Seven Year Old Male with Tricuspid Endocarditis.

Pediatric endocarditis, a rare entity in developed countries, remains a challenging diagnosis to make in children. We present an uncommon etiology of shortness of breath on exertion (SOBOE) in a 7-year-old male presenting with two weeks of nocturnal fever, malaise and fatigue following a viral prodrome. Point of care ultrasound (POCUS) led to suspicion for a ventricular septal defect (VSD) with tricuspid valve (TV) endocarditis, which was ultimately confirmed by formal echocardiography. This ultrasound diagnosis allowed emergency clinicians to order blood cultures under the suspicion of endocarditis as well as expedited antibiotic treatment.

Analysis of eye-tracking behaviours in a pediatric trauma simulation.

ABSTRACTEye-tracking devices are able to capture eye movements, which are further characterized by fixations. The application of eye tracking in a trauma setting has not been explored. Visual fixation can be utilized as a surrogate measure of attention during the management of a trauma patient. We aimed to determine the feasibility of using eye tracking and to characterize eye tracking behaviours of pediatric emergency medicine physicians during management of a simulated pediatric trauma patient. Each participant was equipped with a head-mounted eye-tracking device during a standardized simulated pediatric trauma scenario. Each session was video recorded, with visual fixations defined as >0.2 seconds, and characterized by start time, duration, and the area of interest. Data from seven videos were analysed; 35% of eye fixations were directed towards the mannequin, 16% towards the monitor, and 13% towards the bedside doctor. Visual eye tracking in a trauma simulation is feasible. Frequency of fixations tends to be highest towards the patient. Eye tracking within trauma simulation may provide new insights into quality improvement and inform advancements in pediatric trauma.

Intervention-Induced Motor Cortex Plasticity in Hemiparetic Children With Perinatal Stroke.

BACKGROUND: Clinical trials are suggesting efficacy of intensive therapy combined with brain stimulation to improve hand function in hemiparetic children with perinatal stroke. However, individual variability exists and the underlying neuroplasticity mechanisms are unknown. Exploring primary motor cortex (M1) neurophysiology, and how it changes with such interventions, may provide valuable biomarkers for advancing personalized neurorehabilitation. METHODS: Forty-five children (age 6-19 years) with hemiparesis participated in PLASTIC CHAMPS, a blinded, sham-controlled, factorial clinical trial. All received 80 hours of goal-directed intensive upper extremity therapy. They were randomized into 4 groups: repetitive transcranial magnetic stimulation (rTMS) of contralesional M1, constraint therapy, both, or neither. Stimulus recruitment curves (SRC), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) for lesioned and contralesional M1 were investigated using TMS. Clinical assessments including the Assisting Hand Assessment (AHA) and Canadian Occupational Performance Measure (COPM) were conducted pre- and postintervention. RESULTS: All children completed the intervention and both function (AHA) and goal performance (COPM) improved with additive effects of rTMS and constraint ( P < .01). After intervention, motor-evoked potential (MEP) amplitudes from the contralesional M1 to the less-affected hand increased (n = 16, P < .02). SRC from the contralesional M1 to the less-affected hand increased (n = 25, P < .01). SICI of the contralesional M1 to the less-affected hand decreased (n = 30, P < .04). No changes were observed for ICF in either hemisphere ( P > .12). CONCLUSION: TMS applied before/after intensive neuromodulation therapies can explore M1 neurophysiology and plasticity in children with cerebral palsy. Increased MEP sizes and decreased SICI may reflect mechanisms of interventional plasticity and be potential biomarkers of individualized medicine.

Interhemispheric motor interactions in hemiparetic children with perinatal stroke: Clinical correlates and effects of neuromodulation therapy.

OBJECTIVE: Brain stimulation and constraint therapy may enhance function after perinatal stroke but mechanisms are unknown. We characterized interhemispheric interactions (IHI) in hemiparetic children and explored their relationship to motor function and neuromodulation. METHODS: Forty-five hemiparetic perinatal stroke subjects aged 6-19 years completed a clinical trial of repetitive-transcranial magnetic stimulation (rTMS) and constraint therapy. Paired-pulse TMS measured IHI in cases and normal controls. Suprathreshold conditioning stimuli preceded contralateral test stimuli bidirectionally: stroke to non-stroke (SNS) and non-stroke to stroke (NSS). Primary outcome was the interhemispheric ratio (IHR) between conditioned and test only MEP amplitudes X100 (<100 implied inhibition). Motor outcomes at baseline and post-intervention were compared to IHR. RESULTS: Procedures were well tolerated. IHI occurred bidirectionally in controls. Eighteen stroke participants had complete data. IHR were increased in stroke participants in both directions. SNS IHR was >100 (facilitation) in 39% of measurements and correlated with better motor function. NSS IHR correlated with poorer motor function. Intervention-induced clinical change was not associated with IHR. CONCLUSIONS: Interhemispheric interactions are altered and related to clinical function, but not necessarily neuromodulation, in children with perinatal stroke. SIGNIFICANCE: Adding interhemispheric interactions to evolving models of developmental plasticity following early injury may advance neuromodulation strategies.

Cortical excitability after pediatric mild traumatic brain injury.

INTRODUCTION: Mild traumatic brain injury (mTBI) outcomes are variable, and 10-15% may suffer from prolonged symptoms beyond 3 months that impair the child's return to normal activities. Neurophysiological mechanisms of mTBI are incompletely understood, particularly in children, but alterations in cortical excitability have been proposed to underlie post-concussion syndrome. Improved understanding is required to advance interventions and improve outcomes. OBJECTIVE/HYPOTHESIS: To determine if cortical excitability is altered in children with mTBI, and its association with clinical symptoms. METHODS: This was a cross-sectional controlled cohort study. School-aged children (8-18 years) with mTBI were compared to healthy controls. Cortical excitability was measured using multiple TMS paradigms in children with (symptomatic) and without (recovered) persistent symptoms one-month post-injury. Primary outcome was the cortical silent period (cSP), a potential neurophysiological biomarker of GABAergic inhibition. Secondary outcomes included additional TMS neurophysiology, safety and tolerability. Associations between neurophysiology parameters and clinical symptoms were evaluated. RESULTS: Fifty-three children with mTBI (55% male; mean age 14.1 SD: 2.4 years; 35 symptomatic and 27 asymptomatic participants) and 28 controls (46% male; mean age 14.3 SD: 3.1 years) were enrolled. cSP duration was similar between groups (F (2, 73) = 0.55, p = 0.582). Log10 long interval intracortical inhibition (LICI) was reduced in symptomatic participants compared to healthy controls (F (2, 59) = 3.83, p = 0.027). Procedures were well tolerated with no serious adverse events. CONCLUSIONS: TMS measures of cortical excitability are altered at one month in children with mTBI. Long interval cortical inhibition is decreased in children who remain symptomatic at one month post-injury.

Contralesional Corticomotor Neurophysiology in Hemiparetic Children With Perinatal Stroke.

BACKGROUND: Perinatal stroke causes most hemiparetic cerebral palsy. Ipsilateral connections from nonlesioned hemisphere to affected hand are common. The nonlesioned primary motor cortex (M1) determines function and is a potential therapeutic target but its neurophysiology is poorly understood. OBJECTIVE: We aimed to characterize the neurophysiological properties of the nonlesioned M1 in children with perinatal stroke and their relationship to clinical function. METHODS: Fifty-two participants with hemiparetic cerebral palsy and magnetic resonance imaging-confirmed perinatal stroke and 40 controls aged 8 to 18 years completed the same transcranial magnetic stimulation (TMS) protocol. Single-pulse TMS to nonlesioned M1 determined rest and active motor thresholds (RMT/AMT), motor-evoked potential (MEP) latencies, and stimulus recruitment curves (SRC: 100%-150% RMT). Paired-pulse TMS evaluated short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF). Ipsilateral (IP) participants (ipsilateral MEP ≥0.05 mV in ≥5/20 trials) were compared with contralateral MEP only, nonipsilateral (NI) participants. Assisting Hand and Melbourne assessments quantified clinical function. RESULTS: Twenty-five IP were compared with 13 NI (n = 38, median age 12 years, 66% male). IP had lower motor function. SRC to unaffected hand were comparable between IP and NI while IP had smaller ipsilateral SRC. Ipsilateral MEP latencies were prolonged (23.5 ± 1.8 vs 22.2 ± 1.5 ms contra, P < .001). Contralateral SICI was different between IP (-42%) and NI (-20%). Ipsilateral SICI was reduced (-20%). Contralateral ICF was comparable between groups (+43%) and ipsilaterally (+43%). Measures correlated between contralateral and ipsilateral sides. CONCLUSION: Neurophysiology of nonlesioned M1 and its relationship to motor function is measureable in children with perinatal stroke. Correlation of excitability and intracortical circuitry measures between contralateral and ipsilateral sides suggests common control mechanisms.

Treatment of dysphasia with rTMS and language therapy after childhood stroke: Multimodal imaging of plastic change.

Expressive dysphasia accompanies left inferior frontal gyrus (IFG/Broca) injury. Recovery may relate to interhemispheric balance with homologous, contralesional IFG but is unexplored in children. We evaluated effects of inhibitory rTMS to contralesional IFG combined with intensive speech therapy (SLT). A 15year-old, right-handed male incurred a left middle cerebral artery stroke. After 30months, severe non-fluent dysphasia impacted quality of life. Language networks, neuronal metabolism and white matter pathways were explored using MRI. Language function was measured longitudinally. An intensive SLT program was combined with contralesional inhibitory rTMS of right pars triangularis. Procedures were well tolerated. Language function improved persisting to four months. Post-treatment fMRI demonstrated increased left perilesional IFG activations and connectivity at rest. Bilateral changes in inositol and glutamate metabolism were observed. Contralesional, inhibitory rTMS appears safe in childhood stroke-induced dysphasia. We observed clinically significant improvements after SLT coupled with rTMS. Advanced neuroimaging can evaluate intervention-induced plasticity.

Brain stimulation and constraint for perinatal stroke hemiparesis: The PLASTIC CHAMPS Trial.

OBJECTIVE: To determine whether the addition of repetitive transcranial magnetic stimulation (rTMS) and/or constraint-induced movement therapy (CIMT) to intensive therapy increases motor function in children with perinatal stroke and hemiparesis. METHODS: A factorial-design, blinded, randomized controlled trial (clinicaltrials.gov/NCT01189058) assessed rTMS and CIMT effects in hemiparetic children (aged 6-19 years) with MRI-confirmed perinatal stroke. All completed a 2-week, goal-directed, peer-supported motor learning camp randomized to daily rTMS, CIMT, both, or neither. Primary outcomes were the Assisting Hand Assessment and the Canadian Occupational Performance Measure at baseline, and 1 week, 2 and 6 months postintervention. Outcome assessors were blinded to treatment. Interim safety analyses occurred after 12 and 24 participants. Intention-to-treat analysis examined treatment effects over time (linear mixed effects model). RESULTS: All 45 participants completed the trial. Addition of rTMS, CIMT, or both doubled the chances of clinically significant improvement. Assisting Hand Assessment gains at 6 months were additive and largest with rTMS + CIMT (ß coefficient = 5.54 [2.57-8.51], p = 0.0004). The camp alone produced large improvements in Canadian Occupational Performance Measure scores, maximal at 6 months (Cohen d = 1.6, p = 0.002). Quality-of-life scores improved. Interventions were well tolerated and safe with no decrease in function of either hand. CONCLUSIONS: Hemiparetic children participating in intensive, psychosocial rehabilitation programs can achieve sustained functional gains. Addition of CIMT and rTMS increases the chances of improvement. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that combined rTMS and CIMT enhance therapy-induced functional motor gains in children with stroke-induced hemiparetic cerebral palsy.

Evaluating developmental motor plasticity with paired afferent stimulation.

AIM: Brain plasticity mechanisms are probably different in children but remain poorly understood. Paired afferent stimulation (PAS) combines peripheral sensory stimulation with transcranial magnetic stimulation (TMS) of primary motor cortex to induce rapid, reversible, topographically specific increases in primary motor cortex excitability suggestive of long-term potentiation in adults. Our aim was to determine frequency, characteristics, age effects, and reproducibility of PAS in school-age children. METHOD: Typically developing right-handed children (6-18y) were recruited. Median nerve stimulation was delivered 25ms before suprathreshold primary motor cortex stimulation (0.2Hz, 7.5min). Primary outcome was changed in the amplitude of motor evoked potentials (MEPs) at five time points after PAS (0, 15, 30, 45, 75min) expressed as area under the curve. Reproducibility was evaluated. Secondary outcomes included stimulus response curves and safety/tolerability. RESULTS: Of 28 children (20 males, mean age 12y), 64% demonstrated PAS effects (11 definite, seven probable). PAS effects were sustained across all time points to 75min (p=0.004). Stimulus response curve scores increased after PAS (n=9, p=0.02). PAS effect and age were not correlated. PAS was highly reproducible (p=0.925, r=0.283). Tolerability was favorable without adverse events. INTERPRETATION: PAS effects are present and reproducible in children. Pediatric PAS paradigms appear safe and tolerable. PAS may provide insight into endogenous developmental plasticity, informing future studies in children with cerebral palsy and other motor disorders.

Limitations of split-night polysomnography for the diagnosis of nocturnal hypoventilation and titration of non-invasive positive pressure ventilation in amyotrophic lateral sclerosis.

Split-night polysomnography is performed at our centre in all patients with ALS who require assessment for nocturnal hypoventilation and their response to non-invasive ventilation. The purpose of this study was to determine how successful this practice has been, reflected by whether a complete assessment was achieved by a single split-night polysomnogram. We undertook a systematic, retrospective review of all consecutive split-night polysomnograms in ALS patients between 2005 and 2012. A total of 47 cases were reviewed. Forty-three percent of patients had an incomplete test, resulting in a recommendation to repeat the polysomnogram. Poor sleep efficiency and absence of REM sleep in the diagnostic portion of the study were strongly associated with incomplete studies. Clinical variables that reflect severity of ALS (FVC, PaCO2, ALSFRS-R) and use of REM-suppressing antidepressants or sedative-hypnotics were not associated with incomplete split-night polysomnogram. In conclusion, a single, split-night polysomnogram is frequently inconclusive for the assessment of nocturnal hypoventilation and complete titration of non-invasive positive pressure ventilation in patients with ALS. Poor sleep efficiency and absence of REM sleep are the main limitations of split-night polysomnography in this patient population.

Glutamate alterations associated with transcranial magnetic stimulation in youth depression: a case series.

OBJECTIVE: We hypothesized an increase in dorsolateral prefrontal cortex (DLPFC) glutamate levels would occur after 3 weeks of repetitive transcranial magnetic stimulation (rTMS) treatment and a decrease in major depressive disorder (MDD) symptoms. METHODS: We report 6 patients (4 females) 15 to 21 years of age with treatment-resistant MDD. Participants had a mean (SD) age of 18.7 (1.95) years and a mean (SD) IQ of 102.3 (3.39). Short echo proton magnetic resonance spectroscopy (¹H-MRS) was used to quantify glutamate levels in the left DLPFC (4.5 cc) before and after rTMS treatment. Repetitive transcranial magnetic stimulation was localized to the left DLPFC and applied for 15 consecutive weekdays (120% resting motor threshold; 40 pulses over 4 seconds [10 Hz]; intertrain interval, 26 seconds; 75 trains; 3000 pulses). Treatment response was defined as a greater than 50% reduction in Hamilton Depression Rating Scale scores. Short echo proton magnetic resonance spectroscopy data were analyzed with LCModel to determine glutamate concentration. RESULTS: After rTMS, treatment responders (n = 4) showed an increase (relative to baseline) in left DLPFC glutamate levels (11%), which corresponded to an improvement in depressive symptom severity (68% Hamilton Depression Rating Scale score reduction). Treatment nonresponders (n = 2) had elevated baseline glutamate levels compared to responders in that same region, which decreased with rTMS (-10%). Procedures were generally well tolerated with no adverse events. CONCLUSIONS: Repetitive transcranial magnetic stimulation is feasible and possibly efficacious in adolescents with MDD. In responders, rTMS may act by induced elevations in elevating DFPLC glutamate levels in the left DLPFC, thereby leading to symptom improvement.