Hemifacial Spam: Endoscopic Assistance in Facial Nerve Decompression With Lateral Spread Response Corroboration: 2-Dimensional Operative Video.

This video depicts the case of a 48-yr-old female with 3 yr of progressive left hemifacial spasm (HFS) refractory to medication. Magnetic resonance imaging showed a large anterior inferior cerebellar artery (AICA) and also a labyrinthine artery loop around the facial nerve (FN) root exit zone. A large bony eminence was also noted in the superior and lateral aspects of the porous acousticus (PA). She preferred surgery if "cure" was possible in lieu of Botox injections. A left retro sigmoid craniotomy was performed with brainstem auditory evoked responses (BAERs) and FN monitoring along with lateral spread response (LSR) assessment. The large bony prominence was drilled in its lateral aspect. Despite this, visualization was still limited and therefore we utilized a 30-degree-angled endoscope to observe the vessels caudal and cranial to the FN. This view prompted us to then drill further at the PA to decompress the FN as well as mobilize the labyrinthine artery away from the nerve. The LSR showed a dramatic improvement when FN decompression was accomplished, and then a further improvement with arterial mobilization and Teflon pledget placement. The BAERS remained at baseline throughout. FN function and hearing were intact on postoperative clinical assessment. Her symptomatic improvement was recorded at 12 mo after surgery. This video illustrates a more complex case of microvascular decompression with skull base concepts and techniques. The patient provided consent for the procedure and use of her images and operative video for publication.

Multimodality 3D Superposition and Automated Whole Brain Tractography: Comprehensive Printing of the Functional Brain.

Whole brain tractography using diffusion tensor imaging (DTI) sequences can be used to map cerebral connectivity; however, this can be time-consuming due to the manual component of image manipulation required, calling for the need for a standardized, automated, and accurate fiber tracking protocol with automatic whole brain tractography (AWBT). Interpreting conventional two-dimensional (2D) images, such as computed tomography (CT) and magnetic resonance imaging (MRI), as an intraoperative three-dimensional (3D) environment is a difficult task with recognized inter-operator variability. Three-dimensional printing in neurosurgery has gained significant traction in the past decade, and as software, equipment, and practices become more refined, trainee education, surgical skills, research endeavors, innovation, patient education, and outcomes via valued care is projected to improve. We describe a novel multimodality 3D superposition (MMTS) technique, which fuses multiple imaging sequences alongside cerebral tractography into one patient-specific 3D printed model. Inferences on cost and improved outcomes fueled by encouraging patient engagement are explored.

National variation in costs and mortality for leukodystrophy patients in US children's hospitals.

BACKGROUND: Inherited leukodystrophies are progressive, debilitating neurological disorders with few treatment options and high mortality rates. Our objective was to determine national variation in the costs for leukodystrophy patients and to evaluate differences in their care. METHODS: We developed an algorithm to identify inherited leukodystrophy patients in deidentified data sets using a recursive tree model based on International Classification of Disease, 9th Edition, Clinical Modification, diagnosis and procedure charge codes. Validation of the algorithm was performed independently at two institutions, and with data from the Pediatric Health Information System (PHIS) of 43 US children's hospitals, for a 7-year period between 2004 and 2010. RESULTS: A recursive algorithm was developed and validated, based on six International Classification of Disease, 9th Edition, Clinical Modification, codes and one procedure code that had a sensitivity up to 90% (range 61-90%) and a specificity up to 99% (range 53-99%) for identifying inherited leukodystrophy patients. Inherited leukodystrophy patients comprise 0.4% of admissions to children's hospitals and 0.7% of costs. During 7 years, these patients required $411 million of hospital care, or $131,000/patient. Hospital costs for leukodystrophy patients varied at different institutions, ranging from two to 15 times more than the average pediatric patient. There was a statistically significant correlation between higher volume and increased cost efficiency. Increased mortality rates had an inverse relationship with increased patient volume that was not statistically significant. CONCLUSIONS: We developed and validated a code-based algorithm for identifying leukodystrophy patients in deidentified national datasets. Leukodystrophy patients account for $59 million of costs yearly at children's hospitals. Our data highlight potential to reduce unwarranted variability and improve patient care.

Determinants of health care use in a population-based leukodystrophy cohort.

OBJECTIVES: To determine the costs for children with leukodystrophies and whether high costs are associated with characteristic clinical features or resources use. STUDY DESIGN: We determined health care costs in a population cohort of 122 patients with leukodystrophies, including inpatient, outpatient, and emergency department use, during a 9-year period. We analyzed differences in patients with high costs (>85th percentile) and their health care use. RESULTS: Patients with leukodystrophy had significant variability in resource use, with the top 15th percentile of patients accounting for 73% of costs ($9.6 million). The majority of costs, 81% ($10.8 million), arose from inpatient hospitalization. High-cost patients had more and longer hospitalizations, increased requirements for intensive unit care and mechanical ventilation, and significantly more infections. Importantly, bone marrow transplantation did not solely account for the difference between high-cost and low-cost groups. CONCLUSION: Inpatient hospitalization is the greatest source of health care resource use in patients with leukodystrophies. A minority of patients account for the majority of costs, primarily attributable to an increased volume of hospitalization. Strategies to improve care and reduce costs will need to reduce inpatient stays and target modifiable reasons for hospitalization.

Hypoxia disruption of vertebrate CNS pathfinding through ephrinB2 Is rescued by magnesium.

The mechanisms of hypoxic injury to the developing human brain are poorly understood, despite being a major cause of chronic neurodevelopmental impairments. Recent work in the invertebrate Caenorhabditis elegans has shown that hypoxia causes discrete axon pathfinding errors in certain interneurons and motorneurons. However, it is unknown whether developmental hypoxia would have similar effects in a vertebrate nervous system. We have found that developmental hypoxic injury disrupts pathfinding of forebrain neurons in zebrafish (Danio rerio), leading to errors in which commissural axons fail to cross the midline. The pathfinding defects result from activation of the hypoxia-inducible transcription factor (hif1) pathway and are mimicked by chemical inducers of the hif1 pathway or by expression of constitutively active hif1α. Further, we found that blocking transcriptional activation by hif1α helped prevent the guidance defects. We identified ephrinB2a as a target of hif1 pathway activation, showed that knock-down of ephrinB2a rescued the guidance errors, and showed that the receptor ephA4a is expressed in a pattern complementary to the misrouting axons. By targeting a constitutively active form of ephrinB2a to specific neurons, we found that ephrinB2a mediates the pathfinding errors via a reverse-signaling mechanism. Finally, magnesium sulfate, used to improve neurodevelopmental outcomes in preterm births, protects against pathfinding errors by preventing upregulation of ephrinB2a. These results demonstrate that evolutionarily conserved genetic pathways regulate connectivity changes in the CNS in response to hypoxia, and they support a potential neuroprotective role for magnesium.

Gal80 intersectional regulation of cell-type specific expression in vertebrates.

Characterization and functional manipulation of specific groups of neurons in the vertebrate central nervous system (CNS) remains a major hurdle for understanding complex circuitry and functions. In zebrafish, the Gal4/UAS system has permitted expression of transgenes and enhancer trap screens, but is often limited by broad expression domains. We have developed a method for cell-type specific expression using Gal80 inhibition of Gal4-dependent expression. We show that native Gal4 is able to drive strong expression, that Gal80 can inhibit this expression, and that overlapping Gal4 and Gal80 expression can achieve "intersectional" expression in spatially and genetically defined subsets of neurons. We also optimize Gal80 for expression in vertebrates, track Gal80 expression with a co-expressed fluorescent marker, and use a temperature-sensitive allele of Gal80 to temporally regulate its function. These data demonstrate that Gal80 is a powerful addition to the genetic techniques available to map and manipulate neural circuits in zebrafish.