Currently, treatment of brain tumors is limited to resection, chemotherapy, and radiotherapy. Thermal ablation has been recently explored. High-intensity focused ultrasound (HIFU) is being explored as an alternative. Specifically, the authors propose delivering HIFU internally to the tumor with an MRI-guided robotic assistant (MRgRA). The advantage of the authors’ interstitial device over external MRI-guided HIFU (MRgHIFU) is that it allows for conformal, precise ablation and concurrent tissue sampling. The authors describe their workflow for MRgRA HIFU delivery.

BackgroundGlioblastoma (GBM) is the most common primary malignant brain tumor in adults. Ubiquitously expressed volume-regulated anion channels (VRAC) are thought to play a role in cell proliferation, migration, and apoptosis. VRAC are heteromeric channel complexes assembled from proteins belonging to the leucine-rich repeat-containing 8A (LRRC8A through E), among which LRRC8A plays an indispensable role. In the present work, we used an RNAi approach to test potential significance of VRAC and LRRC8A in GBM survival and sensitivity to chemotherapeutic agents.MethodsPrimary GBM cells were derived from a human surgical tissue sample. LRRC8A expression was determined with quantitative RT-PCR and downregulated using siRNA. The effects of LRRC8A knockdown on GBM cell viability, proliferation, and sensitivity to chemotherapeutic agents were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and Coulter counter assays. Cell cycle progression was further explored using fluorescence-activated cell sorting analysis of propidium iodide-stained cells.ResultsTemozolomide (TMZ), carmustine, and cisplatin reduced GBM cell survival with the IC50 values of ~1,250, 320, and 30 µM, respectively. Two of three tested gene-specific siRNA constructs, siLRRC8A_3 and siLRRC8A_6, downregulated LRRC8A expression by >80% and significantly reduced GBM cell numbers. The most potent siLRRC8A_3 itself reduced viable cell numbers by ≥50%, and significantly increased toxicity of the sub-IC50 concentrations of TMZ (570 µM) and carmustine (167 µM). In contrast, the effects of siLRRC8A_3 and cisplatin (32 µM) were not additive, most likely because cisplatin uptake is VRAC-dependent. The results obtained in primary GBM cells were qualitatively recapitulated in U251 human GBM cell line.ConclusionDownregulation of LRRC8A expression reduces GBM cell proliferation and increases sensitivity to the clinically used TMZ and carmustine. These findings indicate that VRAC represents a potential target for the treatment of GBM, alone or in combination with the current standard-of-care.

Early neurosurgical procedures dealt mainly with treatment of head trauma, especially skull fractures. Since the early medical writings by Hippocrates, a great deal of respect was given to the dura mater, and many other surgeons warned against violating the dura. It was not until the 19th century that neurosurgeons started venturing beneath the dura, deep into the brain parenchyma. With this advancement, brain retraction became an essential component of intracranial surgery. Over the years brain retractors have been created pragmatically to provide better visualization, increased articulations and degrees of freedom, greater stability, less brain retraction injury, and less user effort. Brain retractors have evolved from simple handheld retractors to intricate brain-retraction systems with hand-rest stabilizers. This paper will focus on the history of brain retractors, the different types of retractors, and the progression from one form to another.

Background: Because of the commonality of diagnostic magnetic resonance imaging (MRI), MRI conditional technology has increased throughout the device industry. It is often difficult to be aware of MRI specifications for each device. Objectives: We provide a review of the clinical experience with MRI and spinal cord stimulation (SCS) devices and develop a general reference of current device/MRI specifications. Methods: We reviewed the available literature on the clinical experience with SCS devices and examined its specifications. Results: We developed a user-friendly table of the specific compatibility of SCS devices in the USA and the European Union, and examined the existing literature on the clinical experience with MRI and SCS devices. We share our experience with obtaining spine MRI with MRI conditional SCS leads. Conclusion: By describing SCS device specifications and reviewing the literature, we provide a guide to implanting and treating physicians on obtaining MRIs in patients who have SCS devices.

Object Many neurosurgeons obtain repeat head CT at the first clinic follow-up visit for nonoperative cerebral contusion and traumatic subarachnoid hemorrhage (tSAH). The authors undertook a single-center, retrospective study to determine whether outpatient CT altered clinical decision-making. Methods The authors evaluated 173 consecutive adult patients admitted to their institution from April 2006 to August 2012 with an admission diagnosis of cerebral contusion or tSAH and at least 1 clinic follow-up visit with CT. Patients with epidural, subdural, aneurysmal subarachnoid, or intraventricular hemorrhage, and those who underwent craniotomy, were excluded. Patient charts were reviewed for new CT findings, new patient symptoms, and changes in treatment plan. Patients were stratified by neurological symptoms into 3 groups: 1) asymptomatic; 2) mild, nonspecific symptoms; and 3) significant symptoms. Mild, nonspecific symptoms included minor headaches, vertigo, fatigue, and mild difficulties with concentration, short-term memory, or sleep; significant symptoms included moderate to severe headaches, nausea, vomiting, focal neurological complaints, impaired consciousness, or new cognitive impairment evident on routine clinical examination. Results One hundred seventy-three patients met inclusion criteria, with initial clinic follow-up obtained within approximately 6 weeks. Of the 173 patients, 104 (60.1%) were asymptomatic, 68 patients (39.3%) had mild, nonspecific neurological symptoms, and 1 patient (1.0%) had significant neurological symptoms. Of the asymptomatic patients, 3 patients (2.9%) had new CT findings and 1 of these patients (1.0%) underwent a change in treatment plan because of these findings. This change involved an additional clinic appointment and CT to monitor a 12-mm chronic subdural hematoma that ultimately resolved without treatment. Of the patients with mild, nonspecific neurological symptoms, 6 patients (8.8%) had new CT findings and 3 of these patients (4.4%) underwent a change in treatment plan because of these findings; none of these patients required surgical intervention. The single patient with significant neurological symptoms did not have any new CT findings. Conclusions Repeat outpatient CT of asymptomatic patients after nonoperative cerebral contusion and tSAH is very unlikely to demonstrate significant new pathology. Given the cost and radiation exposure associated with CT, imaging should be reserved for patients with significant symptoms or focal findings on neurological examination.

Brain metastases are the most common form of brain cancer. Increasing knowledge of primary tumor biology, actionable molecular targets and continued improvements in systemic and radiotherapy regimens have helped improve survival but necessitate multidisciplinary collaboration between neurosurgical, medical and radiation oncologists. In this review, we will discuss the advances of targeted therapies to date and discuss findings of studies investigating the synergy between these therapies and stereotactic radiosurgery for non-small cell lung cancer, breast cancer, melanoma, and renal cell carcinoma brain metastases.

Meningiomas are the most common intracranial primary tumor in adults. Surgery is the predominant therapeutic modality for symptomatic meningiomas. Although the majority of meningiomas are benign, there exists a subset of meningiomas that are clinically aggressive. Recent advances in genetics and epigenetics have uncovered molecular alterations that drive tumor meningioma biology with prognostic and therapeutic implications. In this review, we will discuss the advances on molecular determinants of therapeutic response in meningiomas to date and discuss findings of targeted therapies in meningiomas.

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