Interaction Between the PERK/ATF4 Branch of the Endoplasmic Reticulum Stress and Mitochondrial One-Carbon Metabolism Regulates Neuronal Survival After Intracerebral Hemorrhage.

Recent investigations have revealed that oxidative stress can lead to neuronal damage and disrupt mitochondrial and endoplasmic reticulum functions after intracerebral hemorrhage (ICH). However, there is limited evidence elucidating their role in maintaining neuronal homeostasis. Metabolomics analysis, RNA sequencing, and CUT&Tag-seq were performed to investigate the mechanism underlying the interaction between the PERK/ATF4 branch of the endoplasmic reticulum stress (ERS) and mitochondrial one-carbon (1C) metabolism during neuronal resistance to oxidative stress. The association between mitochondrial 1C metabolism and the PERK/ATF4 branch of the ERS after ICH was investigated using transcription factor motif analysis and co-immunoprecipitation. The findings revealed interactions between the GRP78/PERK/ATF4 and mitochondrial 1C metabolism, which are important in preserving neuronal homeostasis after ICH. ATF4 is an upstream transcription factor that directly regulates the expression of 1C metabolism genes. Additionally, the GRP78/PERK/ATF4 forms a negative regulatory loop with MTHFD2 because of the interaction between GRP78 and MTHFD2. This study presents evidence of disrupted 1C metabolism and the occurrence of ERS in neurons post-ICH. Supplementing exogenous NADPH or interfering with the PERK/ATF4 could reduce symptoms related to neuronal injuries, suggesting new therapeutic prospects for ICH.

A New Classification of Anterior Choroidal Artery Aneurysms and Its Clinical Application.

Background and Purpose: The aim of this study was to compare the different subtypes of anterior choroidal artery (AChoA) aneurysm based on a new classification and to analyze the risk factors according to individual endovascular treatment (EVT). Methods: In the new classification, AChoA aneurysms are classified into independent type (I type) and dependent type (II type) based on the relationship between the AChoA and the aneurysm. II type aneurysms have three subtypes, IIa (neck), IIb (body), and IIc (direct). We retrospectively analyzed 52 cases of AChoA aneurysm treated in our center between 2015 to 2019. There were 13 (25.0%) I type aneurysms, 24 (46.2%) IIa aneurysms, 15 (28.8%) IIb aneurysms, and no IIc type; 28 cases had a subarachnoid hemorrhage. According to our preoperative EVT plan for the different subtypes: II type should achieve Raymond-Roy Occlusion Class 1 (RROC 1) where possible. To protect the AChoA, it is best to preserve the neck of the IIa type aneurysms (RROC 2), and RROC 3 is enough for IIb type. Results: Ten asymptomatic cases with minimal aneurysms were treated conservatively. Of the other cases, 42 were treated with individualized EVT (26 with a simple coil, 6 with balloon-assisted coiling, 7 with stent-assisted coiling, and 3 by flow diverter. Different subtypes had different RROC (Z = 14.026, P = 0.001). IIb type aneurysms (χ2 = 7.54, P = 0.023) were one of the factors related to temporary or permanent AChoA injury during surgery. Overall, two patients (IIa = 1, IIb = 1) developed contralateral hemiparesis. Conclusions: The new classification diagram clearly shows the features of all types of AChoA aneurysm and makes EVT planning more explicit. The II type (particularly IIb) was a potential risk factor for AChoA injury.

Long term follow-up and outcomes in adult patients with thalamic gliomas.

OBJECTIVES: To investigate the optimal treatment and prognosis of thalamic glioma in adult patients. PATIENTS AND METHODS: We retrospectively analyzed the adult patients with thalamic glioma admitted to our hospital from May 2005 to September 2016. Patients were divided into two groups according to their treatment: surgery-based combined treatment and intensity modulated radiation therapy (IMRT)-based treatment. Univariate chi-square test and multivariate logistic regression were used to identify independent factors for the treatment modality. A log-rank test, adjusting for propensity score, was used to compare the overall survival (OS) and progression-free survival (PFS) of patients between the two groups. RESULTS: Fifty-eight adult patients with thalamic gliomas were included in the analysis. Of them, 31 were treated with surgery-based treatment, and 27 were treated with IMRT-based treatment. The overall survival (OS) and progression-free survival (PFS) of patients between the two groups were not significantly different (median OS 16.0 (range 1.0-163.0) months vs. 10.0 (range 1.0-118.0) months, p = 0.344 and median PFS 10.0 (range 1.0-163.0) months vs. 6.0 (range 1.0-118.0) months, p = 0.464, respectively) even after adjusting for potential confounding factors. CONCLUSIONS: The OS and PFS of adult patients with thalamic glioma were not significantly different between patients in the surgical group and in the IMRT group. IMRT might be an acceptable alternative to surgery for adult patients with unresectable thalamic glioma.

Subcutaneous Metastasis of Atypical Meningioma: Case Report and Literature Review.

BACKGROUND: Meningioma, a neoplasm of the meninges, is usually a benign localized tumor. Extraneural metastasis is an extremely rare complication of meningiomas, and only a few cases have been reported to date. The present study reports a case of scalp metastasis of an atypical meningioma and discusses the types of atypical meningiomas and their management options. CASE DESCRIPTION: A 69-year-old man presented with scalp metastasis of an atypical meningioma. Six years after the right frontoparietal meningioma lesion was completely resected, an isolated subcutaneous metastasis developed at the right frontal region of the scalp, originating at the scar left by the first surgery. Postoperative histologic examination of the subcutaneous tumor revealed the features of an atypical meningioma. CONCLUSIONS: This study highlights that resection of meningiomas is still associated with a risk of iatrogenic metastasis. Surgeons should carefully wash out the operative field and change surgical tools frequently to avoid the potential risk of metastasis.

Clinical and Molecular Characteristics of Thalamic Gliomas: Retrospective Report of 26 Cases.

OBJECTIVE: Thalamic glioma is a type of midline glioma with poor outcomes. In the present study, we investigated the clinical and molecular features of thalamic gliomas in Chinese patients. METHODS: The data from 26 patients with thalamic glioma who had undergone surgery at Shanghai Huashan Hospital from January 2011 to August 2015 were retrospectively analyzed. Various clinical and molecular factors were evaluated to explore their effects on prognosis. H3K27M mutation status and its association with relevant molecular factors were also investigated. RESULTS: The mean age of the patients was 38.88 years, and no significant difference was found in sex. The most common initial symptoms were headaches (38.46%; 10 of 26) and motor deficits (30.77%; 8 of 26). The H3K27M mutation was identified in 12 patients, and mutant thalamic glioma showed less frequent O-6-methylguanine DNA methyltransferase (MGMT) promoter methylation compared with the wild-type group (P = 0.015; χ1 test). Multivariate analysis showed that the H3K27M mutation was an independent unfavorable prognostic factor for overall survival. MGMT promoter unmethylation and the TP53 mutation were identified as negative prognostic factors for progression-free survival. CONCLUSIONS: Our results revealed the clinical and molecular characteristics of thalamic glioma in China. Our data have shown the absence of MGMT promoter methylation in H3K27M mutant thalamic glioma, validating it as a hallmark of H3K27M mutant gliomas. In addition, H3K27M mutation was identified as the sole unfavorable prognostic factor on overall survival. MGMT promoter unmethylation and TP53 mutation were identified as independent prognostic factors for progression-free survival.