Changing Trends in Brain Imaging Technique for Pediatric Patients with Ventriculoperitoneal Shunts.

BACKGROUND: Children with ventriculoperitoneal shunts (VPS) undergoing brain computed tomography (CT) for shunt malfunction evaluation are at risk for later malignancy due to radiation exposure. We aimed to determine if and how hospitals have adopted radiation-avoiding magnetic resonance imaging (MRI) techniques. METHODS: We performed a secondary analysis of the Pediatric Health Information System (PHIS) database. Children with VPS presenting to acute wards at 31 PHIS hospitals between January 1, 2007 and January 2, 2015 and receiving noncontrast neuroimaging on day of service 0/1 were included. Outcome measures were (1) incidence of MRI over time and (2) comparison of demographic characteristics between hospitals with MRI representing higher versus lower proportions (>15% or <15%) of total brain imaging. RESULTS: MRIs increased by 18.1% from 2007 to 2015. Hospitals were assigned to high-use (n = 12) or minimal-use (n = 19) MRI groups based on year 2014/2015 MRI percentages. The only identified difference was an older mean age in the high-use group (8.1 vs. 7.5 years; p = 0.03). CONCLUSIONS: MRI is increasingly used to evaluate patients with VPS. Hospitals with more MRI use had older patients and no increase in cost or length of stay. Initiating local quality improvement projects may help identify barriers to MRI uptake and increase use.

The Weekend Effect on Morbidity and Mortality Among Pediatric Epilepsy Admissions.

BACKGROUND: Pediatric epilepsy is one of the most common neurological disorders with low mortality and high morbidity, often requiring hospitalization. Weekend admissions have been shown to be associated with worse outcomes compared with their weekday counterparts. To date, no study has assessed the impact of weekend admission on clinical and quality outcomes in the pediatric epilepsy population. METHODS: Children with epilepsy were identified from the 2000, 2003, 2006, and 2009 Kids Inpatient Database. Quality outcomes were identified using the Centers of Medicare and Medicaid Services' hospital acquired conditions International Classification of Diseases, Ninth Edition; Clinical Modification (ICD-9CM) codes. Multivariable analyses were conducted to assess the association between weekend admission and inpatient mortality and hospital acquired condition occurrence. RESULTS: A total of 526,765 pediatric epilepsy discharges were identified, with 80% occurring on weekdays and 20% on weekends. Overall, the hospital acquired condition rate was 3.6% (3.2% vs 5.2% for weekday versus weekend) and inpatient mortality was 1.5% (1.2% vs 1.7%). Patients admitted on the weekend had 28% higher rates of hospital acquired conditions and 21% higher inpatient mortality rates compared with their weekday counterparts. Patients seen at nonpediatric centers had 10% to 28% lower rates of mortality, but 5% to 13% higher hospital acquired condition rates than those at pediatric centers. CONCLUSIONS: Weekend admission is significantly associated with worse clinical and quality outcomes compared with weekday admissions among pediatric epilepsy inpatients. Weekend admissions likely represent unplanned, at risk admissions, coupled with less staffing. Further study is needed to isolate clinical and systemic factors to decrease this disparity in this highly comorbid pediatric subgroup.

Pineal germ cell tumors: Two cases with review of histopathologies and biomarkers.

Pineal germ cell tumors (GCTs) are primarily seen in pediatric and Asian populations. These tumors are divided into germinomatous and non-germinomatous GCTs (NGGCTs). GCTs are thought to arise by misplacement of totipotent stem cells en route to gonads during embryogenesis. Intracranial GCTs display an affinity to develop along the pineal-suprasellar axis and have variable manifestations dependent upon the location of the tumor. Management and outcomes are driven by histopathologies. In this study, we highlight two cases of pineal GCTs and present a review of the literature with an emphasis on histopathologies and biomarkers.

Infra-Conus Single-Level Laminectomy for Selective Dorsal Rhizotomy: Technical Advance.

BACKGROUND/AIMS: Selective dorsal rhizotomy for spastic cerebral palsy is an effective and well-validated surgical approach. Multiple techniques have been described in the past including multiple laminectomies and a single-level laminectomy at the level of the conus. There is considerable technical challenge involved with a single-level laminectomy approach. METHODS: We report here a modification of the single-level laminectomy that selectively analyzes each individual nerve root with electromyography to separate dorsal and ventral nerve roots through comparison of stimulus responses. RESULTS: In 18 children with cerebral palsy who underwent this operation there was a mean improvement in the Modified Ashworth Scale of 2.0 with no reported incidence of muscle weakness, sensory loss, or neurogenic bladder. CONCLUSION: This approach allows for a modification of selective dorsal rhizotomy through a single-level laminectomy and tailors the selection of nerve root sectioning to the individual patient of interest while still maintaining its effectiveness.

PP2A inhibition with LB100 enhances cisplatin cytotoxicity and overcomes cisplatin resistance in medulloblastoma cells.

The protein phosphatase 2A (PP2A) inhibitor, LB100, has been shown in pre-clinical studies to be an effective chemo- and radio-sensitizer for treatment of various cancers. We investigated effects associated with LB100 treatment alone and in combination with cisplatin for medulloblastoma (MB) in vitro and in vivo in an intracranial xenograft model. We demonstrated that LB100 had a potent effect on MB cells. By itself, LB100 inhibited proliferation and induced significant apoptosis in a range of pediatric MB cell lines. It also attenuated MB cell migration, a pre-requirement for invasion. When used in combination, LB100 enhanced cisplatin-mediated cytotoxic effects. Cell viability in the presence of 1 uM cisplatin alone was 61% (DAOY), 100% (D341), and 58% (D283), but decreased with the addition of 2 µM of LB100 to 26% (DAOY), 67% (D341), and 27% (D283), (p < 0.005). LB100 suppressed phosphorylation of the STAT3 protein and several STAT3 downstream targets. Also, LB100 directly increased cisplatin uptake and overcame cisplatin-resistance in vitro. Finally, LB100 exhibited potent in vivo anti-neoplastic activity in combination with cisplatin in an intracranial xenograft model.

Surgery of the mind, mood, and conscious state: an idea in evolution.

Since the beginning of recorded history, humans have sought a physical means of altering disordered behavior and consciousness. This quest has spawned numerous innovations in neurosurgery and the neurosciences, from the earliest prehistoric attempts at trepanation to the electrocortical and anatomic localization of cerebral function that emerged in the 19th century. At the start of the 20th century, the overwhelming social impact of psychiatric illness intersected with the novel but imperfect understanding of frontal lobe function, establishing a decades-long venture into the modern origin of psychosurgery, the prefrontal lobotomy. The subsequent social and ethical ramifications of the widespread overuse of transorbital lobotomies drove psychosurgery to near extinction. However, as the pharmacologic treatment of psychiatric illness was established, numerous concomitant technical and neuroscientific innovations permitted the incremental development of a new paradigm of treating the disordered mind. In this article, we retrospectively examine these early origins of psychosurgery and then look to the recent past, present, and future for emerging trends in surgery of the psyche. Recent decades have seen a revolution in minimalism, noninvasive imaging, and functional manipulation of the human cerebrum that have created new opportunities and treatment modalities for disorders of the human mind and mood. Early contemporary efforts were directed at focal lesioning of abnormal pathways, but deep-brain stimulation now aims to reversibly alter and modulate those neurologic activities responsible for not only psychiatric disorders, but also to modulate and even to augment consciousness, memory, and other elements of cerebral function. As new tools become available, the social and medical impact of psychosurgery promises to revolutionize not only neurosurgery, but also humans' capability for positively impacting life and society.

Surgery of the mind, mood, and conscious state: an idea in evolution.

Since the beginning of recorded history, humans have sought a physical means of altering disordered behavior and consciousness. This quest has spawned numerous innovations in neurosurgery and the neurosciences, from the earliest prehistoric attempts at trepanation to the electrocortical and anatomic localization of cerebral function that emerged in the 19th century. At the start of the 20th century, the overwhelming social impact of psychiatric illness intersected with the novel but imperfect understanding of frontal lobe function, establishing a decades-long venture into the modern origin of psychosurgery, the prefrontal lobotomy. The subsequent social and ethical ramifications of the widespread overuse of transorbital lobotomies drove psychosurgery to near extinction. However, as the pharmacologic treatment of psychiatric illness was established, numerous concomitant technical and neuroscientific innovations permitted the incremental development of a new paradigm of treating the disordered mind. In this article, we retrospectively examine these early origins of psychosurgery and then look to the recent past, present, and future for emerging trends in surgery of the psyche. Recent decades have seen a revolution in minimalism, noninvasive imaging, and functional manipulation of the human cerebrum that have created new opportunities and treatment modalities for disorders of the human mind and mood. Early contemporary efforts were directed at focal lesioning of abnormal pathways, but deep-brain stimulation now aims to reversibly alter and modulate those neurologic activities responsible for not only psychiatric disorders, but also to modulate and even to augment consciousness, memory, and other elements of cerebral function. As new tools become available, the social and medical impact of psychosurgery promises to revolutionize not only neurosurgery, but also humans' capability for positively impacting life and society.

Man, mind, and machine: the past and future of virtual reality simulation in neurologic surgery.

OBJECTIVE: To review virtual reality in neurosurgery, including the history of simulation and virtual reality and some of the current implementations; to examine some of the technical challenges involved; and to propose a potential paradigm for the development of virtual reality in neurosurgery going forward. METHODS: A search was made on PubMed using key words surgical simulation, virtual reality, haptics, collision detection, and volumetric modeling to assess the current status of virtual reality in neurosurgery. Based on previous results, investigators extrapolated the possible integration of existing efforts and potential future directions. RESULTS: Simulation has a rich history in surgical training, and there are numerous currently existing applications and systems that involve virtual reality. All existing applications are limited to specific task-oriented functions and typically sacrifice visual realism for real-time interactivity or vice versa, owing to numerous technical challenges in rendering a virtual space in real time, including graphic and tissue modeling, collision detection, and direction of the haptic interface. CONCLUSIONS: With ongoing technical advancements in computer hardware and graphic and physical rendering, incremental or modular development of a fully immersive, multipurpose virtual reality neurosurgical simulator is feasible. The use of virtual reality in neurosurgery is predicted to change the nature of neurosurgical education, and to play an increased role in surgical rehearsal and the continuing education and credentialing of surgical practitioners.

Real-time image-guided direct convective perfusion of intrinsic brainstem lesions. Technical note.

Recent preclinical studies have demonstrated that convection-enhanced delivery (CED) can be used to perfuse the brain and brainstem with therapeutic agents while simultaneously tracking their distribution using coinfusion of a surrogate magnetic resonance (MR) imaging tracer. The authors describe a technique for the successful clinical application of this drug delivery and monitoring paradigm to the brainstem. Two patients with progressive intrinsic brainstem lesions (one with Type 2 Gaucher disease and one with a diffuse pontine glioma) were treated with CED of putative therapeutic agents mixed with Gd-diethylenetriamene pentaacetic acid (DTPA). Both patients underwent frameless stereotactic placement of MR imaging-compatible outer guide-inner infusion cannulae. Using intraoperative MR imaging, accurate cannula placement was confirmed and real-time imaging during infusion clearly demonstrated progressive filling of the targeted region with the drug and Gd-DTPA infusate. Neither patient had clinical or imaging evidence of short- or long-term infusate-related toxicity. Using this technique, CED can be used to safely perfuse targeted regions of diseased brainstem with therapeutic agents. Coinfused imaging surrogate tracers can be used to monitor and control the distribution of therapeutic agents in vivo. Patients with a variety of intrinsic brainstem and other central nervous system disorders may benefit from a similar treatment paradigm.

Proteomic comparison of oligodendrogliomas with and without 1pLOH.

OBJECTIVE: Chemoresistance is a widespread therapeutic challenge in glial tumors. The molecular basis of chemoresistance is poorly understood, precluding advances in glioma treatment and leaving gliomas among the most lethal tumors. Oligodendrogliomas provide a unique model to study the molecular basis of chemoresistance, as there are two distinct genetic subtypes with significant differences in chemosensitivity. Despite a high morphological similarity, tumors with allelic loss on the short arm of chromosome 1 (1pLOH) are more chemosensitive than those without 1pLOH. METHODS: In order to identify candidate proteins potentially responsible for glioma chemosensitivity, we compared the proteome of four oligodendrogliomas with and five without 1pLOH using comparative proteomic profiling. Proteomic analysis was performed by two-dimensional protein gel electrophoresis and subsequent computerized gel analysis for detection of distinguishing patterns of protein expression. Differentially expressed proteins were identified using Liquid Chromatography/Mass Spectrometry. Differential expression of select proteins was confirmed by Western blotting. RESULTS: We identified seven candidate proteins that are overexpressed in oligodendrogliomas without 1pLOH. Two of these proteins (glyoxalase I and Rho GDP dissociation inhibitor) have previously been shown to enhance chemoresistance in other tumors. In turn, we identified twelve overexpressed proteins in tumors with 1pLOH that have previously been reported to induce chemosensitivity in other forms of human neoplasia. CONCLUSIONS: These identified proteins are potential targets for pharmacological therapy and may also be useful as biomarkers for differentiation of chemoresistant and chemosensitive oligodendroglioma.

Fine mapping of a cis-acting sequence element in yellow fever virus RNA that is required for RNA replication and cyclization.

We present fine mapping of a cis-acting nucleotide sequence found in the 5' region of yellow fever virus genomic RNA that is required for RNA replication. There is evidence that this sequence interacts with a complementary sequence in the 3' region of the genome to cyclize the RNA. Replicons were constructed that had various deletions in the 5' region encoding the capsid protein and were tested for their ability to replicate. We found that a sequence of 18 nucleotides (residues 146 to 163 of the yellow fever virus genome, which encode amino acids 9 to 14 of the capsid protein) is essential for replication of the yellow fever virus replicon and that a slightly longer sequence of 21 nucleotides (residues 146 to 166, encoding amino acids 9 to 15) is required for full replication. This region is larger than the core sequence of 8 nucleotides conserved among all mosquito-borne flaviviruses and contains instead the entire sequence previously proposed to be involved in cyclization of yellow fever virus RNA.