Unruptured brain arteriovenous malformations causing seizures localize to one common brain network.

Seizures are a frequent symptom of unruptured brain arteriovenous malformations (bAVMs). However, the brain regions responsible for these seizures remain unclear. To identify the brain regions causally involved in bAVM-related seizures, we retrospectively reviewed 220 patients with unruptured bAVMs. Using voxel-based lesion-symptom mapping (VLSM) analyses, we tested whether individual brain regions were associated with unruptured bAVM-related seizures. The result revealed that unruptured bAVMs causing seizures are anatomically heterogeneous at the voxel level. Subsequently, lesion network mapping (LNM) analyses was performed to determine whether bAVMs causing seizures belonged to a distributed brain network. LNM analyses indicated that these lesions were located in a functional network characterized by connectivity to the left caudate and precuneus. Moreover, the discrimination performance of the identified seizure network was evaluated in discovery set by calculating the individualized network damage score and was tested in validation set. Based on the calculated network damage scores, patients were divided into low-, medium-, and high-risk groups. The prevalence of seizures significantly differed among the three risk categories in both discovery (p = .003) and validation set (p = .004). Finally, we calculated the percentage of voxels in the canonical resting-state networks that overlapped with the seizure-susceptible brain regions to investigate the involvement of resting-state networks. With an involvement percentage over 50%, the frontoparietal control (82.9%), limbic function (76.7%), and default mode network (69.3%) were considered to be impacted in bAVM-related seizures. Our study identified the seizure-susceptible brain regions for unruptured bAVMs, which could be a plausible neuroimaging biomarker in predicting possible seizures.

Simplex cerebral cavernous malformations with MAP3K3 mutation have distinct clinical characteristics.

Objectives: To investigate the clinical characteristics of cerebral cavernous malformations (CCMs) with MAP3K3 somatic mutation. Methods: We performed a retrospective review of our CCMs database between May 2017 and December 2019. The patients with simplex CCMs identified to harbor a MAP3K3 or CCM gene somatic mutation were included. Clinical characteristics were recorded. Univariate and multivariate logistic analyses were used to assess the risk factors associated with hemorrhage events of CCMs. To explore the underlying mechanism, we transfected MEKK3-I441M-overexpressing and CCM2-knockdown lentiviruses into human umbilical vein endothelial cells (HUVECs) and investigated thrombomodulin (TM) and tight junctions (TJs) protein expression by western blotting and immunofluorescence. Finally, immunohistochemistry was used to validate TM and TJs protein expression in surgical samples. Results: Fifty simplex CCMs patients were included, comprising 38 MAP3K3 mutations and 12 CCM gene mutations. Nine (23.7%) patients with MAP3K3 mutations and 11(91.7%) patients with CCM gene mutations exhibited overt hemorrhage, respectively. Multivariate logistic analyses revealed that MAP3K3 mutation was associated with a lower risk of hemorrhage events. In the vitro experiments, ZO-1 expression was not reduced in MEKK3-I441M-overexpressing HUVECs compared with wild type, whereas it was significantly decreased in CCM2-knockdown HUVECs compared with control. In the MEKK3-I441M-overexpressing HUVECs, TM expression was increased, and the NF-κB pathway was significantly activated. After treatment with an NF-κB signaling inhibitor, TM expression was further upregulated. Meanwhile, TM expression was increased, but the NF-κB pathway was not activated in CCM2-knockdown HUVECs. Accordingly, immunohistochemistry showed that ZO-1 expression in the MAP3K3-mutant samples was significantly higher than that in the CCM-mutant samples. TM expression in the MAP3K3-mutant lesions was significantly lower than that in the CCM-mutant samples. Conclusion: Simplex CCMs with MAP3K3 mutation occasionally present with overt hemorrhage, which is associated with the biological function of MAP3K3 mutation.

Machine Learning-Enabled Determination of Diffuseness of Brain Arteriovenous Malformations from Magnetic Resonance Angiography.

The diffuseness of brain arteriovenous malformations (bAVMs) is a significant factor in surgical outcome evaluation and hemorrhagic risk prediction. However, there are still predicaments in identifying diffuseness, such as the judging variety resulting from different experience and difficulties in quantification. The purpose of this study was to develop a machine learning (ML) model to automatically identify the diffuseness of bAVM niduses using three-dimensional (3D) time-of-flight magnetic resonance angiography (TOF-MRA) images. A total of 635 patients with bAVMs who underwent TOF-MRA imaging were enrolled. Three experienced neuroradiologists delineated the bAVM lesions and identified the diffuseness on TOF-MRA images, which were considered the ground-truth reference. The U-Net-based segmentation model was trained to segment lesion areas. Eight mainstream ML models were trained through the radiomic features of segmented lesions to identify diffuseness, based on which an integrated model was built and yielded the best performance. In the test set, the Dice score, F2 score, precision, and recall for the segmentation model were 0.80 [0.72-0.84], 0.80 [0.71-0.86], 0.84 [0.77-0.93], and 0.82 [0.69-0.89], respectively. For the diffuseness identification model, the ensemble-based model was applied with an area under the Receiver-operating characteristic curves (AUC) of 0.93 (95% CI 0.87-0.99) in the training set. The AUC, accuracy, precision, recall, and F1 score for the diffuseness identification model were 0.95, 0.90, 0.81, 0.84, and 0.83, respectively, in the test set. The ML models showed good performance in automatically detecting bAVM lesions and identifying diffuseness. The method may help to judge the diffuseness of bAVMs objectively, quantificationally, and efficiently.

Neurological outcomes of untreated brainstem cavernous malformations in a prospective observational cohort and literature review.

BACKGROUND: Haemorrhages of brainstem cavernous malformations (CMs) can lead to neurological deficits, the natural history of which is uncertain. The study aimed to evaluate the neurological outcomes of untreated brainstem CMs and to identify the adverse factors associated with worsened outcomes. METHODS: From 2009 to 2015, 698 patients (321 women) with brainstem CMs were entered into the prospective cohort after excluding patients lost to follow-up (n=43). All patients were registered, clinical data were collected and scheduled follow-up was performed. RESULTS: After a median follow-up of 60.9 months, prospective haemorrhages occurred in 167 patients (23.9%). The mean modified Rankin Scale scores at enrolment and at censoring time were 1.6 and 1.2. Neurological status was improved, unchanged and worsened in 334 (47.9%), 293 (42.0%) and 71 (10.2%) patients, respectively; 233 (33.4%) recovered to normal levels. Lesions crossing the axial midpoint (relative risk (RR) 2.325, p=0.003) and developmental venous anomaly (DVA) (RR 1.776, p=0.036) were independently significantly related to worsened outcomes. The percentage of worsened outcomes was 5.3% (18 of 337) in low-risk patients (neither DVA nor crossing the axial point) and increased to 26.0% (13 of 50) in high-risk patients (with both DVA and crossing the axial point). The percentage of worsened outcomes significantly increased as the number of prospective haemorrhages increased (from 1.5% (8 of 531, if 0 prospective ictus) to 37.5% (48 of 128, if 1 ictus) and 38.5% (15 of 39, if >1 ictus)). CONCLUSIONS: The neurological outcomes of untreated brainstem CMs were improved/unchanged in majority of patients (89.8%) with a fatality rate of 1.7% in our cohort, which seemed to be favourable. Radiological features significantly predicted worsened outcomes. Our results provide evidence for clinical consultation and individualised treatment. The referral bias of our cohort was underlined.

The clinical, radiological, and immunohistochemical characteristics and outcomes of primary intracranial gliosarcoma: a retrospective single-centre study.

Primary intracranial gliosarcoma is a rare malignant brain tumour, and the most effective treatment for gliosarcoma remains unclear. This study aimed to identify risk factors for progression-free survival (PFS) and overall survival (OS) in these cases. This retrospective single-centre study evaluated 103 patients (median age, 51 years; 67 men [65%]) with primary intracranial gliosarcoma between 2006 and 2017. Treatments included surgery (GTR, 63 patients; STR, 39 patients; biopsy, 1 patient), radiotherapy (adjuvant, 76 patients; exclusive treatment, 1 patient), and chemotherapy (adjuvant temozolomide, 52 patients; adjuvant nimustine/teniposide, 19 patients; adjuvant bevacizumab, 1 patient; exclusive nimustine/teniposide treatment, 1 patient). The median OS was 13.3 months, and the median PFS was 9.1 months. In the multivariate analyses, the poor prognostic factors were ependymal lining enhancement of the lateral ventricle (PFS, HR 2.406, p = 0.005; OS, HR 2.946, p = 0.009) and enhancement in the motor functional cortex (PFS, HR 2.892, p = 0.002; OS, HR 2.639, p = 0.009). Good OS was predicted by adjuvant radiotherapy alone (HR 0.071, p < 0.001), adjuvant temozolomide-based chemotherapy alone (HR 0.063, p = 0.005), adjuvant temozolomide-based chemotherapy with concurrent radiotherapy (HR 0.056, p < 0.001), and salvage surgery at recurrence (HR 0.449, p = 0.031). The present study revealed that, in patients with primary intracranial gliosarcoma, enhancement in the functional motor cortex and ependymal lining enhancement of the lateral ventricle were both poor prognostic factors. Survival was optimized in cases treated using maximal safe resection followed by adjuvant temozolomide-based chemotherapy with concurrent radiotherapy. Furthermore, salvage surgery provided meaningful therapeutic benefits for recurrent gliosarcoma.

Surgical management and long-term outcomes of primary intracranial leiomyosarcoma: a case series and review of literature.

Primary intracranial leiomyosarcomas (PILMSs) are extremely rare neoplasms, and their management remains unclear. The authors aimed to enunciate the radiological features and design a treatment protocol based on previously published cases combined with our series. Clinical data from all 12 cases of PILMS treated at their institute between 2008 and 2018 were reviewed. Meanwhile, they searched the Ovid MEDLINE, Embase, PubMed, Web of Science and Cochrane databases using the keywords "leiomyosarcoma" and "intracranial," "central nervous system," "cerebral," or "brain" Previously published data were processed and used according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The authors' cohort included 4 males (33.3%) and 8 females (66.7%) ranging in age from 13 to 67 years with a mean of 44.1 ± 5.0 years. Gross total resection (GTR), subtotal resection, and partial resection were achieved in 8 (66.7%), 3 (25%), and 1 (8.3%) patient, respectively, and only four patients (33.3%) received adjuvant therapy after surgery. After a mean follow-up of 30.5 ± 7.6 months, 6 patients (50%) experienced recurrences, and all of them died at the final. Twenty-seven patients (15 were male and 12 were female), in the literature cases, were identified between January 1980 and November 2019, presenting with PILMS. GTR and non-GTR were achieved in 21 (77.8%) and 6 (22.2%) patients, respectively. Postoperative radiotherapy was administrated in 17 patients (63.0%), and postoperative chemotherapy was administrated in 9 patients (33.3%), After a mean follow-up of 22.2 ± 4.1 months, recurrence and death occurred in 8 (36.4%) and 4 (14.8%) cases, respectively. In the pooled cases, the univariate analysis model revealed that only GTR was a significantly favorable factor for increased progression-free survival (hazard ratio 0.270, 95% confidence interval = 0.093-0.787, p = 0.016) and overall survival (hazard ratio 0.255, 95% confidence interval = 0.073-0.890, p = 0.032). GTR was recommended as an optimal treatment; meanwhile, postoperative radiation was also a choice to help increase the survival of patients of PILMS.

Safety of Aspirin Use in Patients With Stroke and Small Unruptured Aneurysms.

OBJECTIVE: We initiated a multicenter, prospective cohort study to test the hypothesis that aspirin is safe for patients with ischemic cerebrovascular disease (ICVD) harboring unruptured intracranial aneurysms (UIAs) <7 mm. METHODS: This prospective, multicenter cohort study consecutively enrolled 1,866 eligible patients with ICVD harboring UIAs <7 mm in diameter from 4 hospitals between January 2016 and August 2019. Baseline and follow-up patient information, including the use of aspirin, was recorded. The primary endpoint was aneurysm rupture. RESULTS: After a total of 4,411.4 person-years, 643 (37.2%) patients continuously received aspirin treatment. Of all included patients, rupture occurred in 12 (0.7%). The incidence rate for rupture (IRR) was 0.27 (95% confidence interval [CI] 0.15-0.48) per 100 person-years. The IRRs were 0.39 (95% CI 0.21-0.72) and 0.06 (95% CI 0.010-0.45) per 100 person-years for the nonaspirin and aspirin groups, respectively. In the multivariate analysis, uncontrolled hypertension and UIAs 5 to <7 mm were associated with a high rate of aneurysm rupture, whereas aspirin use was associated with a low rate of aneurysm rupture. Compared with other groups, the high-risk group (UIAs 5 to <7 mm with concurrent uncontrolled hypertension) without aspirin had higher IRRs. CONCLUSION: Aspirin is a safe treatment for patients with concurrent small UIAs and ICVD. Patients who are not taking aspirin in the high-risk group warrant intensive surveillance. CLINICALTRIALSGOV IDENTIFIER: NCT02846259. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients harboring UIAs <7 mm with ICVD, aspirin does not increase the risk of aneurysm rupture.

Aspirin and Growth of Small Unruptured Intracranial Aneurysm: Results of a Prospective Cohort Study.

BACKGROUND AND PURPOSE: The role of aspirin in unruptured intracranial aneurysm (UIA) growth remains largely unknown. We aim to identify whether aspirin is associated with a lower rate of UIA growth in patients with UIA <7 mm. METHODS: This prospective cohort study consecutively enrolled patients with UIAs <7 mm with ischemic cerebrovascular disease between January 2016 and December 2019. Baseline and follow-up patient information, including the use of aspirin and blood pressure level, were recorded. Patients were considered aspirin users if they took aspirin, including standard- and low-dose aspirin, ≥3× per week. The primary end point was aneurysm growth in any direction or an indisputable change in aneurysm shape. RESULTS: Among the 315 enrolled patients, 272 patients (86.3%) underwent imaging examinations during follow-up (mean follow-up time, 19.6±12.7 months). A total of 113 patients were continuously treated with aspirin. UIA growth occurred in 31 (11.4%) patients. In the multivariate Cox analysis, specific aneurysm locations (anterior communicating artery, posterior communicating artery, or middle cerebral artery; hazard ratio, 2.89 [95% CI, 1.22-6.88]; P=0.016) and a UIA size of 5 to <7 mm (hazard ratio, 7.61 [95% CI, 3.02-19.22]; P<0.001) were associated with a high risk of UIA growth, whereas aspirin and well-controlled blood pressure were associated with a low risk of UIA growth (hazard ratio, 0.29 [95% CI, 0.11-0.77]; P=0.013 and hazard ratio, 0.25 [95% CI, 0.10-0.66]; P=0.005, respectively). The cumulative annual growth rates were as high as 40.0 and 53.3 per 100 person-years in the high-risk patients (>1 risk factor) with and without aspirin, respectively. CONCLUSIONS: Aspirin therapy and well-controlled blood pressure are associated with a low risk of UIA growth; the incidence of UIA growth in high-risk patients in the first year is high, warranting intensive surveillance in this patient group. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02846259.

Prognostic and predictive value of an immune infiltration signature in diffuse lower-grade gliomas.

BACKGROUNDLower-grade gliomas (LGGs) vary widely in terms of the patient's overall survival (OS). There is no current, valid method that could exactly predict the survival. The effects of intratumoral immune infiltration on clinical outcome have been widely reported. Thus, we aim to develop an immune infiltration signature to predict the survival of LGG patients.METHODSWe analyzed 1216 LGGs from 5 public data sets, including 2 RNA sequencing data sets and 3 microarray data sets. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to select an immune infiltration signature and build a risk score. The performance of the risk score was assessed in the training set (329 patients), internal validation set (140 patients), and 4 external validation sets (405, 118, 88, and 136 patients).RESULTSAn immune infiltration signature consisting of 20 immune metagenes was used to generate a risk score. The performance of the risk score was thoroughly verified in the training and validation sets. Additionally, we found that the risk score was positively correlated with the expression levels of TGF-ß and PD-L1, which were important targets of combination immunotherapy. Furthermore, a nomogram incorporating the risk score, patient's age, and tumor grade was developed to predict the OS, and it performed well in all the training and validation sets (C-index: 0.873, 0.881, 0.781, 0.765, 0.721, and 0.753).CONCLUSIONThe risk score based on the immune infiltration signature has reliable prognostic and predictive value for patients with LGGs and is a potential biomarker for the cotargeting immunotherapy.FUNDINGThis work was supported by The National Natural Science Foundation of China (grant nos. 81472370 and 81672506), the Natural Science Foundation of Beijing (grant no. J180005), the National High Technology Research and Development Program of China (863 Program, grant no. 2014AA020610), and the National Basic Research Program of China (973 Program, grant no. 2014CB542006).

A clinical study of ocular motor nerve functions after petroclival meningioma resection.

BACKGROUND: Ocular motor dysfunction is one of the most common postoperative complications of petroclival meningioma. However, its incidence, recovery rate, and independent risk factors remain poorly explored. METHODS: A prospective analysis of 31 petroclival meningiomas was performed. Operative approaches were selected by utilizing a new 6-region classification of petroclival meningiomas we proposed. Two scores were used to evaluate the functions of the oculomotor and abducens nerves. Pearson correlation analysis and binary logistic regression analysis were used to identify independent risk factors for intraoperative oculomotor and abducens nerve injury. RESULTS: Postoperative new-onset dysfunctions in the pupillary light reflex and eye/eyelid movements as well as abducens paralysis were detected in eight (25.8%), ten (32.3%) and twelve (38.7%) cases, respectively. Their corresponding recovery rates after 6 months of follow-up were 75% (6/8), 80% (8/10), and 83.3% (10/12), respectively, and their mean times to start recovery were 4.03, 2.43, and 2.5 months, respectively. Tumor invasion into the suprasellar region/sphenoid sinus was the only risk factor for dysfunctions in both the pupillary light reflex (p = 0.001) and eye/eyelid movements (p = 0.002). Intraoperative utilization of the infratrigeminal interspace was the only risk factor for dysfunction in eyeball abduction movement (p = 0.004). CONCLUSIONS: Dysfunctions of the oculomotor and abducens nerves recovered within 6 months postoperatively. Tumor extension into the suprasellar region/sphenoid sinus was the only risk factor for oculomotor nerve paralysis. Eye/eyelid movements were more sensitive than the pupillary light reflex in reflecting nerve dysfunctions. Intraoperative utilization of the infratrigeminal interspace was the only risk factor for abducens nerve paralysis.

MicroRNA-195 Functions as a Tumor Suppressor by Directly Targeting Fatty Acid Synthase in Malignant Meningioma.

OBJECTIVE: Meningiomas are among the most common primary intracranial tumors. Up to 20% of cases will show increased malignancy at histological examination (World Health Organization grade II or III). Effective pharmacotherapy, except for radiotherapy, is lacking. Therefore, it is necessary to study the pathogenesis of malignant meningioma to provide more treatment strategies. METHODS: RNA sequencing and micro-RNA (miRNA) microarray detection were applied to identify differentially expressed messenger RNAs (mRNAs) and miRNAs in benign and malignant meningioma. The miRDB and TargetScan databases were used to predict the potential interaction between miRNAs and mRNAs. A proliferation assay was used to evaluate the cell growth. A wound healing assay and Transwell assay were performed to assess the cell migration and invasion abilities, respectively. The interaction between miRNA and mRNA was identified using a luciferase reporter assay. RESULTS: We found fatty acid synthase (FASN) was significantly upregulated in malignant meningioma compared with benign meningioma. Knockdown of FASN significantly inhibited proliferation, migration, and invasion of IOMM-Lee cells. Moreover, miR-195 was verified to directly target FASN using a luciferase reporter assay. Upregulation of miR-195 also significantly inhibited proliferation, migration, and invasion of IOMM-Lee cells. Furthermore, we performed bioinformatics analysis to predict the competing endogenous RNAs (ceRNAs) and found that NUP210, SPIRE2, SLC7A1, and DMTN might function as ceRNAs of FASN by sponging miR-195 in meningioma. CONCLUSIONS: Our results have suggested a tumor suppressive role for miR-195 in the tumorigenesis and progression of malignant meningioma by targeting FASN. In addition, NUP210, SPIRE2, SLC7A1, and DMTN might act as ceRNAs to regulate FASN expression by sponging miR-195.

Therapeutic Strategies and Prognostic Factors Based on 121 Spinal Neurenteric Cysts.

BACKGROUND: Limited data existed to guide the management of intraspinal neurenteric cysts (ISNECs). OBJECTIVE: To evaluate the risk factors for progression-free survival (PFS), elucidate the radiological features of ISNECs, and propose a treatment protocol. METHODS: From 2003 to 2015, 121 patients with pathologically confirmed ISNECs treated at our institute were included in this study. Pertinent risk factors were evaluated. RESULTS: Gross total resection (GTR) was achieved in 55 (44.6%) patients; 106 (87.6%), 12 (9.9%), and 3 (2.5%) ISNECs were classified as Wilkins A, B, and C, respectively. After a median follow-up duration of 64.2 mo, recurrence occurred in 25 (22.7%) patients, with a median PFS time of 43.1 mo. The actuarial PFS rates at 5 and 10 yr were 73.2% and 66.2%, respectively. The actuarial overall survival rates at 5 and 10 yr were 100% and 97.6%, respectively. Non-GTR (hazard ratio [HR], 5.836; 95% confidence interval [CI], 1.698-20.058; P = .005), Wilkins B/C (HR, 3.129; 95% CI, 1.009-9.702; P = .048), and a history of surgical resection (HR, 3.690; 95% CI, 1.536-8.864; P = .004) were adverse factors. CONCLUSION: GTR and Wilkins A were favorable factors for PFS. If tolerable, GTR alone was advocated as an optimal treatment. Because of the benign nature and favorable prognosis, non-GTR was an alternative if GTR failed. Close follow-up was needed because of the recurrent tendency of ISNEC. Future study with a large cohort is necessary to verify our findings.

Identification and validation of a 21-mRNA prognostic signature in diffuse lower-grade gliomas.

PURPOSE: Diffuse low-grade and intermediate-grade gliomas, also known as lower-grade gliomas (LGGs), are a class of central nervous system tumors. Overall survival varies greatly between patients, highlighting the importance of evaluating exact outcomes to facilitate individualized clinical management. We aimed to identify an mRNA-based prognostic signature to predict the survival of patients with LGGs. METHODS: A total of 874 LGGs from two public datasets were included. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to select the most prognostic mRNAs and build a risk score. A nomogram incorporating the risk score and clinical factors was established for individualized survival prediction. The performance of the nomogram was assessed in the training set (329 patients), internal validation set (140 patients), and external validation set (405 patients). RESULTS: 21 most prognostic mRNAs remained following the LASSO Cox regression. The 21-mRNA signature successfully stratified patients into high- and low-risk groups (P < 0.001 for all datasets in Kaplan-Meier analysis). Subsequent gene set enrichment analysis identified 19 essential biological processes in high-risk LGGs. Furthermore, a nomogram incorporating the risk score, age, grade, and 1p/19q status was developed with favorable calibration and high predictive accuracy in the training set and validation sets (C-index: 0.877, 0.878, and 0.812, respectively). CONCLUSION: The 21-mRNA signature has reliable prognostic value for LGGs and might facilitate the effective stratification and individualized management of patients.

Primary intracranial malignant melanoma: proposed treatment protocol and overall survival in a single-institution series of 15 cases combined with 100 cases from the literature.

OBJECTIVE: The overall survival and pertinent adverse factors for primary intracranial malignant melanoma (PIMM) have not been previously determined. This aim of this study was to determine the rates of progression-free survival (PFS) and overall survival (OS) and identify the adverse factors for PIMM. METHODS: This study included 15 cases from the authors' own series and 100 cases with detailed clinical data that were obtained from the literature from 1914 to 2018 using the Ovid Medline, EMBASE, PubMed, Cochrane, and EBSCO databases. Patient demographics, treatment (surgery, chemotherapy, and radiotherapy [RT]), PFS, and OS were reviewed. Data from prior publications were processed and used according to PRISMA guidelines. RESULTS: Diffuse lesions were identified in 24 (20.9%) patients, who had a younger age (p < 0.001). The mean follow-up time was 16.6 months, and 76 (66.1%) deaths occurred. The 6-month, 1-year, 3-year, and 5-year OS rates of the whole cohort were 62.8%, 49.9%, 28.9%, and 17.2%, respectively, with an estimated median survival time (EMST) of 12.0 months. The multivariate analysis revealed that gross-total resection (GTR) (HR 0.299, 95% CI 0.180-0.497, p < 0.001), radiotherapy (HR 0.577, 95% CI 0.359-0.929, p = 0.024), and chemotherapy (HR 0.420, 95% CI 0.240-0.735, p = 0.002) predicted a better OS. The EMST was 5.0 months in patients with diffuse-type PIMM and 13.0 months in patients with the solitary type. Patients receiving GTR with adjuvant RT and/or chemotherapy (GTR + [RT and/or chemo]) had significantly higher 1-year and 5-year OS rates (73.0% and 40.1%, respectively) and a longer EMST (53 months) than patients who underwent GTR alone (20.5 months) or RT and/or chemotherapy without GTR (13.0 months). CONCLUSIONS: Optimal outcomes could be achieved by radical resection plus postoperative radiotherapy and/or chemotherapy. Patients with diffuse PIMM have a more severe clinical spectrum and poorer survival than patients with solitary PIMM. Immunotherapy and targeted therapy show promise as treatment options for PIMM based on results in patients with brain metastases from extracranial melanoma.

Surgical management and long-term outcomes of intracranial giant cell tumors: a single-institution experience with a systematic review.

OBJECTIVE: Intracranial giant cell tumors (GCTs) are extremely rare neoplasms with dismal survival and recurrence rates. The authors aimed to confirm independent adverse factors for progression-free survival (PFS) and to propose an optimal treatment algorithm. METHODS: The authors reviewed the clinical data of 43 cases of intracranial GCTs in their series. They also reviewed 90 cases of previously reported GCTs in the English language between 1982 and 2017 using Ovid MEDLINE, Embase, PubMed, and Cochrane databases with keywords of "giant cell tumor" or "osteoclastoma" and "skull," "skull base," "temporal," "frontal," "sphenoid," or "occipital." These prior publication data were processed and used according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Aforementioned risk factors for the authors' series and the pooled cases were evaluated in patients not lost to follow-up (m = 38 and n = 128, respectively). RESULTS: The authors' cohort included 28 males and 15 females with a mean age of 30.5 years. Gross-total resection (GTR) was achieved in 15 (34.9%) patients. Fifteen patients (39.5%) who did not undergo GTR received postoperative radiotherapy with a mean total dose of 54.7 ± 4.1 Gy. After a mean follow-up of 71.3 months, 12 (31.6%) patients experienced recurrence, and 4 (10.5%) died of disease. The actuarial 5-year PFS and overall survival (OS) were 68.6% and 90.0% in the authors' cohort, respectively. A multivariate Cox regression analysis verified that partial resection (HR 7.909, 95% CI 2.296-27.247, p = 0.001), no radiotherapy (HR 0.114, 95% CI 0.023-0.568, p = 0.008), and Ki-67 ≥ 10% (HR 7.816, 95% CI 1.584-38.575, p = 0.012) were independent adverse factors for PFS. Among the 90 cases in the literature, GTR was achieved in 49 (54.4%) cases. Radiotherapy was administered to 33 (36.7%) patients with a mean total dose of 47.1 ± 5.6 Gy. After a mean follow-up of 31.5 months, recurrence and death occurred in 17 (18.9%) and 5 (5.6%) cases, respectively. Among the pooled cases, the 5-year PFS and OS were 69.6% and 89.2%, respectively. A multivariate model demonstrated that partial resection (HR 4.792, 95% CI 2.909-7.893, p < 0.001) and no radiotherapy (HR 0.165, 95% CI 0.065-0.423, p < 0.001) were independent adverse factors for poor PFS. CONCLUSIONS: GTR and radiotherapy were independent favorable factors for PFS of intracranial GCTs. Based on these findings, GTR alone or GTR plus radiotherapy was advocated as an optimal treatment; otherwise, partial resection plus radiotherapy with a dose ≥ 45 Gy, if tolerable, was a secondary alternative. Lack of randomized data of the study was stressed, and future studies with larger cohorts are necessary to verify these findings.Systematic review no.: CRD42018090878 (crd.york.ac.uk/PROSPERO/).

Surgical management and prognostic factors for primary intracranial myxoma: a single-institute experience with a systematic review.

OBJECTIVEPrimary intracranial myxomas (PICMs) are extremely rare neoplasms, and their management and prognostic factors remain ambiguous. The authors aimed to elaborate the radiological features, evaluate the risk factors for progression-free survival (PFS), and propose a treatment protocol based on pooled data from cases treated at their institute and those found in the literature.METHODSClinical data from all cases of PICMs treated at the authors' institute and those cases reported in the English-language literature between 1987 and December 2017 were reviewed. The authors searched the Ovid MEDLINE, Embase, PubMed, and Cochrane databases using the keywords "myxoma" and "central nervous system," "intracranial," "cerebral," "skull base," "skull," or "brain." Previously published data were processed and used according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk factors in the pooled cohort were evaluated.RESULTSCases from the authors' institute included 21 males and 9 females, with a mean age of 35.7 ± 1.7 years. Gross-total resection (GTR) and non-GTR were achieved in 6 (20.0%) and 24 (80.0%) patients, respectively. After a mean follow-up of 86.7 ± 14.1 months, recurrence occurred in 6 (24%) patients, for a median PFS time of 85.2 months (range 36.0-136.0 months) and no deaths. In the literature between 1987 and 2017, 35 cases of PICM were identified in 14 males and 21 females with a mean age of 31.7 ± 3.2 years. GTR and non-GTR were achieved in 23 (65.7%) and 9 (25.7%) cases, respectively. After a mean follow-up of 25.8 ± 6.9 months (range 1.0-156.0 months), recurrence occurred in 4 (14.3%) patients, for a median PFS time of 11.0 months (range 3.0-36.0 months) and no deaths. Actuarial PFS rates at 1, 5, and 10 years were 93.0%, 80.6%, and 67.9%, respectively. A multivariate model demonstrated that GTR (HR 0.058, 95% CI 0.005-0.680, p = 0.023) was the only factor that favored PFS.CONCLUSIONSPICMs are rare neoplasms with a slightly higher occurrence in males. GTR was the only favorable factor for PFS. Based on statistical results, GTR alone, if tolerable, is advocated as the optimal treatment for PICM. Nevertheless, conservative excision may be preferred to avoid damage to vital structures. PICMs have a tendency to recur within a few years of the initial surgery if resection is incomplete; therefore, close postoperative follow-up is mandatory. Future studies with larger cohorts are necessary to verify the study findings.Systematic review registration no.: CRD42018091517 (www.crd.york.ac.uk/prospero/).

Proposed Treatment Paradigm for Intracranial Chondrosarcomas Based on Multidisciplinary Coordination.

OBJECTIVES: There was no consensus regarding the treatment of intracranial chondrosarcoma (CSA). The study aimed to evaluate the adverse factors for progression-free survival (PFS) and overall survival (OS) and to propose a treatment strategy for CSA. METHODS: The clinical chart and radiographic data of 106 consecutive cases (mesenchymal and conventional CSA in 18 and 88 patients, respectively) of surgically treated CSAs were retrospectively reviewed. RESULTS: Gross total resection was achieved in 43 patients (40.6%), and adjuvant radiotherapy was administered in 45 patients. After a mean follow-up duration of 47.8 months, 38 patients (37.3%) experienced recurrence. PFS and disease-specific OS at 5 years was 57.7% and 74.4%. Independent adverse factors for PFS were previous surgery (hazard ratio [HR] 2.261; P = 0.028), increased lesion size (HR, 1.298; P = 0.026), extent of surgical resection (HR, 3.226; P < 0.001), malignant pathology (HR, 2.018; P = 0.003), and postoperative radiotherapy (HR, 3.246; P = 0.001). The stereotactic radiosurgery subgroup presented best 5-year PFS of 88.9%, and a linear accelerator prolonged the mean PFS time (57.0 months) compared with no radiation (38.1 months). In the incomplete resection subgroup (n = 63), radiotherapy significantly benefited tumor control (HR, 2.101; P = 0.016). Extent of surgical resection (HR, 1.797; P = 0.026) and malignant disease (HR, 1.717; P = 0.030) were associated with OS. CONCLUSIONS: Intracranial CSAs were not completely amendable by surgery alone. Gross total resection as far as possible plus radiation were necessary for mesenchymal CSA and conventional CSA with active growth or residual tumor. Stereotactic radiosurgery was an alternative if proton therapy was unavailable. A future study with a large cohort is required to verify our findings.

Intradural Extramedullary Bronchogenic Cyst: Clinical and Radiologic Characteristics, Surgical Outcomes, and Literature Review.

OBJECTIVE: An intradural extramedullary bronchogenic cyst (IEBC) is a congenital malformation and an extremely rare type of endodermal cyst. This study aims to report the clinical and radiologic characteristics and surgical outcomes of IEBCs and to review the available literature. METHODS: The medical records of 6 patients (3 female) with pathologically confirmed bronchogenic cysts involving the spinal cord between 2009 and 2016 were retrospectively reviewed, and follow-up evaluations were performed. RESULTS: Of the 6 symptomatic lesions, 4 were located in the cervical vertebra, 1 at the lumbar vertebra, and the remaining 1 at the craniocervical junction. Radiographs showed signals similar to cerebral spinal fluid on all magnetic resonance imaging sequences without contrast enhancement. Total resection was achieved in 3 patients. Histopathology revealed simple and pseudostratified respiratory epithelium with benign subepithelial mucous glands and fat components neighboring the cyst. After a mean follow-up duration of 49.2 months, 2 asymptomatic residual lesions regrew after nontotal resection. In previous literature including 19 cases, most IEBCs (84.2%) tended to be homogeneous and well demarcated on radiologic images, and 85.7% were not contrast enhancing. Cervical or upper thoracic segments were predilection sites with intradural extramedullary localization. The majority of IEBCs had similar benign histological features. The recurrence rate was 15.4% after nontotal resection but nil after total resection. CONCLUSIONS: IEBCs displayed an indolent course, and the most effective management with positive outcomes was total resection. Nontotal resection, cystic fenestration, and biopsy, which were associated with recurrence, should be avoided.

Surgical Management and Outcomes of Intracranial Chondromas: a Single-Center Case Series of 66 Patients.

OBJECTIVE: Management of intracranial chondromas (ICDs) is difficult. This study aims to propose a tailored management strategy based on our management of ICDs. METHODS: A retrospective review was performed in 66 patients who received surgical operations at our institute. Clinical charts and radiographs were reviewed, follow-up was performed, and adverse factors for progression-free survival (PFS) and overall survival were evaluated. RESULTS: The preoperative and postoperative Karnofsky performance status was 81.8 and 72.3, respectively. The mean tumor size was 3.5 cm. Gross total resection was achieved in 15 patients (22.7%). Six patients (10.3%) received postoperative radiation. After a mean follow-up duration of 85.5 months, recurrence occurred to 15 patients (28.8%) with surgery alone, and no recurrence was observed in patients receiving postoperative radiotherapy. Six patients (10.3%) died due to tumor progression. The risk factors affecting the PFS included age <33 years (hazard rate [HR] 6.876; 95% confidence interval [CI] 1.599-29.560; P = 0.010), tumor size ≥3.1 cm (HR 6.138; 95% CI 1.259-29.926; P = 0.025), tumor with evident atypia/mitotic activity (HR 4.672; 95% CI 1.352-16.152; P = 0.015), and partial resection (HR 12.841; 95% CI 3.004-54.896; P = 0.001). In all patients, the PFS rate was 75% at 5 years and 64% at 10 years; in addition, the overall survival rate was 93% at 5 years and 83% at 10 years. CONCLUSIONS: The therapeutic strategy for ICDs should be individualized and should consider preoperative variables. Gross total resection was attempted if the tumors were resectable; otherwise, subtotal resection was an alternative. In patients with partial resection and evident atypia/mitotic activity, consultation with an oncologist for radiotherapy was recommended.