Direct Convective Delivery for Nervous System Gene Therapy.

Convection-enhanced delivery for central nervous system gene therapy is an emerging treatment strategy to modify the course of previously untreatable or inadequately treated neurologic conditions, including brain tumors, metabolic disorders, epilepsy, and neurodegenerative disorders. Ongoing nervous system gene therapy clinical trials highlight advantages and ongoing challenges to this therapeutic paradigm.

Spinal cord hemangioblastomas in von Hippel-Lindau disease.

Background: von Hippel-Lindau disease (VHL) is an autosomal dominant familial neoplasia syndrome. The most common manifestation of VHL is central nervous system hemangioblastomas. VHL patients will often develop multiple hemangioblastomas along their craniospinal axis over their lifetime.

Persistent GDNF Expression 45 Months after Putaminal Infusion of AAV2-GDNF in a Patient with Parkinson's Disease.

Objective: Gene therapy by convection-enhanced delivery of type 2 adeno-associated virus-glial cell derived neurotrophic factor (AAV2-GDNF) to the bilateral putamina seeks to increase GDNF gene expression and treat Parkinson's disease (PD).

Methods: A 63-year-old man with advanced PD received AAV2-GDNF in a clinical trial. He died from pneumonia after anterior cervical discectomy and fusion 45 months later.

Preoperative prescription opioid use as an independent predictor of 90-day mortality and adverse events in craniotomy and craniectomy patients.

Objective: A growing body of literature suggests that preoperative opioid exposure is an independent predictor of poor outcomes in surgical patients. No outcomes data exist on preoperative opioid use and craniotomies/craniectomies. The objective of this study was to determine the impact of preoperative opioid use on 90-day adverse events after craniotomy or craniectomy.

Adjuvant convection-enhanced delivery for the treatment of brain tumors.

Background: Malignant gliomas are a therapeutic challenge and remain nearly uniformly fatal. While new targeted chemotherapeutic agentsagainst malignant glioma have been developed in vitro, these putative therapeutics have not been translated into successful clinical treatments. The lack of clinical effectiveness can be the result of ineffective biologic strategies, heterogeneous tumor targets and/or the result of poortherapeutic distribution to malignant glioma cells using conventional nervous system delivery modalities (intravascular, cerebrospinal fluid and/orpolymer implantation), and/or ineffective biologic strategies.

Survey of United States neurosurgeons on firearm injury prevention.

Objective: Firearm-related injuries and deaths are an endemic problem in the US, posing a burden on the healthcare system with significant social and economic consequences. As front-line care providers for these patients, neurosurgeons are both knowledgeable about these injuries and credible messengers in the public discussion of ways to reduce firearm injuries. The purpose of this study was to explore US-based neurosurgeons' views and behaviors regarding firearms to understand and define a potential role for neurosurgical organizations in advocacy efforts to reduce firearm death and injuries.

Proteostasis Modulation in Germline Missense von Hippel Lindau Disease.

Purpose: Missense mutated von Hippel Lindau (VHL) protein (pVHL) maintains intrinsic function but undergoes proteasomal degradation and tumor initiation and/or progression in VHL disease. Vorinostat can rescue missense mutated pVHL and arrest tumor growth in preclinical models. We asked whether short-term oral vorinostat could rescue pVHL in central nervous system hemangioblastomas in patients with germline missense VHL.

A 13-Year-Old Male With Left Eye Swelling.

A 13-year-old male presented with a 10-day history of left eye swelling and pain. These symptoms prompted presentation to the emergency department. He had no significant past medical history and no preceding fevers or chills.

Long-term safety of MRI-guided administration of AAV2-GDNF and gadoteridol in the putamen of individuals with Parkinson's disease.

Direct putaminal infusion of adeno-associated virus vector (serotype 2) (AAV2) containing the human glial cell line-derived neurotrophic factor (GDNF) transgene was studied in a phase I clinical trial of participants with advanced Parkinson's disease (PD). Convection-enhanced delivery of AAV2-GDNF with a surrogate imaging tracer (gadoteridol) was used to track infusate distribution during real-time intraoperative magnetic resonance imaging (iMRI). Pre-, intra-, and serial postoperative (up to 5 years after infusion) MRI were analyzed in 13 participants with PD treated with bilateral putaminal co-infusions (52 infusions in total) of AAV2-GDNF and gadoteridol (infusion volume, 450 mL per putamen).

Degenerative Spine Disorders and Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune inflammatory disease that results in demyelination of the central nervous system (CNS). MS affects as many as 350,000 individuals in the United States and commonly presents before the age of 45 years. Patients with MS, as the general population, are likely to encounter degenerative changes of the spine as they age, and this can pose a unique challenge to both patients with MS and physicians, as both conditions can have a great deal of symptomatic overlap despite stark differences in management.

Resident Night Float or 24-hour Call Hospital Coverage: Impact on Training, Patient Outcome, and Length of Stay.

Objective: The impact of neurosurgical resident hospital coverage system, performed via a night float (12-hour shifts overnight) or a 24-hour call, on neurological surgery resident training and patient care is unknown.

Design: Retrospective review comparing night float and 24-hour call coverage on trainee surgical experience, elective time, annual program surveys, patient outcomes, and length of stay.

Setting: The Ohio State Wexner Medical Center Neurosurgery residency program, Columbus, Ohio.

An Update on Gene Therapy Approaches for Parkinson's Disease: Restoration of Dopaminergic Function.

At present there is a significant unmet need for clinically available treatments for Parkinson's disease (PD) patients to stably restore balance to dopamine network function, leaving patients with inadequate management of symptoms as the disease progresses. Gene therapy is an attractive approach to impart a durable effect on neuronal function through introduction of genetic material to reestablish dopamine levels and/or functionally recover dopaminergic signaling by improving neuronal health. Ongoing clinical gene therapy trials in PD are focused on enzymatic enhancement of dopamine production and/or the restoration of the nigrostriatal pathway to improve dopaminergic network function.

Hemangioblastoma of the Peripheral Nervous System: A Critical Analysis of Its Rarity in Von Hippel-Lindau Disease.

Von Hippel-Lindau (VHL) disease is a multisystem disease cause by germline mutations of the VHL tumor suppressor gene. Hemangioblastomas are the most common manifestation of VHL disease and can occur in the central nervous system in up to 90% of these patients. By contrast, we found only one true case of a peripheral nervous system (PNS) hemangioblastoma in the setting of VHL.

Large Adult Spinal Diffuse Midline Histone H3 Lysine27-to-Methionine-Mutant Glioma With Intramedullary and Extramedullary Components Presenting With Progressive Hydrocephalus: A Case Report Highlighting Unique Imaging Findings and Treatment.

Diffuse midline glioma with histone H3 lysine27-to-methionine mutation (H3 K27M mutation) is a rare, aggressive tumor that is designated as World Health Organization (WHO) grade IV regardless of histologic features. Preoperative diagnosis remains challenging due to limited evidence regarding distinctive clinical and imaging characteristics. We describe the case of a young woman who presented with progressively worsening headaches due to communicating hydrocephalus.