Navigating the ventricles: Novel insights into the pathogenesis of hydrocephalus.

Congenital hydrocephalus occurs in one in 500-1000 babies born in the United States and acquired hydrocephalus may occur as the consequence of stroke, intraventricular and subarachnoid hemorrhage, traumatic brain injuries, brain tumors, craniectomy or may be idiopathic, as in the case of normal pressure hydrocephalus. Irrespective of its prevalence and significant impact on quality of life, neurosurgeons still rely on invasive cerebrospinal fluid shunt systems for the treatment of hydrocephalus that are exceptionally prone to failure and/or infection. Further understanding of this process at a molecular level, therefore, may have profound implications for improving treatment and quality of life for millions of individuals worldwide.

Checkpoint inhibitor immunotherapy for glioblastoma: current progress, challenges and future outlook.

Introduction: Despite maximal surgical resection and chemoradiation, glioblastoma (GBM) continues to be associated with significant morbidity and mortality. Novel therapeutic strategies are urgently needed. Given success in treating multiple other forms of cancer, checkpoint inhibitor immunotherapy remains foremost amongst novel therapeutic strategies that are currently under investigation.

The clinical importance of medulloblastoma extent of resection: a systematic review.

Background: Although the majority of current medulloblastoma adjuvant therapy protocols treat patients with ≥ 1.5 cm residual tumor as high risk with increased craniospinal irradiation, the true prognostic significance of extent of resection (EOR) in medulloblastoma is unknown.

Objectives: We sought to synthesize the body of literature on EOR and survival to determine if a definitive association exists.

Chronic infection of a Brindley sacral nerve root stimulator.

The Finetech-Brindley sacral anterior root stimulator (SARS) is implanted for the treatment of bladder dysfunction following spinal cord injury (SCI) and has been successful in improving micturition in many patients with SCI. This case describes a 62-year-old man who presented with a chronic Staphylococcus aureus infection of a Brindley SARS 26 years after implantation following a T5 American Spinal Injury Association A spinal cord injury (T5 ASIA A SCI). He presented with chronic sacral osteomyelitis with a history of periodic implant erosion through the skin.

How Surgical Trainees Handle Catastrophic Errors: A Qualitative Study.

Objective: Surgical trainees are often subject to the negative consequences of medical error, and it is therefore important to determine how trainees cope with error and to find ways of supporting trainees when catastrophic events occur. This article examines how trainees interpret catastrophic surgical outcomes and ways to provide support for trainees who have experienced catastrophic events.

Design: Totally 23 semistructured interviews were conducted with surgical trainees.

Ankrd11 is a chromatin regulator involved in autism that is essential for neural development.

Ankrd11 is a potential chromatin regulator implicated in neural development and autism spectrum disorder (ASD) with no known function in the brain. Here, we show that knockdown of Ankrd11 in developing murine or human cortical neural precursors caused decreased proliferation, reduced neurogenesis, and aberrant neuronal positioning. Similar cellular phenotypes and aberrant ASD-like behaviors were observed in Yoda mice carrying a point mutation in the Ankrd11 HDAC-binding domain.

STAT3 promotes survival of mutant photoreceptors in inherited photoreceptor degeneration models.

Inherited photoreceptor degenerations (IPDs), a group of incurable progressive blinding diseases, are caused by mutations in more than 200 genes, but little is known about the molecular pathogenesis of photoreceptor (PR) death. Increased retinal expression of STAT3 has been observed in response to many retinal insults, including IPDs, but the role of this increase in PR death is unknown. Here, we show that the expression of Stat3 is increased in PRs of the Tg(RHO P347S) and Prph2(rds) (/+) mouse models of IPD and is activated by tyrosine phosphorylation.

Best practice guidelines for stroke in Cameroon: An innovative and participatory knowledge translation project.

Background: Although the adherence to stroke guidelines in high-income countries has been shown to be associated with improved patient outcomes, the research, development and implementation of rehabilitation related guidelines in African countries is lacking.

Objectives: The purpose of this article is to describe how a group of front-line practitioners collaborated with academics and students to develop best practice guidelines (BPG) for the management and rehabilitation of stroke in adult patients in Cameroon.

Method: A working group was established and adapted internationally recognised processes for the development of best practice guidelines.

Attitudes toward neurosurgery in a low-income country: a qualitative study.

Objective: To adapt a study exploring the needs of neurosurgery patients in a tertiary care hospital in Canada to examine, for the first time, the perspectives of neurosurgery patients in a low-income country with limited health care resources.

Methods: Semistructured interviews were conducted with 25 neurosurgery patients at Tikur Anbessa Specialized Teaching Hospital in Addis Ababa, Ethiopia. Interviews were conducted in Amharic or Oromo, translated into English, and subjected to modified thematic analysis.

Improving information provision for neurosurgical patients: a qualitative study.

Background: Patients confronted with the daunting prospect of a potentially life-altering procedure with uncertain outcome demonstrate high levels of anxiety and need for information. Regardless, many patients are left unsatisfied by the amount of information received from physicians. This study sought to examine the information-seeking patterns of patients and suggest ways to optimize the communication of medical information, specifically within the context of neurosurgery.

Endothelin-2 deficiency causes growth retardation, hypothermia, and emphysema in mice.

To explore the physiological functions of endothelin-2 (ET-2), we generated gene-targeted mouse models. Global Et2 knockout mice exhibited severe growth retardation and juvenile lethality. Despite normal milk intake, they suffered from internal starvation characterized by hypoglycemia, ketonemia, and increased levels of starvation-induced genes.

Endothelin-2-mediated protection of mutant photoreceptors in inherited photoreceptor degeneration.

Expression of the Endothelin-2 (Edn2) mRNA is greatly increased in the photoreceptors (PRs) of mouse models of inherited PR degeneration (IPD). To examine the role of Edn2 in mutant PR survival, we generated Edn2(-/-) mice carrying homozygous Pde6b(rd1) alleles or the Tg(RHO P347S) transgene. In the Edn2(-/-) background, PR survival increased 110% in Pde6b(rd1/rd1) mice at post-natal (PN) day 15, and 60% in Tg(RHO P347S) mice at PN40.

Evidence of severe mitochondrial oxidative stress and a protective effect of low oxygen in mouse models of inherited photoreceptor degeneration.

The role of oxidative stress within photoreceptors (PRs) in inherited photoreceptor degeneration (IPD) is unclear. We investigated this question using four IPD mouse models (Pde6b(rd1/rd1), Pde6b(atrd1/atrd1), Rho(-/-) and Prph2(rds/rds)) and compared the abundance of reduced glutathione (GSH) and the activity of mitochondrial NADH:ubiquinone oxidoreductase (complex I), which is oxidative stress sensitive, as indirect measures of redox status, in the retinas of wild type and IPD mice. All four IPD mutants had significantly reduced retinal complex I activities (14-29% of wild type) and two showed reduced GSH, at a stage prior to the occurrence of significant cell death, whereas mitochondrial citrate synthase, which is oxidative stress insensitive, was unchanged.

The genomic, biochemical, and cellular responses of the retina in inherited photoreceptor degenerations and prospects for the treatment of these disorders.

The association of more than 140 genes with human photoreceptor degenerations, together with studies of animal models of these monogenic diseases, has provided great insight into their pathogenesis. Here we review the responses of the retina to photoreceptor mutations, including mechanisms of photoreceptor death. We discuss the roles of oxidative metabolism, mitochondrial reactive oxygen species, metabolic stress, protein misfolding, and defects in ciliary proteins, as well as the responses of Müller glia, microglia, and the retinal vasculature.