Lack of causal association between epilepsy and dementia: A Mendelian randomization analysis.

OBJECTIVE: Epidemiological studies have reported an association between epilepsy and dementia. However, the causal relationship between epilepsy and the risk of dementia is not clear. We aimed to inspect the causal effect of epilepsy on memory loss and dementia. METHODS: We analyzed summary data of epilepsy, memory loss, and dementia from the genome-wide association study (GWAS) using the two-sample Mendelian randomization (MR) method. We used the estimated odds ratio of memory loss and dementia associated with each of the genetically defined traits to infer evidence for a causal relationship with the following exposures: all epilepsy, focal epilepsy (including focal epilepsy with hippocampal sclerosis, lesion-negative focal epilepsy, and focal epilepsy with other lesions), and genetic generalized epilepsy (including childhood absence epilepsy, generalized tonic-clonic seizures alone, Juvenile absence epilepsy, and Juvenile myoclonic epilepsy). RESULTS: According to the result of MR using the inverse variance weighted method (IVW), we found that genetically predicted epilepsy did not causally increase the risk of memory loss and dementia (p > 0.05). Results of the MR-Egger and weighted median method were consistent with the IVW method. CONCLUSIONS: No evidence has been found to support the notion that epilepsy can result in memory loss and dementia. The associations observed in epidemiological studies could be attributed, in part, to confounding or nongenetic determinants.

Treatment with a flow diverter-assisted coil embolization for ruptured blood blister-like aneurysms of the internal carotid artery: a technical note and analysis of single-center experience with pooled data.

Treatment of blood blister-like aneurysms (BBAs) of the supraclinoid internal carotid artery (ICA) with flow diverters (FDs) has become widespread in recent years. However, ruptured blood blister-like aneurysm (BBA) of ICA treatment with flow diverter-assisted coil embolization (FDAC) remains controversial. Moreover, limited direct comparative studies have been conducted between the two treatment modalities, FDs and FDAC, for BBAs. The purpose of this study was to document our experience and evaluate the effectiveness and safety of FDAC. We conducted a retrospective analysis of clinical and radiological information from ten patients who experienced ruptured BBAs of the supraclinoid ICA at our center from January 2021 to February 2023. The technical details of FDAC for ruptured BBAs were described, and the technical steps were named "pipeline embolization device (PED)-Individualized shaping(microcatheter)-Semi deploying-Rivet(coils)-Massage(microwire)" as the PEISSERM technique. Clinical outcomes were assessed using the modified Rankin Scale (mRS), whereas radiological results were determined through angiography. A pooled analysis was implemented, incorporating data from literature sources that reported perioperative and long-term clinical and angiographic outcomes of ruptured BBAs treated with FD and FDAC strategies, along with our data. Data in our analysis pool were categorized into FD and FDAC strategy groups to explore the preferred treatment modalities for BBAs. The PEISSERM technique was utilized to treat ten patients, seven males, and three females, with an average age of 41.7 years. A single PED was deployed in conjunction with coils in all ten patients. All PEDs were documented to have good wall apposition. The immediate postoperative angiograms demonstrated Raymond grade I in ten aneurysms. Angiographic follow-up of nine patients at 4-25 months showed total occlusion of the aneurysms. At the most recent follow-up, the mRS scores of nine patients hinted at a good prognosis. Pooled analysis of 233 ICA-BBA cases of FD revealed a technical success rate of 91% [95% confidence interval (CI), 0.88 to 0.95], a rate of complete occlusion of 79% (95% CI, 0.73 to 0.84), a recurrence rate of 2% (95% CI, 0.00 to 0.04), a rebleed rate of 2% (95% CI, 0.00 to 0.04), and the perioperative stroke rate was 8% (95% CI, 0.04 to 0.11). The perioperative mortality was 4% (95% CI, 0.01 to 0.07). The long-term good clinical outcome rate was 85% (95% CI, 0.80 to 0.90). The mortality rate was 6% (95% CI, 0.03 to 0.09). Results from the subgroup analysis illustrated that the FDAC strategy for BBAs had a significantly higher immediate postoperative complete occlusion rate (P < 0.001), total occlusion rate (P = 0.016), and a good outcome rate (P = 0.041) compared with the FD strategy. The FDAC strategy can yield a higher rate of good outcomes than the FD strategy. The PEISSERM technique employed by the FDAC is a reliable and effective treatment approach as it can minimize the hemodynamic burden of BBA's fragile dome, thereby achieving an excellent occlusion rate. The PEISSERM technique in the FDAC strategy contributes to understanding the BBA's treatment and offers a potentially optimal treatment for BBA.

RIP1/RIP3/MLKL mediates dopaminergic neuron necroptosis in a mouse model of Parkinson disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder and is characterized by severe neuronal loss. Necroptosis, or programmed cell necrosis, is mediated by the receptor interacting protein kinase-1 and -3/mixed lineage kinase domain-like protein (RIP1/RIP3/MLKL) pathway, and is involved in several neurodegenerative diseases. Here we aimed to explore the involvement of necroptosis in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride (MPTP)-induced PD and determine the potential mechanisms. We found that the protein levels of RIP1, RIP3, and MLKL increased significantly in a MPTP-induced mouse PD model. High expression of RIP1/RIP3/MLKL was associated with severe loss of dopaminergic neurons. Pretreatment with necrostatin-1 or the knockout of the RIP3/MLKL gene to block necroptosis pathway dramatically ameliorated PD by increasing dopamine levels and rescuing the loss of dopaminergic neurons, independent of the apoptotic pathway. Moreover, upregulation of inflammatory cytokines in MPTP-treated mice was partially inhibited by deletion of RIP3 or MLKL gene, indicating that a positive feedback loop exists between these genes and inflammatory cytokines. Our data indicate that RIP1/RIP3/MLKL-mediated necroptosis is involved in the pathogenesis of MPTP-induced PD. Downregulating the expression of RIP1, RIP3, or MLKL can significantly attenuate MPTP-induced PD. Future therapy targeting necroptosis may be a promising new option.

Serum Ngb (Neuroglobin) Is Associated With Brain Metabolism and Functional Outcome of Aneurysmal Subarachnoid Hemorrhage.

Background and Purpose- Hypoxic-ischemic brain damage is a well-recognized physiopathologic mechanism after aneurysmal subarachnoid hemorrhage (aSAH). The Ngb (neuroglobin) is a hemoprotein predominantly expressed in the brain with a high affinity for oxygen. Relationship between serum Ngb level and brain metabolism in aSAH patients has not been investigated previously. Methods- Thirty-six consecutive severe aSAH patients (Glasgow Coma Scale score ≤8 on admission) with multimodal neuromonitoring and 36 matched healthy subjects were included. Serum Ngb level was analyzed in combination with other time-matched cerebral microdialysis parameters, brain tissue oxygen tension, and 12-month neurological outcomes. Results- Serum Ngb level was correlated positively with cerebral microdialysis parameters and brain tissue oxygen tension ( P<0.001). Poor functional outcome (modified Rankin Scale score >3) 12 months after aSAH was associated with higher Ngb level but independent of age, sex, and disease severity ( P<0.001). A similar association was found between high Ngb level and neuropsychological test results indicative of impairments in cognition, visual conceptualization, and frontal executive functions ( P<0.001). Conclusions- Ngb may be a potential biomarker for reflecting brain tissue oxygen tension, brain metabolism, and functional outcome in severe aSAH patients and merits further study in the context of aSAH.

Lower Serum Iron and Hemoglobin Levels are Associated with Acute Seizures in Patients with Ruptured Cerebral Aneurysms.

BACKGROUND AND OBJECTIVE: The aim of the study is to investigate the value of serum iron and hemoglobin levels for predicting acute seizures following aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Clinical and laboratorial data from patients with ruptured intracranial aneurysms were collected in the retrospective study. Age, sex, symptom onset, history of diabetes and hypertension, history of coronary artery disease, temperature, Hunt-Hess grade, Fisher grade, aneurysm location, hemoglobin, serum potassium, sodium, calcium, phosphorus, and iron were collected. Acute seizures were determined as seizures within 1 week following aSAH. Propensity score matching (PSM) analyses were performed to correct imbalances in patient characteristics between seizure and non-seizure groups. RESULTS: A total of 760 patients were included. Incidence of acute seizures following aSAH was 6.4%. In the univariate analysis, significant differences were detected in age, admission Hunt-Hess grade, Fisher grade, hemoglobin, serum sodium, and serum iron between seizure and non-seizure groups. In multivariate logistic regression model, lower serum iron was considered as a risk factor for acute seizures (OR 0.182, 95% CI 0.084-0.393, p = 0.000), as well as lower hemoglobin (OR 0.977, 95% CI 0.962-0.993, p = 0.004) and higher serum sodium (OR 1.072, 95% CI 1.003-1.145, p = 0.039). After PSM, there were no significant differences in age, admission Hunt-Hess grade, Fisher grade, and serum sodium between seizure and non-seizure groups. The matched seizure group had lower serum iron and hemoglobin levels compared with the matched non-seizure group (p < 0.05). The optimal cutoff value for serum iron and hemoglobin levels as a predictor of acute seizure after aSAH was determined as 9.9 mmol/L (sensitivity was 81.63% and the specificity was 65.40%) and 119 g/L (sensitivity was 63.27% and the specificity was 70.18%), respectively. CONCLUSIONS: Serum iron and hemoglobin levels were inversely associated with a high risk of acute seizures following aSAH.

18F-FDG-PET/CT for Localizing the Epileptogenic Focus in Patients with Different Types of Focal Cortical Dysplasia.

Purpose: To determine the diagnostic and localization value of 18F-fluorodeoxyglucose-positron emission tomography (PET)/computed tomography (CT) in patients with focal cortical dysplasia (FCD) who underwent epilepsy surgery. Methods: One hundred and eight patients with pathologically proven FCD who underwent surgery for refractory epilepsy were retrospectively analyzed. All patients underwent magnetic resonance imaging (MRI), 18F-FDG-PET/CT, and video electroencephalography. An MRI diagnosis of FCD was defined as MRI+. A PET/CT diagnosis of FCD was defined as PET/CT+. Results: MRI and PET/CT detected FCD in 20.37% and 93.52% of patients, respectively. The difference was significant. Twenty-one patients were MRI+/PET+, 80 were MRI-/PET+, six were MRI-/PET-, and one was MRI+/PET-. The MRI positivity rate was lowest in patients with FCD type IIIa (5.6%, P < 0.05). Prevalence of MRI-/PET+ was highest in patients with FCD type IIIa (88.89%, P < 0.05). Conclusion: PET/CT is superior to MRI in detecting FCD. FCD type IIIa was more likely than other types to show MRI-/PET+. This suggests that PET/CT has particular diagnostic value for FCD type IIIa patients with negative MRI findings.

Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients: An Open-Label, Multicenter, and Randomized Controlled Trial.

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

[Expression and clinical significance of tumor necrosis factor-alpha and its receptors in non-specific chronic encephalitis and non-encephalitis relative intractable epilepsy].

OBJECTIVE: To explore the expression and clinical significance of tumor necrosis factor-alpha (TNF-α) and its receptors p55 and p75 in non-specific chronic encephalitis relative intractable epilepsy (NCERE) and non-NCERE. METHODS: Immunohistochemical SABC staining was employed to detect the foci of 24 cases of intractable epilepsy (NCERE, n = 10; non-NCERE, n = 14) and 10 cases of the expression of TNF-α and its receptors p55 and p75 in normal brain tissues (control group) to analyze their clinical significance. RESULTS: All expressions of the control group were negative. TNF-α and its receptors p55 and p75 were differentially expressed in neuron cytoplasm between NCERE and non-NCERE. No statistical significance existed between NCERE and non-NCERE (P > 0.05). There was a positive correlation between the expressions of receptors p55 and p75 (r = 0.897, P < 0.05). CONCLUSION: By binding its receptors and the synergistic effect between receptors p55 and p75, TNF-αis involved in the generation and development of NCERE and non-NCERE. However it appears to have nothing to do with the etiology of epilepsy.

[Activation of mTOR in maldeveloped balloon cells and dysmorphic neurons of type II focal cortical dysplasia].

OBJECTIVE: To investigate whether mammalian target of rapamycin (mTOR) kinase was abnormally activated in maldeveloped balloon cells and dysmorphic neurons of focal cortical dysplasia (FCD) with refractory epilepsy. METHODS: A total of 12 archival cases of FCD typeIIwith medically intractable epilepsy treated between 2008 and 2010 were retrieved. Perilesional brain tissue was used as control specimens (n = 8). The expression of phosphorylated p-AKT (Ser473), p-mTOR (Ser2448) and p-P70S6K (Thr389) was investigated by imunocytochemistry. RESULTS: The expression of p-AKT (Ser473), p-mTOR (Ser2448) and p-P70S6K (Thr389) was found in meldeveloped balloon cells and dysmorphic neurons of FCD. A weak stain in a small amount of pyramid neurons was also found in the control group. CONCLUSION: Abnormal activation of mTOR in maldeveloped balloon cells and dysmorphic neurons of FCD may be a key molecular mechanism underlying the histological changes and repeated seizures.

The causal relationship between circulating biomarkersand the risk of bipolar disorder: A two-sample Mendelian randomization study.

OBJECTIVE: To identify susceptible biomarkers for the development of bipolar disorder (BD), we conducted a Mendelian Randomization (MR) design to screen circulating proteins for the potential risk of bipolar disorder systematically. METHODS: We performed a two-sample Mendelian randomization (MR) analysis to estimate the causality of 4782 human circulating proteins on the risk of bipolar disorder. 376 circulating biomarkers were selected in MR estimation (4406 circulating proteins with less than 3 SNPs were excluded) with 5368 European descents. GWAS meta-analysis of the potential role of all-cause bipolar disorder arose from the Psychiatric Genomics Consortium (41,917 cases, 371,549 controls). RESULTS: After IVW and sensitivity analysis, 4 circulating proteins having causal effects on bipolar disorder were identified. ISG15, as a key player in the innate immune response, decreased the risk of bipolar disorder causally (OR = 0.92, 95% CI = 0.89-0.94, P = 1.46e-09). Furthermore, MLN decreased the risk of bipolar disorder causally (OR = 0.94, 95% CI = 0.91-0.97, P = 1.04e-04). In addition, SFTPC (OR = 0.91, 95% CI = 0.86-0.96, P = 4.47e-04) and VCY (OR = 0.86, 95% CI = 0.77-0.96, P = 8.55e-03) presented a suggestive association with bipolar disorder. CONCLUSIONS: Our findings indicated that ISG15 and MLN showed evidence of causality in bipolar disorder and provided a promising target for the diagnosis and treatment of diseases.

Serum neuronal pentraxin 2 is related to cognitive dysfunction and electroencephalogram slow wave/fast wave frequency ratio in epilepsy.

BACKGROUND: Cognitive dysfunction in epileptic patients is a high-incidence complication. Its mechanism is related to nervous system damage during seizures, but there is no effective diagnostic biomarker. Neuronal pentraxin 2 (NPTX2) is thought to play a vital role in neurotransmission and the maintenance of synaptic plasticity. This study explored how serum NPTX2 and electroencephalogram (EEG) slow wave/fast wave frequency ratio relate to cognitive dysfunction in patients with epilepsy. AIM: To determine if serum NPTX2 could serve as a potential biomarker for diagnosing cognitive impairment in epilepsy patients. METHODS: The participants of this study, conducted from January 2020 to December 2021, comprised 74 epilepsy patients with normal cognitive function (normal group), 37 epilepsy patients with cognitive dysfunction [epilepsy patients with cognitive dysfunction (ECD) group] and 30 healthy people (control group). The mini-mental state examination (MMSE) scale was used to evaluate cognitive function. We determined serum NPTX2 levels using an enzyme-linked immunosorbent kit and calculated the signal value of EEG regions according to the EEG recording. Pearson correlation coefficient was used to analyze the correlation between serum NPTX2 and the MMSE score. RESULTS: The serum NPTX2 level in the control group, normal group and ECD group were 240.00 ± 35.06 pg/mL, 235.80 ± 38.01 pg/mL and 193.80 ± 42.72 pg/mL, respectively. The MMSE score was lowest in the ECD group among the three, while no significant difference was observed between the control and normal groups. In epilepsy patients with cognitive dysfunction, NPTX2 level had a positive correlation with the MMSE score (r = 0.367, P = 0.0253) and a negative correlation with epilepsy duration (r = -0.443, P = 0.0061) and the EEG slow wave/fast wave frequency ratio value in the temporal region (r = -0.339, P = 0.039). CONCLUSION: Serum NPTX2 was found to be related to cognitive dysfunction and the EEG slow wave/fast wave frequency ratio in patients with epilepsy. It is thus a potential biomarker for the diagnosis of cognitive impairment in patients with epilepsy.

Decreased SPTBN2 expression regulated by the ceRNA network is associated with poor prognosis and immune infiltration in low­grade glioma.

The majority of low-grade gliomas (LGGs) in adults invariably progress to glioblastoma over time. Spectrin ß non-erythrocytic 2 (SPTBN2) is detected in numerous tumors and is involved in tumor occurrence and metastasis. However, the specific roles and detailed mechanisms of SPTBN2 in LGG are largely unknown. The present study performed pan-cancer analysis for the expression and prognosis of SPTBN2 in LGG using The Cancer Genome Atlas and The Genotype-Tissue Expression. Western blotting was used to detect the amount of SPTBN2 between glioma tissues and normal brain tissues. Subsequently, based on expression, prognosis, correlation and immune infiltration, non-coding RNAs (ncRNAs) were identified that regulated SPTBN2 expression. Finally, tumor immune infiltrates associated with SPTBN2 and prognosis were performed. Lower expression of SPTBN2 was correlated with an unfavorable outcome in LGG. A significant correlation between the low SPTBN2 mRNA expression and poor clinicopathological features was observed, including wild-type isocitrate dehydrogenase status (P<0.001), 1p/19q non-codeletion (P<0.001) and elders (P=0.019). The western blotting results revealed that, compared with normal brain tissues, the amount of SPTBN2 was significantly lower in LGG tissues (P=0.0266). Higher expression of five microRNAs (miRs/miRNAs), including hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-16-5p, hsa-miR-34c-5p and hsa-miR-424-5p, correlated with poor prognosis by targeting SPTBN2 in LGG. Subsequently, four long ncRNAs (lncRNAs) [ARMCX5-GPRASP2, BASP1-antisense RNA 1 (AS1), EPB41L4A-AS1 and LINC00641] were observed in the regulation of SPTBN2 via five miRNAs. Moreover, the expression of SPTBN2 was significantly correlated with tumor immune infiltration, immune checkpoint expression and biomarkers of immune cells. In conclusion, SPTBN2 was lowly expressed and correlated with an unfavorable prognosis in LGG. A total of six miRNAs and four lncRNAs were identified as being able to modulate SPTBN2 in a lncRNA-miRNA-mRNA network of LGG. Furthermore, the current findings also indicated that SPTBN2 possessed anti-tumor roles by regulating tumor immune infiltration and immune checkpoint expression.

High Plasma Fibrinogen Level Elevates the Risk of Cardiac Complications Following Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Cardiac complications are related to poor prognosis after spontaneous intracerebral hemorrhage (ICH). This study aims to predict the cardiac complications arising from small intracranial hematoma at ultraearly stage. METHODS: The data of this work were derived from the Risk Stratification and Minimally Invasive Surgery in Acute ICH Patients study (ClinicalTrials.gov Identifier: NCT03862729). This work included patients with ICH but without brain herniation, as confirmed by a brain computed tomography scan within 48 hours of symptom onset. Every Patient's information recorded at the emergent department, including clinical, laboratory, electrocardiogram, and medical records, was derived from the electronic data capture. Cardiac complications were defined as the occurrence of myocardial damage, arrhythmias, and ischemic electrocardiogram changes during hospitalization. Variables associated with cardiac complications were filtrated by univariate and multivariate regression analyses. Independent risk factors were used to form the early predictive model. The restricted cubic splines were employed to investigate the nonlinear associations in a more sophisticated and scholarly manner. RESULTS: A total of 587 ICH patients were enrolled in this work, including 72 patients who suffered from cardiac complications after ICH. Out of the 78 variables, 24 were found to be statistically significant in the univariate logistic regression analysis. These significant variables were then subjected to multivariate logistic regression analysis and utilized for constructing risk models. Multivariate logistic regression analysis showed high plasma fibrinogen (FIB) level [odds ratio (OR) per standard deviation (SD) 1.327, 95% confidence intervals (CI) 1.037-1.697; P = 0. 024)] and older age (OR per SD 1.777, 95% CI 1.344-2.349; P ＜0.001) were associated with a higher incidence of cardiac complications after ICH. High admission pulse rate (OR 0.620, 95% CI 0.451-0.853; P = 0. 003) was considered a protective factor for cardiac complications after ICH. In the restricted cubic spline regression model, FIB and cardiac complications following ICH were positively correlated and almost linearly (P for nonlinearity = 0.073). The reference point for FIB in predicting cardiac complications after ICH was 2.64 g/L. CONCLUSIONS: Emergent factors, including plasma FIB level, age, and pulse rate, might be independently associated with cardiac complications after ICH, which warrants attention in the context of treatment.

[Surgical outcome and prognostic factors in focal cortical dysplasia with intractable epilepsy].

OBJECTIVE: To analyze surgical outcome and relevant surgical parameters including resection extent of epileptogenic zone,pathological subtype, brain MRS and MRI results in FCD with intractable epilepsy. METHODS: We retrospectively analyzed surgical outcomes of 35 patients with intractable epilepsy related to focal cortical dysplasia, accepted surgery in the first affiliated hospital of Fujian Medical University from January 2008 to January 2010, with 12-36 months of postoperative follow-up. The relevance between complete resection, pathological subtype, MRS and MRI result and surgical outcome were statistically evaluated. RESULTS: 22 patients (66.7%) were Engel class I, 5 patients (14.3%) were class II, 6 patients (17.2%) were class III, 2 patients (5.8%) were class IV. Complete resection of epileptogenic zone (P < 0.05), FCD type I (P < 0.05) correlated significantly with favorable surgical outcome. Other factors such as MRI results, abnormal NAA/CHO + Cr ratio on the contralateral side of epileptogenic zone, as well as MRS-accurate lateralization did not influence outcome. CONCLUSION: Overall, the surgical outcome of FCD is favorable. Complete resection, FCD type I correlates significantly with favorable surgical outcome.

Integrative and comparative single-cell analysis reveals transcriptomic difference between human tumefactive demyelinating lesion and glioma.

Tumefactive demyelinating lesion (TDL) is an immune-mediated disease which can be misdiagnosed as glioma. At present, there is no study comparing difference between the two disorders at the cellular level. Here, we perform integrative and comparative single-cell RNA sequencing (ScRNA-seq) transcriptomic analysis on TDL and glioma lesions. At single-cell resolution, TDL is comprised primarily of immune cells, which is completely different from glioma. The integrated analysis reveals a TDL-specific microglial subset involving in B cell activation and proliferation. Comparative analysis highlights remyelination function of glial cells and demyelination function of T cells in TDL. Subclustering and pseudotime trajectory analysis of T cells in TDL reveal their heterogeneity and diverse functions involving in TDL pathogenesis and recovery process. Our study identifies substantial differences between TDL and glioma at single-cell resolution. The observed heterogeneity and potentially diverse functions of cells in TDL may be critical in disease progression.

Elevated Hexose-6-Phosphate Dehydrogenase Regulated by OSMR-AS1/hsa-miR-516b-5p Axis Correlates with Poor Prognosis and Dendritic Cells Infiltration of Glioblastoma.

Objective Glioblastoma (GBM), a type of malignant glioma, is the most aggressive type of brain tumor and is associated with high mortality. Hexose-6-phosphate dehydrogenase (H6PD) has been detected in multiple tumors and is involved in tumor initiation and progression. However, the specific role and mechanism of H6PD in GBM remain unclear. Methods We performed pan-cancer analysis of expression and prognosis of H6PD in GBM using the Genotype-Tissue Expression Project (GTEx) and The Cancer Genome Atlas (TCGA). Subsequently, noncoding RNAs regulating H6PD expression were obtained by comprehensive analysis, including gene expression, prognosis, correlation, and immune infiltration. Finally, tumor immune infiltrates related to H6PD and survival were performed. Results Higher expression of H6PD was statistically significantly associated with an unfavorable outcome in GBM. Downregulation of hsa-miR-124-3p and hsa-miR-516b-5p in GBM was detected from GSE90603. Subsequently, OSMR-AS1 was observed in the regulation of H6PD via hsa-miR-516b-5p. Moreover, higher H6PD expression significantly correlated with immune infiltration of dendritic cells, immune checkpoint expression, and biomarkers of dendritic cells. Conclusions The OSMR-AS1/ miR-516b-5p axis was identified as the highest-potential upstream ncRNA-related pathway of H6PD in GBM. Furthermore, the present findings demonstrated that H6PD blockading might possess antitumor roles via regulating dendritic cell infiltration and immune checkpoint expression.

Correction: Zhang et al. Admission Serum Iron as an Independent Risk Factor for Postoperative Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Propensity-Matched Analysis. Brain Sci. 2022, 12, 1183.

We would like to submit the following corrections to our recently published paper [...].

Admission Serum Iron as an Independent Risk Factor for Postoperative Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Propensity-Matched Analysis.

This study aimed to investigate the association between serum iron (SI) and postoperative delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). We retrospectively analyzed 985 consecutive adult patients diagnosed with aSAH. Demographic, clinical, and laboratory data were recorded. Univariate and multivariate analyses were employed to assess the association between SI and DCI. Propensity-score matching (PSM) analysis was implemented to reduce confounding. Postoperative DCI developed in 14.38% of patients. Lower SI upon admission was detected in aSAH patients with severe clinical conditions and severe aSAH. SI was negatively correlated with WFNS grade (r = −0.3744, p < 0.001) and modified Fisher (mFisher) grade (r = −0.2520, p < 0.001). Multivariable analysis revealed lower SI was independently associated with DCI [odds ratios (OR) 0.281, 95% confidence interval (CI) 0.177−0.448, p < 0.001], while WFNS grade and mFisher grade were not. The receiver-operating characteristics (ROC) curve analysis of SI for DCI gave an area under the curve (AUC) of 0.7 and an optimal cut-off of 7.5 µmol/L (95% CI 0.665 to 0.733, p < 0.0001). PSM demonstrated the DCI group had a significantly lower SI than the non-DCI group (10.91 ± 6.86 vs. 20.34 ± 8.01 µmol/L, p < 0.001). Lower SI remained a significant independent predictor for DCI and an independent poor prognostic factor of aSAH in multivariate analysis (OR 0.363, 95% CI 0.209−0.630, p < 0.001). The predictive performance of SI for poor outcome had a corresponding AUC of 0.718 after PSM. Lower SI upon admission is significantly associated with WFNS grade, mFisher grade, and predicts postoperative DCI and poor outcome at 90 days following aSAH.

Novel machine learning models to predict pneumonia events in supratentorial intracerebral hemorrhage populations: An analysis of the Risa-MIS-ICH study.

Background: Stroke-associated pneumonia (SAP) contributes to high mortality rates in spontaneous intracerebral hemorrhage (sICH) populations. Accurate prediction and early intervention of SAP are associated with prognosis. None of the previously developed predictive scoring systems are widely accepted. We aimed to derive and validate novel supervised machine learning (ML) models to predict SAP events in supratentorial sICH populations. Methods: The data of eligible supratentorial sICH individuals were extracted from the Risa-MIS-ICH database and split into training, internal validation, and external validation datasets. The primary outcome was SAP during hospitalization. Univariate and multivariate analyses were used for variable filtering, and logistic regression (LR), Gaussian naïve Bayes (GNB), random forest (RF), K-nearest neighbor (KNN), support vector machine (SVM), extreme gradient boosting (XGB), and ensemble soft voting model (ESVM) were adopted for ML model derivations. The accuracy, sensitivity, specificity, and area under the curve (AUC) were adopted to evaluate the predictive value of each model with internal/cross-/external validations. Results: A total of 468 individuals with sICH were included in this work. Six independent variables [nasogastric feeding, airway support, unconscious onset, surgery for external ventricular drainage (EVD), larger sICH volume, and intensive care unit (ICU) stay] for SAP were identified and selected for ML prediction model derivations and validations. The internal and cross-validations revealed the superior and robust performance of the GNB model with the highest AUC value (0.861, 95% CI: 0.793-0.930), while the LR model had the highest AUC value (0.867, 95% CI: 0.812-0.923) in external validation. The ESVM method combining the other six methods had moderate but robust abilities in both cross-validation and external validation and achieved an AUC of 0.843 (95% CI: 0.784-0.902) in external validation. Conclusion: The ML models could effectively predict SAP in sICH populations, and our novel ensemble model demonstrated reliable robust performance outcomes despite the populational and algorithmic differences. This attempt indicated that ML application may benefit in the early identification of SAP.