Bringing high-grade arteriovenous malformations under control: clinical outcomes following multimodality treatment in children.

OBJECTIVE:Brain arteriovenous malformations (AVMs) consist of dysplastic blood vessels with direct arteriovenous shunts that can hemorrhage spontaneously. In children, a higher lifetime hemorrhage risk must be balanced with treatment-related morbidity. The authors describe a collaborative, multimodal strategy resulting in effective and safe treatment of pediatric AVMs. METHODS:A retrospective analysis of a prospectively maintained database was performed in children with treated and nontreated pediatric AVMs at the University of California, San Francisco, from 1998 to 2017. Inclusion criteria were age ≤ 18 years at time of diagnosis and an AVM confirmed by a catheter angiogram. RESULTS:The authors evaluated 189 pediatric patients with AVMs over the study period, including 119 ruptured (63%) and 70 unruptured (37%) AVMs. The mean age at diagnosis was 11.6 ± 4.3 years. With respect to Spetzler-Martin (SM) grade, there were 38 (20.1%) grade I, 40 (21.2%) grade II, 62 (32.8%) grade III, 40 (21.2%) grade IV, and 9 (4.8%) grade V lesions. Six patients were managed conservatively, and 183 patients underwent treatment, including 120 resections, 82 stereotactic radiosurgery (SRS), and 37 endovascular embolizations. Forty-four of 49 (89.8%) high-grade AVMs (SM grade IV or V) were treated. Multiple treatment modalities were used in 29.5% of low-grade and 27.3% of high-grade AVMs. Complete angiographic obliteration was obtained in 73.4% of low-grade lesions (SM grade I-III) and in 45.2% of high-grade lesions. A periprocedural stroke occurred in a single patient (0.5%), and there was 1 treatment-related death. The mean clinical follow-up for the cohort was 4.1 ± 4.6 years, and 96.6% and 84.3% of patients neurologically improved or remained unchanged in the ruptured and unruptured AVM groups following treatment, respectively. There were 16 bleeding events following initiation of AVM treatment (annual rate: 0.02 events per person-year). CONCLUSIONS:Coordinated multidisciplinary evaluation and individualized planning can result in safe and effective treatment of children with AVMs. In particular, it is possible to treat the majority of high-grade AVMs with an acceptable safety profile. Judicious use of multimodality therapy should be limited to appropriately selected patients after thorough team-based discussions to avoid additive morbidity. Future multicenter studies are required to better design predictive models to aid with patient selection for multimodal pediatric care, especially with high-grade AVMs

Cost-effective therapeutic hypothermia treatment device for hypoxic ischemic encephalopathy

Despite recent advances in neonatal care and monitoring, asphyxia globally accounts for 23% of the 4 million annual deaths of newborns, and leads to hypoxic-ischemic encephalopathy (HIE). Occurring in five of 1000 live-born infants globally and even more in developing countries, HIE is a serious problem that causes death in 25%–50% of affected neonates and neurological disability to at least 25% of survivors. In order to prevent the damage caused by HIE, our invention provides an effective whole-body cooling of the neonates by utilizing evaporation and an endothermic reaction. Our device is composed of basic electronics, clay pots, sand, and urea-based instant cold pack powder. A larger clay pot, lined with nearly 5 cm of sand, contains a smaller pot, where the neonate will be placed for therapeutic treatment. When the sand is mixed with instant cold pack urea powder and wetted with water, the device can extract heat from inside to outside and maintain the inner pot at 17°C for more than 24 hours with monitoring by LED lights and thermistors. Using a piglet model, we confirmed that our device fits the specific parameters of therapeutic hypothermia, lowering the body temperature to 33.5°C with a 1°C margin of error. After the therapeutic hypothermia treatment, warming is regulated by adjusting the amount of water added and the location of baby inside the device. Our invention uniquely limits the amount of electricity required to power and operate the device compared with current expensive and high-tech devices available in the United States. Our device costs a maximum of 40 dollars and is simple enough to be used in neonatal intensive care units in developing countries

FoxP1 orchestration of ASD-relevant signaling pathways in the striatum

Mutations in the transcription factor Forkhead box p1 (FOXP1) are causative for neurodevelopmental disorders such as autism. However, the function of FOXP1 within the brain remains largely uncharacterized. Here, we identify the gene expression program regulated by FoxP1 in both human neural cells and patient-relevant heterozygous Foxp1 mouse brains. We demonstrate a role for FoxP1 in the transcriptional regulation of autism-related pathways as well as genes involved in neuronal activity. We show that Foxp1 regulates the excitability of striatal medium spiny neurons and that reduction of Foxp1 correlates with defects in ultrasonic vocalizations. Finally, we demonstrate that FoxP1 has an evolutionarily conserved role in regulating pathways involved in striatal neuron identity through gene expression studies in human neural progenitors with altered FOXP1 levels. These data support an integral role for FoxP1 in regulating signaling pathways vulnerable in autism and the specific regulation of striatal pathways important for vocal communication

Efficacy of using a 3D printed lumbosacral spine phantom in improving trainee proficiency and confidence in CT-guided spine procedures

Abstract Background Minimally-invasive spine procedures provide targeted, individualized diagnosis and pain management for patients. Competence in these procedures is acquired through experience and training. We created a 3D printed model of a degenerative lumbosacral spine with scoliosis and spondylosis, using materials that mimic bone and soft tissue density under CT. In this study, we evaluate the efficacy of using such a spine model to improve novice trainee confidence and proficiency in performing CT-guided facet joint injections. Results Thirteen medical students with no prior exposure to CT-guided spine procedures were divided into two groups. Both groups received an introductory didactic lecture, as well as identical pre- and post- test assessments. The Training group (7 students) received two separate training sessions using the simulation model. The Control group (6 students) received only one training session. The Training group demonstrated significantly fewer needle readjustments during the second simulation session, compared with the first session (p = 0.005). Both groups demonstrated significant increase in confidence in ability to perform CT-guided spine procedures on the post-test (p = 0.004 for the Control group and p = 0.00001 for the Training group). Conclusion A 3D printed lumbosacral spine phantom with realistic spondylosis can be made to facilitate novice training in minimally-invasive spine procedures. Training using a realistic lumbosacral spine model helps novices acquire the skills and confidence to perform CT-guided spine procedures

Peroneal Nerve Repair with Cross-Bridge Ladder Technique: Parallel End-to-Side Neurorrhaphies

Background Multiple nerve transfer techniques are used to treat patients with nerve injuries when a primary repair is not possible. These techniques are categorized to end-to-end, end-to-side, and side-to-side neurorrhaphy. Our study aims to explore the utility of the cross-bridge ladder technique (H-shaped), which has shown promising results in animal models and probably underutilized clinically. Methods Four patients with significant loss of ankle dorsiflexion were seen in the clinic and underwent evaluation, including electrodiagnostic studies. A cross-bridge ladder repair technique was used between the tibial nerve as the donor and the common peroneal nerve as the recipient via one or two nerve grafts coapted in parallel with end-to-side neurorrhaphies. Dorsiflexion strength was measured preoperatively using the Medical Research Council (MRC) grading system and at each postoperative follow-up appointment. Results All four patients had suffered persistent and severe foot drop (MRC of 0) following trauma that had occurred between 6 and 15 months preoperatively. Three of the four patients improved to an MRC of 2 several months postoperatively. The last patient had an immediate improvement to an MRC of 2 by his first month and had a complete recovery of ankle dorsiflexion within 4 months from surgery. Conclusion We demonstrate the utility and clinical outcomes of the cross-bridge ladder technique in patients with persistent and prolonged foot drop following trauma. Both early and late recovery were seen while all patients regained motor function, with some patients continuing to improve up to the most recent follow-up. IRB Approval: Obtained 2013–1411-CP00