Publications by authors named "Adam Kirton"

199 Publications

Robotic transcranial magnetic stimulation motor maps and hand function in adolescents.

Physiol Rep 2021 Apr;9(7):e14801

Calgary Pediatric Stroke Program, Alberta Children's Hospital, Calgary, Alberta, Canada.

Introduction: Transcranial magnetic stimulation (TMS) motor mapping can characterize the neurophysiology of the motor system. Limitations including human error and the challenges of pediatric populations may be overcome by emerging robotic systems. We aimed to show that neuronavigated robotic motor mapping in adolescents could efficiently produce discrete maps of individual upper extremity muscles, the characteristics of which would correlate with motor behavior.

Methods: Typically developing adolescents (TDA) underwent neuronavigated robotic TMS mapping of bilateral motor cortex. Representative maps of first dorsal interosseous (FDI), abductor pollicis brevis (APB), and abductor digiti minimi (ADM) muscles in each hand were created. Map features including area (primary), volume, and center of gravity were analyzed across different excitability regions (R100%, R75%, R50%, R25%). Correlations between map metrics and validated tests of hand motor function (Purdue Pegboard Test as primary) were explored.

Results: Twenty-four right-handed participants (range 12-18 years, median 15.5 years, 52% female) completed bilateral mapping and motor assessments with no serious adverse events or dropouts. Gender and age were associated with hand function and motor map characteristics. Full motor maps (R100%) for FDI did not correlate with motor function in either hand. Smaller excitability subset regions demonstrated reduced variance and dose-dependent correlations between primary map variables and motor function in the dominant hemisphere.

Conclusions: Hand function in TDA correlates with smaller subset excitability regions of robotic TMS motor map outcomes. Refined motor maps may have less variance and greater potential to quantify interventional neuroplasticity. Robotic TMS mapping is safe and feasible in adolescents.
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http://dx.doi.org/10.14814/phy2.14801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020044PMC
April 2021

Cord Blood Cytokine Levels Correlate With Types of Placental Pathology in Extremely Preterm Infants.

Front Pediatr 2021 11;9:607684. Epub 2021 Mar 11.

Section of Pediatric Neurology, Department of Pediatrics, University of Calgary, Calgary, AB, Canada.

Placental abnormalities are associated with inflammation and have been linked to brain injury in preterm infants. We studied the relationship between placental pathology and the temporal profiles of cytokine levels in extremely pre-term infants. We prospectively enrolled 55 extremely preterm infants born between June 2017 and July 2018. Levels of 27 cytokines were measured in blood drawn from the umbilical artery at birth and from infants at 1-3 and 21-28 days of life. Placental pathology was grouped as normal (N), inflammation (I), vasculopathy (V), or combined vasculopathy and inflammation (V+I). Complete data was available from 42 patients. Cord blood median levels of cytokines differed between groups with the highest levels observed in group V+I as compared to groups N, I and V for the following: Eotaxin ( = 0.038), G-CSF ( = 0.023), IFN-γ ( = 0.002), IL-1ra ( < 0.001), IL-4 ( = 0.005), IL-8 ( = 0.010), MCP-1 ( = 0.011), and TNFα ( = 0.002). analysis revealed sex differences between and within the placental pathology groups. Specific types of placental pathology may be associated with differential cytokine profiles in extremely pre-term infants. Sampling from cord blood may help assess the pathological status of the placenta and potentially infer outcome risks for the infant.
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http://dx.doi.org/10.3389/fped.2021.607684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991101PMC
March 2021

Head circumference trajectory in children with perinatal stroke.

J Child Neurol 2021 Mar 8:883073821996103. Epub 2021 Mar 8.

Calgary Pediatric Stroke Program, Alberta Children's Hospital, Calgary, Alberta, Canada.

Background: Perinatal stroke is a leading cause of hemiparetic cerebral palsy and lifelong disability. Neurodevelopmental outcomes are difficult to predict and markers of long-term poor outcome continue to be investigated. Deceleration in growth of head circumference has been associated with worse developmental outcomes in neonatal brain injury. We hypothesized that perinatal stroke would result in decreased rates of head growth during childhood that would be associated with worse developmental outcomes.

Methods: Patients with magnetic resonance imaging (MRI)-confirmed neonatal arterial ischemic stroke and arterial presumed perinatal ischemic stroke were identified from a population-based research cohort (Alberta Perinatal Stroke Project). Demographics and occipital-frontal circumference data were collected from medical records. Head growth was compared to typically developing control charts using a 2-tailed test. The Fisher exact test was used to examine associations between Pediatric Stroke Outcome Measures (PSOM) scores and occipital-frontal head circumference.

Results: Three hundred fifteen occipital-frontal head circumference measurements were collected from 102 patients (48 female, 54 male), over a median of 3.2 years (standard deviation = 5.18, range = 0-18.3). After 3 months for female patients and 1 year for male patients, occipital-frontal head circumference deviated and remained below normal growth trajectories ( < .05) with a large effect size (Cohen >0.8). Poor outcome (PSOM ≥ 1) was associated with smaller occipital-frontal head circumference ( < .05).

Conclusion: Head growth deceleration is observed in children with perinatal arterial ischemic stroke and is associated with poor outcome. Head circumference may be a tool to alert clinicians to the potential of abnormal neurologic outcome.
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http://dx.doi.org/10.1177/0883073821996103DOI Listing
March 2021

Perinatal Stroke: A Practical Approach to Diagnosis and Management.

Neoreviews 2021 Mar;22(3):e163-e176

Department of Pediatrics, Section of Neurology; and.

Perinatal stroke is a focal vascular brain injury that occurs from the fetal period to 28 days of postnatal age. With an overall incidence of up to 1 in 1,000 live births, the most focused lifetime risk for stroke occurs near birth. Perinatal stroke can be classified by the timing of diagnosis, vessel involvement, and type of injury. Timing of diagnosis may be in the acute neonatal period or retrospectively after a period of normal development, followed by abnormal neurologic findings, with the injury presumed to have occurred around the time of birth. Strokes may be arterial or venous, ischemic, and/or hemorrhagic. Within these classifications, 6 perinatal stroke diseases are recognizable, based on clinical and radiographic features. Morbidity is high in perinatal stroke, because it accounts for most cases of hemiparetic cerebral palsy, with disability lasting a lifetime. Additional complications include disorders of sensation and vision, language delays, cognitive and learning deficits, epilepsy, and mental health consequences that affect the entire family. Advances in neonatal neurocritical care may afford opportunity to minimize brain injury and improve outcomes. In the chronic timeframe, progress made in neuroimaging and brain mapping is revealing the developmental plasticity that occurs, informing new avenues for neurorehabilitation. This review will summarize the diagnosis and management of each perinatal stroke disease, highlighting their similarities and distinctions and emphasizing a patient- and family-centered approach to management.
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http://dx.doi.org/10.1542/neo.22-3-e163DOI Listing
March 2021

Bilateral transcranial magnetic stimulation of the supplementary motor area in children with Tourette syndrome.

Dev Med Child Neurol 2021 Feb 25. Epub 2021 Feb 25.

Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Aim: To explore the feasibility and possible effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to the supplementary motor area (SMA) on tic severity and motor system neurophysiology in children with Tourette syndrome.

Method: Ten children with Tourette syndrome (eight males, two females; 9-15y) participated in this open-label, phase 1 clinical trial. Treatment consisted of 1800 low-frequency (1Hz) neuronavigated robotic rTMS (100% resting motor threshold) to the SMA, bilaterally for 15 sessions. The primary outcome was a change in Yale Global Tic Severity Scale (YGTSS) total score from baseline to posttreatment. Secondary outcome measures included changes in magnetic resonance spectroscopy metabolite concentrations, TMS neurophysiology measures, TMS motor maps, and clinical assessments (anxiety, depression) from baseline to the end of treatment.

Results: The YGTSS score decreased from baseline after treatment (p<0.001; Cohen's d=2.9). All procedures were well-tolerated.

Interpretation: Robot-driven, neuronavigated bilateral rTMS of the SMA is feasible in children with Tourette syndrome and appears to reduce tic severity.
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http://dx.doi.org/10.1111/dmcn.14828DOI Listing
February 2021

Protocol for a cost-utility analysis of neurostimulation and intensive camp-based therapy for children with perinatal stroke and hemiparesis based on a multicentre clinical trial.

BMJ Open 2021 01 19;11(1):e041444. Epub 2021 Jan 19.

School of Public Policy, University of Calgary, Calgary, Alberta, Canada

Introduction: Perinatal stroke leads to cerebral palsy (CP) and lifelong disability for thousands of Canadian children. Hemiparesis, referring to impaired functionality in one side of the body, is a common complication of perinatal stroke. Standard long-term care for hemiparetic CP focuses on rehabilitation therapies. Early research suggests that patients with hemiparesis may benefit from adjunctive neuromodulation treatments such as transcranial direct current stimulation (tDCS). tDCS uses electric current to stimulate targeted areas of the brain non-invasively, potentially enhancing the effects of motor learning therapies. This protocol describes an economic evaluation to be conducted alongside a randomised controlled trial (RCT) to assess the incremental cost of tDCS added to a camp-based therapy compared with camp-based therapy alone per quality-adjusted life year (QALY) gained in children with hemiparetic CP.

Methods And Analysis: The Stimulation for Perinatal Stroke Optimising Recovery Trajectories (SPORT) trial is a multicentre RCT evaluating tDCS added to a 2-week camp-based therapy for children aged 6-18 years with perinatal ischaemic stroke and disabling hemiparetic CP affecting the upper limb. Outcomes are assessed at baseline, 1 week, 2 months and 6 months following intervention. Cost and quality of life data are collected at baseline and 6 months and results will be used to conduct a cost-utility analysis (CUA). The evaluation will be conducted from the perspectives of the public healthcare system and society. The CUA will be conducted over a 6-month time horizon.

Ethics And Dissemination: Ethical approval for the SPORT trial and the associated economic evaluation has been given by the research ethics boards at each of the study sites. The findings of the economic evaluation will be submitted for publication in a peer reviewed academic journal and submitted for presentation at conference.

Trial Registration Number: NCT03216837; Post-results.
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http://dx.doi.org/10.1136/bmjopen-2020-041444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817786PMC
January 2021

Canadian Platform for Trials in Noninvasive Brain Stimulation (CanStim) Consensus Recommendations for Repetitive Transcranial Magnetic Stimulation in Upper Extremity Motor Stroke Rehabilitation Trials.

Neurorehabil Neural Repair 2021 02;35(2):103-116

McGill University, Montreal, Quebec, Canada.

. To develop consensus recommendations for the use of repetitive transcranial magnetic stimulation (rTMS) as an adjunct intervention for upper extremity motor recovery in stroke rehabilitation clinical trials. . The Canadian Platform for Trials in Non-Invasive Brain Stimulation (CanStim) convened a multidisciplinary team of clinicians and researchers from institutions across Canada to form the CanStim Consensus Expert Working Group. . Four consensus themes were identified: (1) patient population, (2) rehabilitation interventions, (3) outcome measures, and (4) stimulation parameters. Theme leaders conducted comprehensive evidence reviews for each theme, and during a 2-day Consensus Meeting, the Expert Working Group used a weighted dot-voting consensus procedure to achieve consensus on recommendations for the use of rTMS as an adjunct intervention in motor stroke recovery rehabilitation clinical trials. . Based on best available evidence, consensus was achieved for recommendations identifying the target poststroke population, rehabilitation intervention, objective and subjective outcomes, and specific rTMS parameters for rehabilitation trials evaluating the efficacy of rTMS as an adjunct therapy for upper extremity motor stroke recovery. . The establishment of the CanStim platform and development of these consensus recommendations is a first step toward the translation of noninvasive brain stimulation technologies from the laboratory to clinic to enhance stroke recovery.
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http://dx.doi.org/10.1177/1545968320981960DOI Listing
February 2021

Structural and functional connectivity of motor circuits after perinatal stroke: A machine learning study.

Neuroimage Clin 2020 19;28:102508. Epub 2020 Nov 19.

Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Calgary Pediatric Stroke Program, Alberta Children's Hospital, Calgary, AB, Canada; Alberta Children's Hospital Research Institute, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Department of Radiology, University of Calgary, Calgary, AB, Canada; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.

Developmental neuroplasticity allows young brains to adapt via experiences early in life and also to compensate after injury. Why certain individuals are more adaptable remains underexplored. Perinatal stroke is an ideal human model of neuroplasticity with focal lesions acquired near birth in a healthy brain. Machine learning can identify complex patterns in multi-dimensional datasets. We used machine learning to identify structural and functional connectivity biomarkers most predictive of motor function. Forty-nine children with perinatal stroke and 27 controls were studied. Functional connectivity was quantified by fluctuations in blood oxygen-level dependent (BOLD) signal between regions. White matter tractography of corticospinal tracts quantified structural connectivity. Motor function was assessed using validated bimanual and unimanual tests. RELIEFF feature selection and random forest regression models identified predictors of each motor outcome using neuroimaging and demographic features. Unilateral motor outcomes were predicted with highest accuracy (8/54 features r = 0.58, 11/54 features, r = 0.34) but bimanual function required more features (51/54 features, r = 0.38). Connectivity of both hemispheres had important roles as did cortical and subcortical regions. Lesion size, age at scan, and type of stroke were predictive but not highly ranked. Machine learning regression models may represent a powerful tool in identifying neuroimaging biomarkers associated with clinical motor function in perinatal stroke and may inform personalized targets for neuromodulation.
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http://dx.doi.org/10.1016/j.nicl.2020.102508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704459PMC
November 2020

Goals of children with unilateral cerebral palsy in a brain stimulation arm rehabilitation trial.

Dev Med Child Neurol 2021 May 24;63(5):584-591. Epub 2020 Dec 24.

Alberta Children's Hospital Research Institute, Calgary, AB, Canada.

Aim: To explore relationships between category classifications for children's rehabilitation goals, outcomes, and participant characteristics.

Method: Children with hemiparetic cerebral palsy due to perinatal stroke rated self-selected goals with the Canadian Occupational Performance Measure (COPM) and completed the Assisting Hand Assessment (AHA) and Box and Block Test (BBT), at baseline and 6 months, in a randomized, controlled 10-day neuromodulation rehabilitation trial using repetitive transcranial magnetic stimulation. Goals were classified with the Canadian Model of Occupational Performance and Engagement and the International Classification of Functioning, Disability and Health. Analysis included standard linear regression.

Results: Data for 45 participants (mean age 11y 7mo, SD 3y 10mo, range 6-19y, 29 males, 16 females) on 186 goals were included. Self-care goal percentage corresponded with baseline BBT by age (standardized ß=-0.561, p=0.004). Leisure goal percentage corresponded with baseline BBT (standardized ß=0.419, p=0.010). AHA change corresponded with productivity goals (standardized ß=0.327, p=0.029) and age (standardized ß=0.481, p=0.002). COPM change corresponded with baseline COPM and age by AHA change (p<0.05).

Interpretation: Younger children with lower motor function were more likely to select self-care goals while those with better function tended to select leisure goals. Functional improvement corresponded with older age and productivity goals. COPM change scores reflected functional improvement among older children. Children chose functionally and developmentally appropriate goals. Consequently, children should be free to set goals that matter to them.

What This Paper Adds: Children in a brain stimulation trial chose divergent upper extremity functional goals. Younger children with lower ability chose more self-care goals. Children with higher ability chose more leisure goals. Older children's goal ratings reflected objective functional motor gains. Children chose goals appropriate to their function and level of development.
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http://dx.doi.org/10.1111/dmcn.14763DOI Listing
May 2021

Effects of Transcranial Direct Current Stimulation on Motor Function in Children 8-12 Years With Developmental Coordination Disorder: A Randomized Controlled Trial.

Front Hum Neurosci 2020 11;14:608131. Epub 2020 Dec 11.

Alberta Children's Hospital Research Institute (ACHRI), Calgary, AB, Canada.

Developmental coordination disorder (DCD) is a neurodevelopmental motor disorder occurring in 5-6% of school-aged children. It is suggested that children with DCD show deficits in motor learning. Transcranial direct current stimulation (tDCS) enhances motor learning in adults and children but is unstudied in DCD. We aimed to investigate if tDCS, paired with motor skill training, facilitates motor learning in a pediatric sample with DCD. Twenty-eight children with diagnosed DCD (22 males, mean age: 10.62 ± 1.44 years) were randomized and placed into a treatment or sham group. Anodal tDCS was applied (1 mA, 20 min) in conjunction with fine manual training over 5 consecutive days. Children's motor functioning was assessed with the Purdue Pegboard Test and Jebsen-Taylor Hand Function Test at baseline, post-intervention and 6 weeks following intervention. Group differences in rates of motor learning and skill transfer/retention were examined using linear mixed modeling and repeated measures ANOVAs, respectively. There were no serious adverse events or drop-outs and procedures were well-tolerated. Independent of group, all participants demonstrated improved motor scores over the 5 training days [, < 0.001, 95% CI (0.152, 0.376)], with no skill decay observed at retention. There was no interaction between intervention group and day [, = 0.086, 95% CI (-0.020, 0.297)]. Children with DCD demonstrate motor learning with long-term retention of acquired skill. Motor cortex tDCS did not enhance motor learning as seen in other populations. Before conclusions of tDCS efficacy can be drawn, additional carefully designed trials with reproducible results are required. ClinicalTrials.gov: NCT03453983.
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http://dx.doi.org/10.3389/fnhum.2020.608131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759610PMC
December 2020

Advancing Brain-Computer Interface Applications for Severely Disabled Children Through a Multidisciplinary National Network: Summary of the Inaugural Pediatric BCI Canada Meeting.

Front Hum Neurosci 2020 3;14:593883. Epub 2020 Dec 3.

Department of Pediatrics and Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Thousands of youth suffering from acquired brain injury or other early-life neurological disease live, mature, and learn with only limited communication and interaction with their world. Such cognitively capable children are ideal candidates for brain-computer interfaces (BCI). While BCI systems are rapidly evolving, a fundamental gap exists between technological innovators and the patients and families who stand to benefit. Forays into translating BCI systems to children in recent years have revealed that kids can learn to operate simple BCI with proficiency akin to adults. BCI could bring significant boons to the lives of many children with severe physical impairment, supporting their complex physical and social needs. However, children have been neglected in BCI research and a collaborative BCI research community is required to unite and push pediatric BCI development forward. To this end, the pediatric BCI Canada collaborative network (BCI-CAN) was formed, under a unified goal to cooperatively drive forward pediatric BCI innovation and impact. This article reflects on the topics and discussions raised in the foundational BCI-CAN meeting held in Toronto, ON, Canada in November 2019 and suggests the next steps required to see BCI impact the lives of children with severe neurological disease and their families.
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http://dx.doi.org/10.3389/fnhum.2020.593883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744376PMC
December 2020

Preoperative Transcranial Direct Current Stimulation in Glioma Patients: A Proof of Concept Pilot Study.

Front Neurol 2020 19;11:593950. Epub 2020 Nov 19.

Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.

Transcranial direct current stimulation (tDCS) has been used extensively in patient populations to facilitate motor network plasticity. However, it has not been studied in patients with brain tumors. We aimed to determine the feasibility of a preoperative motor training and tDCS intervention in patients with glioma. In an exploratory manner, we assessed changes in motor network connectivity following this intervention and related these changes to predicted electrical field strength from the stimulated motor cortex. Patients with left-sided glioma (n=8) were recruited in an open label proof of concept pilot trial and participated in four consecutive days of motor training combined with tDCS. The motor training consisted of a 60-min period where the subject learned to play the piano with their right hand. Concurrently, they received 40 min of 2 mA anodal tDCS of the left motor cortex. Patients underwent task and resting state fMRI before and after this intervention. Changes in both the connectivity of primary motor cortex (M1) and general connectivity across the brain were assessed. Patient specific finite element models were created and the predicted electrical field (EF) resulting from stimulation was computed. The magnitude of the EF was extracted from left M1 and correlated to the observed changes in functional connectivity. There were no adverse events and all subjects successfully completed the study protocol. Left M1 increased both local and global connectivity. Voxel-wide measures, not constrained by a specific region, revealed increased global connectivity of the frontal pole and decreased global connectivity of the supplementary motor area. The magnitude of EF applied to the left M1 correlated with changes in global connectivity of the right M1. In this proof of concept pilot study, we demonstrate for the first time that tDCS appears to be feasible in glioma patients. In our exploratory analysis, we show preoperative motor training combined with tDCS may alter sensorimotor network connectivity. Patient specific modeling of EF in the presence of tumor may contribute to understanding the dose-response relationship of this intervention. Overall, this suggests the possibility of modulating neural networks in glioma patients.
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http://dx.doi.org/10.3389/fneur.2020.593950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710969PMC
November 2020

Children with Tic Disorders Show Greater Variability in an Arm-Position-Matching Proprioceptive Task.

Mov Disord 2021 03 7;36(3):782-784. Epub 2020 Dec 7.

Department of Clinical Neurosciences, Psychiatry, Pediatrics and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.

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http://dx.doi.org/10.1002/mds.28413DOI Listing
March 2021

Automated quantification of spike-wave activity may be used to predict the development of electrical status epilepticus in sleep (ESES) in children with perinatal stroke.

Clin Neurophysiol 2021 Jan 13;132(1):146-153. Epub 2020 Nov 13.

Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary AB T2N 1N4, Canada; Department of Pediatrics, Section of Neurology, Cumming School of Medicine, University of Calgary, Calgary AB T2N 1N4, Canada; Alberta Children's Hospital, Calgary AB T3B 6A8, Canada. Electronic address:

Objective: Continuous spike and wave in slow-wave sleep (CSWS), an epileptic encephalopathy, occurs after perinatal stroke where it is associated with cognitive decline. CSWS features a distinct EEG pattern, electrical status epilepticus in sleep (ESES). Biomarkers for the prediction of ESES have not been identified but will facilitate earlier diagnosis and treatment. We hypothesized that spike-frequency and differences in power spectra would be predictive of subsequent ESES.

Methods: A cross-sectional study comparing EEG spike-frequency and Power before the development of ESES in patients with perinatal stroke, patients with focal epilepsy, and appropriate controls.

Results: 43 patients met the inclusion criteria; 11 stroke-ESES, 10 stroke controls, 14 epilepsy-ESES, 8 epilepsy controls. ESES patients had higher pre-diagnosis mean spike-frequency (24.0 ± 24 versus 6.6 ± 9.1 SW/min, p = 0.002) than patients that did not develop ESES; these differences present ~ 3 years before ESES diagnosis. Pre-diagnosis, normalized delta power (1-4 Hz) was higher in the stroke-ESES group (105.7 ± 58 dB/Hz) compared to stroke controls (57.4 ± 45 dB/Hz, p = 0.036).

Conclusion: Spike-frequency and delta power may represent EEG biomarkers of the risk of developing ESES in children with perinatal stroke.

Significance: EEG biomarkers may be used by clinicians to assess which patients are more at-risk for ESES. Using spike-frequency, clinicians may be able to identify patients at risk of developing ESES.
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http://dx.doi.org/10.1016/j.clinph.2020.11.003DOI Listing
January 2021

Reliability of robotic transcranial magnetic stimulation motor mapping.

J Neurophysiol 2021 01 4;125(1):74-85. Epub 2020 Nov 4.

Calgary Pediatric Stroke Program, Alberta Children's Hospital, Calgary, Alberta, Canada.

Robotic transcranial magnetic stimulation (TMS) is a noninvasive and safe tool that produces cortical motor maps using neuronavigational and neuroanatomical images. Motor maps are individualized representations of the primary motor cortex (M1) topography that may reflect developmental and interventional plasticity. Results of TMS motor map reliability testing have been variable, and robotic measures are undefined. We aimed to determine the short- and long-term reliability of robotic TMS motor maps. Twenty healthy participants underwent motor mapping at baseline, 24 h, and 4 wk. A 12 × 12 grid (7-mm spacing) was placed over the left M1, centered over the hand knob area. Four suprathreshold stimulations were delivered at each grid point. First dorsal interosseous (FDI) motor-evoked potentials (MEPs) were analyzed offline to generate map characteristics of area, volume, center of gravity (COG), and hotspot magnitude. Subsets of each outcome corresponding to 75%, 50%, and 25% of each map were determined. Reliability measures including intraclass correlation coefficient (ICC), minimal detectable change (MDC), and standard error of measure (SEM) were calculated. Map volume, COG, and hotspot magnitude were the most reliable measures (good-to-excellent) over both short- and long-term sessions. Map area reliability was poor-to-moderate for short- and long-term sessions. Smaller map percentile subsets showed decreased variability but only minimal improvements in reliability. MDC for most outcomes was >50%. Procedures were well tolerated with no serious adverse events. Robotic TMS motor mapping is relatively reliable over time, but careful consideration of specific outcomes is required for this method to interrogate plasticity in the human motor system. Robotic transcranial magnetic stimulation (TMS) is a noninvasive and safe tool that produces cortical motor maps-individualized representations of the primary motor cortex (M1) topography-that may reflect developmental and interventional plasticity. This study is the first to evaluate short- and long-term relative and absolute reliability of TMS mapping outcomes at various M1 excitability levels using novel robotic neuronavigated TMS.
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http://dx.doi.org/10.1152/jn.00527.2020DOI Listing
January 2021

Population Based Birth Prevalence of Disease-Specific Perinatal Stroke.

Pediatrics 2020 11;146(5)

Pediatrics,

Background: Perinatal stroke encompasses multiple disease-specific cerebrovascular syndromes that cause lifelong neurodevelopmental morbidity for millions worldwide. Acute presentations include neonatal arterial ischemic stroke (NAIS), neonatal cerebral sinovenous thrombosis, and neonatal hemorrhagic stroke (NHS). Delayed presentations include arterial presumed perinatal ischemic stroke, periventricular venous infarction, and presumed perinatal hemorrhagic stroke. Our objective was to define the birth prevalence of all subtypes of perinatal stroke by using a population-based cohort.

Methods: The Alberta Perinatal Stroke Project is a research cohort established in 2008 in southern Alberta, Canada, with prospective (2008-2017) and retrospective (1990-2008) enrollment leveraging universal health care at a single tertiary care pediatric center. The primary outcome was the estimated birth prevalence of each perinatal stroke syndrome, secondary outcomes were birth prevalence over time, sex ratios, and change in age at diagnosis. Analysis included Poisson regression, Wilcoxon rank test, and Fisher exact test.

Results: The overall estimated birth prevalence of term-born perinatal stroke was 1:1100. The estimated birth prevalence was 1:3000 for NAIS, 1:7900 for arterial presumed perinatal ischemic stroke, 1:6000 for periventricular venous infarction, 1:9100 for cerebral sinovenous thrombosis, 1:6800 for NHS, and 1:65000 for presumed perinatal hemorrhagic stroke. The apparent birth prevalence of NAIS and NHS increased over time. There were more males affected than females. The age at diagnosis decreased for late-presenting stroke types.

Conclusions: The estimated birth prevalence of term perinatal stroke is higher than previous estimates, which may be explained by population-based sampling of disease-specific states. This emphasizes the need for further studies to better understand the disease-specific pathophysiology to improve treatment and prevention strategies.
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http://dx.doi.org/10.1542/peds.2020-013201DOI Listing
November 2020

Antenatal diagnosis of fetal intraventricular hemorrhage: systematic review and meta-analysis.

Dev Med Child Neurol 2021 02 22;63(2):144-155. Epub 2020 Oct 22.

Department of Pediatrics, Section of Neurology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Aim: To determine how the severity of antenatally diagnosed germinal matrix-intraventricular hemorrhage (GMH-IVH) relates to morbidity and mortality, and to explore potential risk factors.

Method: We conducted a systematic review and individual patient data meta-analysis of antenatally diagnosed fetal GMH-IVH. The primary outcomes were mortality and morbidity. Potential associations with clinical factors during pregnancy were explored. Analysis employed Fisher's exact test and logistic regression.

Results: We included 240 cases from 80 studies. Presence of venous infarction was associated with mortality (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.4-13.25), motor impairment (OR 103.2, 95% CI 8.6-1238), epilepsy (OR 6.46, 95% CI 2.64-16.06), and developmental delay (OR 8.55, 95% CI 2.12-48.79). Shunt placement was associated with gestational age at GMH-IVH diagnosis and in utero progression. Many cases had uncomplicated pregnancies but possible co-occurring conditions included twin gestation, small for gestational age, and congenital anomalies.

Interpretation: Severity of fetal GMH-IVH, specifically venous infarction, is associated with overall mortality and morbidity. Risk factors for fetal GMH-IVH are poorly understood and controlled studies are required.

What This Paper Adds: Preterm germinal matrix-intraventricular hemorrhage (GMH-IVH) grading can be applied to fetuses. Many fetal germinal matrix hemorrhages occur in otherwise typical pregnancies. Half of fetuses with post-hemorrhagic ventricular dilatation receive a shunt after delivery. Fetuses with grade I or II GMH-IVH have few sequelae. Fetuses with periventricular hemorrhagic infarction have a high burden of motor impairment.
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http://dx.doi.org/10.1111/dmcn.14713DOI Listing
February 2021

Efficacy of Melatonin for Sleep Disturbance in Children with Persistent Post-Concussion Symptoms: Secondary Analysis of a Randomized Controlled Trial.

J Neurotrauma 2021 Apr 23;38(8):950-959. Epub 2020 Oct 23.

Department of Paediatrics, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada.

Sleep disturbances are commonly reported in children with persistent post-concussion symptoms (PPCS). Melatonin treatment is often recommended, yet supporting evidence is scarce. We aimed to evaluate the efficacy of treatment with melatonin for sleep disturbance in youth with PPCS following mild traumatic brain injury (mTBI). This article is a secondary analysis of a clinical trial of melatonin compared with placebo to treat PPCS. Youth (8-18 years of age) with PPCS and significant sleep-related problems (SRPs) at 4-6 weeks post-injury were eligible. Exclusion criteria: significant medical/psychiatric history; previous concussion/mTBI within 3 months. Treatment groups were: placebo, melatonin 3 mg, or melatonin 10 mg. Primary outcome was change in SRPs measured using the Post-Concussion Symptom Inventory (PCSI) after 2 weeks of treatment. Secondary outcomes included change in actigraphy sleep efficiency, duration, onset latency, and wake-after-sleep-onset. Behavior was measured using Behaviour Assessment for Children (2nd edition). Seventy-two participants (mean age 14.0, standard deviation [SD] = 2.6) years; 60% female) with PPCS and significant sleep disturbance were included in the secondary analysis: placebo ( = 22); melatonin 3 mg ( = 25); melatonin 10 mg ( = 25). Sixty-four participants had actigraphy data. SRPs decreased across all groups over time with a significant effect of melatonin 3 mg (3.7; 95% confidence interval [CI]: 2.1, 5.4) compared with placebo (7.4; 95% CI: 4.2, 10.6) and melatonin 10 mg (6.4; 95% CI: 3.6, 9.2). Sleep duration increased in the melatonin 3 mg (43 min; 95% CI: 6, 93) and melatonin 10 mg groups (55 min; 95% CI: 5, 104) compared with placebo. A per protocol analysis demonstrated improved sleep efficiency in the melatonin 10 mg group ( = 0.029). No serious adverse events were reported. Depressive symptoms significantly decreased with melatonin 3 mg (-4.7; 95% CI: -9.2, -.2) but not with melatonin 10 mg (-1.4, 95% CI: -5.9, 3.2) treatment compared with placebo. Changes in cognition or behavior were otherwise not significantly different between treatment groups. Short-term melatonin is a well-tolerated treatment for sleep disturbance in youth with PPCS following mTBI. In this context, it may also be associated with a reduction in depressive symptoms.
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http://dx.doi.org/10.1089/neu.2020.7154DOI Listing
April 2021

Developmental Remodelling of the Motor Cortex in Hemiparetic Children With Perinatal Stroke.

Pediatr Neurol 2020 11 6;112:34-43. Epub 2020 Aug 6.

Calgary Pediatric Stroke Program, Alberta Children's Hospital, Calgary, Alberta, Canada; Alberta Children's Hospital Research Institute (ACHRI), Calgary, Alberta, Canada; Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada; Department of Neurosciences, University of Calgary, Calgary, Alberta, Canada. Electronic address:

Background: Perinatal stroke often leads to lifelong motor impairment. Two common subtypes differ in timing, location, and mechanism of injury: periventricular venous infarcts (PVI) are fetal white matter lesions while most arterial ischemic strokes (AIS) are cortical injuries acquired near term birth. Both alter motor system development and primary motor cortex (M1) plasticity, often with retained ipsilateral corticospinal fibers from the non-lesioned motor cortex (M1').

Methods: Task-based functional magnetic resonance imaging was used to define patterns of motor cortex activity during paretic and unaffected hand movement. Peak coordinates of M1, M1', and the supplementary motor area in the lesioned and intact hemispheres were compared to age-matched controls. Correlations between displacements and clinical motor function were explored.

Results: Forty-nine participants included 14 PVI (12.59 ± 3.7 years), 13 AIS (14.91 ± 3.9 years), and 22 controls (13.91 ± 3.4 years). AIS displayed the greatest M1 displacement from controls in the lesioned hemisphere while PVI locations approximated controls. Peak M1' activations were displaced from the canonical hand knob in both PVI and AIS. Extent of M1 and M1' displacement were correlated (r = 0.50, P = 0.025) but were not associated with motor function. Supplementary motor area activity elicited by paretic tapping was displaced in AIS compared to controls (P = 0.003).

Conclusion: Motor network components may be displaced in both hemispheres after perinatal stroke, particularly in AIS and those with ipsilateral control of the affected limb. Modest correlations with clinical function may support that more complex models of developmental plasticity are needed to inform targets for individualized neuromodulatory therapies in children with perinatal stroke.
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http://dx.doi.org/10.1016/j.pediatrneurol.2020.08.004DOI Listing
November 2020

Developmental neuroplasticity of the white matter connectome in children with perinatal stroke.

Neurology 2020 11 4;95(18):e2476-e2486. Epub 2020 Sep 4.

From the Calgary Pediatric Stroke Program (B.T.C., A.H., E.K.-L., H.L.C., A.K.); and Hotchkiss Brain Institute (B.T.C., A.H., E.K.-L., X.L., H.L.C., A.K.), Alberta Children's Hospital Research Institute (B.T.C., A.H., E.K.-L., X.L., H.L.C., A.K.), and Departments of Pediatrics (H.L.C., A.K.) and Clinical Neuroscience (A.K.), Cumming School of Medicine, University of Calgary, Canada.

Objective: To employ diffusion imaging connectome methods to explore network development in the contralesional hemisphere of children with perinatal stroke and its relationship to clinical function. We hypothesized alterations in global efficiency of the intact hemisphere would correlate with clinical disability.

Methods: Children with unilateral perinatal arterial (n = 26) or venous (n = 27) stroke and typically developing controls (n = 32) underwent 3T diffusion and T1 anatomical MRI and completed established motor assessments. A validated atlas coregistered to whole-brain tractography for each individual was used to estimate connectivity between 47 regions. Graph theory metrics (assortativity, hierarchical coefficient of regression, global and local efficiency, and small worldness) were calculated for the left hemisphere of controls and the intact contralesioned hemisphere of both stroke groups. Validated clinical motor assessments were then correlated with connectivity outcomes.

Results: Global efficiency was higher in arterial strokes compared to venous strokes ( < 0.001) and controls ( < 0.001) and was inversely associated with all motor assessments (all < 0.012). Additional graph theory metrics including assortativity, hierarchical coefficient of regression, and local efficiency also demonstrated consistent differences in the intact hemisphere associated with clinical function.

Conclusions: The structural connectome of the contralesional hemisphere is altered after perinatal stroke and correlates with clinical function. Connectomics represents a powerful tool to understand whole brain developmental plasticity in children with disease-specific cerebral palsy.
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http://dx.doi.org/10.1212/WNL.0000000000010669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682831PMC
November 2020

Complementary and Alternative Therapy Use in Children with Cerebral Palsy.

Can J Neurol Sci 2020 Aug 28:1-7. Epub 2020 Aug 28.

Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.

Objective: To describe complementary and alternative medicine (CAM) use amongst children with cerebral palsy (CP) in Canada and to identify factors associated with CAM use.

Methods: We conducted a cross-sectional study, utilising data from the Canadian CP Registry. We explored the association between CAM use and regional, socioeconomic and CP phenotypic variables, and parental perception of the family-centredness of clinical care using the Measures of Process of Care-56 (MPOC-56). Chi-square analyses were performed, and odds ratios (OR) and 95% confidence intervals (CI) were obtained. Mann-Whitney U tests were used to compare MPOC-56 scores between CAM users and non-CAM users.

Results: The study sample consisted of 313 families of which 27% reported CAM use in the past year. Children with CP using CAM were more likely to reside in Western Canada (OR 3.3, 95% CI 1.6-6.7), live in a two-parent household (OR 3.5, 95% CI 1.5-8.4), have an ataxic/hypotonic or dyskinetic CP subtype (OR 3.0, 95% CI 1.5-6.1) and have a greater motor impairment (OR 2.8, 95% CI 1.7-4.9). MPOC-56 subscale scores were not significantly associated with CAM use.

Conclusion: Physicians need to be aware of existing CAM therapies, the level of evidence supporting their efficacy (beneficence), their associated risks of adverse events (non-maleficence) and enable fair access to care that may be of benefit to each child.
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http://dx.doi.org/10.1017/cjn.2020.188DOI Listing
August 2020

Use of consensus methods to determine the early clinical signs of cerebral palsy.

Paediatr Child Health 2020 Aug 8;25(5):300-307. Epub 2019 May 8.

School of Physical and Occupational Therapy, McGill University, Montreal, Quebec.

Objectives: To develop expert-informed content regarding the early motor attributes of cerebral palsy (CP) that should prompt physician referral for diagnostic assessment of CP, as well as concurrent referral recommendations. This content will be used in the creation of knowledge translation (KT) tools for primary care practitioners and parents.

Methods: Two nominal group processes were conducted with relevant stakeholders, representing Canadian '' and ', using an integrated KT approach.

Results: Six attributes were identified that should prompt referral for diagnosis. If the child demonstrates: Early handedness <12 months; stiffness or tightness in the legs between 6 and 12 months; persistent fisting of the hands >4 months; persistent head-lag >4 months; inability to sit without support >9 months; any asymmetry in posture or movement. Five referral recommendations were agreed upon: Motor intervention specialist (physical therapy and/or occupational therapy) for ALL; speech-language pathology IF there is a communication delay; audiology IF there is parental or healthcare professional concern regarding a communication delay; functional vision specialist (e.g., optometrist or occupational therapist) IF there is a vision concern (e.g., not fixating, following, or tracking); feeding specialist (e.g., occupational therapist, speech-language pathologist) IF there are feeding difficulties (e.g., poor sucking, poor swallowing, choking, and/or not gaining weight).

Conclusion: Rigorous consensus methods provided the initial evidence necessary to inform the content of tools to assist primary care providers in the early detection of CP. Results will be validated through a Delphi process with international experts, and user-friendly formats of this KT tool will be developed collaboratively with stakeholders.
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http://dx.doi.org/10.1093/pch/pxz061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395325PMC
August 2020

Association of neonatal inflammatory markers and perinatal stroke subtypes.

Neurology 2020 09 29;95(9):e1163-e1173. Epub 2020 Jul 29.

From the Departments of Pediatrics (A.M., A.N.-A., S.B., K.Y., A.N., A.K.), Clinical Neurosciences (A.M., P.d.J., A.K.), and Community Health Sciences (A.N.-A.), Cumming School of Medicine, University of Calgary, Alberta, Canada.

Objective: To examine the relationship between neonatal inflammatory cytokines and perinatal stroke using a systems biology approach analyzing serum and blood-spot cytokines from 47 patients.

Methods: This was a population-based, controlled cohort study with prospective and retrospective case ascertainment. Participants were recruited through the Alberta Perinatal Stroke Project. Stroke was classified as neonatal arterial ischemic stroke (NAIS), arterial presumed perinatal ischemic stroke (APPIS), or periventricular venous infarction (PVI). Biosamples were stored blood spots (retrospective) and acute serum (prospective). Controls had comparable gestational and maternal ages. Sixty-five cytokines were measured (Luminex). Hierarchical clustering analysis was performed to create heat maps. The Fisher linear discriminant analysis was used to create projection models to determine discriminatory boundaries between stroke types and controls.

Results: A total of 197 participants were analyzed (27 with NAIS, 8 with APPIS, 12 with PVI, 150 controls). Cytokines were quantifiable with quality control measures satisfied (standards testing, decay analysis). Linear discriminant analysis had high accuracy in using cytokine profiles to separate groups. Profiles in participants with PVI and controls were similar. NAIS separation was accurate (sensitivity 77%, specificity 97%). APPIS mapping was also distinguishable from NAIS (sensitivity 86%, specificity 99%). Classification tree analysis generated similar diagnostic accuracy.

Conclusions: Unique inflammatory biomarker signatures are associated with specific perinatal stroke diseases. Findings support an acquired pathophysiology and suggest the possibility that at-risk pregnancies might be identified to develop prevention strategies.

Classification Of Evidence: This study provides Class III evidence that differences in acute neonatal serum cytokine profiles can discriminate between patients with specific perinatal stroke diseases and controls.
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http://dx.doi.org/10.1212/WNL.0000000000010309DOI Listing
September 2020

Imaging Developmental and Interventional Plasticity Following Perinatal Stroke.

Can J Neurol Sci 2021 Mar 30;48(2):157-171. Epub 2020 Jul 30.

Calgary Pediatric Stroke Program, Alberta Children's Hospital, Calgary, AB, Canada.

Perinatal stroke occurs around the time of birth and leads to lifelong neurological disabilities including hemiparetic cerebral palsy. Magnetic resonance imaging (MRI) has revolutionized our understanding of developmental neuroplasticity following early injury, quantifying volumetric, structural, functional, and metabolic compensatory changes after perinatal stroke. Such techniques can also be used to investigate how the brain responds to treatment (interventional neuroplasticity). Here, we review the current state of knowledge of how established and emerging neuroimaging modalities are informing neuroplasticity models in children with perinatal stroke. Specifically, we review structural imaging characterizing lesion characteristics and volumetrics, diffusion tensor imaging investigating white matter tracts and networks, task-based functional MRI for localizing function, resting state functional imaging for characterizing functional connectomes, and spectroscopy examining neurometabolic changes. Key challenges and exciting avenues for future investigations are also considered.
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http://dx.doi.org/10.1017/cjn.2020.166DOI Listing
March 2021

Executive behavior and functional abilities in children with perinatal stroke and the associated caregiver impact.

Child Neuropsychol 2021 Jan 28;27(1):83-95. Epub 2020 Jul 28.

Department of Pediatrics, University of Alberta , Edmonton, Canada.

Perinatal stroke is the most common form of stroke in childhood and is followed by a variety of outcomes, with many children experiencing specific functional and neuropsychological deficits. The association of these outcomes with the psychosocial impact caregivers face is not well documented. The goal of our pilot study was to examine caregivers' perception of executive behavior and functional abilities among children with perinatal stroke, and how these outcomes impact the caregivers. We administered three questionnaires to primary caregivers of children with perinatal stroke to obtain caregiver-reported measures of (1) executive behavior of their child (Behavior Rating Inventory of Executive Function, Second Edition), (2) the functional abilities of their child (Pediatric Evaluation of Disability Inventory Computer Adaptive Test), and (3) the psychosocial impact experienced by the caregiver themselves (Parental Outcome Measure). Participants included 20 children (mean age = 9.3 years, range = 6-16 years) with perinatal stroke and their primary caregivers. Functional abilities in the children were rated as clinically impaired in the domains of daily activities and mobility. Half of the children exhibited clinically impaired ratings on at least one executive behavior domain, but the mean scores for these domains did not reach clinically impaired levels. Greater ratings of problems in daily activities for the child was associated with greater caregiver guilt ( = -0.55, = 0.02). Caregivers of children with perinatal stroke who experience limitations in performing daily activities should be more closely monitored for adverse impact and be provided the necessary support and education to alleviate the associated guilt.
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http://dx.doi.org/10.1080/09297049.2020.1796953DOI Listing
January 2021

Robotic assessment of rapid motor decision making in children with perinatal stroke.

J Neuroeng Rehabil 2020 07 14;17(1):94. Epub 2020 Jul 14.

Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada.

Background: Activities of daily living frequently require children to make rapid decisions and execute desired motor actions while inhibiting unwanted actions. Children with hemiparetic cerebral palsy due to perinatal stroke may have deficits in executive functioning in addition to motor impairments. The objective of this study was to use a robotic object hit and avoid task to assess the ability of children with hemiparetic cerebral palsy to make rapid motor decisions.

Methods: Forty-five children with hemiparetic cerebral palsy due to perinatal stroke and 146 typically developing children (both groups ages 6-19 years) completed a robotic object hit and avoid task using the Kinarm Exoskeleton. Objects of different shapes fell from the top of the screen with increasing speed and frequency. Children were instructed to hit two specific target shapes with either hand, while avoiding six distractor shapes. The number of targets and distractors hit were compared between children with hemiparetic cerebral palsy and typically developing children, accounting for age effects. We also compared performance to a simpler object hit task where there were no distractors.

Results: We found that children with hemiparetic cerebral palsy hit a greater proportion of total distractors compared to typically developing children, demonstrating impairments in inhibitory control. Performance for all children improved with age. Children with hemiparetic cerebral palsy hit a greater percentage of targets with each arm on the more complex object hit and avoid task compared to the simpler object hit task, which was not found in typically developing children.

Conclusions: Children with hemiparetic cerebral palsy due to perinatal stroke demonstrated impairments in rapid motor decision making including inhibitory control, which can impede their ability to perform real-world tasks. Therapies that address both motor performance and executive functions are necessary to maximize function in children with hemiparetic cerebral palsy.
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http://dx.doi.org/10.1186/s12984-020-00714-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362540PMC
July 2020

Transcranial Static Magnetic Field Stimulation of the Motor Cortex in Children.

Front Neurosci 2020 19;14:464. Epub 2020 May 19.

Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Background: Non-invasive neuromodulation is an emerging therapy for children with early brain injury but is difficult to apply to preschoolers when windows of developmental plasticity are optimal. Transcranial static magnetic field stimulation (tSMS) decreases primary motor cortex (M1) excitability in adults but effects on the developing brain are unstudied.

Objective/hypothesis: We aimed to determine the effects of tSMS on cortical excitability and motor learning in healthy children. We hypothesized that tSMS over right M1 would reduce cortical excitability and inhibit contralateral motor learning.

Methods: This randomized, sham-controlled, double-blinded, three-arm, cross-over trial enrolled 24 healthy children aged 10-18 years. Transcranial Magnetic Stimulation (TMS) assessed cortical excitability via motor-evoked potential (MEP) amplitude and paired pulse measures. Motor learning was assessed via the Purdue Pegboard Test (PPT). A tSMS magnet (677 Newtons) or sham was held over left or right M1 for 30 min while participants trained the non-dominant hand. A linear mixed effect model was used to examine intervention effects.

Results: All 72 tSMS sessions were well tolerated without serious adverse effects. Neither cortical excitability as measured by MEPs nor paired-pulse intracortical neurophysiology was altered by tSMS. Possible behavioral effects included contralateral tSMS inhibiting early motor learning ( < 0.01) and ipsilateral tSMS facilitating later stages of motor learning ( < 0.01) in the trained non-dominant hand.

Conclusion: tSMS is feasible in pediatric populations. Unlike adults, tSMS did not produce measurable changes in MEP amplitude. Possible effects of M1 tSMS on motor learning require further study. Our findings support further exploration of tSMS neuromodulation in young children with cerebral palsy.
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http://dx.doi.org/10.3389/fnins.2020.00464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248312PMC
May 2020

A Case of Neuromuscular Electrical Stimulation for Childhood Stroke Hyperkinesis: A Brief Report.

Dev Neurorehabil 2020 Aug 7;23(6):407-411. Epub 2020 Jun 7.

Alberta Children's Hospital , Calgary, AB, Canada.

Aim: Some conditions within specific populations are so rare rigorous evidence is unavailable. Childhood hyperkinesis is one example, yet presents an opportunity to examine sensation's contribution to motor function.

Methods: The patient experienced functional difficulty from hyperkinesis as a result of childhood stroke. Home-based passive neuromuscular electrical stimulation (NMES) was implemented an hour/day, six days/week, over 6 weeks (36 hours). Clinical and robotic measures (Assisting Hand Assessment, Box and Block Test, Jebsen Taylor Test of Hand Function, Kinarm) were administered before and after the intervention and at 9 months.

Results: NMES was feasible and well tolerated. Clinically important gains of arm function were maintained at 9 months. Robotic measures showed improved hyperkinesis, namely reduced movement segmentation and improved target approximation, in addition to improved proprioceptive function after NMES.

Conclusion: This case study illustrates the use of NMES within a previously unexplored population and highlights the potential importance of sensory systems to motor gains.
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http://dx.doi.org/10.1080/17518423.2020.1773956DOI Listing
August 2020

Spectrum of cerebral arteriopathies in children with arterial ischemic stroke.

Neurology 2020 06 26;94(23):e2479-e2490. Epub 2020 May 26.

From the Section of Pediatric Neurology (M.F.R.), Department of Pediatrics and Child Health, University of Manitoba, Children's Hospital Research Institute of Manitoba, Winnipeg, Canada; Department of Neurology and Pediatrics (K.A.S., H.J.F.), University of California, San Francisco; University of Toronto (A.-M.S.); Division of Neurology (G.A.d.V., N.D., A.L.), The Hospital for Sick Children, University of Toronto, Ontario; Department of Pediatrics and Clinical Neurosciences (A.K.), Cumming School of Medicine, University of Calgary, Alberta, Canada; Department of Neurology (C.A.-L.), University of Washington, Seattle; Department of Neuropediatrics (B.W.), Charité University Medicine Berlin, Germany; Department of Neurology (J.L.C.), George Washington University, Washington, DC; Department of Neurology (M.T.M.), Royal Children's Hospital Melbourne, Murdoch Children's Research Institute and University of Melbourne, Australia; Boston Children's Hospital (M.R.), Harvard Medical School, Boston, MA; and Division of Child Neurology (T.J.B.), Department of Pediatrics and the Hemophilia and Thrombosis Center, University of Colorado, Denver.

Objective: To determine that children with arterial ischemic stroke (AIS) due to an identifiable arteriopathy are distinct from those without arteriopathy and that each arteriopathy subtype has unique and recognizable clinical features.

Methods: We report a large, observational, multicenter cohort of children with AIS, age 1 month to 18 years, enrolled in the International Pediatric Stroke Study from 2003 to 2014. Clinical and demographic differences were compared by use of the Fisher exact test, with linear step-up permutation min- adjustment for multiple comparisons. Exploratory analyses were conducted to evaluate differences between cases of AIS with and without arteriopathy and between arteriopathy subtypes.

Results: Of 2,127 children with AIS, 725 (34%) had arteriopathy (median age 7.45 years). Arteriopathy subtypes included dissection (27%), moyamoya (24.5%), focal cerebral arteriopathy-inflammatory subtype (FCA-i; 15%), diffuse cerebral vasculitis (15%), and nonspecific arteriopathy (18.5%). Children with arteriopathic AIS were more likely to present between 6 and 9 years of age (odds ratio [OR] 1.93, = 0.029) with headache (OR 1.55, = 0.023), multiple infarctions (OR 2.05, < 0.001), sickle cell anemia (OR 2.9, = 0.007), and head/neck trauma (OR 1.93, = 0.018). Antithrombotic use and stroke recurrence were higher in children with arteriopathy. Among arteriopathy subtypes, dissection was associated with male sex, older age, headache, and anticoagulant use; FCA-i was associated with hemiparesis and single infarcts; moyamoya was associated with seizures and recurrent strokes; and vasculitis was associated with bilateral infarctions.

Conclusion: Specific clinical profiles are associated with cerebral arteriopathies in children with AIS. These observations may be helpful indicators in guiding early diagnosis and defining subgroups who may benefit most from future therapeutic trials.
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http://dx.doi.org/10.1212/WNL.0000000000009557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455362PMC
June 2020

Guidelines for TMS/tES clinical services and research through the COVID-19 pandemic.

Brain Stimul 2020 Jul - Aug;13(4):1124-1149. Epub 2020 May 12.

Laureate Institute for Brain Research, Tulsa, OK, USA. Electronic address:

Background: The COVID-19 pandemic has broadly disrupted biomedical treatment and research including non-invasive brain stimulation (NIBS). Moreover, the rapid onset of societal disruption and evolving regulatory restrictions may not have allowed for systematic planning of how clinical and research work may continue throughout the pandemic or be restarted as restrictions are abated. The urgency to provide and develop NIBS as an intervention for diverse neurological and mental health indications, and as a catalyst of fundamental brain research, is not dampened by the parallel efforts to address the most life-threatening aspects of COVID-19; rather in many cases the need for NIBS is heightened including the potential to mitigate mental health consequences related to COVID-19.

Objective: To facilitate the re-establishment of access to NIBS clinical services and research operations during the current COVID-19 pandemic and possible future outbreaks, we develop and discuss a framework for balancing the importance of NIBS operations with safety considerations, while addressing the needs of all stakeholders. We focus on Transcranial Magnetic Stimulation (TMS) and low intensity transcranial Electrical Stimulation (tES) - including transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS).

Methods: The present consensus paper provides guidelines and good practices for managing and reopening NIBS clinics and laboratories through the immediate and ongoing stages of COVID-19. The document reflects the analysis of experts with domain-relevant expertise spanning NIBS technology, clinical services, and basic and clinical research - with an international perspective. We outline regulatory aspects, human resources, NIBS optimization, as well as accommodations for specific demographics.

Results: A model based on three phases (early COVID-19 impact, current practices, and future preparation) with an 11-step checklist (spanning removing or streamlining in-person protocols, incorporating telemedicine, and addressing COVID-19-associated adverse events) is proposed. Recommendations on implementing social distancing and sterilization of NIBS related equipment, specific considerations of COVID-19 positive populations including mental health comorbidities, as well as considerations regarding regulatory and human resource in the era of COVID-19 are outlined. We discuss COVID-19 considerations specifically for clinical (sub-)populations including pediatric, stroke, addiction, and the elderly. Numerous case-examples across the world are described.

Conclusion: There is an evident, and in cases urgent, need to maintain NIBS operations through the COVID-19 pandemic, including anticipating future pandemic waves and addressing effects of COVID-19 on brain and mind. The proposed robust and structured strategy aims to address the current and anticipated future challenges while maintaining scientific rigor and managing risk.
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http://dx.doi.org/10.1016/j.brs.2020.05.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217075PMC
July 2020