Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of emerging developments in the management of newly diagnosed glioblastoma.

TARGET POPULATION: These recommendations apply to adult patients with newly diagnosed or suspected glioblastoma. IMAGING: Question What imaging modalities are in development that may be able to provide improvements in diagnosis, and therapeutic guidance for individuals with newly diagnosed glioblastoma? RECOMMENDATION: Level III: It is suggested that techniques utilizing magnetic resonance imaging for diffusion weighted imaging, and to measure cerebral blood and magnetic spectroscopic resonance imaging of N-acetyl aspartate, choline and the choline to N-acetyl aspartate index to assist in diagnosis and treatment planning in patients with newly diagnosed or suspected glioblastoma. SURGERY: Question What new surgical techniques can be used to provide improved tumor definition and resectability to yield better tumor control and prognosis for individuals with newly diagnosed glioblastoma? RECOMMENDATIONS: Level II: The use of 5-aminolevulinic acid is recommended to improve extent of tumor resection in patients with newly diagnosed glioblastoma. Level II: The use of 5-aminolevulinic acid is recommended to improve median survival and 2 year survival in newly diagnosed glioblastoma patients with clinical characteristics suggesting poor prognosis. Level III: It is suggested that, when available, patients be enrolled in properly designed clinical trials assessing the value of diffusion tensor imaging in improving the safety of patients with newly diagnosed glioblastoma undergoing surgery. NEUROPATHOLOGY: Question What new pathology techniques and measurement of biomarkers in tumor tissue can be used to provide improved diagnostic ability, and determination of therapeutic responsiveness and prognosis for patients with newly diagnosed glioblastomas? RECOMMENDATIONS: Level II: Assessment of tumor MGMT promoter methylation status is recommended as a significant predictor of a longer progression free survival and overall survival in patients with newly diagnosed with glioblastoma. Level II: Measurement of tumor expression of neuron-glia-2, neurofilament protein, glutamine synthetase and phosphorylated STAT3 is recommended as a predictor of overall survival in patients with newly diagnosed with glioblastoma. Level III: Assessment of tumor IDH1 mutation status is suggested as a predictor of longer progression free survival and overall survival in patients with newly diagnosed with glioblastoma. Level III: Evaluation of tumor expression of Phosphorylated Mitogen-Activated Protein Kinase protein, EGFR protein, and Insulin-like Growth Factor-Binding Protein-3 is suggested as a predictor of overall survival in patients with newly diagnosed with glioblastoma. RADIATION: Question What radiation therapy techniques are in development that may be used to provide improved tumor control and prognosis for individuals with newly diagnosed glioblastomas? RECOMMENDATIONS: Level III: It is suggested that patients with newly diagnosed glioblastoma undergo pretreatment radio-labeled amino acid tracer positron emission tomography to assess areas at risk for tumor recurrence to assist in radiation treatment planning. Level III: It is suggested that, when available, patients be with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of radiation dose escalation, altered fractionation, or new radiation delivery techniques. CHEMOTHERAPY: Question What emerging chemotherapeutic agents or techniques are available to provide better tumor control and prognosis for patients with newly diagnosed glioblastomas? RECOMMENDATION: Level III: As no emerging chemotherapeutic agents or techniques were identified in this review that improved tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of chemotherapy. MOLECULAR AND TARGETED THERAPY: Question What new targeted therapy agents are available to provide better tumor control and prognosis for individuals with newly diagnosed glioblastomas? RECOMMENDATION: Level III: As no new molecular and targeted therapies have clearly provided better tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of molecular and targeted therapies IMMUNOTHERAPY: Question What emerging immunotherapeutic agents or techniques are available to provide better tumor control and prognosis for patients with newly diagnosed glioblastomas? RECOMMENDATION: Level III: As no immunotherapeutic agents have clearly provided better tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of immunologically-based therapies. NOVEL THERAPIES: Question What novel therapies or techniques are in development to provide better tumor control and prognosis for individuals with newly diagnosed glioblastomas? RECOMMENDATIONS: Level II: The use of tumor-treating fields is recommended for patients with newly diagnosed glioblastoma who have undergone surgical debulking and completed concurrent chemoradiation without progression of disease at the time of tumor-treating field therapy initiation. Level II: It is suggested that, when available, enrollment in properly designed studies of vector containing herpes simplex thymidine kinase gene and prodrug therapies be considered in patients with newly diagnosed glioblastoma.

Scoping Review and Commentary on Prognostication for Patients with Intracerebral Hemorrhage with Advances in Surgical Techniques.

INTRODUCTION: The intracerebral hemorrhage (ICH) score provides an estimate of 30-day mortality for patients with intracerebral hemorrhage in order to guide research protocols and clinical decision making. Several variations of such scoring systems have attempted to optimize its prognostic value. More recently, minimally invasive surgical techniques are increasingly being used with promising results. As more patients become candidates for surgical intervention, there is a need to re-discuss the best methods for predicting outcomes with or without surgical intervention. METHODS: We systematically performed a scoping review with a comprehensive literature search by two independent reviewers using the PubMed and Cochrane databases for articles pertaining to the "intracerebral hemorrhage score." Relevant articles were selected for analysis and discussion of potential modifications to account for increasing surgical indications. RESULTS: A total of 64 articles were reviewed in depth and identified 37 clinical grading scales for prognostication of spontaneous intracerebral hemorrhage. The original ICH score remains the most widely used and validated. Various authors proposed modifications for improved prognostic accuracy, though no single scale showed consistent superiority. Most recently, scales to account for advances in surgical techniques have been developed but lack external validation. CONCLUSION: We provide the most comprehensive review to date of prognostic grading scales for patients with intracerebral hemorrhage. Current prognostic tools for patients with intracerebral hemorrhage remain limited and may overestimate risk of a poor outcome. As minimally invasive surgical techniques are developed, prognostic scales should account for surgical candidacy and outcomes.

Intracranial thrombosed anastomosing hemangioma: Case report.

An anastomosing hemangioma is a relatively new diagnosis of a benign vascular lesion that is typically found in the genitourinary tract. On imaging, anastomosing hemangiomas have a broad differential diagnosis and can resemble malignant lesions such as angiosarcoma. Here we present a case of a 33-year-old male with seizures who on imaging was found to have a presumed recurrent intracranial meningioma. After surgical resection of his lesion, this case was pathologically diagnosed as having anastomosing hemangioma. To our knowledge, this is the first report of a case of a thrombosed anastomosing hemangioma located at intracranial and intradural region.

Evidence-Based Perioperative Protocol for Ventriculoperitoneal Shunt Infection Reduction at a Single Institution.

OBJECTIVE: Ventriculoperitoneal shunt infections are common and result in significant morbidity, mortality, and health care expenditure. The objective of this study was to create an evidence-based perioperative shunt infection prevention protocol and analyze its efficacy by comparing the incidence of shunt infection before and after implementation at one institution. METHODS: A perioperative ventriculoperitoneal shunt surgery protocol was developed based on a systematic literature review with the goal of reducing infection rates. Patients undergoing shunt surgery at Upstate Medical University Hospital, from before and after implantation of the perioperative shunt surgery protocol, were retrospectively analyzed and compared. Retrospective data collection included shunt infection incidence as a primary outcome and clinical features of patients from both cohorts. RESULTS: The pre-protocol and post-protocol cohorts included 226 and 285 patients, respectively. Twenty (8.8%) pre-protocol shunt infections and 16 (5.6%) post-protocol shunt infections were identified (P = 0.156). The relative risk of shunt infection between cohorts was 0.97 (95% confidence interval: 0.92-1.02). CONCLUSIONS: Although shunt infection rates pre-protocol and post-protocol were not significantly different, a trend toward fewer shunt infections was observed with protocol implementation. Suboptimal compliance at our institution may have limited accurate assessment of protocol efficacy. Similar future studies may benefit from objectively assessing protocol compliance.

Hyperosmotic intraventricular drug delivery of DV1 in the management of intracranial metastatic breast cancer in a mouse model.

Advances in therapies for breast cancer with cerebral metastases has been slow, despite this being a common diagnosis, due to limited drug delivery by the blood brain barrier. Improvements in drug delivery for brain metastasis to target the metastases and bypass the blood brain barrier are necessary. In our study, we delivered an inhibitor of chemokine receptor 4 by convection enhanced delivery in a hyperosmotic solution to prevent brain metastasis in a mouse model of metastatic breast cancer. We found the inhibitor limited metastatic disease and more interestingly, the hyperosmotic solution targeted tumor tissue allowing for a higher accumulation of the therapy into tumor tissue. This finding has the potential to improve delivery of chemotherapeutic agents to brain metastases.

Brain Abscess of Basal Ganglia Presenting with Persistent Hiccups.

BACKGROUND: Brain abscesses are well-known to neurologic surgeons with well-recognized presentations, which include seizures, neurologic deficit, and headache. Rare symptoms may lead to a delay in diagnosis, which can be life threatening in the setting of a brain abscess. CASE DESCRIPTION: We present the case of a 46-year-old male with intractable hiccups found to have an abscess of the right basal ganglia. The brain abscess was treated by frameless stereotactic-guided aspiration. The patient's hiccups improved after surgical aspiration and medical management. CONCLUSIONS: A comprehensive literature review confirmed brain abscess as a rare cause of intractable hiccups. In addition, there are few reports of lesions of the basal ganglia causing intractable hiccups. Aspiration and medical therapy resulted in resolution of the hiccups. Knowledge of the hiccup reflex arc and unusual presentation of basal ganglia lesions may shorten time to diagnosis.

Tunable Lipidoid-Telodendrimer Hybrid Nanoparticles for Intracellular Protein Delivery in Brain Tumor Treatment.

A strategy to precisely engineer lipidoid-telodendrimer binary hybrid nanoparticles that offer enhanced cell membrane permeability for therapeutic proteins to reach the intracellular targets is established. The highly controllable biochemical and physical properties of the nanoparticles make them promising for protein-based brain cancer treatment with the assistance of convection-enhanced delivery.

Delayed Presentation of a Cervical Spinal Epidural Abscess of Dental Origin after a Fall in an Elderly Patient.

Spinal epidural abscesses are an uncommon cause of spinal cord injury but, depending on the size and presence of neurological deficits, urgent neurosurgical intervention may be required. We present a unique case of a patient presenting with a spinal epidural collection several days after a fall. While a spinal epidural hematoma was suspected based on the patient's history and MRI findings, a spinal epidural abscess was found during surgery. The patient underwent laminectomy and instrumented fusion with successful treatment of her infection.

Affinity-controlled protein encapsulation into sub-30 nm telodendrimer nanocarriers by multivalent and synergistic interactions.

Novel nanocarriers are highly demanded for the delivery of heterogeneous protein therapeutics for disease treatments. Conventional nanoparticles for protein delivery are mostly based on the diffusion-limiting mechanisms, e.g., physical trapping and entanglement. We develop herein a novel linear-dendritic copolymer (named telodendrimer) nanocarrier for efficient protein delivery by affinitive coating. This affinity-controlled encapsulation strategy provides nanoformulations with a small particle size (<30 nm), superior loading capacity (>50% w/w) and maintained protein bioactivity. We integrate multivalent electrostatic and hydrophobic functionalities synergistically into the well-defined telodendrimer scaffold to fine-tune protein binding affinity and delivery properties. The ion strength and density of the charged groups as well as the structure of the hydrophobic segments are important and their combinations in telodendrimers are crucial for efficient protein encapsulation. We have conducted a series of studies to understand the mechanism and kinetic process of the protein loading and release, utilizing electrophoresis, isothermal titration calorimetry, Förster resonance energy transfer spectroscopy, bio-layer interferometry and computational methods. The optimized nanocarriers are able to deliver cell-impermeable therapeutic protein intracellularly to kill cancer cells efficiently. In vivo imaging studies revealed cargo proteins preferentially accumulate in subcutaneous tumors and retention of peptide therapeutics is improved in an orthotopic brain tumor, these properties are evidence of the improved pharmacokinetics and biodistributions of protein therapeutics delivered by telodendrimer nanoparticles. This study presents a bottom-up strategy to rationally design and fabricate versatile nanocarriers for encapsulation and delivery of proteins for numerous applications.

Fine-tuning vitamin E-containing telodendrimers for efficient delivery of gambogic acid in colon cancer treatment.

Certain natural products such as gambogic acid (GA) exhibit potent antitumor effects. Unfortunately, administration of these natural products is limited by their poor solubility in conventional pharmaceutical solvents. In this study, a series of telodendrimers, composed of linear polyethylene glycol (PEG)-blocking-dendritic oligomer of cholic acid (CA) and vitamin E (VE), have been designed with architectures optimized for efficient delivery of GA and other natural anticancer compounds. Two of the telodendrimers with segregated CA and VE domains self-assembled into stable cylindrical and/or spherical nanoparticles (NPs) after being loaded with GA as observed under transmission electron microscopy (TEM), which correlated with the dynamic light scattering (DLS) analysis of sub-30 nm particle sizes. A very high GA loading capacity (3:10 drug/polymer w/w) and sustained drug release were achieved with the optimized telodendrimers. These novel nanoformulations of GA were found to exhibit similar in vitro cytotoxic activity against colon cancer cells as the free drug. Near-infrared fluorescence small animal imaging revealed preferential accumulation of GA-loaded NPs into tumor tissue. The optimized nanoformulation of GA achieved superior antitumor efficacy compared to GA-Cremophor EL formulation at equivalent doses in HT-29 human colon cancer xenograft mouse models. Given the mild adverse effects associated with this natural compound and the enhanced anticancer effects via tumor targeted telodendrimer delivery, the optimized GA nanoformulation is a promising alternative to the traditional chemotherapy in colon cancer treatment.

Bony fusion in a chronic cervical bilateral facet dislocation.

BACKGROUND: Cervical facet dislocation injuries typically present shortly after occurrence due to the pain and neurologic deficit that can be associated with this injury. Bilateral dislocations of the facet joint require prompt evaluation, reduction, and surgical intervention. Rare case reports present bilateral dislocations presenting in a delayed fashion. CASE REPORT: We report the case of a 60-year-old male who presented with mild neck pain 1 year after initial injury. Computed topography of the cervical spine showed healing with bony fusion of a bilateral C6-7 facet dislocation. Given the chronic healed nature of the injury and minimal symptoms, the patient is being followed without intervention. CONCLUSIONS: Although most bilateral facet dislocations present and are treated immediately after injury; this case illustrates that some may be missed during initial evaluation. Once healed, these injuries may be stable without surgical intervention.

Ventriculoperitoneal shunt infection with non-typhoidal Salmonella species in an infant.

Shunt infections are common in pediatric neurosurgery. We present a case of a 3-month-old male with a history of a ventriculoperitoneal shunt for posthemorrhagic hydrocephalus after premature birth who presented to the emergency department with irritability and decreased oral intake. His presentation was concerning for shunt infection and evaluation for this was undertaken. He was found to have a shunt infection due to non-Salmonellatyphi species, a rare cause of meningitis in children in the United States and rarer cause of shunt infection. With effective treatment for this organism, the patient did well and was discharged home in good condition.