Response of treatment-naive brain metastases to stereotactic radiosurgery.

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS.

Facilitating Repeat Intracarotid Injections in Mouse Models by a Novel Injection Site Repair Technique.

Given recent advances in the delivery of novel antitumor therapeutics using endovascular selective intraarterial delivery methods in neuro-oncology, there is an urgent need to develop methods for intracarotid injections in mouse models, including methods to repair the carotid artery in mice after injection to allow for subsequent injections. We developed a method of intracarotid injection in a mouse model to deliver therapeutics into the internal carotid artery (ICA) with two alternative procedures. During injection, the needle is inserted into the common carotid artery (CCA) after tying a suture around the external carotid artery (ECA) and injected therapeutics are delivered into the ICA.

Chimeric oncolytic adenovirus evades neutralizing antibodies from human patients and exhibits enhanced anti-glioma efficacy in immunized mice.

Oncolytic viruses are a promising treatment for patients with high-grade gliomas, but neutralizing antibodies can limit their efficacy in patients with prior virus exposure or upon repeated virus injections. Data from a previous clinical trial using the oncolytic adenovirus Delta-24-RGD showed that generation of anti-viral neutralizing antibodies may affect the long-term survival of glioma patients. Past studies have examined the effects of neutralizing antibodies during systemic virus injections, but largely overlooked their impact during local virus injections into the brain.

Intraoperative language mapping guided by real-time visualization of gamma band modulation electrocorticograms: Case report and proof of concept.

Background: Electrocorticography (ECoG) language mapping is often performed extraoperatively, frequently involves offline processing, and relationships with direct cortical stimulation (DCS) remain variable. We sought to determine the feasibility and preliminary utility of an intraoperative language mapping approach guided by real-time visualization of electrocorticograms.

Methods: A patient with astrocytoma underwent awake craniotomy with intraoperative language mapping, utilizing a dual iPad stimulus presentation system coupled to a real-time neural signal processing platform capable of both ECoG recording and delivery of DCS.

Subependymomas of the fourth ventricle: To operate or not to operate?

Background: There is a paucity of literature regarding the clinical characteristics and management of subependymomas of the fourth ventricle due to their rarity. Here, we describe the operative and non-operative management and outcomes of patients with such tumors.

Methods: This retrospective single-institution case series was gathered after Institutional Review Board (IRB) approval.

Concurrent IDH1 and IDH2 mutations in glioblastoma: A case report.

Isocitrate dehydrogenase (IDH) mutations are cornerstone diagnostic features in glioma classification. IDH mutations are typically characterized by mutually exclusive amino acid substitutions in the genes encoding for the and the enzyme isoforms. We report our institutional case of a diffuse astrocytoma with progression to secondary glioblastoma and concurrent IDH1/IDH2 mutations.

Transcranial magnetic stimulation tractography and the facilitation of gross total resection in a patient with a motor eloquent glioblastoma: illustrative case.

Background: In patients with perieloquent tumors, neurosurgeons must use a variety of techniques to maximize survival while minimizing postoperative neurological morbidity. Recent publications have shown that conventional anatomical features may not always predict postoperative deficits. Additionally, scientific conceptualizations of complex brain function have shifted toward more dynamic, neuroplastic theories instead of traditional static, localizationist models.

Transcranial magnetic stimulation (TMS) seeded tractography provides superior prediction of eloquence compared to anatomic seeded tractography.

Background: For patients with brain tumors, maximizing the extent of resection while minimizing postoperative neurological morbidity requires accurate preoperative identification of eloquent structures. Recent studies have provided evidence that anatomy may not always predict eloquence. In this study, we directly compare transcranial magnetic stimulation (TMS) data combined with tractography to traditional anatomic grading criteria for predicting permanent deficits in patients with motor eloquent gliomas.

An interdisciplinary consensus on the management of brain metastases in patients with renal cell carcinoma.

Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery.

Surgical Management of Brain Metastasis: Challenges and Nuances.

Brain metastasis is the most common type of intracranial tumor. The contemporary management of brain metastasis is a challenging issue and traditionally has carried a poor prognosis as these lesions typically occur in the setting of advanced cancer. However, improvement in systemic therapy, advances in radiation techniques and multimodal therapy tailored to the individual patient, has given hope to this patient population.

Mutations of the DNA repair gene PNKP in a patient with microcephaly, seizures, and developmental delay (MCSZ) presenting with a high-grade brain tumor.

Polynucleotide Kinase-Phosphatase (PNKP) is a bifunctional enzyme that possesses both DNA 3'-phosphatase and DNA 5'-kinase activities, which are required for processing termini of single- and double-strand breaks generated by reactive oxygen species (ROS), ionizing radiation and topoisomerase I poisons. Even though PNKP is central to DNA repair, there have been no reports linking PNKP mutations in a Microcephaly, Seizures, and Developmental Delay (MSCZ) patient to cancer. Here, we characterized the biochemical significance of 2 germ-line point mutations in the PNKP gene of a 3-year old male with MSCZ who presented with a high-grade brain tumor (glioblastoma multiforme) within the cerebellum.

Perfusion-guided endovascular super-selective intra-arterial infusion for treatment of malignant brain tumors.

Background: Survival for glioblastoma remains very poor despite decades of research, with a 5-year survival of only 5%. The technological improvements that have revolutionized treatment of ischemic stroke and brain aneurysms have great potential in providing more precise and selective delivery of cancer therapeutic agents to brain tumors.

Methods: We describe for the first time the use of perfusion guidance to enhance the precision of endovascular super-selective intra-arterial (ESIA) infusions of mesenchymal stem cells loaded with Delta-24 (MSC-D24) in the treatment of glioblastoma (NCT03896568).

The Role of Immune Checkpoint Inhibitors in Leptomeningeal Disease: A Systematic Review.

Background/aim: Leptomeningeal disease (LMD) is a debilitating complication of advanced malignancies. Immune-checkpoint inhibitors (ICIs) may alter disease course. We analyzed the role and toxicity of ICIs in LMD.

Predictors of mortality and tumor recurrence in desmoplastic infantile ganglioglioma and astrocytoma-and individual participant data meta-analysis (IPDMA).

Purpose: Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are classified together as grade I neuronal and mixed neuronal-glial tumor of the central nervous system by the World Health Organization (WHO). These tumors are rare and have not been well characterized in terms of clinical outcomes. We aimed to identify clinical predictors of mortality and tumor recurrence/progression by performing an individual patient data meta-analysis (IPDMA) of the literature.

Subtemporal, Transapical, and Transcavernous Approach to Clip Low-Lying Basilar Tip Aneurysm: 2-Dimensional Operative Video.

Basilar tip aneurysm clipping is technically challenging because of the depth of operative corridor, rarity in presentation, and important perforators supplying deep, critical structures. Two major approaches to basilar tip aneurysms include (1) a frontotemporal (transorbital) trans-sylvian approach for most aneurysms and (2) a modified subtemporal approach for aneurysms with low-lying necks. A 53-yr-old woman presented to our institution with a large unruptured basilar tip aneurysm notable for a low, broad neck (6.

RNAi technology targeting the fusion breakpoint: an opportunity for precision medicine.

Background: Fusion genes form as a result of abnormal chromosomal rearrangements linking previously separate genes into one transcript. The FGFR3-TACC3 fusion gene (F3-T3) has been shown to drive gliomagenesis in glioblastoma (GBM), a cancer that is notoriously resistant to therapy. However, successful targeting of F3-T3 via small molecular inhibitors has not revealed robust therapeutic responses, and specific targeting of F3-T3 has not been achieved heretofore.

Window of Opportunity Clinical Trials to Evaluate Novel Therapies for Brain Tumors.

Despite significant improvement in understanding of molecular underpinnings driving glioblastoma, there is minimal improvement in overall survival of patients. This poor outcome is caused in part by traditional designs of early phase clinical trials, which focus on clinical assessments of drug toxicity and response. Window of opportunity trials overcome this shortcoming by assessing drug-induced on-target molecular alterations in post-treatment human tumor specimens.

Expansile duraplasty and obex exploration compared with bone-only decompression for Chiari malformation type I in children: retrospective review of outcomes and complications.

Objective: While a select population of pediatric patients with Chiari malformation type I (CM-I) remain asymptomatic, some patients present with tussive headaches, neurological deficits, progressive scoliosis, and other debilitating symptoms that necessitate surgical intervention. Surgery entails a variety of strategies to restore normal CSF flow, including increasing the posterior fossa volume via bone decompression only, or bone decompression with duraplasty, with or without obex exploration. The indications for duraplasty and obex exploration following bone decompression remain controversial.

Genetically engineered macrophages persist in solid tumors and locally deliver therapeutic proteins to activate immune responses.

Background: Though currently approved immunotherapies, including chimeric antigen receptor T cells and checkpoint blockade antibodies, have been successfully used to treat hematological and some solid tumor cancers, many solid tumors remain resistant to these modes of treatment. In solid tumors, the development of effective antitumor immune responses is hampered by restricted immune cell infiltration and an immunosuppressive tumor microenvironment (TME). An immunotherapy that infiltrates and persists in the solid TME, while providing local, stable levels of therapeutic to activate or reinvigorate antitumor immunity could overcome these challenges faced by current immunotherapies.

Incorporating genomic signatures into surgical and medical decision-making for elderly glioblastoma patients.

Glioblastoma (GBM) is the most common type of malignant primary brain tumor in adults. It is a uniformly fatal disease (median overall survival 16 months) even with aggressive resection and an adjuvant temozolomide-based chemoradiation regimen. Age remains an independent risk factor for a poor prognosis.

Microsurgical Resection of a Primary Intraosseous Meningioma Encasing the Superior Sagittal Sinus.

Primary intraosseous meningiomas (PIMs) are an infrequent variant of meningiomas characterized by hyperostosis and brain compression. En bloc surgical resection of giant PIMs involving critical structures such as venous sinuses or cranial nerves could be associated with significant morbidity. The objective of this report is to demonstrate the safety and feasibility of piecemeal resection of PIMs involving the superior sagittal sinus and frontal sinus.

Pseudoaneurysm of the Superficial Temporal Artery After Intracranial Pressure Monitoring Device Placement: Case Report of a Rare Complication.

Background And Importance: Pseudoaneurysms involving the superficial temporal artery (STA), either iatrogenic or caused by direct trauma, are rare. The STA is prone to injury due to its long course throughout the scalp. Injuries can cause cosmetic defects and/or skin breakdown leading to further complications.

Stochastic growth pattern of untreated human glioblastomas predicts the survival time for patients.

Glioblastomas are highly malignant brain tumors. Knowledge of growth rates and growth patterns is useful for understanding tumor biology and planning treatment logistics. Based on untreated human glioblastoma data collected in Trondheim, Norway, we first fit the average growth to a Gompertz curve, then find a best fitted white noise term for the growth rate variance.