Epidemiological characteristics, clinical presentations, and prognoses of pediatric brain tumors: Experiences of national center for children's health.

Background: We aimed to describe the epidemiological characteristics, clinical presentations, and prognoses in a national health center for children. Methods: From January 2015 to December 2020, 484 patients aged 0-16 years, who were diagnosed with brain tumors and received neurosurgery treatment, were enrolled in the study. Pathology was based on the World Health Organization 2021 nervous system tumor classification, and tumor behaviors were classified according to the International Classification of Diseases for Oncology, third edition. Results: Among the 484 patients with brain tumors, the median age at diagnosis was 4.62 [2.19, 8.17] years (benign tumors 4.07 [1.64, 7.13] vs. malignant tumors 5.36 [2.78, 8.84], p=0.008). The overall male-to-female ratio was 1.33:1(benign 1.09:1 vs. malignant 1.62:1, p=0.029). Nausea, vomiting, and headache were the most frequent initial symptoms. The three most frequent tumor types were embryonal tumors (ET, 22.8%), circumscribed astrocytic gliomas (20.0%), and pediatric-type diffuse gliomas (11.0%). The most common tumor locations were the cerebellum and fourth ventricle (38.67%), the sellar region (22.9%) and ventricles (10.6%). Males took up a higher proportion than females in choroid plexus tumors (63.6%), ET (61.1%), ependymal tumors (68.6%), and germ cell tumors (GCTs, 78.1%). Patients were followed for 1 to 82 months. The overall 5-year survival rate was 77.5%, with survival rates of 91.0% for benign tumors and 64.6% for malignant tumors. Conclusion: Brain tumors presented particularly sex-, age-, and regional-dependent epidemiological characteristics. Our results were consistent with previous reports and might reflect the real epidemiological status in China.

SUZ12 Loss Amplifies the Ras/ERK Pathway by Activating Adenylate Cyclase 1 in NF1-Associated Neurofibromas.

Patients with germline neurofibromatosis type 1 (NF1) microdeletions frequently exhibit hereditary syndromes such as cardiovascular anomalies and have an increased risk of malignant peripheral nerve sheath tumors (MPNSTs). This study aimed to identify the genes codeleted with SUZ12 that are related to MPNST. We used differential gene expression and enrichment analyses to analyze the SUZ12-mutant and SUZ12-wild-type gene expression profiles in the GSE118186 and GSE66743 datasets in Gene Expression Omnibus (GEO). PPI network analysis combined with MPNST patient survival analysis was used to identify ADCY1, which catalyzes the conversion of ATP to cAMP, as a key gene. Moreover, chromatin immunoprecipitation sequencing (ChIP-Seq) showed that the distribution of H3K27me3 in the ADCY1 promoter region and gene body was significantly reduced in SUZ12-mutant cells. To verify the role of ADCY1 in SUZ12 mutation, we used RNA interference and plasmid transfection to interfere with SUZ12 expression in plexiform neurofibroma (pNF) and MPNST cell lines and then treated the cells with forskolin, IBMX and H89. ERK phosphorylation was accelerated and prolonged after siRNA transfection, especially in ipNF05.5 cells, and the intensity and duration of ERK activation were reduced after SUZ12 overexpression. Importantly, the level of p-ERK was consistent with that of Rap1-GTP. Moreover, H89 completely blocked Rap1 activation and the changes in the p-ERK level after SUZ12 siRNA transfection. In conclusion, our findings suggested that SUZ12 loss potentiates the effects of NF1 mutations by amplifying Ras signaling through the ADCY1/cAMP/Rap1/ERK pathway and that SUZ12 may serve as a therapeutic and prognostic biomarker in NF1-associated neurofibromas.

Central functional reorganization and recovery following facial-hypoglossal neurorrhaphy for facial paralysis.

OBJECTIVE: Functional deficits induced by nerve injuries can be restored by achieving effective reinnervation of the denervated targets and functional reorganization of the central nervous system after nerve reconstruction. In this study, we investigated the effect and extent of cortical functional reorganization related to the ability of transferred hypoglossal neurons to restore facial function in facial paralysis patients after a surgical bridge of neurorrhaphy ectopically between the ipsilateral hypoglossal nerve and injured facial nerve. METHODS: We treated 23 patients (35.4 ± 10.3 years, 10 males) and followed them up for 2.9 ± 0.61 years. We used motor-task-related functional magnetic resonance imaging to map activation change at multiple time points before and after neurorrhaphy; 20 normal subjects were included as control. RESULTS: All patients regained facial function to some extent after neurorrhaphy. Enhanced activation in motor-related cortices gradually returned to normal levels and was positively correlated with regained facial function. The related cortical functional areas included the left middle temporal gyrus, left inferior frontal gyrus, insula, bilateral motor cortex and the supplementary motor area extending to the paracingulate involved in intensive eye closing, as well as the left superior temporal gyrus, right putamen and the bilateral motor cortex involved in lip pursing. Intriguingly, significant correlations were found between the pre-surgery activation while intensive eye closing in bilateral motor cortex and recovery of facial nerve function induced by the neurorrhaphy treatment. CONCLUSION: This is the first study mapping activation change in motor cortices at multiple time points before and after repair of the facial nerve. The cortex functional reorganization found may suggest potential treatment targets in the central nervous system for adjuvant therapies such as repetitive transcranial magnetic stimulation to further improve functional recovery.

Prediction of postoperative motor deficits using intraoperative motor-evoked potentials in middle cerebral artery aneurysm.

To explore the relationship between postoperative motor deficits and the duration of reduced motor-evoked potentials (MEPs) in patients with middle cerebral artery (MCA) aneurysm. This study included 285 cases of MCA aneurysm treated with clipping surgery with MEP monitoring. The effects of MEP changes on postoperative motor function were assessed, and the key time point for minimizing the incidence of postoperative motor dysfunction was found through receiver operating characteristic (ROC) curve analysis. Motor dysfunction was significantly associated with the occurrence of MEP changes, and patients with irreversible changes were more likely to suffer motor dysfunction than were those with reversible changes. The critical duration of MEP changes that minimized the risk of postoperative motor dysfunction was 8.5 min. This study revealed that MEP monitoring is an effective method for preventing ischemic brain injury during surgical treatment of MCA aneurysm and proposes a critical cutoff for the duration of MEP deterioration of 8.5 min for predicting postoperative motor dysfunction.

A prediction of postoperative neurological deficits following intracranial aneurysm surgery using somatosensory evoked potential deterioration duration.

Although the application of somatosensory evoked potential (SSEP) in intracranial aneurysm surgery has been well demonstrated, the relationship between the duration of SSEP deterioration and postoperative neurological deficits (PNDs) is still not clear. The objectives of this study were (1) to detect the relationship between the SSEP deterioration duration and PND; and (2) detect the relationship between SSEP deterioration duration and postoperative computed tomography (CT) findings. Data from 587 patients were reviewed and 40 patients with SSEP deterioration were enrolled. Four patients presented irreversible disappearance and 36 patients presented reversible deterioration (including 9 [25%] patients with reversible reduction and 27 [75%] patients with reversible disappearance). In the patients with reversible SSEP deterioration, 17 patients had PNDs, and the SSEP deterioration duration was 42 ± 46 min, ranging from 5 to 180 min. Nineteen patients did not have PNDs, and their duration of SSEP deterioration was 11 ± 9 min (range 2-40 min). The SSEP deterioration duration significantly differed between patients with or without PND (P < 0.01). Eleven minutes is the optimal cut-off value of motor evoked potential change duration avoiding PND (area under the curve = 0.84). Patients with a SSEP deteriorating duration > 11 min had a significant higher incidence rate of abnormal CT finding postoperatively (p < 0.05). According to these results, we conclude that the duration of SSEP deterioration is extremely important to postoperative neurological function, and in order to avoid PND, the SSEP deterioration duration must not exceed 10 min. The SSEP deterioration duration is also associated with postoperative CT findings.

Prediction of postoperative motor deficits using motor evoked potential deterioration duration in intracranial aneurysm surgery.

OBJECTIVE: The study aimed to investigate the predictive value of motor evoked potential (MEP) deterioration duration for postoperative motor deficits in patients undergoing intracranial aneurysm surgery. METHODS: Data from 587 patients were reviewed and 92 patients with MEP deterioration were enrolled. MEP deterioration duration was compared between patients with and without postoperative motor deficits. Receiver operating characteristic (ROC) curve analysis was performed to define the threshold value for predicting postoperative motor deficit risk. Additionally, the association between MEP deterioration duration and postoperative CT findings was explored. RESULTS: Patients with postoperative motor deficits had a significantly longer MEP deterioration duration (p < 0.01). An MEP deterioration duration greater than or equal to 13 min was identified as an independent predictor of immediate (p < 0.01), short-term (p < 0.01), and long-term postoperative motor deficits (p < 0.05). There was no significant association between MEP deterioration duration and new CT abnormalities. CONCLUSION: MEP deterioration duration could be used for predicting intracranial aneurysm surgical outcome. SIGNIFICANCE: The study first proposed a threshold value of MEP deterioration duration (13 min) for predicting the risk of postoperative motor deficits in patients undergoing intracranial aneurysm surgery.

Neuronavigation-Guided Corticospinal Tract Mapping in Brainstem Tumor Surgery: Better Preservation of Motor Function.

OBJECTIVE: To evaluate a new technique in brainstem surgery, neuronavigation (NN)-guided corticospinal tract (CST) mapping, in a retrospective study of patients undergoing brainstem tumor surgery. METHODS: We studied 40 patients with a brainstem tumor who were enrolled in this study. Patients whose worst preoperative muscle strength of the 4 limbs was greater than 3 levels from normal on the Lovett scale were divided into 2 groups: a treatment group of 21 patients who underwent NN-guided CST mapping and routine intraoperative neurophysiology monitoring (IONM) and a control group of 19 patients who underwent routine NN and IONM. Preoperative muscle strength and postoperative (day 90 postsurgery) muscle strength were assessed and compared between the 2 groups. RESULTS: In the NN-guided CST mapping group, 3 patients (14.3%) had a decrease in muscle strength by 1 level postoperatively, and no patient experienced a decrease of >1 level. In the control group, 4 patients (21.1%) had a 1-level decrease in muscle strength, and 5 (26.3%) had a decrease of >1 level. Patients in the NN-guided CST mapping group had significantly better surgical outcomes compared with those in the control group (P = 0.018, Fisher exact test). CONCLUSIONS: Brainstem tumor resection using NN-guided CST mapping achieved better preservation of motor function compared with routine NN and IONM. NN-guided CST mapping not only decreased the difficulty of the surgery, but also significantly improved the efficiency of surgery.

IDH1 mutation is associated with a higher preoperative seizure incidence in low-grade glioma: A systematic review and meta-analysis.

PURPOSE: Gliomas, particularly low-grade gliomas (LGGs), are highly epileptogenic. Seizure is the most common presenting sign of LGG patients and significantly decreases their quality of life. Accordingly, there is a need for a better understanding of the mechanisms and risk factors of glioma-related epilepsy. The current study aimed to perform a comprehensive meta-analysis to investigate the correlation of isocitrate-dehydrogenase 1 (IDH1), an important molecular biomarker for glioma classification and prognosis, to preoperative seizure incidence in LGG. METHODS: PUBMED, EMBASE, and Web of Science databases were searched for relevant studies. The odds ratio (OR) and corresponding 95% confidence interval (CI) were used as the primary measures to assess the correlation between IDH1 mutation and preoperative seizure incidence. RESULTS: A total of 722 LGG patients, including 555 patients with IDH1 mutation and 167 patients with wild-type IDH1 were enrolled in the current meta-analysis. The pooled OR was 2.47 (95% CI 1.70-3.57, Z = 4.78, p < 0.01). No significant heterogeneity was observed among all included studies and no publication bias was identified. CONCLUSION: The current meta-analysis identified that IDH1 mutation was correlated to a higher preoperative seizure incidence in LGG. This result would generate impetus for research on the mechanisms behind this correlation, and provide a new idea for the individualized treatment of glioma-related epilepsy.

Predictive Value of Intraoperative Facial Motor Evoked Potentials in Vestibular Schwannoma Surgery Under 2 Anesthesia Protocols.

OBJECTIVE: We sought to validate the feasibility of facial motor evoked potential (FMEP) in facial nerve (FN) monitoring during vestibular schwannoma (VS) surgery under 2 anesthesia protocols and to examine its value for postoperative prognosis. METHODS: This prospective study included 106 patients with VS who underwent microsurgical excision between May 2014 and November 2016 at the Beijing Tiantan Hospital, Capital Medical University, China. All patients were investigated for FMEP elicited by transcranial electrical stimulation in the contralateral facial motor cortex. The patients randomly received total intravenous anesthesia or combined intravenous-inhalation anesthesia. Postoperative FN function was evaluated 7-10 days after surgery (short-term) and at the last follow-up (long-term) using the House-Brackmann (HB) grading system. HB grades 1 and 2 were deemed satisfactory, whereas HB grades 3-6 were deemed unsatisfactory. The value of the final-to-start FMEP ratio for predicting short-term and long-term postoperative FN functions was examined. RESULTS: Valid FMEPs were obtained in 97 patients, which were recorded from the mentalis muscle. The FMEP amplitude ratio was significantly correlated with short-term and long-term postoperative FN functions. Receiver operating characteristic curve analysis showed that the FMEP ratio cut-off values of 77.4% (area under the curve = 0.797) and 56.9% (area under the curve = 0.900) predicted satisfactory FN function 7-10 days after surgery and at the last follow-up, respectively. No statistically significant difference was found in FMEP quantitative parameters between the 2 anesthesia protocols. CONCLUSION: The FMEP amplitude ratio is a valuable predictor for postoperative FN function. FMEP ratio ≥57% is predictive of satisfactory long-term FN function.

Intermedin Enlarges the Vascular Lumen by Inducing the Quiescent Endothelial Cell Proliferation.

OBJECTIVE: Intermedin plays an important role in vascular remodeling and significantly improves blood perfusion, but the precise mechanism remains unclear. Herein, we aimed to define whether vascular lumen enlargement is responsible for the intermedin-increased blood perfusion and explore the underlying cellular and molecular mechanisms. APPROACH AND RESULTS: To study the role of intermedin, we generated the IMD-KO (Adm2-/-) mice using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) system. Intermedin significantly promoted vascular lumen enlargement in vitro (fibrin beads assay) and in vivo (murine retinas), which contributed to the improved blood perfusion in both physiological (retinal) and pathological (tumor) angiogenic models. We designed experiments to calculate the endothelial cell (EC) size and found that the lumen enlargement is because of EC proliferation but not because of a change in cell shape. ECs that construct vessel walls are considered quiescent cells because they are in a state of contact inhibition and show reduced responsiveness to VEGF (vascular endothelial growth factor). Using immunoprecipitation, Western blot assay, and fluorescent microscopy, we found that intermedin induced the formation of a signaling complex containing CRLR (calcitonin receptor-like receptor)/ß-arr1 (ß-arrestin1)/Src in ECs and promoted it internalizing into cytoplasm in a clathrin-dependent manner to activate downstream ERK1/2 (extracellular signal-regulated kinase 1/2). Importantly, this effect was not abrogated by cell-cell contacts of ECs. Through this mechanism, intermedin could reactivate the quiescent ECs to proliferate, resulting in continuous lumen expanding and a more effective blood perfusion. CONCLUSIONS: Our findings suggest a novel mechanism that may explain how quiescent ECs overcome the contact inhibition and regain the ability to proliferate for continuous vascular lumen enlargement.