Assessing Postoperative Motor Risk in Insular Low-Grade Gliomas Patients: The Potential Role of Presurgery MRI Corticospinal Tract Shape Measures.

BACKGROUND: Insular low-grade gliomas (LGGs) are surgically challenging due to their proximity to critical structures like the corticospinal tract (CST). PURPOSE: This study aims to determine if preoperative CST shape metrics correlate with postoperative motor complications in insular LGG patients. STUDY TYPE: Retrospective. POPULATION: 42 patients (mean age 40.26 ± 10.21 years, 25 male) with insular LGGs. FIELD STRENGTH/SEQUENCE: Imaging was performed using 3.0 Tesla MRI, incorporating T1-weighted magnetization-prepared rapid gradient-echo, T2-weighted space dark-fluid with spin echo (SE), and diffusional kurtosis imaging (DKI) with gradient echo sequences, all integrated with echo planar imaging. ASSESSMENT: Shape metrics of the CST, including span, irregularity, radius, and irregularity of end regions (RER and IER, respectively), were compared between the affected and healthy hemispheres. Total end region radius (TRER) was determined as the sum of RER 1 and RER 2. The relationships between shape metrics and postoperative short-term (4 weeks) and long-term (>8 weeks) motor disturbances assessing by British Medical Research Council grading system, was analyzed using multivariable regression models. STATISTICAL TESTING: Paired t-tests compared CST metrics between hemispheres. Logistic regression identified associations between these metrics and motor disturbances. The models were developed using all available data and there was no independent validation dataset. Significance was set at P < 0.05. RESULTS: Short-term motor disturbance risk was significantly related to TRER (OR = 199.57). Long-term risk significantly correlated with IER 1 (OR = 59.84), confirmed as a significant marker with an AUC of 0.78. Furthermore, the CST on the affected side significantly had the greater irregularity, larger TRER and RER 1, and smaller span compared to the healthy side. DATA CONCLUSION: Preoperative evaluation of TRER and IER 1 metrics in the CST may serve as a tool for assessing the risk of postoperative motor complications in insular LGG patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Exploring MGMT methylation-driven structural connectivity changes in insular gliomas: a tractography and graph theoretical analysis.

OBJECTIVES: This study aims to explore the relationship between the methylation levels of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter and the structural connectivity in insular gliomas across hemispheres. METHODS: We analyzed 32 left and 29 right insular glioma cases and 50 healthy controls, using differential tractography, correlational tractography, and graph theoretical analysis to investigate the correlation between structural connectivity and the methylation level. RESULTS: The differential tractography results revealed that in left insular glioma, the volume of affected inferior fronto-occipital fasciculus (IFOF, p = 0.019) significantly correlated with methylation levels. Correlational tractography results showed that the quantitative anisotropy (QA) value of peritumoral fiber tracts also exhibited a significant correlation with methylation levels (FDR < 0.05). On the other hand, in right insular glioma, anterior internal part of the reticular tract, IFOF, and thalamic radiation showed a significant correlation with methylation levels but at a different correlation direction from the left side (FDR < 0.05). The graph theoretical analysis showed that in the left insular gliomas, only the radius of graph was significantly lower in methylated MGMT group than unmethylated group (p = 0.047). No significant correlations between global properties and methylation levels were observed in insular gliomas on both sides. CONCLUSION: Our findings highlight a significant, hemisphere-specific correlation between MGMT promoter methylation and structural connectivity in insular gliomas. This study provides new insights into the genetic influence on glioma pathology, which could inform targeted therapeutic strategies.

A preliminary study on corticospinal tract morphology in incidental and symptomatic insular low-grade glioma: implications for post-surgical motor outcomes.

OBJECTIVE: Our study aimed to investigate the shape and diffusion properties of the corticospinal tract (CST) in patients with insular incidental and symptomatic low-grade gliomas (LGGs), especially those in the incidental group, and evaluate their association with post-surgical motor function. METHODS: We performed automatic fiber tracking on 41 LGG patients, comparing macroscopic shape and microscopic diffusion properties of CST between ipsilateral and contralateral tracts in both incidental and symptomatic groups. A correlation analysis was conducted between properties of CST and post-operative motor strength grades. RESULTS: In the incidental group, no significant differences in mean diffusion properties were found between bilateral CST. While decreased anisotropy of the CST around the superior limiting sulcus and increased axial diffusivity of the CST near the midbrain level were noted, there was no significant correlation between pre-operative diffusion metrics and post-operative motor strength. In comparison, we found significant correlations between the elongation of the affected CST in the preoperative scans and post-operative motor strength in short-term and long-term follow ups (p = 1.810 × 10-4 and p = 9.560 × 10-4, respectively). CONCLUSIONS: We found a significant correlation between CST shape measures and post-operative motor function outcomes in patients with incidental insular LGGs. CST morphology shows promise as a potential prognostic factor for identifying functional deficits in this patient population.

[Clinical characteristics and GAA gene mutation in children with glycogen storage disease type II: an analysis of 3 cases].

Glycogen storage disease type II (GSD II) is an autosomal recessive disorder caused by a deficiency of the lysosomal glycogen-hydrolyzing enzyme acid α-glucosidase (GAA) and can affect multiple systems including the heart and skeletal muscle. The aim of this study was to investigate three children with GSD II confirmed by GAA gene analysis and to report their clinical characteristics and gene mutations. One case was classified as infantile-onset GSD II, and two cases as late-onset GSD II. The infantile-onset patient (aged 4 months) showed no weight increase and had dyspnea, muscle hypotonia, and increased alanine aminotransferase and creatine kinase; echocardiography showed hypertrophic cardiomyopathy. The late-onset patients (aged 8 years and 13 years respectively) showed persistently elevated liver enzymes; one of them had recurrent respiratory tract infection and restrictive ventilation disorder, and the other case showed significantly increased creatase but normal electromyographic findings. Peripheral blood genetic testing for GAA gene showed six pathogenic mutations in the three cases, and the mutations c.2738C>T and c.568C>T had not been reported. Therefore, peripheral blood genetic testing for GAA gene is an effective diagnostic method.

[Roles of cardiac mast cells and Toll-like receptor 4 in viral myocarditis among mice].

OBJECTIVE: To investigate the role and significance of cardiac mast cells and Toll-like receptor 4 (TLR4) in the development and progression of viral myocarditis (VMC). METHODS: Forty-eight Balb/c mice were randomly divided into a control group (n=24) and a model group (n=24). Coxsackievirus B3 was intraperitoneally injected into the model group mice to establish a VMC model. In each group, cardiac tissues were collected from 8 mice at 7, 14 and 28 days after the model was established. The cardiac tissues were stained with hematoxylin and eosin as well as Masson trichrome to observe pathological changes in cardiac tissues. The number and degranulation of cardiac mast cells at each time point were measured and evaluated by toluidine blue staining and transmission electron microscopy. The mRNA and protein expression of TLR4 in cardiac tissues was measured by RT-PCR and immunohistochemistry. In the model group, the correlation between number of cardiac mast cells and mRNA expression of TLR4 at all time points was analyzed. RESULTS: The model group had significantly higher pathological scores of cardiac tissues than the control group at all time points (P<0.05). The myocardial collagen volume fraction in the model group at 28 days was significantly higher than in the control group at all time points and higher than in the model group at 7 and 14 days (P<0.05). At each time point, the model group had a significantly increased number of mast cells (P<0.05), and significantly increased mRNA and protein expression of TLR4 (P<0.05) compared with the control group. In the model group, the number of cardiac mast cells was positively correlated with the mRNA expression of TLR4 at all time points (R²=0.877, P<0.05). CONCLUSIONS: Mice with VMC have significantly increased numbers of cardiac mast cells and expression of TLR4 compared with control mice at all time points, suggesting that mast cells and TLR4 may play important roles in the inflammatory response and fibrosis of VMC.

[Effects of mTOR inhibitor rapamycin on Smad 3 protein and collagen type I expression in rat myocardial fibroblasts infected with coxsackie virus B 3].

OBJECTIVE: Mammalian target of rapamycin (mTOR) plays a central role in controlling cell proliferation, survival and growth. We investigated the role of mTOR signal transduction on viral myocarditis by observing the effect of mTOR inhibitor rapamycin on Smad 3 and collagen type I expression in rat myocardial fibroblasts infected with coxsackievirus B 3 (CVB 3). METHODS: Primary cultured myocardial fibroblasts of SD rats infected with CVB 3 were treated with or without rapamycin. The Smad 3 and collagen type I expression of the cells were determined by RT-PCR and Western blot. RESULTS: (1) mTOR/beta-actin ratio was dose-dependently reduced (1 nmol/L, 0.381 +/- 0.022; 10 nmol/L, 0.282 +/- 0.014; 100 nmol/L, 0.263 +/- 0.012 vs. control 1.45 +/- 0.04, all P < 0.05 vs. control) after 48 hours rapamycin treatments and time-dependently reduced after 10 nmol/L rapamycin treatment (24 h, 0.203 +/- 0.021; 48 h, 0.163 +/- 0.022; 72 h, 0.144 +/- 0.013 vs. 0 h, 0.341 +/- 0.022, all P < 0.05 vs.0 h) in CVB 3 infected myocardial fibroblasts. (2) Smad 3/beta-actin ratio of myocardial fibroblasts was significantly increased in CVB 3 infected cardial fibroblasts and this increase could be significantly attenuated by rapamycin (control, 0.63 +/- 0.06; CVB 3, 1.18 +/- 0.03; CVB 3 + Rapamycin, 0.77 +/- 0.08 by RT-PCR and 0.89 +/- 0.07, 2.27 +/- 0.13 and 0.131 +/- 0.013 by Western blot). Collagen type I/beta-actin ratio was also significantly increased by CVB 3 and this increase could be reversed by rapamycin (1.13 +/- 0.06, 1.303 +/- 0.012, 0.82 +/- 0.03 by RT-PCR). CONCLUSION: Rapamycin can inhibit the Smad 3 and collagen type I expressions in CVB 3 infected myocardial fibroblasts suggesting that the mTOR signal pathway may play an important role in the pathogenesis of CVB 3 induced myocardial fibrosis.

[Effeet of rapamycin on mTOR and eIF-4E expression in coxsackievirus B3-induced rat myocardial cells].

OBJECTIVE: To observe the effeet of rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), on mTOR and eukaryotic initiation factor-4E(eIF-4E)expression in coxsac-kievirus B3 (CVB3)-induced rat myocardial cells and to investigate the role of mTOR/eIF-4E signal pathway in viral myocarditis. METHODS: To construct a cell model of viral myocarditis with primary cultured myocardial cells. Myocardial cells infected by CVB3 were treated with 10 nmol/L rapamycin according to the cell toxicity test. The mTOR and eIF-4E expressions of cells were determined by RT-PCR and Western Blot. RESULTS: Rapamycin inhibited the degeneration of CVB3-induced myocardial cells. Expressions of mTOR and eIF-4E mRNA or protein in CVB3-induced myocardial cells were significantly upregulated compared with the control group (P < 0.05), and rapamycin (10 nmol/L) inhibited the upregulation (P < 0.05). CONCLUSION: Rapamycin can downregulate the expressions of mTOR and eIF-4E in CVB3-induced myocardial cells, suggesting that mTOR/eIF-4E signal transduction may play an important role in viral myocarditis.

[Rapamycin affects eIF- 4E expression in rat myocardial fibroblasts infected by Coxsackievirus B3].

OBJECTIVE: This study examined the effect of rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), on eukaryotic initiation factor (eIF- 4E) expression in rat myocardial fibroblasts infected by Coxsackievirus B3 (CVB3) in order to identify the drug target for treatment of viral myocarditis. METHODS: Primary cultured rat myocardial fibroblasts were treated with CVB3 with multiplicity of infection (MOI=0.5 PFU/cell). The experiment consisted of four groups in which the cultured rat fibroblasts cells were treated with CVB3, rapamycin (10 nM) and CVB3 + rapamycin or placebo (control). Experimental model of CVB3-infected myocardial fibroblasts was confirmed by detection of CVB3 mRNA expression with RT-PCR and observation of morphological changes of the infected cells with microscopy. eIF-4E expression was determined by both RT-PCR and Western Blot methods. RESULTS: Morphological changes were found in the fibroblasts treated with MOI 0.5 PFU/cell of CVB3 by transmission electron microscope and the viral particles were found in the cytoplasm. CVB3 mRNA was expressed in CVB3-infected fibroblasts after 1, 2, and 3 days after infection and 2 days after passage. The gray scale values of the eIF- 4E /beta -actin in the control, the CVB3, the rapamycin and the CVB3+rapamycin groups were 0.73 +/- 0.07, 0.87 +/- 0.03, 0.32 +/- 0.03 and 0.56 +/- 0.04 respectively detected by RT-PCR, and were 0.79 +/- 0.09, 1.35 +/- 0.12, 0.55 +/- 0.04, and 0.62 +/- 0.07 respectively detected by Western blot. EIF- 4E expression in the CVB3 group was higher than that in the control group. Both the rapamycin and the CVB3+rapamycin groups had lower eIF- 4E expression than the control and the CVB3 groups. CONCLUSIONS: CVB3 can infect myocardial fibroblasts and up-regulate the eIF- 4E expression in rat myocardial fibroblasts. Rapamycin can inhibit eIF- 4E expression and may be a potential medicine for treatment of viral myocarditis. It was suspected that mTOR/eIF- 4E signal pathway in rat myocardial fibroblasts might play an important role in the pathogenesis of viral myocarditis.