Preconditioning with Trehalose Protects the Bone Marrow-Derived Mesenchymal Stem Cells Under Oxidative Stress and Enhances the Stem Cell-Based Therapy for Cerebral Ischemic Stroke.

Bone marrow-derived mesenchymal stem cell (BMSC) transplantation has emerged as a potential treatment for ischemic stroke. Preconditioning with pharmacological agents before cell transplantation has been shown to increase the efficiency of cell therapy. In this study, trehalose (Tre), an autophagy inducer, was used as a pharmacological agent to treat BMSCs, and the neuroprotective effect of BMSCs preconditioned with Tre on cerebral ischemia was assessed. BMSCs were treated in vitro with different concentrations of Tre. Immunofluorescence staining of LC3B was performed to detect autophagy, and Western blotting for LC3, Beclin1, p-AMPK, and p-mTOR was performed. Flow cytometry and Western blotting analysis were performed to measure cell apoptosis in the presence of hydrogen peroxide (H2O2). Enzyme-linked immunosorbent assay was used to test the secretion levels of neurotrophic factors. An in vivo ischemia/reperfusion model was generated by middle cerebral artery occlusion in male Sprague Dawley rats, and Tre-preconditioned BMSCs were administered intralesionally 24 hours after ischemic injury. Histopathological examination and neurological function studies were conducted. In vitro, Tre promotes autophagy of BMSCs through the activation of the AMPK signal pathway. Tre protected BMSCs from H2O2-induced cell viability reduction and apoptosis. Moreover, Tre pretreatment increased the secretion of brain-derived neurotrophic factor, vascular endothelial growth factor, and hepatocyte growth factor. In vivo, preconditioning with Tre could further enhance the survival of BMSCs, reduce infarct size, alleviate cell apoptosis, abate vessel decrease, and ultimately improve functional recovery. Our study indicates that Tre can enhance the survival of BMSCs under oxidative stress and enhance BMSC-based treatment of ischemia/reperfusion injury.

Prediction of the trans-stenotic pressure gradient with arteriography-derived hemodynamic features in patients with idiopathic intracranial hypertension.

The pathogenesis of idiopathic intracranial hypertension (IIH) is attributed to segmental stenosis of the venous sinus. The current treatment paradigm requires a trans-stenotic pressure gradient of ≥8 mmHg or ≥6 mmHg threshold. This study aimed to develop a machine learning screening method to identify patients with IIH using hemodynamic features. A total of 204 venous manometry instances (n = 142, training and validation; n = 62, test) from 135 patients were included. Radiomic features extracted from five arteriography perfusion parameter maps were selected using least absolute shrinkage and selection operator and then entered into support vector machine (SVM) classifiers. The Thr8-23-SVM classifier was created with 23 radiomic features to predict if the pressure gradient was ≥8 mmHg. On an independent test dataset, prediction sensitivity, specificity, accuracy, and AUC were 0.972, 0.846, 0.919, and 0.980, respectively (95% confidence interval: 0.980-1.000). For the 6 mmHg threshold, thr6-28-SVM incorporated 28 features, and its sensitivity, specificity, accuracy, and AUC were 0.923, 0.956, 0.935, and 0.969, respectively (95% confidence interval: 0.927-1.000). The trans-stenotic pressure gradient result was associated with perfusion pattern changes, and SVM classifiers trained with arteriography perfusion map-derived radiomic features could predict the 8 mmHg and 6 mmHg dichotomized trans-stenotic pressure gradients with favorable accuracy.

Non-contrast head CT alone for thrombectomy in acute ischemic stroke: analysis of the ANGEL-ACT registry.

BACKGROUD: The goal of this study was to determine if the choice of imaging paradigm performed in the emergency department influences the procedural or clinical outcomes after mechanical thrombectomy (MT). METHODS: This is a retrospective comparative outcome study which was conducted from the ANGEL-ACT registry. Comparisons were made between baseline characteristics and clinical outcomes of patients with acute ischemic stroke undergoing MT with non-contrast head computed tomography (NCHCT) alone versus patients undergoing NCHCT plus non-invasive vessel imaging (NVI) (including CT angiography (with or without CT perfusion) and magnetic resonance angiography). The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included change in mRS score from baseline to 90 days, the proportions of mRS 0-1, 0-2, and 0-3, and dramatic clinical improvement at 24 hours. The safety outcomes were any intracranial hemorrhage (ICH), symptomatic ICH, and mortality within 90 days. RESULTS: A total of 894 patients met the inclusion criteria; 476 (53%) underwent NCHCT alone and 418 (47%) underwent NCHCT + NVI. In the NCHCT alone group, the door-to-reperfusion time was shorter by 47 min compared with the NCHCT + NVI group (219 vs 266 min, P<0.001). Patients in the NCHCT alone group showed a smaller increase in baseline mRS score at 90 days (median 3 vs 2 points; P=0.004) after adjustment. There were no significant differences between groups in the remaining clinical outcomes. CONCLUSIONS: In patients selected for MT using NCHCT alone versus NCHCT + NVI, there were improved procedural outcomes and smaller increases in baseline mRS scores at 90 days.

McCune-Albright syndrome associated with pituitary adenoma: a clinicopathological study of ten cases and literature review.

BACKGROUND: McCune-Albright syndrome (MAS) is a rare genetic, non-inheritable disease and is characterized by fibrous dysplasia, hyperendocrinism, and café-au-lait macules. Pituitary adenomas could be concurrent with this syndrome but clinicopathological features and the surgical management of such disorders is unclear. METHODS: We retrospectively reviewed ten MAS-associated pituitary adenoma patients with follow-up in Beijing Tiantan Hospital and analyzed their clinicohistological data, surgical strategies, neuro-imaging, genetic mutations, and prognosis. Moreover, a critical review of the English language literature was also conducted. RESULTS: All of the ten MAS-associated adenoma patients underwent surgeries to remove the tumor (nine transsphenoidal approaches and one transcranial approach). None of these patients had a decompression of the optic canal. Notably, the growth hormone (GH), prolactin (PRL), and IGF-1 level had a significant reduction after the resection of the tumor while vision improvement was observed in most patients (6/7) with visual deficits. No tumor recurrence was observed during the follow-up from 16 to 150 months. The pathological examination showed a moderate Ki-67 LI (mean 1.19%, range from 0.1% to 3.3%) and the positive staining of Gsα and PKA C-beta. GNAS gene mutation (R201C) was detected in one patient. CONCLUSIONS: Hormone excess (including GH and PRL) could be significantly reduced and the visual deficits are greatly improved after the surgery without the decompression of the optic canal. In addition, MAS-associated pituitary adenomas have a moderate expression of Ki-67 and positive expression of Gsα and PKA C-beta, indicating a mildly proliferative nature of these tumors and the possible linking between MAS and adenomas.

Intracranial Choroid Plexus Carcinomas: Report of 11 Cases from a Single Institution.

BACKGROUND: Choroid plexus carcinoma is a central nervous system tumor pathologically corresponding to World Health Organization grade III. Choroid plexus carcinoma mainly affects pediatric patients with a poor prognosis. Due to its rarity, standardized treatment has not yet been outlined. METHODS: We retrospectively analyzed 11 patients with histopathologically diagnosed choroid plexus carcinoma between January 2008 and December 2016. They were treated with surgical resection with or without adjuvant therapies. The clinical profiles and outcomes were analyzed. RESULTS: The mean age at diagnosis was 16.0 years (median, 7.0 years; range, 4 months to ∼59 years). Gross total resection was achieved in 9 cases, and subtotal resection in 2 cases. Seven patients received adjuvant radiotherapy, and 2 patients underwent chemotherapy. The mean overall survival was 34.8 months, and the mean progression-free survival was 24.5 months. During the follow-up period, 4 patients succumbed to central nervous system dissemination of choroid plexus carcinoma including 2 patients with malignant transformation from atypical choroid plexus papilloma to choroid plexus carcinoma and 1 patient treated with the combined chemotherapy protocol. CONCLUSIONS: In this study, we described the clinicoradiologic characteristics of choroid plexus carcinomas. Surgical resection is the mainstream treatment. Due to the paucity of clinical evidence, the standard regimen of adjuvant therapies still needs further research.

Retrospective investigation of hereditary syndromes in patients with medulloblastoma in a single institution.

PURPOSE: To investigate the incidence rate of hereditary disease in patients with medulloblastoma. METHODS: The genetic reports of 129 patients with medulloblastoma from January 2016 to December 2019 were retrospectively analyzed. A panel sequence of 39 genes (Genetron Health) were used for all patients to evaluate the tumor subgroup. Four genes (TP53, APC, PTCH1, SUFU) were screened to routinely rule out germline mutation. RESULTS: Five patients (3.9%) were found with hereditary disease, and all belonged to the sonic hedgehog (SHH) subgroup. Two patients were retrospectively diagnosed with Gorlin-Goltz disease with germline PTCH1 and SUFU mutations. One patient (PTCH1 mutation) accepted whole craniospinal irradiation and had scalp nevoid basal cell carcinoma 5 years later. The other patient (SUFU mutation) accepted chemotherapy and had local tumor relapse 1 year later. Three patients were diagnosed with Li-Fraumeni syndrome and carried the TP53 mutation; all three patients died. One of the patients had bone osteosarcoma, while all three had early tumor relapse. CONCLUSION: Patients with SHH medulloblastoma should routinely undergo genetic testing. We propose that whole genome, whole exome sequence, or custom-designed panel-targeted exome sequencing should be performed.

Restoring electrical connection using a conductive biomaterial provides a new therapeutic strategy for rats with spinal cord injury.

Spinal cord injury (SCI) involves damage to the central nervous system, and there is no effective treatment available currently. The injured spinal cord is unable to transmit physiological electrical signals caudal to the location of the injury after a complete transection. In this study, we attempted to use a conductive biomaterial as a novel scaffold to aid SCI repair. A composite biomaterial was fabricated by embedding conductive polypyrrole (PPy) in an electrospun polylactic acid (PLA) nanofibrous scaffold (PLA/PPy scaffold), and an electrospun PLA nanofibrous scaffold without the PPy component was used as a control. The scaffolds were implanted into rats having complete T9 spinal cord resection. Immunofluorescent staining, western blot analysis, and TUNEL assay were used to study histological changes in injured spinal cord tissues. Our data demonstrated that PLA/PPy scaffolds had beneficial effects, as evident from the motor evoked-potentials (MEPs) test and Basso, Beattie, and Bresnahan (BBB) locomotion rating scale. Implantation of the PLA/PPy scaffold significantly alleviated secondary tissue damage by reducing apoptosis and autophagy in neural cells in comparison with the implantation of the control PLA scaffold. Notably, six weeks after injury, the use of PLA/PPy scaffolds significantly reduced the activation of astrocytes and increased axonal regeneration, as indicated by immunofluorescent markers (GFAP and NF200) in the region of injury. Our present study suggests that restoring electrical conductivity using a biological scaffold is beneficial to the microenvironment and favorable for the regeneration and functional recovery of spinal cord tissue in an SCI rat model.

Cerebral Fat Embolism as Complication of Facial Fat Graft: Retrospective Analysis of Clinical Characteristics, Treatment, and Prognosis.

BACKGROUND: Cerebral fat embolism (CFE) is a rare complication that usually occurs after trauma injury. The incidence of CFE due to aesthetic surgery is extremely rare and can lead to fatal outcome. Due to the rarity of this complication, there is still lack of knowledge and standardization of the treatment. CASE DESCRIPTION: Herein, we reported 6 cases of CFE that occurred in patients who underwent cosmetic surgery. Among 5 patients who had large artery occlusion, 3 patients survived and 2 patients died due to progression of the disease. One patient had the ophthalmic artery occlusion. In addition, embolectomy was performed in 5 patients and 3 patients had decompressive craniectomy following endovascular treatment due to severe brain edema. CONCLUSIONS: CFE is associated with high morbidity and mortality, and early surgical intervention can improve the prognosis.

Transcallosal Anterior Interforniceal Approach for Removal of Superior Midbrain Cavernous Malformations in Children: A Retrospective Series of 10 Cases in a Single Center.

BACKGROUND: Surgical treatment of brainstem cavernous malformations (CMs) remains a great challenge for neurosurgeons. Several cases published in the literature have addressed surgical approaches. However, no surgical approach has been reported to provide better exposure for CMs located in the superior midbrain. METHODS: We presented 10 cases of superior midbrain CMs in children treated in Beijing Tiantan Hospital from 2002 to 2016. The most common presenting signs and symptoms were hydrocephalus and cranial nerve deficit. We used the transcallosal anterior interforniceal approach in all patients to remove the CM lesion. RESULTS: Total resection was achieved in all patients. During the follow-up period, temporary short-term memory impairment was present in 5 patients, unilateral ptosis occurred in 1 patient, and upward gaze dysfunction occurred in 2 patients. There was complete neurologic functional improvement for cranial nerves. Exacerbation of hydrocephalus occurred in 4 patients requiring additional ventriculoperitoneal shunt postoperatively. CONCLUSIONS: The transcallosal anterior interforniceal approach can provide good exposure and direct visualization to superior midbrain CMs. Complications are short-term and reversible.

Gunshot penetrating brain injury in children: report of three cases with review of the literature.

INTRODUCTION: Gunshot penetrating brain injury is common in military conflict area and in urban violence area, but similar incident in pediatric population is rarely reported. CASE REPORT: We reported three cases of gunshot penetrating brain injury in children. Two patients had a good recovery after surgery and no significant deficit on his neurologic function, the other patient was not having surgery due to the severity of the condition. CONCLUSIONS: We suggest surgery should be performed immediately to prevent further injury and refractory brain edema due to the injury, in any case of penetrating brain injury; a good prognosis can be achieved from early surgery and with appropriate post-operative treatment.

Retrospective Analysis of the Clinical Characteristics, Therapeutic Aspects, and Prognostic Factors of 18 Cases of Childhood Pineoblastoma.

BACKGROUND: Pineoblastoma is a rare malignant tumor of the pineal gland, which is more common in children. METHODS: We retrospectively reviewed 18 cases of pineoblastoma in children (10 girls), including general, clinical, and therapeutic information, and factors affecting prognosis. RESULTS: The median age of the children was 51.7 months (range, 19-156 months). Presenting symptoms included vomiting (64.70%), headache (47.06%), weak or unsteady walking (35.29%), and nausea (29.41%). Rarer symptoms (1 patient each) included limb rigidity, inability to speak, double vision, fever, and Parinaud syndrome. Five and 13 children, respectively, underwent subtotal and gross total resection; 5 and 13 children received adjuvant craniospinal irradiation therapy and chemotherapy. Two children received both craniospinal irradiation and chemotherapy. The 5-year overall survival of the patients was 27.8% (5/18). The survival rate of children older than 4 years (66.7%) was significantly higher than that of younger children (8.3%). The 5-year overall survival rate of boys (50.7%) was higher than that of girls (10.0%); that of children who underwent gross total resection (30.8%) was higher than that of children who underwent subtotal resection (20.0%); and that of children treated with adjuvant craniospinal irradiation (50.7%) was higher than that of those not given craniospinal irradiation (10.0%). However, in each of these 3 comparisons the differences were not significant. CONCLUSION: Pineoblastoma is rare but often fatal, especially in children younger than 4 years. Survival rates tend to be higher in boys, children undergoing gross total resection (rather than subtotal), and those given craniospinal irradiation.

Primary Spinal Cord Melanoma: A Case Report and a Systemic Review of Overall Survival.

BACKGROUND: The incidence of primary spinal cord melanoma (PSCM) is rare. Several case series and case reports have been published in the literature. However, the predictive factors of PSCM survival and management options are not discussed in detail. METHODS: We present a case of PSCM; total resection was achieved and chemotherapy was given postoperatively. A comprehensive search was performed on PubMed's electronic database using the words "primary spinal cord melanoma." Survival rates with various gender, location, treatment, and metastasis condition were collected from the published articles and analyzed. RESULTS: Fifty nine cases were eligible for the survival analysis; 54% were male and 46% were female. Patient sex did not influence overall survival. The most common location was the thorax. Patient sex and tumor location did not influence overall survival. The major presenting symptoms were weakness and paresthesia of the extremities. Metastasis or dissemination was noted in 45.16% of 31 patients. In the Kaplan-Meier survival analysis, patients who had metastasis had the worst prognosis. Extent of resection was not related to mortality. Patients who received surgery and surgery with adjuvant therapy had a better median survival than did those who had adjuvant therapy alone. Prognosis was worst in those patients who underwent only adjuvant therapy without surgery (5 months). CONCLUSIONS: Surgery is the first treatment of choice in treating PSCM. The goal of tumor resection is to reduce symptoms. Adjuvant therapy after surgery had a beneficial effect on limiting the metastasis.

Lhermitte-Duclos Disease (Dysplastic Gangliocytoma of the Cerebellum) and Cowden Syndrome: Clinical Experience From a Single Institution with Long-Term Follow-Up.

BACKGROUND: Adult-onset Lhermitte-Duclos disease (LDD) and Cowden syndrome (CS) are considered a single phakomatosis that belongs to PTEN hamartoma tumor syndrome (PHTS) now. There is still controversy regarding the diagnosis and treatment. The authors describe the clinical features of LDD and CS with long-term follow up. METHODS: From January 2001 to January 2017, 18 patients were admitted to the neurosurgery department of Beijing Tiantan Hospital. The authors analyzed the medical records of each patient and followed every case. RESULTS: Seventeen of 18 patients underwent surgery to remove the tumor. The results of pathologic analysis revealed LDD. There was obvious enhancement on magnetic resonance imaging (MRI) in 2 patients who received gamma knife and radiotherapy before surgery. During surgery, it is difficult to determine the exact margin. Tumors were removed gross totally in 9 patients, partially in 6 patients, and only subtotally in 2 patients. CS was diagnosed in 11 patients. Two patients received DNA analysis, revealing heterozygous mutation of exon 5 in an 11-year-old girl. There was no recurrence of the tumor during follow-up. CONCLUSIONS: LDD has the unique appearance on T2-weighted MRI. The most difficult aspect of surgery is determining the actual margins of the tumor. Total resection is difficult in some patients. There was no tumor recurrence after long-term follow-up in our case series. For pediatric LDD patients, DNA analysis should be performed to rule out CS.

Impact of tumor location and fourth ventricle infiltration in medulloblastoma.

BACKGROUND: Medulloblastoma is the most common intracranial malignancy in children; with comprehensive treatment the 5-year overall survival (OS) is now greater than 80 %. Only few studies have addressed the relation of tumor location with patient's prognosis. Based on experiences in our institution, we further classified the tumor location. This study aimed to investigate the impact of tumor location and fourth ventricle infiltration in medulloblastoma (MB) prognosis. METHODS: We retrospectively followed all MB patients at the Beijing Tiantan Hospital between 2004 and 2007 to investigate treatment outcomes and prognostic factors in MB patients. The data of 119 patients were collected. Tumor removal was performed in all patients, and all patients received postsurgical radiotherapy or chemotherapy. The patients were subclassified into three subtypes according to tumor location and tumor infiltration into the fourth ventricular floor (V4 floor). The prognostic factors were analyzed using Kaplan-Meier and Cox regression analysis. RESULTS: The median follow-up period was 75 months (range, 6-127 months). A total of 65 patients experienced recurrence or progression, and 56 patients were still alive at the time of follow-up. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 47.1 ± 4.6 % and 54.6 ± 4.6 %, respectively. CONCLUSIONS: According to the multivariate analysis, large cell and anaplastic (LC/A) subtype, patient age, and metastasis were found to be independent prognostic factors. Tumors with V4 floor infiltration exhibited a trend toward recurrence (P = 0.054). This investigation is the largest single-institution study of MB cases in China. The LC/A subtype, patient age, and metastasis were important prognostic factors. V4 floor infiltration was correlated with metastasis and younger age.