Spontaneous cerebrospinal fluid rhinorrhea associated with an incidental pituitary adenoma.

Spontaneous cerebrospinal fluid (CSF) rhinorrhea presenting as the sole symptom of untreated pituitary adenoma is rare, with only 15 cases having been reported in the English literature. All these untreated pituitary adenoma contributing to spontaneous CSF rhinorrhea were diagnosed by the preoperative neuroimaging. Herein, we described an extraordinary rare patient with a pituitary microadenoma, presenting with spontaneous CSF rhinorrhea as the sole symptom. However, this pituitary microadenoma was only found incidentally at surgery, not preoperatively. To the best knowledge of us, this is the first reported case of spontaneous CSF rhinorrhea associated with an untreated pituitary adenoma diagnosed at surgery.

SOX9-activated PXN-AS1 promotes the tumorigenesis of glioblastoma by EZH2-mediated methylation of DKK1.

Increasing evidence has validated the essential regulation of long non-coding RNAs (lncRNAs) in the biological process of tumours. LncRNA PXN-AS1 has been discovered to be as a tumour suppressor in pancreatic cancer; however, its function and mechanism remain greatly unknown in glioblastoma (GBM). Our present study indicated that PXN-AS1 was highly expressed in GBM tissues and cells. Besides, the knock-down of PXN-AS1 was closely associated with the inhibitory proliferation and inducing apoptosis of GBM cells. PXN-AS1 inhibition was also found to restrain GBM tumour growth. Importantly, SOX9 functioned as a transcription factor and activated PXN-AS1 expression, and overexpressed PXN-AS1 rescued the inhibitory role of down-regulated SOX9 in GBM cell growth. Subsequently, it was discovered that PXN-AS1 activated Wnt/ß-catenin pathway. DKK1 was widely known as an inhibitor gene of Wnt/ß-catenin pathway, and its expression was negatively associated with PXN-AS1 and SOX9. Interestingly, we found that PXN-AS1 could recruit EZH2 to mediate the H3K27me3 level of DKK1 promoter. Restoration experiments manifested that DKK1 knock-down counteracted PXN-AS1 depletion-mediated repression in GBM cell growth. All facts pointed out that PXN-AS1 might be of importance in exploring the therapeutic strategies of GBM.

Bilateral remote cerebellar hemorrhage following surgical clipping a ruptured supratentorial aneurysm.

Remote cerebellar hemorrhage (RCH) is a rare and severe complication after supratentorial surgery, with various risk factors and mechanisms remaining uncertain. Herein, we report a 64-year-old female patient suffered bilateral RCH following surgical clipping a ruptured aneurysm of internal carotid artery bifurcation. RCH is considered as venous in origin, and is likely the result of intra-operative or post-operative loss of CSF. Thus, appropriate control and close monitor the intra-operative and post-operative loss of CSF is of great importance for preventing the occurrence of RCH.

Remote Intracranial Hemorrhage Secondary to Brain Tumor Surgery.

Postoperative remote intracranial hemorrhage (rICH) secondary to craniotomy surgery is an extremely rare but catastrophic complication. The present study aimed to investigate the incidence and the possible pathophysiological mechanism of rICH after brain tumor surgery. The clinical data from 9 rICH cases among 4588 patients undergoing brain tumor surgery were collected retrospectively. Remote intracranial hemorrhage occurred in 9 cases, including 6 cases of remote epidural hemorrhage (rEDH), 2 cases of remote subdural hemorrhage (rSDH), and 1 case of remote cerebellar hemorrhage (rCBH). Among the 9 cases, 2 were males and 7 were females, with an age range of 22 to 63 years (mean of 44.3 years). The incidence of rICH in the patients with ventricular system opening/drainage (4/258) was much higher than the patients without ventricular system opening/drainage (5/4330), and the difference was statistically significant (P < 0.01). Hematoma evacuation was performed in 7 patients with serious neurological status or massive hematoma. The outcome for most of the rICH cases was good, and the Glasgow outcome scale scores of 4-5 were found in 8 cases with a 3-month-long follow-up. Our results suggest that brain tumor surgery with ventricular system opening/drainage was more susceptible to rICH. Paying particlular attention to gradual reduction of intracranial pressure and avoiding excessive loss of cerebrospinal fluid may aid to prevent the occurrence of rICH. The authors suggest that a high index of suspicion, a prompt diagnosis, and emergent management is of vital importance to achieve good prognosis for rICH patients secondary to brain tumor surgery.

Delayed Dural Arteriovenous Fistula at the Transverse-Sigmoid Sinus Secondary to Petroclival Meningioma Surgery Via Far Lateral Approach.

Intracranial dural arteriovenous fistulas (DAVFs) are typified by pathological anastomoses between meningeal arteries and dural venous sinuses or cortical veins. There are many causes contributing to the etiology of DAVFs. Among the variable causes, acquired DAVFs secondary to craniotomy had rarely been reported, especially for delayed DAVFs at the transverse-sigmoid sinus. Till now, there are only 12 published cases of delayed DAVFs at the transverse-sigmoid sinus secondary to craniotomy. Herein, the authors describe such an extraordinary rare case secondary to petroclival meningioma resection via far lateral approach, and to the best knowledge of us, this is the first well-documented case of delayed DAVF at the transverse-sigmoid sinus following far lateral craniotomy. Furthermore, cases of delayed DAVFs at the transverse-sigmoid sinus secondary to craniotomy were reviewed and investigated, and the clinical characteristics and treatment were also broadly discussed.

Identification of a multidimensional transcriptome signature for survival prediction of postoperative glioblastoma multiforme patients.

BACKGROUND: Glioblastoma multiform (GBM) is a devastating brain tumor with maximum surgical resection, radiotherapy plus concomitant and adjuvant temozolomide (TMZ) as the standard treatment. Diverse clinicopathological and molecular features are major obstacles to accurate predict survival and evaluate the efficacy of chemotherapy or radiotherapy. Reliable prognostic biomarkers are urgently needed for postoperative GBM patients. METHODS: The protein coding genes (PCGs) and long non-coding RNA (lncRNA) gene expression profiles of 233 GBM postoperative patients were obtained from The Cancer Genome Atlas (TCGA), TANRIC and Gene Expression Omnibus (GEO) database. We randomly divided the TCGA set into a training (n = 76) and a test set (n = 77) and used GSE7696 (n = 80) as an independent validation set. Survival analysis and the random survival forest algorithm were performed to screen survival associated signature. RESULTS: Six PCGs (EIF2AK3, EPRS, GALE, GUCY2C, MTHFD2, RNF212) and five lncRNAs (CTD-2140B24.6, LINC02015, AC068888.1, CERNA1, LINC00618) were screened out by a risk score model and formed a PCG-lncRNA signature for its predictive power was strongest (AUC = 0.78 in the training dataset). The PCG-lncRNA signature could divide patients into high- risk or low-risk group with significantly different survival (median 7.47 vs. 18.27 months, log-rank test P < 0.001) in the training dataset. Similar result was observed in the test dataset (median 11.40 vs. 16.80 months, log-rank test P = 0.001) and the independent set (median 8.93 vs. 16.22 months, log-rank test P = 0.007). Multivariable Cox regression analysis verified that it was an independent prognostic factor for the postsurgical patients with GBM. Compared with IDH mutation status, O-(6)-methylguanine DNA methyltransferase promoter methylation status and age, the signature was proved to have a superior predictive power. And stratified analysis found that the signature could further separated postoperative GBM patients who received TMZ-chemoradiation into high- and low-risk groups in TCGA and GEO dataset. CONCLUSIONS: The PCG-lncRNA signature was a novel prognostic marker to predict survival and TMZ-chemoradiation response in GBM patients after surgery.

Bundling potent natural toxin cantharidin within platinum (IV) prodrugs for liposome drug delivery and effective malignant neuroblastoma treatment.

Neuroblastoma (NB) is one of the most commonly seen malignancies in childhood and infancy. Cantharidin is a highly potent natural toxin that possesses potent anti-tumor properties on various cancers including NB. However, exposure to cantharidin can cause severe chemical burns and application of cantharidin for cancer therapy is limited. Here we report a strategy of bundling cantharidin within a hybrid platinum (IV) prodrug conjugate. This hydrophobic drug conjugate, ie, CanPt can be further formulated into liposome for drug delivery to minimize the exposure of cantharidin to normal cells for efficient chemotherapeutic agent against NB.

Posttraumatic Intradiploic Pseudomeningocele of the Occipito-Cervical Region.

Pseudomeningocele is a collection of the cerebrospinal fluid in the extradural space due to a defect in the dura-arachnoid layer of the meninge, and manifests as a fibrous capsule in the space of subcutaneous tissues. Classically, growing skull fracture caused by the pseudomeningocele is not uncommon in the pediatric age group. However, a posttraumatic intradiploic pseudomeningoceles is extremely rare, and only a few patients have been described. Herein, the authors present a 6-year-old girl who developed an intradiploic pseudomeningocele of the occipito-cervical region after a severe head trauma.

Feasibility of three-dimensional ultrashort echo time magnetic resonance imaging at 1.5 T for the diagnosis of skull fractures.

OBJECTIVES: To investigate the feasibility of ultrashort echo time (UTE) magnetic resonance imaging (MRI) for the diagnosis of skull fractures. METHODS: The skull fracture models of ten Bama pigs and 364 patients with craniocerebral trauma were subjected to computed tomography (CT), UTE and conventional MRI sequences. The accuracy of UTE imaging in skull fracture diagnosis was analysed using receiver operating characteristic (ROC) curve analysis, McNemar's test and Kappa values. Differences among CT, UTE imaging and anatomical measurement (AM) values for linear fractures (LFs) and depressed fractures (DFs) were compared using one-way ANOVA and a paired-samples t-test. RESULTS: UTE imaging clearly demonstrated skull structures and fractures. The accuracy, validity and reliability of UTE MRI were excellent, with no significant differences between expert readings (P > 0.05; Kappa, 0.899). The values obtained for 42 LFs and 13 DFs in the ten specimens were not significantly different among CT, UTE MRI and AMs, while those obtained for 55 LFs and ten DFs in 44 patients were not significantly different between CT and UTE MRI (P > 0.05). CONCLUSIONS: UTE MRI sequences are feasible for the evaluation of skull structures and fractures, with no radiation exposure, particularly for paediatric and pregnant patients. KEY POINTS: Despite ionising radiation, CT is standard for skull fracture assessment. Conventional MRI cannot depict skull structures. 3D-UTE sequences clearly demonstrate skull structures and fractures. UTE plus conventional MRI are superior to CT in craniocerebral trauma assessment. Paediatric and pregnant patients will benefit from this imaging modality.

Primary Spinal Oligoastrocytoma.

Astrocytomas are the most common intramedullary spinal cord tumors in pediatric and adolescent patients and the incidence decreases with age. Spinal oligoastrocytoma, which is a mixed glioma with distinct astrocytic and oligodendroglial components, is an extremely rare pathology of the spinal cord. To authors' best of knowledge, there are only 7 spinal oligoastrocytomas reported in the English literature. Here, the authors report a patient of a pathologically confirmed spinal oligoastrocytoma, who presented with severe left leg pain and numbness. This patient reminds us of the rarity of spinal oligoastrocytoma, and the treatment and prognosis were also investigated and reviewed.

The Coexistence of Rathke Cleft Cyst and Pituitary Adenoma.

Both of Pituitary adenoma (PA) and Rathke cleft cyst (RCC) are the most common and benign sellar lesions. Generally, the origin of RCC is considered to be derived from remnants of Rathke punch, while PA is formed by proliferation of the anterior wall of Rathke pouch. Although they have a possibility to share a common embryological origin, the coexistence of PA and RCC is extremely rare. Here, the authors report a 50-year-old male patient who was found to have a large cystic sellar lesion, and surgical resection revealed components of a RCC coexisting with a PA. This collision reminded us of the possibility of RCC coexisting with PA. Furthermore, a clinicopathologic relation of them were reviewed and investigated.

MiR-26a enhances the radiosensitivity of glioblastoma multiforme cells through targeting of ataxia-telangiectasia mutated.

Glioblastoma multiforme (GBM) is notoriously resistant to radiation, and consequently, new radiosensitizers are urgently needed. MicroRNAs are a class of endogenous gene modulators with emerging roles in DNA repair. We found that overexpression of miR-26a can enhance radiosensitivity and reduce the DNA repair ability of U87 cells. However, knockdown miR-26a in U87 cells could act the converse manner. Mechanistically, this effect is mediated by direct targeting of miR-26a to the 3'UTR of ATM, which leads to reduced ATM levels and consequent inhibition of the homologous recombination repair pathway. These results suggest that miR-26a may act as a new radiosensitizer of GBM.

Intracranial hemorrhage due to rupture of an anterior communicating artery aneurysm in a patient with pituitary adenoma.

The coexistence of pituitary adenoma (PA) and anterior communicating artery aneurysm is extremely rare, making the diagnosis difficult and the treatment challenging. Herein, we present a PA patient with intracranial hemorrhage due to rupture of an anterior communicating artery aneurysm. For the best diagnosis of intracranial aneurysm among PA patients, cranial magnetic resonance together with three-dimensional time-of-flight magnetic resonance angiography are strongly recommended. Previous treatment of the intracranial aneurysm is advisable and essential to avoid possible catastrophic bleeding during the transsphenoidal or microsurgical removal of PA.

Nonaneurysmal subarachnoid hemorrhage secondary to transsphenoidal surgery for pituitary adenomas.

Nonaneurysmal subarachnoid hemorrhage (SAH) is a rare and severe complication of transsphenoidal surgery for pituitary adenoma(PA). To improve recognition of this complication, we reviewed and examined 4 patients with nonaneurysmal SAH secondary to transsphenoidal surgery for PAs. Furthermore, possible causes contributed to the SAH, and the attention on preventing the occurrence of SAH is reviewed and stressed.

Chondromyxoid fibroma of the frontal bone mimicking meningioma.

Chondromyxoid fibroma (CMF) is a rare benign cartilaginous tumor that usually arises from lower-extremity long-bone metaphyses, with approximately 5.4% of all CMFs presenting in the craniofacial bones. Chondromyxoid fibroma of the frontal bone is exceedingly rare, with only a few cases reported. Herein, we report another case of CMF arising from the frontal bone mimicking meningioma. We suggest that histopathologic examination is of vital importance for the diagnosis of CMF; complete surgical resection is the best treatment option for frontal CMF.

Middle cerebral artery dolichoectasia with radiologic follow-up.

Intracranial dolichoectasia is an angiopathy characterized by dilation, elongation, and tortuosity of the cerebral arteries. It most frequently involves the vertebrobasilar arteries and carotid arteries, whereas a more peripheral location involving the anterior and the middle cerebral arteries (MCAs) is less frequent. We present a male patient with MCA dolichoectasia with radiologic follow-up for 3 years, and no ischemia or intracranial bleeding occurred after the antiplatelet therapy. From the reported case series of MCA dolichoectasia, we suggest that surgical procedure should not be adopted unless accompanied by aneurysm located at dolichoectatic MCA. Moreover, anticoagulation or antiplatelet therapy could be a good treatment of option to prevent ischemic events.

Endoscopic transsphenoidal treatment of a prolactinoma patient with brain and optic chiasmal herniations.

Bromocriptine has been the most widely used and effective agent to treat macroprolactinoma, and chiasmal herniation in a macroprolactinoma patient following the treatment with bromocriptine is a well-recognized complication. However, herniation of the inferior mesial frontal lobe into the sella has been rarely reported. The present clinical report is the second radiographic demonstration of herniation of the inferior mesial frontal lobe into the sella. After the treatment with transsphenoidal endoscopic chiasmopexy, the patient's visual disturbance improved dramatically. We suggest that transsphenoidal endoscopic chiasmopexy is an effective treatment option for the prolactinoma patient with brain and chiasmal herniations following the treatment with bromocriptine.

Management of hemorrhagic dissecting vertebral artery aneurysms involving posterior inferior artery.

We reported 2 cases with hemorrhagic dissecting vertebral artery (VA) aneurysms involving posterior inferior cerebellar artery (PICA), and one was treated with aneurysm trapping and PICA-VA anastomosis, whereas another was treated with coil embolization and VA-to-PICA stent placement. We suggest both bypass surgery and VA-to-PICA stent placement are good options for PICA revascularization.

Cavernous internal carotid artery aneurysm after radiotherapy presenting with external ophthalmoplegia.

Cranial radiotherapy could cause several types of vasculopathies, which include atherosclerotic occlusive diseases, moyamoya disease, and aneurysm formation. To our knowledge, radiation-induced aneurysms of the internal carotid artery (ICA) are extremely rare. Here, we report a 68-year-old woman who presented with external ophthalmoplegia caused by radiotherapy after the transsphenoidal surgery for metastastic tumor of the clivus region, and the angiography demonstrated a giant aneurysm of the cavernous ICA. After the ICA ligation, the patient recovered well without brain ischemia with a 6-month-long follow-up. The present case is extremely rare with external opthalmoplegia caused by the giant cavernous ICA aneurysm, and the radiotherapy after transsphenoidal surgery might have been critical in the formation of the aneurysm.

Duret hemorrhage after lumbar drainage.

Lumbar drainage (LD) is considered as a simple and effective procedure for the treatment of intracerebral hemorrhage with ventricular involvement. However, cerebrospinal fluid overdrainage and hypovolemia due to LD could induce severe fatal complications, which include transtentorial herniation and infratentorial hemorrhage. Here, we describe a 63-year-old man with transtentorial herniations and Duret hemorrhage attributable to LD after the operation of thalamic hematoma removal. This is probably the first reported case of severe complications of LD. Thus, complications related to transtentorial herniations and Duret hemorrhage should be kept in mind while performing LD.