A Survey of Pediatric Neurocritical Care Fellowship Training in North America.

BACKGROUND: Pediatric neurocritical care (PNCC) has emerged as a field to care for children at the intersection of critical illness and neurological dysfunction. PNCC fellowship programs evolved over the past decade to train physicians to fill this clinical need. We aimed to characterize PNCC fellowship training infrastructure and curriculum in the United States and Canada. METHODS: Web-based survey of PNCC fellowship program leaders during November 2019 to January 2020. RESULTS: There were 14 self-identified PNCC fellowship programs. The programs were supported by Child Neurology and/or Pediatric Critical Care Medicine divisions at tertiary/quaternary care institutions. Most programs accepted trainees who were board-eligible or board-certified in child neurology or pediatric critical care medicine. Clinical training consisted mostly of rotations providing PNCC consultation (n = 13) or as a provider on the pediatric intensive care unit-based neurointensive care team (n = 2). PNCC-specific didactics were delivered at most institutions (n = 13). All institutions provided training in electroencephalography use in the intensive care unit and declaration of death by neurological criteria (n = 14). Scholarly activity was supported by most programs, including protected time for research (n = 10). CONCLUSIONS: We characterized PNCC fellowship training in the United States and Canada, which in this continuously evolving field, lays the foundation for exploring standardization of training going forward.

Thrombophilia screening in the routine clinical care of children with arterial ischemic stroke.

BACKGROUND: Current guidelines recommend thrombophilia evaluation in childhood arterial ischemic stroke, but the impact of screening on management is unknown. The objective of the current study is to report the incidence of thrombophilia identified as part of routine clinical care in the context of available literature reports, and to describe the impact of a diagnosis of thrombophilia on patient management. METHODS: We conducted a single-institution retrospective chart review for all children with arterial ischemic stroke occurring between January 1, 2009 and January 1, 2021. We collected thrombophilia screening results, stroke etiology, and management. We also reviewed the literature of thrombophilia testing in childhood arterial ischemic stroke published prior to June 30, 2022. Meta-analysis methods were used to assess prevalence rates. RESULTS: Among children with thrombophilia testing performed, 5% (six of 122 patients) were factor V Leiden heterozygous, 1% (one of 102 patients) were prothrombin gene mutation heterozygous, 1% (one of 122) had protein S deficiency, 20% (23/116 patients) had elevated lipoprotein(a), 3% (three of 110 patients) had elevated homocysteine levels, and 9% (10/112) had elevated antiphospholipid antibodies, only two of whom had persistently elevated levels. There was no change in stroke therapy due to these results. Literature review revealed a wide range of prevalence for most thrombophilia traits, with high cross-study heterogeneity in most cases. CONCLUSIONS: The rates of thrombophilia in our cohort were consistent with that expected in the general population. The identification of thrombophilia did not alter stroke care. However, some of the results were actionable, prompting evaluation for lipid disorders and patient-specific counseling on cardiovascular risk and risk for venous thrombosis.

Phenotypes and Genotypes in Patients with SMC1A-Related Developmental and Epileptic Encephalopathy.

The X-linked SMC1A gene encodes a core subunit of the cohesin complex that plays a pivotal role in genome organization and gene regulation. Pathogenic variants in SMC1A are often dominant-negative and cause Cornelia de Lange syndrome (CdLS) with growth retardation and typical facial features; however, rare SMC1A variants cause a developmental and epileptic encephalopathy (DEE) with intractable early-onset epilepsy that is absent in CdLS. Unlike the male-to-female ratio of 1:2 in those with CdLS associated with dominant-negative SMC1A variants, SMC1A-DEE loss-of-function (LOF) variants are found exclusively in females due to presumed lethality in males. It is unclear how different SMC1A variants cause CdLS or DEE. Here, we report on phenotypes and genotypes of three females with DEE and de novo SMC1A variants, including a novel splice-site variant. We also summarize 41 known SMC1A-DEE variants to characterize common and patient-specific features. Interestingly, compared to 33 LOFs detected throughout the gene, 7/8 non-LOFs are specifically located in the N/C-terminal ATPase head or the central hinge domain, both of which are predicted to affect cohesin assembly, thus mimicking LOFs. Along with the characterization of X-chromosome inactivation (XCI) and SMC1A transcription, these variants strongly suggest that a differential SMC1A dosage effect of SMC1A-DEE variants is closely associated with the manifestation of DEE phenotypes.

Risk of Intracranial Hemorrhage Following Intravenous tPA (Tissue-Type Plasminogen Activator) for Acute Stroke Is Low in Children.

Background and Purpose- Data regarding the safety and efficacy of intravenous tPA (tissue-type plasminogen activator) in childhood acute arterial ischemic stroke are inadequate. The TIPS trial (Thrombolysis in Pediatric Stroke; National Institutes of Health grant R01NS065848)-a prospective safety and dose-finding trial of intravenous tPA in acute childhood stroke-was closed for lack of accrual. TIPS sites have subsequently treated children with acute stroke in accordance with established institutional protocols supporting data collection on outcomes. Methods- Data on children treated with intravenous tPA for neuroimaging-confirmed arterial ischemic stroke were collected retrospectively from 16 former TIPS sites to establish preliminary safety data. Participating sites were required to report all children who were treated with intravenous tPA to minimize reporting bias. Symptomatic intracranial hemorrhage (SICH) was defined as ECASS (European Cooperative Acute Stroke Study) II parenchymal hematoma type 2 or any intracranial hemorrhage associated with neurological deterioration within 36 following tPA administration. A Bayesian beta-binomial model for risk of SICH following intravenous tPA was fit using a prior distribution based on the risk level in young adults (1.7%); to test for robustness, the model was also fit with uninformative and conservative priors. Results- Twenty-six children (age range, 1.1-17 years; median, 14 years; 12 boys) with stroke and a median pediatric National Institutes of Health Stroke Scale score of 14 were treated with intravenous tPA within 2 to 4.5 hours (median, 3.0 hours) after stroke onset. No patient had SICH. Two children developed epistaxis. Conclusions- The estimated risk of SICH after tPA in children is 2.1% (95% highest posterior density interval, 0.0%-6.7%; mode, 0.9%). Regardless of prior assumption, there is at least a 98% chance that the risk is <15% and at least a 93% chance that the risk is <10%. These results suggest that the overall risk of SICH after intravenous tPA in children with acute arterial ischemic stroke, when given within 4.5 hours after symptom onset, is low.

Effect of Custom Foot Insoles on Postural Stability in Figure Skaters While on Ice.

CONTEXT: Improvements in postural stability in figure skaters can play a significant role in performance, as well as reducing fall risk. OBJECTIVE: To explore the effect of custom foot insoles on postural stability in advanced figure skaters. DESIGN: Exploratory study. SETTING: Out of laboratory. PARTICIPANTS: Nine advanced figure skaters were recruited and 7 completed the study (age 38 ± 18.5 y, body-mass index 25 ± 3.6 kg/m2). INTERVENTION: Custom foot insoles. MAIN OUTCOME MEASURES: Primary outcome of changes in postural stability (PS) quantified by center-of-mass sway with secondary outcomes of ankle- and hip-joint sway and joint range of motion. Sway measurements were assessed using body-worn sensors while participants wore skates on ice. PS was assessed in single-leg stance, as well as during gliding on the dominant foot. RESULTS: A significant improvement in static PS was observed after 6-wk use of custom insoles. Center-of-mass sway reduced significantly on average by 48.44% (P = .023), and ankle-joint sway reduced by 45.7% (P = .05) during single-leg-stance balance measurements. During the gliding maneuver nonsignificant changes were observed for both ankle- and knee-joint range of motion. CONCLUSION: The results of this study suggest proof of concept toward benefits of custom insoles in improving postural stability in advanced figure skaters. To generalize the findings, randomized controlled trials with larger sample sizes are warranted.

Estimation of Center of Mass Trajectory using Wearable Sensors during Golf Swing.

This study suggests a wearable sensor technology to estimate center of mass (CoM) trajectory during a golf swing. Groups of 3, 4, and 18 participants were recruited, respectively, for the purpose of three validation studies. Study 1 examined the accuracy of the system to estimate a 3D body segment angle compared to a camera-based motion analyzer (Vicon®). Study 2 assessed the accuracy of three simplified CoM trajectory models. Finally, Study 3 assessed the accuracy of the proposed CoM model during multiple golf swings. A relatively high agreement was observed between wearable sensors and the reference (Vicon®) for angle measurement (r > 0.99, random error <1.2° (1.5%) for anterior-posterior; <0.9° (2%) for medial-lateral; and <3.6° (2.5%) for internal-external direction). The two-link model yielded a better agreement with the reference system compared to one-link model (r > 0.93 v. r = 0.52, respectively). On the same note, the proposed two-link model estimated CoM trajectory during golf swing with relatively good accuracy (r > 0.9, A-P random error <1cm (7.7%) and <2cm (10.4%) for M-L). The proposed system appears to accurately quantify the kinematics of CoM trajectory as a surrogate of dynamic postural control during an athlete's movement and its portability, makes it feasible to fit the competitive environment without restricting surface type. Key pointsThis study demonstrates that wearable technology based on inertial sensors are accurate to estimate center of mass trajectory in complex athletic task (e.g., golf swing)This study suggests that two-link model of human body provides optimum tradeoff between accuracy and minimum number of sensor module for estimation of center of mass trajectory in particular during fast movements.Wearable technologies based on inertial sensors are viable option for assessing dynamic postural control in complex task outside of gait laboratory and constraints of cameras, surface, and base of support.

Sensor-Based Interactive Balance Training with Visual Joint Movement Feedback for Improving Postural Stability in Diabetics with Peripheral Neuropathy: A Randomized Controlled Trial.

BACKGROUND: Individuals with diabetic peripheral neuropathy (DPN) have deficits in sensory and motor skills leading to inadequate proprioceptive feedback, impaired postural balance and higher fall risk. OBJECTIVE: This study investigated the effect of sensor-based interactive balance training on postural stability and daily physical activity in older adults with diabetes. METHODS: Thirty-nine older adults with DPN were enrolled (age 63.7 ± 8.2 years, BMI 30.6 ± 6, 54% females) and randomized to either an intervention (IG) or a control (CG) group. The IG received sensor-based interactive exercise training tailored for people with diabetes (twice a week for 4 weeks). The exercises focused on shifting weight and crossing virtual obstacles. Body-worn sensors were implemented to acquire kinematic data and provide real-time joint visual feedback during the training. Outcome measurements included changes in center of mass (CoM) sway, ankle and hip joint sway measured during a balance test while the eyes were open and closed at baseline and after the intervention. Daily physical activities were also measured during a 48-hour period at baseline and at follow-up. Analysis of covariance was performed for the post-training outcome comparison. RESULTS: Compared with the CG, the patients in the IG showed a significantly reduced CoM sway (58.31%; p = 0.009), ankle sway (62.7%; p = 0.008) and hip joint sway (72.4%; p = 0.017) during the balance test with open eyes. The ankle sway was also significantly reduced in the IG group (58.8%; p = 0.037) during measurements while the eyes were closed. The number of steps walked showed a substantial but nonsignificant increase (+27.68%; p = 0.064) in the IG following training. CONCLUSION: The results of this randomized controlled trial demonstrate that people with DPN can significantly improve their postural balance with diabetes-specific, tailored, sensor-based exercise training. The results promote the use of wearable technology in exercise training; however, future studies comparing this technology with commercially available systems are required to evaluate the benefit of interactive visual joint movement feedback.