Synchronous identification of a dysembryoplastic neuroepithelial tumor (DNET) and an oligodendroglioma in a patient: A case report.

Synchronous gliomas of different histopathology are quite rare in non-syndromic, non-irradiated patients. Although "mixed" gliomas are not infrequent, and malignant gliomas often contain areas of disparate differentiation (e.g., glioblastoma with ependymal differentiation), it is unusual to find gliomas of different lineage presenting concurrently. We present a case of synchronous gliomas, one dysembryoplastic neuroepithelial tumor (DNET) and the other oligodendroglioma.

Astrocytes promote progression of breast cancer metastases to the brain via a KISS1-mediated autophagy.

Formation of metastases, also known as cancer dissemination, is an important stage of breast cancer (BrCa) development. KISS1 expression is associated with inhibition of metastases development. Recently we have demonstrated that BrCa metastases to the brain exhibit low levels of KISS1 expression at both mRNA and protein levels. By using multicolor immunofluorescence and coculture techniques here we show that normal adult astrocytes in the brain are capable of promoting metastatic transformation of circulating breast cancer cells localized to the brain through secretion of chemokine CXCL12. The latter was found in this study to downregulate KISS1 expression at the post-transcriptional level via induction of microRNA-345 (MIR345). Furthermore, we demonstrated that ectopic expression of KISS1 downregulates ATG5 and ATG7, 2 key modulators of autophagy, and works concurrently with autophagy inhibitors, thereby implicating autophagy in the mechanism of KISS1-mediated BrCa metastatic transformation. We also found that expression of KISS1 in human breast tumor specimens inversely correlates with that of MMP9 and IL8, implicated in the mechanism of metastatic invasion, thereby supporting the role of KISS1 as a potential regulator of BrCa metastatic invasion in the brain. This conclusion is further supported by the ability of KISS1, ectopically overexpressed from an adenoviral vector in MDA-MB-231Br cells with silenced expression of the endogenous gene, to revert invasive phenotype of those cells. Taken together, our results strongly suggest that human adult astrocytes can promote brain invasion of the brain-localized circulating breast cancer cells by upregulating autophagy signaling pathways via the CXCL12-MIR345- KISS1 axis.

Recurrent Supplementary Motor Area Syndrome Following Repeat Brain Tumor Resection Involving Supplementary Motor Cortex.

BACKGROUND: Supplementary motor area (SMA) syndrome occurs after surgery involving the SMA and is characterized by contralateral hemiparesis with or without speech impairment (dependent on involvement of the dominant SMA), which is transient and characteristically resolves over the course of weeks to months. Recurrent SMA syndrome after repeat craniotomy has not been previously described. OBJECTIVE: To describe the presentation and clinical course of patients who developed recurrent SMA syndrome after redo resection of tumors involving the SMA. METHODS: We performed a retrospective review of 15 patients who underwent repeated resection of low-grade glioma from the superior and middle frontal gyrus. Of these patients, we identified 6 cases of recurrent SMA syndrome. RESULTS: Six patients had a documented SMA syndrome occurring after initial and subsequent resection of tumor in proximity to the SMA. Intraoperative localization of eloquent motor and language cortex was achieved in each patient by using a combination of somatosensory evoked potentials and electrocortical stimulation mapping. Location of tumor and extent of resection was examined with magnetic resonance imaging. CONCLUSION: This series demonstrates that recurrent SMA syndrome occurs in patients undergoing repeat resection of tumors involving the SMA. The presence of recurrent SMA syndrome provides support for reorganization of SMA function to adjacent ipsilateral cortex after resection. Patients with recurrent neoplasms of the SMA should be counseled on the possibility of recurrent SMA syndrome.

Hypertriglyceridemia, lipemia, and elevated liver enzymes associated with prolonged propofol anesthesia for craniotomy.

: Lipemic blood was noted in the surgical field by a neurosurgeon after 12.5 hours of anesthesia consisting of infusions of propofol (total dose, 14,956 mcg) and remifentanil (total dose, 25,091 mcg). For most of that time, the rate of propofol was 120-160 mcg·kg-1·min-1 and never exceeded 160 mcg·kg-1·min-1. Lipemia was confirmed by allowing a sample of the patient's blood to settle in a syringe. The triglyceride concentration was 15.8 mmol/L. There was no metabolic acidosis or other indications of propofol infusion syndrome. Postoperatively, liver enzymes were elevated (peak aspartate aminotransferase, 420 units/L) but returned to nearly normal within 5 days. The patient recovered from surgery uneventfully. Reports of intraoperative lipemia during propofol anesthesia are very rare but raise concerns about the safety of prolonged propofol infusion.

Treatment of brain metastases.

Brain metastases are associated with substantial morbidity and mortality. Key prognostic classification systems for brain metastases are reviewed. The role of surgery, particularly for single brain metastases, is discussed. This is followed by an overview of radiation, both whole brain and focal, in the treatment of brain metastases. Finally, we review examples of important concepts regarding the role of systemic therapy in the treatment of brain metastases.

Radiosensitization of malignant gliomas following intracranial delivery of paclitaxel biodegradable polymer microspheres.

OBJECT: The aim of this study was to demonstrate that paclitaxel could function as a radiosensitizer for malignant glioma in vitro and in vivo. METHODS: The radiosensitizing effect of paclitaxel was tested in vitro using the human U373MG and rat 9L glioma cell lines. Cell cycle arrest in response to paclitaxel exposure was quantified by flow cytometry. Cells were subsequently irradiated, and toxicity was measured using the clonogenic assay. In vivo studies were performed in Fischer 344 rats implanted with intracranial 9L gliosarcoma. Rats were treated with control polymer implants, paclitaxel controlled-release polymers, radiotherapy, or a combination of the 2 treatments. The study end point was survival. RESULTS: Flow cytometry demonstrated G2-M arrest in both U373MG and 9L cells following 6-12 hours of paclitaxel exposure. The order in which the combination treatment was administered was significant. Exposure to radiation treatment (XRT) during the 6-12 hours after paclitaxel treatment resulted in a synergistic reduction in colony formation. This effect was greater than the effect from either treatment alone and was also greater than the effect of radiation exposure followed by paclitaxel. Rats bearing 9L gliosarcoma tumors treated with paclitaxel polymer administration followed by single-fraction radiotherapy demonstrated a synergistic improvement in survival compared with any other treatment, including radiotherapy followed by paclitaxel treatment. Median survival for control animals was 13 days; for those treated with paclitaxel alone, 21 days; for those treated with XRT alone, 21 days; for those treated with XRT followed by paclitaxel, 45 days; and for those treated with paclitaxel followed by XRT, more than 150 days (p < 0.0001). CONCLUSIONS: These results indicate that paclitaxel is an effective radiosensitizer for malignant gliomas because it renders glioma cells more sensitive to ionizing radiation by causing G2-M arrest, and induces a synergistic response to chemoradiotherapy.

Advanced neuroimaging studies in a patient with brain metastases from transitional cell carcinoma of the bladder.

BACKGROUND AND PURPOSE: The differential diagnosis in single or oligo-brain lesions in metastatic cancer patients remains broad. Advanced imaging studies can be employed to help refine the differential and potentially guide treatment. METHODS: Case report of a 52-year-old male patient with known transitional cell carcinoma of the bladder presented with headaches, cognitive symptoms, and episodic presyncope. Brain magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and octreotide scans were performed to evaluate the underlying etiology of his symptoms. RESULTS: MRI revealed two enhancing mass lesions in left temporal and left cerebellar locations. Both lesions were octreotide avid and MRS of the temporal lesion showed a single large lipid peak at 1.3 ppm, a small NAA peak, and a markedly increased choline:creatine ratio that was relatively characteristic for metastases. Pathology from surgical resection revealed transitional cell carcinoma of the bladder. CONCLUSIONS: Resection of both lesions revealed metastatic transitional cell carcinoma. This is the first report of octreotide scan characteristics in a patient with transitional cell carcinoma with central nervous system (CNS) metastases. The octreotide avidity of these transitional cell CNS metastases suggests the presence of somatostatin receptors that may be considered as a potential therapeutic target.

Chemokines in tumor progression and metastasis.

Chemokines play a vital role in tumor progression and metastasis. Chemokines are involved in the growth of many cancers including breast cancer, ovarian cancer, pancreatic cancer, melanoma, lung cancer, gastric cancer, acute lymphoblastic leukemia, colon cancer, non-small lung cancer, non-hodgkin's lymphoma, etc. The expression of chemokines and their receptors is altered in many malignancies and leads to aberrant chemokine receptor signaling. This review focuses on the role of chemokines in key processes that facilitate tumor progression including proliferation, senescence, angiogenesis, epithelial mesenchymal transition, immune evasion and metastasis.

Gliadel for brain metastasis.

With therapies for systemic malignancy improving, life expectancy for cancer patients is becoming increasingly dependent on control of brain metastatic disease. Despite improvements in surgical and radiotherapy modalities for control of brain metastasis, the prognosis for patients with brain metastases is poor. The development of controlled release polymers has lead to novel new therapies for malignant brain tumors consisting of direct surgical delivery of chemotherapy agents to the tumor bed and sustained chemotherapy release over a prolonged period of time. Although there is a large body of literature in support of BCNU polymer wafer for primary brain malignancy and experimental brain metastases, clinical studies evaluating the BCNU polymer wafer for brain metastatic disease are relatively sparse. In this review, we discuss the role of the BCNU polymer wafer for brain metastasis focusing specifically on rationale for use of locally delivered sustained release polymers, history of the BCNU polymer wafer, and emerging studies examining the role of the BCNU polymer wafer for metastatic brain tumors.

MicroRNAs in brain metastases: big things come in small packages.

Metastatic brain tumors provide a formidable obstacle in the survival of affected cancer patients, an obstacle that current treatment is essentially ineffective against. Our understanding of the metastatic cascade has demonstrated the role of incorrectly regulated protein expression and proved it to be a crucial component of this process. Recently, molecular studies have emphasized the role of microRNAs, small non-coding RNAs that alter protein expression, in the regulation of both normal and abnormal biological processes, including cancer and its metastasis to the brain. Furthermore, studies have demonstrated the ability to distinguish normal from cancerous cells, primary from secondary brain tumors, and correctly categorize metastatic brain tumor tissue of origin based solely on microRNA profiles. Interestingly, manipulation of microRNAs has proven effective in cancer treatment. With the promise of reduced toxicity, increased efficacy, and individually directed therapy, using microRNA in the treatment of metastatic brain tumors may prove very useful. In this review, we focus on the multiple potential microRNA targets for the treatment of metastatic brain lesions as well as current and future directions for its use in gene therapy.

Propionibacterium acnes osteomyelitis occurring 23 years after craniotomy: case report and review of literature.

BACKGROUND AND IMPORTANCE: Propionibacterium acnes is an uncommon pathogen in delayed surgical site infection, and its indolent course can complicate diagnosis and treatment. We report the longest delay between neurosurgery and P acnes infection reported. CLINICAL PRESENTATION: Asymptomatic postoperative P acnes osteomyelitis and tumor recurrence occurring 23 years after initial craniotomy. Initial presentation was of tumor recurrence only, without signs or symptoms of infection. Calvarial osteomyelitis was unexpectedly discovered intraoperatively. Craniectomy and débridement were performed, and there was prolonged antibiotic therapy. CONCLUSION: The longest delay between neurosurgery and asymptomatic P acnes infection is reported. We review the literature for P acnes infection and discuss biofilm formation and its role in delayed surgical infection.

Endoscopic repair of a rare basioccipital meningocele associated with recurrent meningitis.

Anatomical variants of the basiocciput are uncommon and usually clinically benign. While the majority remain undetected, these anomalies rarely manifest as CSF rhinorrhea or recurrent meningitis associated with meningocele. Compromise of the leptomeninges provides an avenue of ingress for pathological organisms and can lead to recurrent meningitis, necessitating operative repair of the defect to prevent infection. A review of the literature reveals only 3 cases in which a congenital basioccipital defect has been associated with a meningocele requiring surgical repair. The authors present a case of recurrent meningitis in an infant with a congenital basioccipital meningocele treated with a minimally invasive endoscopic technique. At the 2-year follow-up the repair remained successful, with no evidence of recurrence of the meningocele or CSF infection. The literature regarding the etiology and treatment of these lesions was reviewed, with an emphasis on the safety and efficacy of the endoscopic approach. Note that recurrent meningitis in the setting of a skull base defect may indicate the presence of other congenital anomalies that will necessitate multidisciplinary care for a patient's long-term well-being.

Resolution of acute hydrocephalus and migration of neurocysticercosis cyst with external ventricular drainage.

Neurocysticercosis is endemic in the developing world, but is becoming more common in the US due to immigration. A 24-year-old man presented with acute hydrocephalus and headaches, nausea, and vomiting. Head CT revealed a 3rd ventricular cyst and immunological studies were suggestive of neurocysticercosis. EVD placement resulted in migration of the cyst interiorly and superiorly with return of normal CSF flow by MRI and resolution of symptoms. Review of this condition is important given increasing incidence in the United States.

Treatment of intermittent obstructive hydrocephalus secondary to a choroid plexus cyst.

The authors present the case of an 11-week-old girl in whom hydrocephalus developed secondary to intermittent obstruction of the third ventricle by a choroid plexus cyst. The patient presented to the emergency department at the authors' institution with a 1-day history of projectile vomiting, lethargy, and dysconjugate gaze. Hydrocephalus was confirmed on head CT. During hospitalization, the symptoms resolved with a decrease in ventricular size. One week later, the patient again presented with similar symptoms, and MR images with 3D-constructive interference in steady state sequences revealed that a cyst was blocking the third ventricle. The patient subsequently underwent endoscopic fenestration of the cyst with resolution of hydrocephalus and symptoms. The authors present a unique description of the diagnosis of intermittent obstructive hydrocephalus caused by a third ventricular region choroid plexus cyst in an infant.

Paradoxical emboli secondary to hepatic pathology: common or coincidental?

Paradoxical cerebral emboli from cardiac and pulmonary sources are well described in the peer-reviewed literature. We outline a case with a hepatic etiology and describe diagnostic and management options. Though this paper represents the first documentation of such, we believe that transpulmonary shunting with concurrent paradoxical cerebral microemboli is more prevalent than recognized. We introduce this case report to compel practitioners to consider paradoxical emboli in selected cirrhotic patients since it can often be difficult to elicit subtle neurologic changes on clinical examination of patients with end stage liver disease.

Spontaneous subdural fluid collections following transection of a fatty filum terminale: case report and review of the literature.

We present the case of a 6-year-old girl who developed bilateral subdural fluid collections following transection of her fatty filum terminale. The patient presented to our emergency department 3 weeks subsequent to surgery, reporting symptoms of headache, nausea, and vomiting. The presence of bilateral subdural fluid collections was confirmed by head computerized tomography. Subdural fluid collections and hematomas have been associated with intracranial hypotension and excessive cerebrospinal fluid leakage; however, there are relatively few cases of subdural fluid collections/hematomas following spine surgery reported in the literature. To our knowledge, this is a unique description of development and resolution of subdural fluid collections following surgical transection of a fatty filum terminale.