Stereotactic Awake Basal Ganglia Electrophysiological Recording and Stimulation (SABERS): A Novel Staged Procedure for Personalized Targeting of Deep Brain Stimulation in Pediatric Movement and Neuropsychiatric Disorders.

Selection of targets for deep brain stimulation (DBS) has been based on clinical experience, but inconsistent and unpredictable outcomes have limited its use in patients with heterogeneous or rare disorders. In this large case series, a novel staged procedure for neurophysiological assessment from 8 to 12 temporary depth electrodes is used to select targets for neuromodulation that are tailored to each patient's functional needs. Thirty children and young adults underwent deep brain stimulation target evaluation with the new procedure: Stereotactic Awake Basal ganglia Electrophysiological Recording and Stimulation (SABERS). Testing is performed in an inpatient neuromodulation monitoring unit over 5-7 days, and results guide the decision to proceed and the choice of targets for permanent deep brain stimulation implantation. Results were evaluated 3-6 months postoperatively with the Burke-Fahn-Marsden Dystonia Rating Scale and the Barry-Albright Dystonia Scale. Stereotactic Awake Basal ganglia Electrophysiological Recording and Stimulation testing allowed modulation to be tailored to specific neurologic deficits in a heterogeneous population, including subjects with primary dystonia, secondary dystonia, and Tourette syndrome. All but one subject were implanted with 4 permanent deep brain stimulation leads. Results showed significant improvement on both scales at postoperative follow-up. No significant adverse events occurred. Use of the Stereotactic Awake Basal ganglia Electrophysiological Recording and Stimulation protocol with evaluation in the neuromodulation monitoring unit is feasible and results in significant patient benefit compared with previously published results in these populations. This new technique supports a significant expansion of functional neurosurgery to predict effective stimulation targets in a wide range of disorders of brain function, including those for which the optimal target is not yet known.

Novel utilization of deep brain stimulation in the pedunculopontine nucleus with globus pallidus internus for treatment of childhood-onset dystonia.

Introduction: Deep brain stimulation (DBS) is a well-documented therapy for dystonia utilized in many adult and pediatric movement disorders. Pedunculopontine nucleus (PPN) has been investigated as a DBS target primarily in adult patients with dystonia or dyskinesias from Parkinson's disease, showing improvement in postural instability and gait dysfunction. Due to the difficulty in targeting PPN using standard techniques, it is not commonly chosen as a target for adult or pediatric pathology. There is no current literature describing the targeting of PPN in DBS for childhood-onset dystonia. Methods: Two pediatric and one young adult patient with childhood-onset dystonia who underwent DBS implantation at our institution were identified. Patient 1 has Mitochondrial Enoyl CoA Reductase Protein-Associated Neurodegeneration (MEPAN) syndrome. Patient 2 has Glutaric Aciduria Type 1 (GA1). Patient 3 has atypical pantothenate kinase-associated neurodegeneration (PKAN). PPN was identified as a potential target for these patients due to axial or orofacial dystonia. Pre- and post-operative videos taken as part of routine clinical assessments were evaluated and scored on the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Barry-Albright Dystonia Scale (BADS). All patients had permanent electrodes placed bilaterally in PPN and globus pallidus internus (GPi). A Likert scale on quality of life was also obtained from the patient/parents as applicable. Results: Significant programming was necessary over the first 3-12 months to optimize patients' response to stimulation. All patients experienced at least a 34% improvement in the BFMDRS score. Patients 2 and 3 also experienced an over 30% improvement in BADS score. All patients/parents appreciated improvement in quality of life postoperatively. Discussion: Deep brain stimulation in PPN was safely and successfully used in two pediatric patients and one young adult patient with childhood-onset dystonia. These patients showed clinically significant improvements in BFMDRS scoring post operatively. This represents the first reported DBS targeting of PPN in pediatric patients, and suggests that PPN is a possible target for pediatric-onset dystonia with axial and orofacial symptoms that may be refractory to traditional pallidal stimulation alone.

What is the effect of benzodiazepines on deep brain activity? A study in pediatric patients with dystonia.

Introduction: Benzodiazepines (BDZs) are commonly used to treat the symptoms of movement disorders; however, deep brain stimulation (DBS) has become a popular treatment for these disorders. Previous studies have investigated the effects of BDZ on cortical activity, no data are currently available on their effects on deep brain regions, nor on these regions' responses to DBS. How the BDZ affects the thalamus and basal ganglia in dystonia patients remains unknown. Methods: DBS recordings were performed in ventral oralis anterior/posterior (VoaVop), ventral intermediate (VIM) and ventral anterior (VA) thalamic subnuclei, as well as globus pallidus interna (GPi) and subthalamic nucleus (STN). Evoked potentials (EP) and frequency domain analysis were performed to determine the BDZ effect on neural activities compared to the control condition (off-BDZ). Three male pediatric patients with dystonia treated with BDZ and undergoing depth electrode evaluation for clinical targeting were recruited for the study. Stimulation was administered at 25 and 55 Hz frequencies and recordings were simultaneously gathered through pairs of externalized stereoelectroencephalography (sEEG) electrodes. EP amplitude and the effect of stimulation on the frequency spectrum of activity were compared at baseline and following clinical administration of BDZ. Results: Frequency analysis showed consistent reductions in activity during BDZ treatment in all studied brain regions for all patients. Evoked potential (EP) analysis showed increased subthalamic nucleus (STN) EP amplitude and decreased ventral intermediate (VIM) and STN EP amplitude during BDZ treatment. Interpretation: BDZs reduce thalamic and basal ganglia activity in multiple regions and alter the efficacy of transmission between these regions. While the mechanism is unknown our results confirm the known widespread effects of this class of medications and identify specific areas within the motor system that are directly affected.

Design and testing of a sew-free origami mask for improvised respiratory protection.

Respiratory aerosols with diameters smaller than 100µm have been confirmed as important vectors for the spread of diseases such as SARS-CoV-2. While disposable and cloth masks afford some protection, they are typically inefficient at filtering these aerosols and require specialized fabrication devices to produce. We describe a fabrication technique that makes use of a folding procedure (origami) to transform any filtration material into a mask. These origami masks can be fabricated by non-experts at minimal cost and effort, provide adequate filtration efficiencies, and are easily scaled to different facial sizes. Using a mannequin fit test simulator, we demonstrate that these masks can provide filtration efficiencies of over 90% while simultaneously providing greater comfort as demonstrated by pressure drops of <20 Pa. We also quantify mask leakage by measuring the variations in filtration efficiency and pressure drop when masks are sealed to the mannequin face compared to when the mask is unsealed but positioned to achieve the best fit. While leakage generally trended with pressure drop, some of the best performing mask media achieved <10% reduction in filtration efficiency due to leakage. Because this mask can provide high filtration efficiencies at low pressure drop compared to commercial alternatives, it is likely to promote greater mask wearing tolerance and acceptance.

Chronic Neurological Disorders and Predisposition to Severe COVID-19 in Pediatric Patients in the United States.

BACKGROUND: We investigated the association between chronic pediatric neurological conditions and the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This matched retrospective case-control study includes patients (n = 71,656) with chronic complex neurological disorders under 18 years of age, with laboratory-confirmed diagnosis of COVID-19 or a diagnostic code indicating infection or exposure to SARS-CoV-2, from 103 health systems in the United States. The primary outcome was the severity of coronavirus disease 2019 (COVID-19), which was classified as severe (invasive oxygen therapy or death), moderate (noninvasive oxygen therapy), or mild/asymptomatic (no oxygen therapy). A cumulative link mixed effects model was used for this study. RESULTS: In this study, a cumulative link mixed effects model (random intercepts for health systems and patients) showed that the following classes of chronic neurological disorders were associated with higher odds of severe COVID-19: muscular dystrophies and myopathies (OR = 3.22; 95% confidence interval [CI]: 2.73 to 3.84), chronic central nervous system disorders (OR = 2.82; 95% CI: 2.67 to 2.97), cerebral palsy (OR = 1.97; 95% CI: 1.85 to 2.10), congenital neurological disorders (OR = 1.86; 95% CI: 1.75 to 1.96), epilepsy (OR = 1.35; 95% CI: 1.26 to 1.44), and intellectual developmental disorders (OR = 1.09; 95% CI: 1.003 to 1.19). Movement disorders were associated with lower odds of severe COVID-19 (OR = 0.90; 95% CI: 0.81 to 0.99). CONCLUSIONS: Pediatric patients with chronic neurological disorders are at higher odds of severe COVID-19. Movement disorders were associated with lower odds of severe COVID-19.

Improvement of speed-accuracy tradeoff during practice of a point-to-point task in children with acquired dystonia.

The tradeoff between speed and accuracy is a well-known constraint for human movement, but previous work has shown that this tradeoff can be modified by practice, and the quantitative relationship between speed and accuracy may be an indicator of skill in some tasks. We have previously shown that children with dystonia are able to adapt their movement strategy in a ballistic throwing game to compensate for increased variability of movement. Here, we test whether children with dystonia can adapt and improve skills learned on a trajectory task. We use a novel task in which children move a spoon with a marble between two targets. Difficulty is modified by changing the depth of the spoon. Our results show that both healthy children and children with acquired dystonia move more slowly with the more difficult spoons, and both groups improve the relationship between speed and spoon difficulty following 1 wk of practice. By tracking the marble position in the spoon, we show that children with dystonia use a larger fraction of the available variability, whereas healthy children adopt a much safer strategy and remain farther from the margins, as well as learning to adapt and have more control over the marble's utilized area by practice. Together, our results show that both healthy children and children with dystonia choose trajectories that compensate for risk and inherent variability, and that the increased variability in dystonia can be modified with continued practice.NEW & NOTEWORTHY This study provides insights into the adaptability of children with dystonia in learning a point-to-point task. We show that these children adjust their strategies to account for increased difficulty in the task. Our findings underscore the potential of task-specific practice in improving motor skills and show higher level of signal-dependent noise can be controlled through repetition and learned strategies, which provides an avenue for the quantitative evaluation of rehabilitation strategies in this challenging group.

Deep brain stimulation in an adolescent with hypomyelination with atrophy of the basal ganglia and cerebellum due to a TUBB4A mutation: illustrative case.

BACKGROUND: Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare genetic disease due to a TUBB4A mutation, with motor features including dystonia. Deep brain stimulation (DBS) can be used to treat dystonia in pediatric populations, although the response is highly variable and preferential toward specific etiologies. OBSERVATIONS: A single pediatric subject with H-ABC received DBS using a staged procedure involving temporary depth electrode placement, identification of optimal stimulation targets, and permanent electrode implantation. After surgery, the patient significantly improved on both the Burke-Fahn-Marsden Dystonia Rating Scale and the Barry-Albright Dystonia Scale. The patient's response suggests that DBS can have potential benefit in H-ABC. LESSONS: TUBB4A mutations are associated with a variety of clinical phenotypes, and there is a lack of clearly identified targets for DBS, with this case being the second reported instance of DBS in this condition. The staged procedure with temporary depth electrode testing is recommended to identify optimal stimulation targets. The response seen in this patient implies that such a staged procedure may provide benefit in other conditions where DBS targets are currently unknown, including rare genetic or metabolic conditions associated with movement disorders.

Globus pallidus internus activity increases during voluntary movement in children with dystonia.

The rate model of basal ganglia function predicts that muscle activity in dystonia is due to disinhibition of thalamus resulting from decreased inhibitory input from pallidum. We seek to test this hypothesis in children with dyskinetic cerebral palsy undergoing evaluation for deep brain stimulation (DBS) to analyze movement-related activity in different brain regions. The results revealed prominent beta-band frequency peaks in the globus pallidus interna (GPi), ventral oralis anterior/posterior (VoaVop) subnuclei of the thalamus, and subthalamic nucleus (STN) during movement but not at rest. Connectivity analysis indicated stronger coupling between STN-VoaVop and STN-GPi compared to GPi-STN. These findings contradict the hypothesis of decreased thalamic inhibition in dystonia, suggesting that abnormal patterns of inhibition and disinhibition, rather than reduced GPi activity, contribute to the disorder. Additionally, the study implies that correcting abnormalities in GPi function may explain the effectiveness of DBS targeting the STN and GPi in treating dystonia.

Impact of COVID-19 pandemic on pediatric healthcare burnout in acute care: a longitudinal study.

BACKGROUND: COVID-19 pandemic introduced significant challenges that may have exacerbated healthcare worker (HCW) burnout. To date, assessments of burnout during COVID-19 pandemic have been cross-sectional, limiting our understanding of changes in burnout. This longitudinal study assessed change across time in pediatric HCW burnout during the COVID-19 pandemic and whether demographic and psychological factors were associated with changes in burnout. METHODS: This longitudinal study included 162 physicians, physician assistants, nurses, and medical technicians within the emergency department (ED), intensive care, perioperative, and inter-hospital transport services in a children's hospital. HCW demographics, anxiety and personality traits were reported via validated measures. HCWs completed the Maslach Burnout Inventory in April 2020 and March 2021. Data were analyzed using generalized estimating equations. RESULTS: The percentage of HCWs reporting high emotional exhaustion and/or depersonalization burnout increased significantly across time (18.5% to 28.4%, P = 0.010). Factors associated with increased emotional exhaustion included working in the ED (P = 0.011) or perioperative department (P < 0.001), being a nurse or medical technician (P's < 0.001), not having children (P < 0.001), and low conscientiousness (P < 0.001). CONCLUSIONS: Pediatric HCW burnout significantly increased over 11-months of the COVID-19 pandemic. Results suggest that certain demographic and psychological factors may represent potential area to target for intervention for future pandemics. IMPACT: This longitudinal study revealed that the COVID-19 pandemic has had a significant impact on pediatric healthcare worker burnout. The percentage of healthcare workers reporting high levels of emotional exhaustion and depersonalization burnout increased significantly over 11-months of the COVID-19 pandemic. Results suggest that certain demographic and psychological factors may represent potential targets for future interventions.

Improvement of speed-accuracy tradeoff during practice of a point to point task in children with secondary dystonia.

The tradeoff between speed and accuracy is a well-known constraint for human movement, but previous work has shown that this tradeoff can be modified by practice, and the quantitative relationship between speed and accuracy may be an indicator of skill in some tasks. We have previously shown that children with dystonia are able to adapt their movement strategy in a ballistic throwing game to compensate for increased variability of movement. Here we test whether children with dystonia can adapt and improve skill learnt on a trajectory task. We use a novel task in which children move a spoon with a marble between two targets. Difficulty is modified by changing the depth of the spoon. Our results show that both healthy children and children with secondary dystonia move more slowly with the more difficult spoons, and both groups improve the relationship between speed and spoon difficulty following one week of practice. By tracking the marble position in the spoon, we show that children with dystonia use a larger fraction of the available variability, whereas healthy children adopt a much safer strategy and remain farther from the margins, as well as learning to adopt and have more control over the marble's utilized area by practice. Together, our results show that both healthy children and children with dystonia choose trajectories that compensate for risk and inherent variability, and that the increased variability in dystonia can be modified with continued practice.

The Effects of Prolonged Vibrotactile EMG-Based Biofeedback on Ankle Joint Range of Motion During Gait in Children with Spastic Cerebral Palsy: A Case Series.

AIMS: The objective of this case series was to examine the feasibility of vibrotactile EMG-based biofeedback (BF) as a home-based intervention tool to enhance sensory information during everyday motor activities and to explore its effectiveness to induce changes in active ankle range of motion during gait in children with spastic cerebral palsy (CP). METHODS: Ten children ages 6 to 13 years with spastic CP were recruited. Participants wore two EMG-based vibro-tactile BF devices for at least 4 hours per day for 1-month on the ankle and knee joints muscles. The device computed the amplitude of the EMG signal of the target muscle and actuated a silent vibration motor proportional to the magnitude of the EMG. RESULTS: Our results demonstrated the feasibility of the augmented sensory information of muscle activity to induce changes of the active ankle range of motion during gait for 6 children with an increase ranging from 8.9 to 51.6% compared to a one-month period without treatment. CONCLUSIONS: Preliminary findings of this case series demonstrate the feasibility of vibrotactile EMG-based BF and suggest potential effectiveness to increase active ankle range of motion, therefore serving as a promising therapeutic tool to improve gait in children with spastic CP.

Application of deep brain stimulation for the treatment of childhood-onset dystonia in patients with MEPAN syndrome.

Introduction: Mitochondrial Enoyl CoA Reductase Protein-Associated Neurodegeneration (MEPAN) syndrome is a rare inherited metabolic condition caused by MECR gene mutations. This gene encodes a protein essential for fatty acid synthesis, and defects cause progressively worsening childhood-onset dystonia, optic atrophy, and basal ganglia abnormalities. Deep brain stimulation (DBS) has shown mixed improvement in other childhood-onset dystonia conditions. To the best of our knowledge, DBS has not been investigated as a treatment for dystonia in patients with MEPAN syndrome. Methods: Two children with MEPAN were identified as possible DBS candidates due to severe generalized dystonia unresponsive to pharmacotherapy. Temporary depth electrodes were placed in six locations bilaterally and tested during a 6-day hospitalization to determine the best locations for permanent electrode placement. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Barry-Albright Dystonia Scale (BADS) were used for preoperative and postoperative testing to quantitatively assess dystonia severity changes. Patient 1 had permanent electrodes placed at the globus pallidus internus (GPi) and pedunculopontine nucleus (PPN). Patient 2 had permanent electrodes placed at the GPi and ventralis intermedius nucleus of the thalamus (VIM). Results: Both patients successfully underwent DBS placement with no perioperative complications and significant improvement in their BFMDRS score. Patient 2 also demonstrated improvement in the BADS. Discussion: We demonstrated a novel application of DBS in MEPAN syndrome patients with childhood-onset dystonia. These patients showed clinically significant improvements in dystonia following DBS, indicating that DBS can be considered for dystonia in patients with rare metabolic disorders that currently have no other proven treatment options.

Increased movement-related signals in both basal ganglia and cerebellar output pathways in two children with dystonia.

The contribution of different brain regions to movement abnormalities in children with dystonia is unknown. Three awake subjects undergoing depth electrode implantation for assessments of potential deep brain recording targets performed a rhythmic figure-8 drawing task. Two subjects had dystonia, one was undergoing testing for treatment of Tourette Syndrome and had neither dystonia nor abnormal movements during testing. Movement-related signals were evaluated by determining the magnitude of task-related frequency components. Brain signals were recorded in globus pallidus internus (GPi), the ventral oralis anterior/posterior (VoaVop) and the ventral intermediate (Vim) nuclei of the thalamus. In comparison to the subject without dystonia, both children with dystonia showed increased task-related activity in GPi and Vim. This finding is consistent with a role of both basal ganglia and cerebellar outputs in the pathogenesis of dystonia. Our results further suggest that frequency analysis of brain recordings during cyclic movements may be a useful tool for analysis of the presence of movement-related signals in various brain regions.

Epidemiology of Neonatal COVID-19 in the United States.

OBJECTIVES: Data on coronavirus disease 2019 (COVID-19) infections in neonates are limited. We aimed to identify and describe the incidence, presentation, and clinical outcomes of neonatal COVID-19. METHODS: Over 1 million neonatal encounters at 109 United States health systems, from March 2020 to February 2021, were extracted from the Cerner Real World Database. COVID-19 diagnosis was assessed using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) laboratory tests and diagnosis codes. Incidence of COVID-19 per 100 000 encounters was estimated. RESULTS: COVID-19 was diagnosed in 918 (0.1%) neonates (91.1 per 100 000 encounters [95% confidence interval 85.3-97.2]). Of these, 71 (7.7%) had severe infection (7 per 100 000 [95% confidence interval 5.5-8.9]). Median time to diagnosis was 14.5 days from birth (interquartile range 3.1-24.2). Common signs of infection were tachypnea and fever. Those with severe infection were more likely to receive respiratory support (50.7% vs 5.2%, P < .001). Severely ill neonates received analgesia (38%), antibiotics (33.8%), anticoagulants (32.4%), corticosteroids (26.8%), remdesivir (2.8%), and COVID-19 convalescent plasma (1.4%). A total of 93.6% neonates were discharged home after care, 1.1% were transferred to another hospital, and discharge disposition was unknown for 5.2%. One neonate (0.1%) with presentation suggestive of multisystem inflammatory syndrome in children died after 11 days of hospitalization. CONCLUSIONS: Most neonates infected with SARS-CoV-2 were asymptomatic or developed mild illness without need for respiratory support. Some had severe illness requiring treatment of COVID-19 with remdesivir and COVID-19 convalescent plasma. SARS-CoV-2 infection in neonates, though rare, may result in severe disease.

Recurrent SARS-CoV-2 Serology Testing and Pandemic Anxiety: A Study of Pediatric Healthcare Workers.

Background: Limited access to SARS-CoV-2 testing has been identified as a potential source of anxiety among healthcare workers (HCWs), but the impact of repeated testing on pandemic-related anxiety in pediatric HCWs has not been examined. We sought to understand the impact of repeated SARS-CoV-2 antibody testing on pediatric HCWs' COVID-19 anxiety. Methods: This longitudinal cohort study was conducted between April and July 2020. Participants, 362 pediatric HCWs, underwent rapid SARS-CoV-2 antibody testing either every 96 h or weekly and were asked to rate their COVID-19 anxiety on a visual analog scale. Changes in self-reported anxiety from the study baseline were calculated for each testing day response. Bivariate analyses, repeated measures, and logistic regression analyses were performed to examine demographics associated with changes in anxiety. Results: Baseline COVID-19 anxiety was significantly higher in HCWs with less than 10 years of experience (Z = −2.63, p = 0.009), in females compared to males (Z = −3.66 p < 0.001), and in nurses compared to other HCWs (F (3,302) = 6.04, p = 0.003). After excluding participants who received a positive test result, repeated measures analyses indicated that anxiety decreased over time (F (5,835) = 3.14, p = 0.008). Of the HCWs who reported decreased anxiety, 57 (29.8%) had a clinically meaningful decrease (≥30%) and Emergency Department (ED) HCWs were 1.97 times more likely to report a clinically meaningful decrease in anxiety (X2 (1) = 5.05, p = 0.025). Conclusions: The results suggest that repeated SARS-CoV-2 antibody serology testing is associated with decreased COVID-19 anxiety in HCWs. Routine screening for the disease may be a helpful strategy in attenuating pandemic-related anxiety in pediatric HCWs.

Assisting Forearm Function in Children With Movement Disorders via A Soft Wearable Robot With Equilibrium-Point Control.

Wearable robots are envisioned to amplify the independence of people with movement impairments by providing daily physical assistance. For portable, comfortable, and safe devices, soft pneumatic-based robots are emerging as a potential solution. However, due to the inherent complexities, including compliance and nonlinear mechanical behavior, feedback control for facilitating human-robot interaction remains a challenge. Herein, we present the design, fabrication, and control architecture of a soft wearable robot that assists in supination and pronation of the forearm. The soft wearable robot integrates an antagonistic pair of pneumatic-based helical actuators to provide active pronation and supination torques. Our main contribution is a bio-inspired equilibrium-point control scheme for integrating proprioceptive feedback and exteroceptive input (e.g., the user's muscle activation signals) directly with the on/off valve behavior of the soft pneumatic actuators. The proposed human-robot controller is directly inspired by the equilibrium-point hypothesis of motor control, which suggests that voluntary movements arise through shifts in the equilibrium state of the antagonistic muscle pair spanning a joint. We hypothesized that the proposed method would reduce the required effort during dynamic manipulation without affecting the error. In order to evaluate our proposed method, we recruited seven pediatric participants with movement disorders to perform two dynamic interaction tasks with a haptic manipulandum. Each task required the participant to track a sinusoidal trajectory while the haptic manipulandum behaved as a Spring-Dominate system or Inertia-Dominate system. Our results reveal that the soft wearable robot, when active, reduced user effort on average by 14%. This work demonstrates the practical implementation of an equilibrium-point volitional controller for wearable robots and provides a foundational path toward versatile, low-cost, and soft wearable robots.

Association of Congenital and Acquired Cardiovascular Conditions With COVID-19 Severity Among Pediatric Patients in the US.

Importance: Identifying the associations between severe COVID-19 and individual cardiovascular conditions in pediatric patients may inform treatment. Objective: To assess the association between previous or preexisting cardiovascular conditions and severity of COVID-19 in pediatric patients. Design, Setting, and Participants: This retrospective cohort study used data from a large, multicenter, electronic health records database in the US. The cohort included patients aged 2 months to 17 years with a laboratory-confirmed diagnosis of COVID-19 or a diagnosis code indicating infection or exposure to SARS-CoV-2 at 85 health systems between March 1, 2020, and January 31, 2021. Exposures: Diagnoses for 26 cardiovascular conditions between January 1, 2015, and December 31, 2019 (before infection with SARS-CoV-2). Main Outcomes and Measures: The main outcome was severe COVID-19, defined as need for supplemental oxygen or in-hospital death. Mixed-effects, random intercept logistic regression modeling assessed the significance and magnitude of associations between 26 cardiovascular conditions and COVID-19 severity. Multiple comparison adjustment was performed using the Benjamini-Hochberg false discovery rate procedure. Results: The study comprised 171 416 pediatric patients; the median age was 8 years (IQR, 2-14 years), and 50.28% were male. Of these patients, 17 065 (9.96%) had severe COVID-19. The random intercept model showed that the following cardiovascular conditions were associated with severe COVID-19: cardiac arrest (odds ratio [OR], 9.92; 95% CI, 6.93-14.20), cardiogenic shock (OR, 3.07; 95% CI, 1.90-4.96), heart surgery (OR, 3.04; 95% CI, 2.26-4.08), cardiopulmonary disease (OR, 1.91; 95% CI, 1.56-2.34), heart failure (OR, 1.82; 95% CI, 1.46-2.26), hypotension (OR, 1.57; 95% CI, 1.38-1.79), nontraumatic cerebral hemorrhage (OR, 1.54; 95% CI, 1.24-1.91), pericarditis (OR, 1.50; 95% CI, 1.17-1.94), simple biventricular defects (OR, 1.45; 95% CI, 1.29-1.62), venous embolism and thrombosis (OR, 1.39; 95% CI, 1.11-1.73), other hypertensive disorders (OR, 1.34; 95% CI, 1.09-1.63), complex biventricular defects (OR, 1.33; 95% CI, 1.14-1.54), and essential primary hypertension (OR, 1.22; 95% CI, 1.08-1.38). Furthermore, 194 of 258 patients (75.19%) with a history of cardiac arrest were younger than 12 years. Conclusions and Relevance: The findings suggest that some previous or preexisting cardiovascular conditions are associated with increased severity of COVID-19 among pediatric patients in the US and that morbidity may be increased among individuals children younger than 12 years with previous cardiac arrest.

NCS Assessments of the Motor, Sensory, and Physical Health Domains.

As part of the National Children's Study (NCS) comprehensive and longitudinal assessment of the health status of the whole child, scientific teams were convened to recommend assessment measures for the NCS. This manuscript documents the work of three scientific teams who focused on the motor, sensory, or the physical health aspects of this assessment. Each domain team offered a value proposition for the importance of their domain to the health outcomes of the developing infant and child. Constructs within each domain were identified and measures of these constructs proposed. Where available extant assessments were identified. Those constructs that were in need of revised or new assessment instruments were identified and described. Recommendations also were made for the age when the assessments should take place.

Transient Complete Resolution of Tourette Syndrome Symptoms Following Personalized Depth Electrode Placement.

Treatment refractory Tourette syndrome has been shown to be improved with deep brain stimulation, but with multiple possible stimulation locations and variable and incomplete benefit. This study presents a single case of complete amelioration of motor and verbal tics in a patient with Tourette syndrome during placement of 12 stereo-EEG electrodes to identify optimal targets for permanent stimulating electrodes. Subsequently, substantial improvement in motor and verbal tic frequency occurred with placement and programming of permanent electrodes in bilateral globus pallidus internus and nucleus accumbens, but without the complete resolution seen during depth electrode placement. We suggest that simultaneous stimulation at multiple patient-specific targets could provide effective control of Tourette symptomatology, but further study will be needed.