A rare case report of infratentorial cisternal angiolipoma with review of literature.

Angiolipomas are slow-growing benign mesenchymal-derived tumors consisting of mature adipocytes and thin-walled blood vessels. While the majority of angiolipomas are found in subcutaneous tissues, rarely there are case reports of intracranial lesions. We present a case of cisternal angiolipoma in a 10-year-old female. She presented with vague symptoms like dizziness without neurological deficits and radiological evaluation confirmed a left-sided infratentorial cisternal partially enhancing mass. She underwent craniotomy and had complete resection of the mass, which was histologically composed of mature adipocytes and blood vessels, consistent with angiolipoma. A review of the literature found only 18 cases of intracranial angiolipoma ever reported with our case representing the first case of infratentorial cisternal region.

Rapid Clot Reduction with Direct Aspiration via 8-F Guide Catheter for Cardioembolic Extracranial Carotid Artery Occlusion: A Guide Catheter Aspiration Technique.

This study reported data that were collected from 11 consecutive patients undergoing treatment for acute cardioembolic extracranial carotid artery (ECCA) occlusion with extensive clot burden via the guide catheter aspiration (GCA) technique. The GCA technique was performed as a direct aspiration using 2 60-mL syringes simultaneously through an 8-F guide catheter. Successful reperfusion was achieved in all 11 patients at the end of thrombectomy, and successful reperfusion was observed in 4 patients after a single GCA procedure pass. A favorable clinical outcome was achieved in 6 (54.5%) cases after 90 days. Thus, the GCA technique is efficacious for patients with cardioembolic ECCA occlusions.

Epigallocatechin Gallate Preferentially Inhibits O6-Methylguanine DNA-Methyltransferase Expression in Glioblastoma Cells Rather than in Nontumor Glial Cells.

OBJECTIVE: O6-methylguanine (O6-meG) DNA-methyltransferase (MGMT) is a main regulator of temozolomide (TMZ) resistance in glioblastomas. Some MGMT inhibitors have been studied in clinical trials but with very little success, because their inhibiting effects were not tumor-selective, and often cause severe toxicity in normal tissues in the presence of TMZ. The goal of this study is to explore whether Epigallocatechin gallate (EGCG), a natural small molecule, could preferentially modulate MGMT in glioblastoma cells. METHODS: Two MGMT-positive glioblastoma cell lines (GBM-XD and T98G) and one nontumor glial cell culture (GliaX) were included in this study. The MGMT promoter methylation status, mRNA abundance, and protein levels were determined before and after EGCG treatment. The mechanisms were characterized. RESULTS: EGCG substantially suppressed mRNA and protein expression of MGMT, and reversed TMZ resistance in MGMT-positive GBM-XD and T98G cells via the WNT/ß-catenin pathway. EGCG prevented ß-catenin translocation into the nucleus and might directly inhibit the transcription factors TCF1 and LEF1. Meanwhile, EGCG enhanced the MGMT expression in the nontumor glial cells, through inhibition of the DNMT1 and demethylation of MGMT promoter. CONCLUSIONS: EGCG preferentially inhibits MGMT and enhances TMZ cytotoxicity in glioblastoma cells rather than in nontumor glial cells.

Trephination mini-craniectomy for traumatic posterior fossa epidural hematomas in selected pediatric patients.

PURPOSE: Posterior fossa epidural hematomas (PFEDH) are uncommon in children but usually require timely surgical intervention due to the risk of life-threatening brainstem compression. We attempt to make the surgical procedure less invasive by treating selected pediatric patients with trephination mini-craniectomy. METHODS: We retrospectively reviewed the clinical courses, radiological findings, surgical procedures, and prognoses of the pediatric patients who were treated in our departments for traumatic PFEDH from January 2010 to January 2015. RESULTS: During this period, a total of 17 patients were surgically treated for PFEDH and 7 were managed with trephination mini-craniectomy for hematoma evacuation. The outcomes were good in all 7 patients as evaluated with Glasgow Outcome Score. There was no mortality in this series. The on average 30-month clinical follow-up showed that patients experienced satisfactory recoveries without complications. CONCLUSION: Our results suggest that trephination mini-craniectomy is a safe surgical technique for selected PFEDH patients with moderate hematoma volume and stabilized neurological functions. However, standard craniectomy is recommend when there are rapid deteriorations in patients' neurological functions or the hematomas are large and exerted severe mass effects.

Delayed surgical repair of cranial burst fracture without strict dura closure: a prudent choice in selected patients?

OBJECTIVES: Surgical management of cranial burst fracture (CBF) usually involves craniotomy to remove the devitalized brain tissues, followed by watertight repair of dural tears. However, there were times when the dural tear was so extensive that a substantially large bone flap would have to be removed in order to expose the retracted dural margins before it could be repaired. In such cases, strict dural repair would incur a significantly higher risk of damages to the surrounding neural tissues and severe bleeding, especially when the fracture was in the vicinity of eloquent cortical areas and sinus. Basing on our own clinical experiences, we suggest strict dural closure is not mandatory for these selected patients. METHODS: A retrospective review of patients who underwent cranial surgery for CBF at our hospital was performed. Computed tomography (CT) and magnetic resonance imaging (MRI) scans were performed to evaluate the extent of dural and brain laceration and the existence of extra-cranial cerebral tissues. Routine craniotomy was delivered to remove the lacerated brain tissues and evacuate the hematoma. The dural defect was only partially fixed with patient's own tissues or artificial dura patch. Then the fractured bone flaps were restored using titanium micro plates and screws. Data including preoperative neurological status, surgery related complications, postoperative cranial fracture healing, and clinical outcomes were obtained through clinical and radiological examinations. RESULTS: From October 2004 to March 2013, a total of four patients diagnosed with CBF were treated by this dural closure sparing technique. Their average age was 18.4 months old and the average area of the skull defects was 91 cm(2), with an average interval between primary injury and surgery of 13 days. The diagnosis of CBF was confirmed by intraoperative findings like extrusion of cerebral tissues out of the lacerated dura mater and skull defects. The postoperative courses were uneventful and all patients' neurological functions improved after surgery. Postoperative three dimensional CT reconstruction of the cranial vault showed the skull fractures healed properly in all patients. No patient developed posttraumatic cerebrospinal fluid leak or epilepsy during the on average 24-month follow-up period. CONCLUSIONS: In those selected cases of CBF in whom an extraordinary large craniotomy would be required to expose the entire retracted dura margins, given satisfactory evacuation of devitalized brain tissues and restoration of the bone flaps were achieved, we suggest strict dura closure is not compulsory.

Spontaneous pseudoaneurysm of the superficial temporal artery in neurofibromatosis type 1: illustrative case.

BACKGROUND: A pseudoaneurysm of the superficial temporal artery is an uncommon clinical entity that has largely been linked with direct traumatic causes. Neurofibromatosis type 1 (NF1)-related vasculopathy is a rare cause of idiopathic arterial bleeding in the craniofacial region. OBSERVATIONS: A 46-year-old male with clinical features of NF1 presented to the hospital with an enlarging and tender right temporal mass without a history of trauma. Computed tomography angiography suggested the development of a pseudoaneurysm, and surgery was performed to resect the mass. Histopathological examinations showed focal interruption of the epithelium layer and elastic lamina, well-demarcated thickening of the smooth muscle layers of the arterial wall, supporting the diagnosis of pseudoaneurysm. LESSONS: NF1-associated vasculopathy is likely the predisposing factor for the development of a superficial temporal artery pseudoaneurysm.

Giant Pediatric Supratentorial Tumor: Clinical Feature and Surgical Strategy.

Purpose: To analyze the clinical character of giant pediatric supratentorial tumor (GPST) and explore prognostic factors. Materials and Methods: We analyzed the clinical data comprising of 35 cases of GPST from a single center between January 2015 and December 2020. The tumor volume was measured by 3D slicer software based on preoperative magnetic resonance imaging (MRI). Glasgow Outcome Scale (GOS) was used to evaluate the short-term prognosis. Result: The tumor volume varied from 27.3 to 632.8 ml (mean volume 129.8 ml/ median volume 82.8 ml). Postoperative histopathological types include ependymoma, pilocytic astrocytoma, choroid plexus papilloma (CPP), craniopharyngioma, primitive neuroectoderm tumor (PNET), choroid plexus carcinoma (CPC), immature teratoma, atypical teratoid rhabdoid tumor (AT/RT), anaplastic astrocytoma, and gangliocytoma. Tumors in children younger than 3 years and tumors located at the hemispheres appeared to be larger than their respective counterparts, though no statistical significance was found. A patient with giant immature teratoma died during the operation because of excessive bleeding. Postoperative complications include cerebrospinal fluid subgaleal collection/effusion, infection, neurological deficits, and seizures. The mean GOS score of patients with GPST in 6 months is 3.43 ± 1.12, and 83% of patients (29/35) showed improvement. Favorable GPST characteristics to indicated better GOS included small tumor (≤100 ml) (p = 0.029), low-grade (WHO I-II) (p = 0.001), and gross total resection (GTR) (p = 0.015). WHO grade was highly correlated with GOS score (correlation coefficient = -0.625, p < 0.001). GTR and tumor volume were also correlated (correlation coefficient = -0.428, p = 0.010). Conclusion: The prognosis of GPST is highly correlated with the histopathological type. Smaller tumors are more likely to achieve GTR and might lead to a higher GOS score. Early diagnosis and GTR of the tumor are important for GPST management.

Absorbable Artificial Dura Versus Nonabsorbable Artificial Dura in Decompressive Craniectomy for Severe Traumatic Brain Injury: A Retrospective Cohort Study in Two Centers.

Background: Severe traumatic brain injury (TBI) patients usually need decompressive craniectomy (DC) to decrease intracranial pressure. Duraplasty is an important step in DC with various dura substitute choices. This study aims to compare absorbable dura with nonabsorbable dura in duraplasty for severe TBI patients. Methods: One hundred and three severe TBI patients who underwent DC and dura repair were included in this study. Thirty-nine cases used absorbable artificial dura (DuraMax) and 64 cases used nonabsorbable artificial dura (NormalGEN). Postoperative complications, mortality and Karnofsky Performance Scale (KPS) score in one year were compared in both groups. Results: Absorbable dura group had higher complication rates in transcalvarial cerebral herniation (TCH) (43.59% in absorbable dura group vs. 17.19% in nonabsorbable dura group, P = 0.003) and CSF leakage (15.38% in absorbable dura group vs. 1.56% in nonabsorbable dura group, P = 0.021). But severity of TCH described with hernial distance and herniation volume demonstrated no difference in both groups. There was no statistically significant difference in rates of postoperative intracranial infection, hematoma progression, secondary operation, hydrocephalus, subdural hygroma and seizure in both groups. KPS score in absorbable dura group (37.95 ± 28.58) was statistically higher than nonabsorbable dura group (49.05 ± 24.85) in one year after operation (P = 0.040), while no difference was found in the rate of functional independence (KPS ≥ 70). Besides, among all patients in this study, TCH patients had a higher mortality rate (P = 0.008), lower KPS scores (P < 0.001) and lower functionally independent rate (P = 0.049) in one year after surgery than patients without TCH. Conclusions: In terms of artificial biological dura, nonabsorbable dura is superior to absorbable dura in treatment of severe TBI patients with DC. Suturable nonabsorbable dura has fewer complications of TCH and CFS leakage, and manifest lower mortality and better prognosis. Postoperative TCH is an important complication in severe TBI which usually leads to a poor prognosis.

[Role of modified external ventricular drainage in the management of children with tuberculous meningitis hydrocephalus].

OBJECTIVE: To explore the role of modified external ventricular drainage (mEVD) in the treatment of tuberculous meningitis obstructive hydrocephalus in children. METHODS: The records were retrospectively reviewed for 30 pediatric patients of tuberculous meningitis with hydrocephalus (TBMH) undergoing surgery between January 2007 and December 2010. The procedures included ventricular abdomen subcutaneous drainage (mEVD) (n = 6), Ommaya reservoir (n = 9) and ventriculoperitoneal shunt (VPS) (n = 15). White cell count and protein content of cerebrospinal fluid were measured repeatedly. And their clinical outcomes were assessed at 6 months post-operation. RESULTS: External drainage was extracted for 4 of 6 TBMH patients after 4 - 6 months of mEVD. Neither intracranial infections nor serious postoperative complications occurred. Two of 6 TBMH received VPS substituting for mEVD. No statistically significant difference in white cell count, protein content of cerebrospinal fluid and outcome was found between the mEVD and VPS groups. CONCLUSION: Ventricular abdomen subcutaneous drainage is both safe and efficacious in the management of children with tuberculous meningitis hydrocephalus. This approach may avoid possible complications and long-term indwelling shunt so that it is worthy of further clinical application.

Successful treatment of pyogenic ventriculitis caused by extensively drug-resistant Acinetobacter baumannii with multi-route tigecycline: A case report.

BACKGROUND: Pyogenic ventriculitis caused by extensively drug-resistant Acinetobacter baumannii (A. baumannii) is one of the most severe complications associated with craniotomy. However, limited therapeutic options exist for the treatment of A. baumannii ventriculitis due to the poor penetration rate of most antibiotics through the blood-brain barrier. CASE SUMMARY: A 68-year-old male patient with severe traumatic brain injury developed pyogenic ventriculitis on postoperative day 24 caused by extensively drug-resistant A. baumannii susceptible to tigecycline only. Successful treatment was accomplished through multi-route administration of tigecycline, including intravenous combined with continuous ventricular irrigation plus intraventricular administration. The pus was cleared on the 3rd day post-irrigation, and cerebrospinal fluid cultures were negative after 12 d. CONCLUSION: Our findings suggest that multi-route administration of tigecycline can be a therapeutic option against pyogenic ventriculitis caused by extensively drug-resistant A. baumannii.

Case Report: Whole-Exome Sequencing of Hypothalamic Hamartoma From an Infant With Pallister-Hall Syndrome Revealed Novel de novo Mutation in the GLI3.

Background: GLI-Kruppel family member 3 (GLI3), a zinc finger transcription factor of the sonic hedgehog pathway, is essential for organ development. Mutations in GLI3 cause several congenital conditions, including Pallister-Hall syndrome (PHS), which is characterized by polydactyly and hypothalamic hamartoma. Most patients are diagnosed soon after birth, and surgical removal of hypothalamic hamartoma in the very young is rarely performed because of associated risks. Case presentation: A 7-month-old boy with PHS features, including a suprasellar lesion, bifid epiglottis, tracheal diverticulum, laryngomalacia, left-handed polydactyly and syndactyly, and omental hernia was referred to our service. His suprasellar lesion was partially removed, and whole-exome sequencing was applied to the resected tumor, his peripheral blood, and blood from his parents. Histopathology confirmed the diagnosis of hypothalamic hamartoma, and molecular profiling revealed a likely pathogenic de novo variant, c.2331C>G (p. H777Q), in GLI3. Magnetic resonance imaging follow-up 1 year later showed some residual tumor, and the patient experienced normal development post operation. Conclusions: We presented a case of PHS that carries a novel GLI3 variant. Hypothalamic hamartoma showed a distinct genetic landscape from germline DNA. These data offer insights into the underlying etiology of hypothalamic hamartoma development in patients with PHS.

Magnesium sulphate in the management of patients with aneurysmal subarachnoid haemorrhage: a meta-analysis of prospective controlled trials.

PRIMARY OBJECTIVE: Experimental and clinical studies have suggested that magnesium has neuroprotective and vasodilatation properties. A meta-analysis was conducted to assess the effectiveness and safety of intravenous magnesium therapy in patients with aneurysmal subarachnoid haemorrhage (SAH). RESEARCH DESIGN: Meta-analysis. METHODS AND PROCEDURES: Medline, EMBASE and the Cochrane Library were searched for prospective controlled trials evaluating intravenous magnesium for treating SAH after a ruptured aneurysm without language restrictions. Two researchers performed the literature search and data extraction independently. MAIN OUTCOMES AND RESULTS: Six prospective controlled trials involving 699 patients were included in this meta-analysis. Magnesium infusion reduced the risk of poor outcome and delayed cerebral ischemia (DCI): the relative risk was 0.62 (95% confidence interval (CI) 0.46-0.83) and 0.73 (95% CI 0.53-1.00), respectively. Sensitivity analyses were consistent with the meta-analysis. The withdrawal rate for adverse effects was higher in the magnesium-treatment arm compared to the placebo arm, RR 9.98 (95% CI 3.04-32.74). CONCLUSION: The meta-analysis suggests that intravenous magnesium therapy reduces the risk of DCI and poor outcome after aneurysmal SAH. Serum magnesium should be routinely monitored for both effectiveness and safety considerations.

Decompressive craniectomy in addition to hematoma evacuation improves mortality of patients with spontaneous basal ganglia hemorrhage.

We conducted a retrospective study to assess the effect of decompressive craniectomy on outcome of patients with spontaneous basal ganglia hemorrhage (SBH). A review of a hospital database was performed to search for patients with a diagnosis of SBH who received hematoma evacuation with (N=38) or without (N=46) decompressive craniectomy in our institute from January 2005 to January 2008. Descriptive statistics revealed that patients in the decompressive craniectomy group were in poorer clinical condition before surgery. Unadjusted analyses found no significant difference between groups in either 30-day mortality or 6-month functional survival (32% v 43%, P=.26, and 55% v 45%, P=.28, respectively). However, after severity adjustment the multivariate logistic regression analysis showed that decompressive craniectomy group was associated with improved 30-day mortality (Exp (B) 0.11, 95% confidence interval 0.02-0.60, P=.01) and 6-month functional survival (Exp (B) 26.97, 95% confidence interval 2.20-317.62, P=.01). In conclusion, our study suggests decompressive craniectomy in addition to hematoma evacuation might improve mortality of deteriorating patients with SBH. Larger, randomized studies are needed to verify this result.

Titanium mesh cranioplasty in pediatric patients after decompressive craniectomy: Appropriate timing for pre-schoolers and early school age children.

PURPOSE: There is little knowledge on the growth of cranial defects, appropriate timing and outcomes of application of titanium mesh for cranioplasty in the pediatric population, especially pre-school age (2-5 years old) and school age (6-12 years old) children. We hypothesised that cranioplasty for pre-schoolers could be delayed to school age due to the expected cranium growth, whereas, for the school age group, it is better to perform routine cranioplasty (3-6 months) to protect the brain and therefore ensure their timely return to school life. MATERIALS AND METHODS: A retrospective review of pediatric patients (2-12 years old) who underwent titanium mesh cranioplasty for cranial defects from 2006 to 2012 was performed. Patient demographic data, radiological data, and clinical information were collected. Specifically, cranial defect sizes were evaluated by three-dimensional (3D) reconstruction of computed tomography data after craniectomy, before cranioplasty and 2-years after cranioplasty. Patients were routinely followed up at an outpatient clinic for complications and school attendance. RESULTS: A total of 18 titanium mesh cranioplasties were performed in 18 patients. The average interval between craniectomy and cranioplasty was 3 years for pre-schoolers and 4 months for the school age group. Patients in the pre-schooler group showed significant enlargements in cranial defects during the interval as compared with the school age group (26% vs. 4%, P < 0.05). There were no surgery-related complications except in one patient, who had titanium mesh exposure 11 months later. Two years after cranioplasty, there was no significant difference in mild cranial defect enlargements between the two groups (11% vs. 6%, P > 0.05). Patients were followed for an average of 5 (range, 2-8) years. All patients had satisfactory recovery of cranial contour, sufficient protection of the brain and active participation in school study. All patients had satisfactory recovery of cranial contour, sufficient protection of the brain and active participation in school. CONCLUSION: Timing of titanium mesh cranioplasty after decompressive craniectomy based on their age is a workable solution for school-age pediatric patients. The enlargement of cranium defects in pre-schoolers supports a delayed repair until school age. The long-term outcomes for these patients with titanium mesh cranioplasty are favourable.

Trends in intracranial meningioma incidence in the United States, 2004-2015.

BACKGROUND: Meningioma incidence was reported to have risen substantially in the United States during the first decade of the 21st century. There are few reports about subsequent incidence trends. This study provides updated data to investigate trends in meningioma incidence by demographic and tumor characteristics at diagnosis in the United states from 2004 to 2015. METHODS: Trends in meningioma incidence were analyzed using data from the Surveillance, Epidemiology, and End Results-18 (SEER-18) registry database of the National Cancer Institute. The joinpoint program was used to calculate annual percent change (APC) in incidence rates. RESULTS: The overall incidence of meningioma increased by 4.6% (95% CI, 3.4-5.9) annually in 2004-2009, but remained stable from 2009 to 2015 (APC, 0; 95% CI, -0.8 to 0.8). Females (10.66 per 100 000 person-years) and blacks (9.52 per 100 000 person-years) had significant predominance in meningioma incidence. Incidence in many subgroups increased significantly up to 2009 and then remained stable until 2015. However, meningioma incidence in young and middle-aged people increased significantly throughout the entire time period from 2004 to 2015 (APC: 3.6% for <20-year-olds; 2.5% for 20-39-year-olds; 1.8% for 40-59-year-olds). The incidence of WHO II meningioma increased during 2011-2015 (APC = 5.4%), while the incidence of WHO III meningioma decreased during 2004-2015 (APC = -5.6%). CONCLUSION: In this study, the incidence of meningioma was found to be stable in recent years. Possible reasons for this finding include changes in population characteristics, the widespread use of diagnostic techniques, and changes in tumor classification and risk factors in the US population.

Simvastatin pretreatment ameliorates t-PA-induced hemorrhage transformation and MMP-9/TIMP-1 imbalance in thromboembolic cerebral ischemic rats.

Background: The use of thrombolysis with tissue-plasminogen activator (t-PA) in patients with acute ischemic stroke (AIS) is limited by increased levels of matrix metalloproteinase-9 (MMP-9) and by the increased risk of hemorrhagic transformation (HT). In this study, we investigated the effects of simvastatin pretreatment on t-PA-induced MMP-9/tissue inhibitor of metalloproteinase-1 (TIMP-1) imbalance and HT aggravation in a rat AIS model. Methods: The rat AIS model was established by autologous blood emboli. Two weeks before surgery, rats were pretreated with simvastatin (60 mg/kg/d), and three hours after surgery, t-PA (10 mg/kg) was administered. MMP-9 and TIMP-1 levels in the infarcted zone and plasma were evaluated by Western blot analysis and ELISA; the level of HT was quantified by determining the hemoglobin content. RhoA activation was determined to clarify the potential effect. Results: The results suggested that pretreatment with simvastatin suppressed the increase in t-PA-induced MMP-9 levels and neutralized the elevated MMP-9/TIMP-1 ratio, but had no effect on TIMP-1 levels. Thrombolysis with t-PA after ischemia improved neurological outcome, but increased intracranial hemorrhage. Moreover, t-PA-induced HT aggravation was reduced by simvastatin pretreatment. In addition, we showed that t-PA-induced activation of RhoA was suppressed by simvastatin, and that t-PA-induced MMP-9/TIMP-1 imbalance and hemorrhage was reduced by Rho kinases (ROCK) inhibitor Y-27632. Conclusion: In this study, we showed that simvastatin pretreatment ameliorated t-PA-induced HT and MMP-9/TIMP-1 imbalance, and demonstrated that the RhoA/ROCK pathway was implicated.

Epidemiological trends, relative survival, and prognosis risk factors of WHO Grade III gliomas: A population-based study.

BACKGROUND: Population-based studies on grade III gliomas are still lacking. The purpose of our study was to investigate epidemiological characteristics, survival, and risk factors of these tumors. PATIENTS AND METHODS: All data of patients with grade III gliomas were extracted from the Surveillance, Epidemiology, and End Results database. This database provides analysis to evaluate age-adjusted incidence, incidence-based mortality, and limited-duration prevalence. The trends of incidence and mortality were modeled using Joinpoint program. Relative survival was also available in this database. Univariate and multivariate analyses were used to access the prognostic significance of risk factors on cancer-specific survival. Nomogram was constructed to predict 3-, 5-, and 10-year survival. RESULTS: Our study showed that during 2000-2013, the incidence was stable and the mortality rate dropped significantly with APC as -1.95% (95% CI: -3.35% to -0.54%). Patients aged 40-59 had the highest prevalent cases. The 1-, 3-, 5-, and 10-year relative survival rates for all patients were 74.7%, 52.8%, 44.4%, and 32.4%. And it varied by risk factors. Cox regression analysis showed older age, male, black race, divorced status, histology of AA, tumor size <3.5 cm and no surgery were associated with worse survival. CONCLUSION: Our study provides reasonable estimates of the incidence, mortality, and prevalence for patients with grade III gliomas during 2000-2013. The results of relative survival and Cox regression analysis revealed that age, race, sex, year of diagnosis, tumor site, histologic type, tumor size, and surgery were the identifiable prognostic indicators. The effects of radiotherapy still need further study. We integrated these risk factors to construct an effective clinical prediction model.

Whole exome sequencing of multiple meningiomas with varying histopathological presentation in one patient revealed distinctive somatic mutation burden and independent clonal origins.

Background: Although meningiomas are common intracranial tumors, multiple meningiomas (MMs) are rare entities in patients without neurofibromatosis type 2. Previous studies suggest most sporadic MMs are of monoclone in origin. Objective: To elucidate the clonal relationship between two sporadic meningiomas from the same patient by using the next-generation sequencing (NGS) platform. Methods: Two MMs, located frontally and parietally on the right side, were surgically removed from a 52-year-old male. Pathological examinations and whole exome sequencing were performed on tumor samples, followed by Sanger sequencing validation. Results: MMs were diagnosed as secretory and fibrous subtypes, respectively, on histology (WHO grade I) and tumor DNA exhibited distinctive somatic mutation patterns. Specifically, the secretory subtype carried more single nucleotide variant while the fibrous subtype had much higher copy number variation. Besides, the two tumors demonstrated different mutation profiles in predisposing genes and known driver mutations. For example, the secretory subtype had missense mutations in TRAF7 and KLF4, while the fibrous subtype had frameshift deletion of NF2 gene in addition to copy number loss of NF2 and SMARCB1, genetic events that have already been associated with the development of meningiomas. Significantly mutated gene analysis revealed novel mutations of LOC729159 in the secretory subtype and RPGRIP1L and DPP6 in the fibrous subtype. Sanger sequencing validated important point mutations in TRAF7 (c.1678G>A, p.G560S), KLF4 (c.1225A>C, p.K409Q) and CDH11 (c.169T>G, p.W57G). Conclusion: Our data suggest the two meningiomas might develop independently in this patient and molecular subtyping by NGS is a valuable supplement to conventional pathology. Further study is needed to ascertain whether these novel genetic events are tumorigenic or simply passenger mutations, as well as their clinical implications.

Solitaire Stent Permanent Implantation as an Effective Rescue Treatment for Emergency Large Artery Occlusion.

BACKGROUND: In this study, we present our experiences on the feasibility of rescue permanent Solitaire stent placement for failed mechanical thrombectomy (MT) and our protocol to avoid ineffective stent placement. METHODS: We retrospectively evaluated the data for consecutive patients admitted into the Second Affiliated Hospital of Wenzhou Medical University and 2 collaboration hospitals from August 2014 to May 2018 for emergency large artery occlusion. The baseline clinical characteristics and radiologic assessment, interventional data, clinical outcome, and angiographic follow-up data were assessed. Notably, we introduced our protocol for antegrade flow assessment before Solitaire stent detachment to ensure an effective stent implantation. RESULTS: Thirty-nine patients (mean age, 68.1 years, mean preprocedural National Institute of Health Scale Score, 22.1) were included, in which 34 patients had anterior circulation large artery occlusion and 5 patients had posterior circulation large artery occlusion. The MT attempts ranged from 1-5 (3.6 on average). The mean onset-to-puncture time was 4.8 hours (ranging from 2.1-7.8 hours) and the mean procedure time was 87.4 minutes (ranging from 32-124 minutes). Modified thrombolysis in cerebral infarction 2b-3 reperfusions were noted in all cases. The immediate, average postprocedure stenosis rate was 25.3%, and the average stenosis rate at the 3-month angiographic follow-up was 34.7% (data from 15 patients). Three patients died. Nineteen (48.7%) patients had good outcome (modified Rankin Scale, mRS ≤2) at the 3-month follow-up. CONCLUSIONS: Permanent Solitaire stent placement might be a feasible therapy for patients with MT-failed emergency large artery occlusion. For a successful revascularization, careful antegrade flow assessment before stent detachment is critical.

FM19G11 inhibits O6 -methylguanine DNA-methyltransferase expression under both hypoxic and normoxic conditions.

FM19G11 is a small molecular agent that inhibits hypoxia-inducible factor-1-alpha (HIF-1α) and other signaling pathways. In this study, we characterized the modulating effects of FM19G11 on O6 -methylguanine DNA-methyltransferase (MGMT), the main regulator of temozolomide (TMZ) resistance in glioblastomas. This study included 2 MGMT-positive cell lines (GBM-XD and T98G). MGMT promoter methylation status, mRNA abundance, and protein levels were determined before and after FM19G11 treatment, and the roles of various signaling pathways were characterized. Under hypoxic conditions, MGMT mRNA and protein levels were significantly downregulated by FM19G11 via the HIF-1α pathway in both GBM-XD and T98G cells. In normoxic culture, T98G cells were strongly positive for MGMT, and MGMT expression was substantially downregulated by FM19G11 via the NF-κB pathway. In addition, TMZ resistance was reversed by treatment with FM19G11. Meanwhile, FM19G11 has no cytotoxicity at its effective dose. FM19G11 could potentially be used to counteract TMZ resistance in MGMT-positive glioblastomas.