥žç»åˆºæ¿€æœ¯æ²»ç–—éš¾æ²»æ€§ç™«ç—«çš„ç–—æ•ˆå’Œå®‰å ¨æ€§.

OBJECTIVES: Vagus nerve stimulation (VNS) is a neuromodulative therapeutic technique for patients with drug-resistant epilepsy who are not suitable for resection or who have experienced a failed resection. This study aims to explore the efficacy and safety of VNS in patients with refractory epilepsy, and to analyze the influential factors for the efficacy. METHODS: A retrospective review of clinical data were conducted for 35 patients, who were treated for refractory epilepsy through VNS surgery in the Department of Neurosurgery, Xiangya Hospital, Central South University from April 2016 to August 2019. All patients were analyzed in terms of the clinical and follow-up data. RESULTS: After a mean follow-up of 26 months (6-47 months), outcome was as follows: 7 patients were MuHugh class I, 13 patients were MuHugh class II, 8 patients were MuHugh class III, and 7 patients were MuHugh class IV-V. The total efficacy rate in the short duration group was significantly higher than that in the long duration group (77.8% vs 50.0%, P=0.013), whereas different ages (P=0.382), gender (P=0.824), types of seizure (P=0.829), and MRI features (P=0.791) showed no correlation with efficacy. None patients developed permanent complication postoperatively. CONCLUSIONS: VNS is a safe and effective option in treating patients with refractory epilepsy, especially for those with short duration.

Clinical outcomes after medial temporal lobe epilepsy surgery: Anterior temporal lobectomy versus selective amygdalohippocampectomy.

OBJECTIVE: To compare the anterior temporal lobectomy (ATL) with transsylvian selective amygdalohippocampectomy (SeAH) in 72 patients with medial temporal lobe epilepsy (MTLE) regarding the seizure control and neuropsychological outcomes.
 Methods: Clinical data and follow-up data were collected and retrospectively analyzed. SeAH and ATL were used in 39 and 33 patients, respectively. All eligible patients were followed up at least one year. Wechsler Adult Intelligence Scale-Revised and the Wechsler Memory Scale-Revised were used to test the patients' neuropsychology before and after the surgery for one year.
 Results: Fifty-nine patients (81.9%) achieved satisfactory seizure control (62.5% Engel Class I and 19.4% Class II). ATL obtained 84.8% satisfactory seizure control (28 patients), and the success rate was 79.5% (31 patients) for SeAH. There was no significant difference in seizure control between SeAH and ATL (P=0.760). The postoperative verbal IQ of SeAH group increased significantly in both side surgery (P<0.05), while the increase was not significant in the group of ATL of both side surgery (P>0.05). Regarding left-side surgery, postoperative verbal memory and total memory were increased significantly in the group of SeAH (P<0.05), while the increases were not significant in the group of ATL (P>0.05). In the right-side surgery, postoperative verbal memory and total memory were increased significantly in the two surgery strategy groups (P<0.05), while no significant increases were seen in non-verbal memory of the two surgery strategy groups (P>0.05).
 Conclusion: Microsurgery for the treatment of refractory MTLE is successful and safe, and should be encouraged. The seizure outcome is not different between ATL and SeAH, while regarding as verbal IQ and verbal memory outcomes, SeAH may be superior to ATL in dominant hemisphere surgery.

Successful surgery for refractory seizures associated with bilateral schizencephaly: two case reports and literature review.

Schizencephaly is a rare malformation of cortical development resulting from cell migration defects that occur unilaterally or bilaterally. The type of the schizencephalic cleft can be open lip or closed lip. Patients suffering from refractory seizures secondary to schizencephaly should be considered for surgical treatment. In this paper, we retrospectively analyzed two patients with confirmed schizencephaly and intractable seizures. The evaluation methods included a medical history assessment, a neurological examination and magnetic resonance imaging (MRI). Continuous intracranial video-electroencephalogram (vEEG) monitoring with surface electrodes and deep electrodes was evaluated to confirm the epileptogenic zones associated with the schizencephalic lesions. Cortical electrical stimulation was performed to evaluate the neurophysiology of the relevant brain regions. Epileptic focus resection was performed close to the schizencephalic cleft according to the results of intracranial EEG and stimulation while preserving neurological functions. MRI revealed bilateral open lip schizencephaly in one patient and closed lip schizencephaly in the other patient. The epileptogenic zones were localized close to the schizencephalic clefts. The seizure outcome was Engel's class Ia in both patients at 1-year follow-up. No significant neurological deficits were found, and their activities of daily life were significantly improved. We conclude that abnormal cortex near the schizencephalic clefts may display an extrinsic epileptogenicity. Accurate localization of the epileptogenic zones using intracranial EEG and electrical stimulation can lead to a seizure-free outcome in patients with refractory epilepsy associated with schizencephaly.

HCN1 pathogenic variants associated with childhood epilepsy in a cohort of Chinese patients.

OBJECTIVE: HCN ion channel family has a widespread expression in neurons, and recently, increasing studies have demonstrated their roles in epilepsies. METHODS: Clinical data of the patients were gathered in a retrospective study. Exon sequencing was used for the patients with unexplained recurrent seizures and varying levels of developmental delay. RESULTS: In this study, eight de novo variants of HCN1 genes were uncovered in eight patients, including six missense variants, one nonsense variant and one frameshift insertion variant; five of them were reported for the first time. The onset age for eight patients ranges from one month to one year. Their main clinical manifestations are epilepsy and varying degrees of developmental delay, and the main type of seizure is focal secondary generalized tonic-clonic seizure. Importantly, in our study, one case presented with a form of migrating focal seizure that has not been reported in the literature. Seizures from five of the eight children were effectively controlled with antiepileptic drugs including valproic acid, levetiracetam and oxcarbazepine. One child developed normally and four children developed mild delay. One child was treated with topiramate, and the convulsion was partially controlled and showed moderate to severe developmental delay. The antiepileptic treatment failed for the other two children, and the two children were treated with sodium valproate, oxcarbazepine, lamotrigine, chlorbazan, levetiracetam and nitrodiazepam successively, but their convulsions were not controlled and showed moderate to severe developmental delay. SIGNIFICANCE: Our research reported eight variants in HCN1 gene causing epilepsy; among these variants, five variants were never reported before. HCN1-related epilepsy usually starts infantile period, and focal secondary generalized tonic-clonic seizure is the most common seizure type. Importantly, we reported the case with migrating focal seizure was rarely reported. Our study expanded both genotype and phenotype for HCN1-related epilepsy.

The m6A reader YTHDC2 promotes the pathophysiology of temporal lobe epilepsy by modulating SLC7A11-dependent glutamate dysregulation in astrocytes.

Rationale: Epilepsy affects over 70 million people globally, with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) often progressing to a drug-resistant state. Recent research has highlighted the role of reactive astrocytes and glutamate dysregulation in epilepsy pathophysiology. This study aims to investigate the involvement of astrocytic xCT, a glutamate-cystine antiporter, and its regulation by the m6A reader protein YTHDC2 in TLE-HS. Methods: A pilocarpine-induced epilepsy model in mice was used to study the role of xCT in reactive astrocytes. The expression of xCT and its regulation by YTHDC2 were assessed through various molecular and cellular techniques. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to measure mRNA and protein levels of xCT and YTHDC2, respectively; immunofluorescence was utilized to visualize their localization and expression in astrocytes. In vivo glutamate measurements were conducted using microdialysis to monitor extracellular glutamate levels in the hippocampus. RNA immunoprecipitation-qPCR (RIP-qPCR) was performed to investigate the binding of YTHDC2 to SLC7A11 mRNA, while methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) was performed to quantify m6A modifications on SLC7A11 mRNA. A dual-luciferase reporter assay was conducted to assess the effect of m6A modifications on SLC7A11 mRNA translation, and polysome profiling was employed to evaluate the translational efficiency of SLC7A11 mRNA. Inhibition experiments involved shRNA-mediated knockdown of SLC7A11 (commonly known as xCT) and YTHDC2 expression in astrocytes. Video-electroencephalogram (EEG) recordings were used to monitor seizure activity in mice. Results: The xCT transporter in reactive astrocytes significantly contributes to elevated extracellular glutamate levels, enhancing neuronal excitability and seizure activity. Increased xCT expression is influenced by the m6A reader protein YTHDC2, which regulates its expression through m6A methylation. Inhibition of xCT or YTHDC2 in astrocytes reduces glutamate levels and effectively controls seizures in a mouse model. Specifically, mice with SLC7A11- or YTHDC2-knockdown astrocytes showed decreased glutamate concentration in the hippocampus and reduced frequency and duration of epileptic seizures. Conclusions: This study highlights the therapeutic potential of targeting YTHDC2 and xCT in reactive astrocytes to mitigate epilepsy. The findings provide a novel perspective on the mechanisms of glutamate dysregulation and their implications in seizure pathophysiology, suggesting that modulation of YTHDC2 and xCT could be a promising strategy for treating TLE.

Targeting microglial GLP1R in epilepsy: A novel approach to modulate neuroinflammation and neuronal apoptosis.

BACKGROUND: Epilepsy is a prevalent disorder of the central nervous system. Approximately, one-third of patients show resistance to pharmacological interventions. The pathogenesis of epilepsy is complex, and neuronal apoptosis plays a critical role. Aberrantly reactive astrocytes, induced by cytokine release from activated microglia, may lead to neuronal apoptosis. This study investigated the role of glucagon-like peptide 1 receptor (GLP1R) in microglial activation in epilepsy and its impact on astrocyte-mediated neurotoxicity. METHODS: We used human hippocampal tissue from patients with temporal lobe epilepsy and a pilocarpine-induced epileptic mouse model to assess neurobiological changes in epilepsy. BV2 microglial cells and primary astrocytes were used to evaluate cytokine release and astrocyte activation in vitro. The involvement of GLP1R was explored using the GLP1R agonist, Exendin-4 (Ex-4). RESULTS: Our findings indicated that reduced GLP1R expression in hippocampal microglia in both epileptic mouse models and human patients, correlated with increased cytokine release and astrocyte activation. Ex-4 treatment restored microglial homeostasis, decreased cytokine secretion, and reduced astrocyte activation, particularly of the A1 phenotype. These changes were associated with a reduction in neuronal apoptosis. In addition, Ex-4 treatment significantly decreased the frequency and duration of seizures in epileptic mice. CONCLUSIONS: This study highlights the crucial role of microglial GLP1R in epilepsy pathophysiology. GLP1R downregulation contributes to microglial- and astrocyte-mediated neurotoxicity, exacerbating neuronal death and seizures. Activation of GLP1R with Ex-4 has emerged as a promising therapeutic strategy to reduce neuroinflammation, protect neuronal cells, and control seizures in epilepsy. This study provides a foundation for developing novel antiepileptic therapies targeting microglial GLP1R, with the potential to improve outcomes in patients with epilepsy.

Predictors of seizure outcomes in patients with diffuse low-grade glioma-related epilepsy after complete glioma removal.

AIMS: We aimed to identify predictors of postoperative seizures in patients with diffuse low-grade glioma (DLGG)-related epilepsy after complete tumor resection in this study. METHODS: We retrospectively collected data from individuals with DLGG-related epilepsy whose tumors were completely resected at Xiangya Hospital, Central South University between January 2014 and January 2020. The predictors of seizure outcomes were assessed by employing univariate analysis and a multivariate logistic regression model in a backward binary logistic regression model. RESULTS: Among the 118 cases that met the inclusion criteria, 83.05% were seizure-free following an average follow-up of 4.27 ± 1.65 years, all of whom were classified as International League Against Epilepsy class I outcome. Univariate and multivariate analyses indicated that seizure duration of >6 years (odds ratio [OR], 6.62; 95% confidence interval [CI], 1.76-24.98; p = 0.005) and first clinical symptoms other than seizures (OR, 4.51; 95% CI, 1.43-14.23; p = 1.010) were both independent predictors of unfavorable seizure outcomes. CONCLUSION: Our results imply that satisfactory seizure outcomes can be achieved in most patients with DLGG-related epilepsy after complete tumor resection. Patients with seizure duration of >6 years or first clinical symptoms other than seizures were more likely to experience postoperative seizure recurrence.

Imaging Genetics in Epilepsy: Current Knowledge and New Perspectives.

Epilepsy is a neurological network disease with genetics playing a much greater role than was previously appreciated. Unfortunately, the relationship between genetic basis and imaging phenotype is by no means simple. Imaging genetics integrates multidimensional datasets within a unified framework, providing a unique opportunity to pursue a global vision for epilepsy. This review delineates the current knowledge of underlying genetic mechanisms for brain networks in different epilepsy syndromes, particularly from a neural developmental perspective. Further, endophenotypes and their potential value are discussed. Finally, we highlight current challenges and provide perspectives for the future development of imaging genetics in epilepsy.

Identification of a Novel Heterozygous Mutation in the EIF2B4 Gene Associated With Vanishing White Matter Disease.

Vanishing white matter disease (VWM) is one of the most common childhood inherited leukoencephalopathies with autosomal recessive inheritance. Mutations in five genes, EIF2B1-5, have been identified as the major cause of VWM. In this study, a targeted gene capture sequencing panel comprising 160 known pathogenic genes associated with leukoencephalopathies was performed in a large Han Chinese family affected by adult-onset VWM, and a novel heterozygous missense mutation (c.1337G > A [p. R446H]) in EIF2B4 (NM_001034116.2) was detected. Further functional studies in HEK 293 cells showed dramatically reduced EIF2Bδ protein levels in the mutated group compared with the wild-type group. This study revealed that a heterozygous missense mutation (c.1337G > A [p. R446H]) in EIF2B4 was potentially associated with the adult-onset mild phenotype of VWM. In contrast to previous reports, autosomal dominant inheritance was also observed in adult-onset VWM.

Genetically proxied gut microbiota, gut metabolites with risk of epilepsy and the subtypes: A bi-directional Mendelian randomization study.

Background: An increasing number of observational studies have revealed an association among the gut microbiota, gut metabolites, and epilepsy. However, this association is easily influenced by confounders such as diet, and the causality of this association remains obscure. Methods: Aiming to explore the causal relationship and ascertain specific gut microbe taxa for epilepsy, we conducted a bi-directional Mendelian randomization (MR) study based on the genome-wide association study (GWAS) data of epilepsy from the International League Against Epilepsy, with the gut microbiota GWAS results from MiBioGen, and summary-level GWAS data of gut microbiota-dependent metabolites trimethylamine N-oxide and its predecessors. Results: Nine phyla, 15 classes, 19 orders, 30 families, and 96 genera were analyzed. A suggestive association of host-genetic-driven increase in family Veillonellaceae with a higher risk of childhood absence epilepsy (odds ratio [OR]: 1.033, confidential interval [CI]: 1.015-1.051, P IVW = 0.0003), class Melainabacteria with a lower risk of generalized epilepsy with tonic-clonic seizures (OR = 0.986, CI = 0.979-0.994, P IVW = 0.0002), class Betaproteobacteria (OR = 0.958, CI = 0.937-0.979, P IVW = 0.0001), and order Burkholderiales (OR = 0.960, CI = 0.937-0.984, P IVW = 0.0010) with a lower risk of juvenile myoclonic epilepsy were identified after multiple-testing correction. Our sensitivity analysis revealed no evidence of pleiotropy, reverse causality, weak instrument bias, or heterogeneity. Conclusion: This is the first MR analysis to explore the potential causal relationship among the gut microbiota, metabolites, and epilepsy. Four gut microbiota features (two class levels, one order level, and one family level) were identified as potential interventional targets for patients with childhood absence epilepsy, generalized epilepsy with tonic-clonic seizures, and juvenile myoclonic epilepsy. Previous associations in numerous observational studies may had been interfered by confounders. More rigorous studies were needed to ascertain the relationship among the gut microbiota, metabolites, and epilepsy.

Resective surgery for patients with frontal lobe diffuse low-grade glioma-related epilepsy: predictors of seizure outcomes.

Background: Diffuse low-grade gliomas (DLGGs) are prone to invade the frontal lobes, with seizures being the most common symptom. However, limited attention has been paid to surgical outcomes and their predictors in patients with frontal DLGG-related epilepsy. Objective: This study aimed to analyze predictors of postoperative seizure outcomes in patients with frontal DLGG-related epilepsy. Design: This is a single-center retrospective study. Methods: This study retrospectively collected data of 115 patients with frontal DLGG-related epilepsy who underwent resective surgery between January 2014 and January 2021. Patients were categorized into favorable and unfavorable seizure outcome groups based on the International League Against Epilepsy (ILAE) classification. Univariate and multivariate analyses were used to identify potential predictors of seizure outcomes. Results: The mean follow-up was 4.11 ± 2.06 years, and 77.4% (89 of 115) of patients were seizure-free. Permanent neurological deficits were observed in 7.0% (8 of 115) of patients. Univariate and multivariate analyses revealed that total tumor removal [odds ratio (OR), 0.31; 95% confidence interval (CI), 0.12-0.82; p = 0.018] and older age at seizure onset (OR, 0.96; 95% CI, 0.93-0.99; p = 0.042) were independent predictors of favorable seizure outcomes. Conclusion: Surgical resection is an effective treatment for frontal DLGG-related epilepsy. Favorable seizure outcomes are more likely to be achieved in patients with complete tumor removal and those with older age at seizure onset.

Expansion of Clinical and Genetic Spectrum of DDX3X Neurodevelopmental Disorder in 23 Chinese Patients.

Aim: De novo DDX3X variants account for 1-3% of unexplained intellectual disability cases in females and very rarely in males. Yet, the clinical and genetic features of DDX3X neurodevelopmental disorder in the Chinese cohort have not been characterized. Method: A total of 23 Chinese patients (i.e., 22 female and 1 male) with 22 de novo DDX3X deleterious variants were detected among 2,317 probands with unexplained intellectual disability (ID) undertaking whole exome sequencing (WES). The age, sex, genetic data, feeding situation, growth, developmental conditions, and auxiliary examinations of the cohort were collected. The Chinese version of the Gesell Development Diagnosis Scale (GDDS-C) was used to evaluate neurodevelopment of DDX3X patients. The Social Communication Questionnaire (SCQ)-Lifetime version was applied as a primary screener to assess risk for autism spectrum disorder (ASD). Result: A total of 17 DDX3X variants were novel and 22 were de novo. Missense variants overall were only slightly more common than loss-of-function variants and were mainly located in two functional subdomains. The average age of this cohort was 2.67 (±1.42) years old. The overlapping phenotypic spectrum between this cohort and previously described reports includes intellectual disability (23/23, 100%) with varying degrees of severity, muscle tone abnormalities (17/23, 73.9%), feeding difficulties (13/23, 56.5%), ophthalmologic problems (11/23, 47.8%), and seizures (6/23, 26.1%). A total of 15 individuals had notable brain anatomical disruption (15/23, 65.2%), including lateral ventricle enlargement, corpus callosum abnormalities, and delayed myelination. Furthermore, 9 patients showed abnormal electroencephalogram results (9/23, 39.1%). Hypothyroidism was first noted as a novel clinical feature (6/23, 26.1%). The five primary neurodevelopmental domains of GDDS-C in 21 patients were impaired severely, and 13 individuals were above the "at-risk" threshold for ASD. Interpretation: Although a certain degree of phenotypic overlap with previously reported cohorts, our study described the phenotypic and variation spectrum of 23 additional individuals carrying DDX3X variants in the Chinese population, adding hypothyroidism as a novel finding. We confirmed the importance of DDX3X as a pathogenic gene in unexplained intellectual disability, supporting the necessity of the application of WES in patients with unexplained intellectual disability.

Synthesis of ginsenoside Rb1-imprinted magnetic polymer nanoparticles for the extraction and cellular delivery of therapeutic ginsenosides.

Background: Panax ginseng (ginseng) is a traditional medicine that is reported to have cardioprotective effects; ginsenosides are the major bioactive compounds in the ginseng root. Methods: Magnetic molecularly imprinted polymer (MMIP) nanoparticles might be useful for both the extraction of the targeted (imprinted) molecules, and for the delivery of those molecules to cells. In this work, plant growth regulators were used to enhance the adventitious rooting of ginseng root callus; imprinted polymeric particles were synthesized for the extraction of ginsenoside Rb1 from root extracts, and then employed for subsequent particle-mediated delivery to cardiomyocytes to mitigate hypoxia/reoxygenation injury. Results: These synthesized composite nanoparticles were first characterized by their specific surface area, adsorption capacity, and magnetization, and then used for the extraction of ginsenoside Rb1 from a crude extract of ginseng roots. The ginsenoside-loaded MMIPs were then shown to have protective effects on mitochondrial membrane potential and cellular viability for H9c2 cells treated with CoCl2 to mimic hypoxia injury. The protective effect of the ginsenosides was assessed by staining with JC-1 dye to monitor the mitochondrial membrane potential. Conclusion: MMIPs can play a dual role in both the extraction and cellular delivery of therapeutic ginsenosides.

Migration characteristics as a prognostic factor in cerebral sparganosis.

OBJECTIVE: To differentiate diagnostic and prognostic factors from the clinical material of patients with cerebral sparganosis in central South China. METHODS: Consecutive patients with cerebral sparganosis from our hospital between 2010 and 2018 were retrospectively enrolled. The clinical manifestations, radiographic features, treatment, and outcomes of these patients were analyzed. RESULTS: Thirty patients with cerebral sparganosis were included, and foci migration on magnetic resonance imaging was detected in 22 patients, from whom we observed 4 migration modes: interlobar migration (50.0%, 11/22); transmidline migration (27.3%, 6/22); transventricular migration (13.6%, 3/22); and cerebellum-brainstem migration (9.1%, 2/22). The percentage of good outcomes was higher in patients with live worm capture than in those without live worm capture (75.0%, 12/16 vs 33.3%, 2/6). Exposure to preoperative antiparasitic medication was associated with worm migration toward the cortical surface, which led to a higher probability of live worm capture. CONCLUSIONS: We propose 4 modes of sparganosis migration that are correlated with worm capture and neurologic prognosis. We found that exposure to antiparasitic medication was associated with worm migration toward the cortical surface, leading to a higher probability of live worm capture. These observations suggest a novel significance for preoperative medication of cerebral sparganosis.