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Background and Objectives: For individuals with cerebral palsy (CP) and caregivers, comorbidities may be a greater challenge than neuromotor impairment. Clinicians may make assumptions regarding risk of comorbidities based simply on term vs preterm birth, but this has not been well examined. To better understand factors affecting comorbidity pattern, we investigated the relationship between gestational age (GA) and imaging pattern on the presence of specific comorbidities., Methods: This is a cross-sectional study of data extracted from the Canadian Cerebral Palsy Registry of children with CP. Multivariable analysis was used to evaluate the relationship between brain injury, GA, and comorbidities. Comorbidities included in the analysis were communication, cognitive, visual, and auditory impairment, seizures in the past year, and gavage feeding. Each comorbidity was assessed as a separate nonexclusive outcome, with GA, MRI pattern, birth weight, postneonatal insult, 5-minute Apgar score, and male sex considered as potential modifiers., Results: The only comorbidity affected by GA on multivariable analysis was seizures within the past year that were more prevalent in term children (odds ratio [OR] 1.1 95% CI 1.0-1.2) and was also affected by Apgar score (OR 0.9 95% CI 0.85-0.94), but not MRI pattern. MRI pattern appeared important for communication impairment (deep gray OR 4.2 95% CI 1.8-10.0; total brain injury OR 8.5, 95% CI 3.2-22.6; malformation OR 2.7, 95% CI 1.3-5.7) and cognitive impairment (deep gray OR 5.6, 95% CI 2.4-13.2; total brain injury OR 10.1, 95% CI 4.0-25.3; malformation OR 3.3, 95% CI 1.6-6.8; watershed OR 3.6, 95% CI 1.4-8.9). Focal injury compared with normal MRI was associated with reduced odds of visual impairment (OR 0.24, 95% CI 0.12-0.48), auditory impairment (OR 0.2195% CI 0.10-0.46) and communication impairment (OR 0.46, 95% CI 0.26-0.82), and overall number of comorbidities (coefficient -0.73, 95% CI -1.2 to -0.31). The number of comorbidities was increased by total brain injury pattern (coefficient 0.65, 95% CI 0.15-1.13) and reduced by focal brain injury (coefficient -0.73, 95% CI -1.2 to -0.31) and increasing 5-minute Apgar score (coefficient -0.11, 95% CI -0.16 to -0.07)., Discussion: In those with brain injuries sufficient to cause CP, development of additional comorbidities is less affected by GA at birth and more related to the underlying cause of CP as reflected by MRI patterns.

Background: To identify if a predetermined set of potential risk factors are associated with spastic diplegic cerebral palsy (SDCP) in term-born children., Methods: This is a case-control study with cases (n = 134) extracted from the Canadian Cerebral Palsy Registry (CCPR) and controls (n = 1950) from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Our primary variable was the SDCP phenotype in term-born children. Possible risk factors were selected a priori and include extreme maternal age (<19 or >35 years), pregnancy complications, maternal disease, substance use, perinatal infection, mode of delivery, perinatal adversity (i.e., neonatal encephalopathy presumably on the basis of intrapartum hypoxia-ischemia), sex, and birth weight. Multivariable analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Multivariable analysis revealed associations between term-born SDCP and pregnancy complications (OR = 4.73; 95% CI = 1.91 to 10.56), maternal disease (OR = 2.52; 95% CI = 1.57 to 3.93), substance use (OR = 3.11; 95% CI = 2.10 to 4.55), perinatal infection (OR = 2.72; 95% CI 1.32 to 5.10), Caesarean section (OR = 2.35; 95% CI = 1.62 to 3.40), and perinatal adversity (OR = 2.91; 95% CI = 1.94 to 4.50). Multiple regression analysis revealed associations between SDCP and pregnancy complications (OR = 3.28; 95% CI 1.20 to 8.15), maternal disease (OR = 2.52; 95% CI 1.50 to 4.12), substance use (OR = 3.59; 95% CI 2.37 to 5.40), perinatal infection (OR = 3.78, 95% CI 1.71 to 7.72), Caesarean section (OR = 2.72; 95% CI 1.82 to 4.03), and perinatal adversity (OR = 4.16; 95% CI 2.67 to 6.70)., Interpretation: Antenatal (pregnancy complications, maternal disease, substance use) and perinatal (infections, Caesarean section, and perinatal adversity) risk factors are associated with an increased risk of SDCP in term-born children, suggesting variable interactions between risk factors to provide a clinicopathologic framework that is different from SDCP observed in preterm-born children., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.7%) as having variants of uncertain significance. Multiple classes of P/LP variants included single-nucleotide variants (SNVs)/indels (6.7%), copy number variations (3.4%) and mitochondrial mutations (1.5%). The COL4A1 gene had the most P/LP SNVs. We also analyzed two pediatric control cohorts (n = 203 trios and n = 89 sib-pair families) to provide a baseline for de novo mutation rates and genetic burden analyses, the latter of which demonstrated associations between de novo deleterious variants and genes related to the nervous system. An enrichment analysis revealed previously undescribed plausible candidate CP genes (SMOC1, KDM5B, BCL11A and CYP51A1). A multifactorial CP risk profile and substantial presence of P/LP variants combine to support WGS in the diagnostic work-up across all CP and related phenotypes., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background and Objectives: Perinatal hypoxic-ischemic brain injury is a leading cause of term-born cerebral palsy, the most common lifelong physical disability. Diagnosis is commonly made in the neonatal period by the combination of neonatal encephalopathy (NE) and typical neuroimaging findings. However, children without a history of neonatal encephalopathy may present later in childhood with motor disability and neuroimaging findings consistent with perinatal hypoxic-ischemic injury. We sought to determine the prevalence of such presentations using the retrospective viewpoint of a large multiregional cerebral palsy registry., Methods: Patient cases were extracted from the Canadian Cerebral Palsy Registry with gestational age >36 weeks, an MRI pattern consistent with hypoxic-ischemic injury (HII, acute total, partial prolonged, or combined), and an absence of postnatal cause for HII. Documentation of NE was noted. Maternal-fetal risk factors, labor and delivery, neonatal course, and clinical outcome were extracted. Comparisons were performed using χ 2 tests and multivariable logistic regression with multiple imputation. Propensity scores were used to assess for bias., Results: Of the 170 children with MRI findings typical for HII, 140 (82.4%, 95% confidence interval [CI] 75.7%-87.7%) had documented NE and 29 (17.0%, 95% CI 11.7%-23.6%) did not. The group without NE had more abnormalities of amniotic fluid volume (odds ratio [OR] 15.8, 95% CI 1.2-835), had fetal growth restriction (OR 4.7, 95% CI 1.0-19.9), had less resuscitation (OR 0.03, 95% CI 0.007-0.08), had higher 5-minute Apgar scores (OR 2.2, 95% CI 1.6-3.0), were less likely to have neonatal seizures (OR 0.004, 95% CI 0.00009-0.03), and did not receive therapeutic hypothermia. MRI was performed at a median 1.1 months (interquartile range [IQR] 0.67-12.8 months) for those with NE and 12.2 months (IQR 6.6-25.9) for those without ( p = 0.011). Patterns of injury on MRI were seen in similar proportions. Hemiplegia was more common in those without documented NE (OR 5.1, 95% CI 1.5-16.1); rates of preserved ambulatory function were similar., Discussion: Approximately one-sixth of term-born children with an eventual diagnosis of cerebral palsy and MRI findings consistent with perinatal hypoxic-ischemic brain injury do not have documented neonatal encephalopathy, which was associated with abnormalities of fetal growth and amniotic fluid volume, and a less complex neonatal course. Long-term outcomes seem comparable with their peers with encephalopathy. The absence of documented neonatal encephalopathy does not exclude perinatal hypoxic-ischemic injury, which may have occurred antenatally and must be carefully evaluated with MRI.

Perinatal stroke causes most hemiparetic cerebral palsy and cognitive dysfunction may co-occur. Compensatory developmental changes in the intact contralesional hemisphere may mediate residual function and represent targets for neuromodulation. We used morphometry to explore cortical thickness, grey matter volume, gyrification, and sulcal depth of the contralesional hemisphere in children, adolescents, and young adults after perinatal stroke and explored associations with motor, attention, and executive function. Participants aged 6-20 years (N = 109, 63% male) with unilateral perinatal stroke underwent T1-weighted imaging. Participants had arterial ischemic stroke (AIS; n = 36), periventricular venous infarction (PVI; n = 37) or were controls (n = 36). Morphometry was performed using the Computational Anatomy Toolbox (CAT12). Group differences and associations with motor and executive function (in a smaller subsample) were assessed. Group comparisons revealed areas of lower cortical thickness in contralesional hemispheres in both AIS and PVI and greater gyrification in AIS compared to controls. Areas of greater grey matter volume and sulcal depth were also seen for AIS. The PVI group showed lower grey matter volume in cingulate cortex and less volume in precuneus relative to controls. No associations were found between morphometry metrics, motor, attention, and executive function. Cortical structure of the intact contralesional hemisphere is altered after perinatal stroke. Alterations in contralesional cortical morphometry shown in perinatal stroke may be associated with different mechanisms of damage or timing of early injury. Further investigations with larger samples are required to more thoroughly explore associations with motor and cognitive function., (© 2023. The Author(s).)

Purpose: This study assessed physical activity (PA) and body composition of ambulatory children and adolescents with cerebral palsy (CP) and their typically developing peers., Methods: Participants included youth with CP (ages 8-18 y and Gross Motor Function Classification System [GMFCS] levels I-III) and their typically developing peers. Outcomes included PA (actigraphy) and fat/lean mass index (FMI/LMI; dual-energy X-ray absorptiometry). Statistical analyses included linear mixed effects models with Bonferroni adjustment. Fixed effects were study group (CP and typically developing); random effects were participant clusters (sex and age). Exploratory analyses included association of body composition and PA, GMFCS level, and CP involvement (unilateral and bilateral)., Results: Seventy-eight participants (CP: n = 40, girls: n = 29; GMFCS I: n = 20; GMFCS II: n = 14; GMFCS III: n = 6) met inclusion criteria. Individuals with CP had lower moderate to vigorous PA (MVPA; β = -12.5; 98.3% confidence interval, -22.6 to -2.5 min; P = .004) and lower LMI (β = -1.1; 97.5% confidence interval, -2.1 to -0.0 kg/m2; P = .020). Exploratory analyses indicated increased LMI with greater MVPA (P = .001), reduced MVPA for GMFCS II (P = .005) and III (P = .001), increased sedentary time for GMFCS III (P = .006), and greater fat mass index with unilateral motor impairment (P = .026)., Conclusions: The findings contribute to the knowledge base of increasing MVPA and LMI deficits with the greater functional impact of CP. Associations of increasing LMI with greater MVPA support efforts targeting enhanced PA participation to promote independent mobility.

Importance: Cerebral palsy (CP) is the most common abnormality of motor development and causes lifelong impairment. Early diagnosis and therapy can improve outcomes, but early identification of infants at risk remains challenging., Objective: To develop a CP prognostic tool that can be applied to all term neonates to identify those at increased risk of developing CP., Design, Setting, and Participants: This case-control study used data from the Canadian Cerebral Palsy Registry (data collected from January 2003 to December 2019) for children with CP and the Alberta Pregnancy Outcomes and Nutrition study (mothers enrolled from May 2009 to September 2012; data extracted in 2020) for controls. There were 2771 children with CP and 2131 controls evaluated; 941 and 144, respectively, were removed for gestational age less than 37 weeks at birth, 565 with CP removed for incomplete data, and 2 controls removed for a diagnosis of CP. Data were analyzed from April to August 2022., Exposures: Potential risk factors were selected a priori based on the literature, including maternal, intrapartum, and infant characteristics., Main Outcomes and Measures: Diagnosis of CP, defined as a disorder of motor function due to a nonprogressive brain abnormality before age 1 year and classified by Gross Motor Function Classification System levels I to V., Results: Of 3250 included individuals, 1752 (53.9%) were male, and the median (IQR) gestational age at birth was 39 (38-40) weeks. Encephalopathy was present in 335 of 1184 infants with CP (28%) and 0 controls. The final prediction model included 12 variables and correctly classified 75% of infants, with a sensitivity of 56% (95% CI, 52-60) and specificity of 82% (95% CI, 81-84). The C statistic was 0.74 (95% CI, 71-76). Risk factors were found to be additive. A proposed threshold for screening is probability greater than 0.3, with a sensitivity of 65% (95% CI, 61-68) and specificity of 71% (95% CI, 69-73). The prognostic tool identified 2.4-fold more children with CP than would have presented with encephalopathy (odds ratio, 13.8; 95% CI, 8.87-22.65; P < .001)., Conclusions and Relevance: In this case-control study, a prognostic model using 12 clinical variables improved the prediction of CP compared with clinical presentation with encephalopathy. This tool can be applied to all term newborns to help select infants for closer surveillance or further diagnostic tests, which could improve outcomes through early intervention.

Aim: To assess the stability of the Gross Motor Functional Classification System (GMFCS) in children with cerebral palsy (CP) from time of preliminary diagnosis (~2 years of age) to time of diagnosis (~5 years of age), and to examine factors associated with reclassification., Method: We conducted a longitudinal study using a sample from the Canadian CP Registry. Stability was analysed by using the percentage of agreement between timepoints and a weighted prevalence and bias adjusted kappa statistic. Univariate and multivariate logistic regressions were performed to identify variables associated with reclassification., Results: The study included 1670 children (857 males, 713 females) with a mean age of 11 years 4 months (SD 4 years, range 3 years 5 months-20 years 1 month) at time of data extraction (3rd September 2019), of which 1435 (85.9%) maintained a stable GMFCS, with a weighted kappa of 0.91 (95% confidence interval 0.89-0.92). Univariate logistic regression showed that initial GMFCS level, CP subtype, and the presence of cognitive impairment were associated with the likelihood of change in the GMFCS level (p < 0.1). In the multivariate analysis, however, the likelihood was associated with initial GMFCS level only (odds ratio 7.10-8.88, p < 0.00)., Interpretation: The GMFCS has good stability in early childhood. For the majority of children, it is predictive of their long-term motor function., What This Paper Adds: The Gross Motor Function Classification System (GMFCS) rating in early childhood is stable over time. There is no directionality in the reclassification of the GMFCS. The initial GMFCS level was related to the likelihood of change in follow-up GMFCS level., (© 2022 Mac Keith Press.)

Objective: The aim of this study was to identify possible risk factors associated with term-born children with cerebral palsy (CP) and periventricular white matter injury (PVWMI) on imaging., Methods: This is a case-controlled study restricted to term-born children with CP with the cases extracted from the Canadian Cerebral Palsy Registry and controls from Alberta Pregnancy Outcomes and Nutrition (APrON) study. A diagnosis of PVWMI was performed based on expert categorization of MRI reports. Risk factor variables were selected a priori; these included pregnancy complications, antenatal toxin exposure, perinatal infection, sex, small for gestational age, and perinatal adversity (i.e., neonatal encephalopathy presumably on the basis of intrapartum hypoxia-ischemia). We used multivariable analyses to calculate odds ratios (ORs) and their 95% CIs., Results: A total of 160 cases (7.06% of the registry sample) were compared with 1,950 controls. Of the term-born PVWMI participants, 59.4% were male and 13.5% were born to mothers of extreme maternal age. Multivariable analysis of each risk factor controlled for weight showed PVWMI is associated with pregnancy complications (OR = 3.35; 95% CI = 2.23-4.94), antenatal toxin exposure (OR = 2.45; 95% CI = 1.67-3.55), perinatal infection (OR = 3.61; 95% CI = 1.96-6.29), and perinatal adversity (OR = 2.03; 95% CI = 1.42-2.94). Term-born male participants were not more likely to experience PVWMI compared with female participants (OR = 1.37; 95% CI = 0.98-1.93). Multiple regression analyses suggested independent associations between PVWMI and pregnancy complications (OR = 3.75; 95% CI 2.46-5.62), antenatal toxin exposure (OR = 2.80; 95% CI 1.88-4.12), perinatal infection (OR = 4.62; 95% CI 2.46-8.42), and perinatal adversity (OR = 2.49; 95% CI = 1.71-3.69)., Discussion: Risk factors such as pregnancy complications, antenatal toxin exposure, perinatal infection, and perinatal adversity are associated with PVWMI in term-born children, suggesting perhaps variable interactions between antenatal and perinatal factors to yield this under-recognized CP phenotype., (© 2022 American Academy of Neurology.)

Brain stimulation combined with intensive therapy may improve hand function in children with perinatal stroke-induced unilateral cerebral palsy (UCP). However, response to therapy varies and underlying neuroplasticity mechanisms remain unclear. Here, we aimed to characterize robotic motor mapping outcomes in children with UCP. Twenty-nine children with perinatal stroke and UCP (median age 11 ± 2 years) were compared to 24 typically developing controls (TDC). Robotic, neuronavigated transcranial magnetic stimulation was employed to define bilateral motor maps including area, volume, and peak motor evoked potential (MEP). Map outcomes were compared to the primary clinical outcome of the Jebsen-Taylor Test of Hand Function (JTT). Maps were reliably obtained in the contralesional motor cortex (24/29) but challenging in the lesioned hemisphere (5/29). Within the contralesional M1 of participants with UCP, area and peak MEP amplitude of the unaffected map were larger than the affected map. When comparing bilateral maps within the contralesional M1 in children with UCP to that of TDC, only peak MEP amplitudes were different, being smaller for the affected hand as compared to TDC. We observed correlations between the unaffected map when stimulating the contralesional M1 and function of the unaffected hand. Robotic motor mapping can characterize motor cortex neurophysiology in children with perinatal stroke. Map area and peak MEP amplitude may represent discrete biomarkers of developmental plasticity in the contralesional M1. Correlations between map metrics and hand function suggest clinical relevance and utility in studies of interventional plasticity., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Brain-computer interfaces (BCIs) are emerging as a new solution for children with severe disabilities to interact with the world. However, BCI technologies have yet to reach end-users in their daily lives due to significant translational gaps. To address these gaps, we applied user-centered design principles to establish a home BCI program for children with quadriplegic cerebral palsy. This work describes the technical development of the software we designed to facilitate BCI use at home. Children and their families were involved at each design stage to evaluate and provide feedback. Since deployment, seven families have successfully used the system independently at home and continue to use BCI at home to further enable participation and independence for their children. Clinical relevance- The design and successful implementation of user-centered software for home use will both inform on the feasibility of BCI as a long-term access solution for children with neurological disabilities as well as decrease barriers of accessibility and availability of BCI technologies for end-users.

Background: Perinatal stroke causes hemiparetic cerebral palsy (HCP) and lifelong disability. Constraint-induced movement therapy (CIMT) and neurostimulation may enhance motor function, but the individual factors associated with responsiveness are undetermined., Objective: We explored the clinical and neurophysiological factors associated with responsiveness to CIMT and/or brain stimulation within a clinical trial., Methods: PLASTIC CHAMPS was a randomized, blinded, sham-controlled trial (n = 45) of CIMT and neurostimulation paired with intensive, goal-directed therapy. Primary outcome was the Assisting Hand Assessment (AHA). Classification trees created through recursive partitioning suggested clinical and neurophysiological profiles associated with improvement at 6-months., Results: Both clinical (stroke side (left) and age >14 years) and neurophysiological (intracortical inhibition/facilitation and motor threshold) were associated with responsiveness across treatment groups with positive predictive values (PPV) approaching 80%., Conclusion: This preliminary analysis suggested sets of variables that may be associated with response to intensive therapies in HCP. Further modeling in larger trials is required.

Aims: In pediatric upper extremity rehabilitation, feasible repetition rates are unknown. Our objectives were to examine repetition rates during rehabilitation and their impact on outcomes., Methods: Children with unilateral cerebral palsy due to perinatal stroke ( n  = 55, median 10 y 7 mo, 30 males) received Constraint-Induced Movement Therapy (CIMT) followed by Bimanual Therapy, each for 5 days. Repetitions were documented during one-on-one therapy (1.5 h/day). Outcomes included the Assisting Hand Assessment (AHA), Jebsen Taylor Test of Hand Function (JTTHF), and Box and Block Test (BBT). Means and standard deviations for motor outcomes and frequencies for repetition rates were calculated. Factors associated with repetition rates and outcome change were explored using standard linear regression., Results: Repetitions/hour averaged 365 ± 165 during CIMT and 285 ± 103 during Bimanual Therapy. Higher repetition rates were associated with higher baseline function by older age, a main effect of younger age, and improving motor skill ( p < .05). Higher repetition rates corresponded with improvement of the AHA and BBT ( p < .05, standardized ß = 0.392, 0.358)., Conclusions: Results suggest high repetition therapy is feasible in school-aged children with perinatal stroke, albeit with high individual variability. Multiple associations between repetition rates and baseline function and change point to the clinical importance of this measurable and potentially modifiable factor.

Aim: To explore clinical factors associated with perinatal arterial ischemic stroke (AIS) and periventricular venous infarction (PVI) in infants who develop unilateral cerebral palsy (CP)., Method: This was a case-control study. Data current to 2019 was extracted from the Canadian Cerebral Palsy Registry (CCPR). Cases were infants born at term with confirmed unilateral CP. Magnetic resonance images were stratified by expert review of reports as definitive perinatal stroke (AIS or PVI). Controls with common data elements were recruited from a population-based study in Alberta. Multivariable regression analyses were performed to estimate associations expressed as odds ratios with 95% confidence intervals., Results: Of 2093 cases from the CCPR, 662 had unilateral CP, of whom 299 (45%) had perinatal stroke: AIS 169 (57%) and PVI 130 (43%). Median age at diagnosis for AIS was 11.9 months (interquartile range: 6.2-25.7mo; range 0.17-104.1mo), and 58.6% were male. Median age at diagnosis for PVI was 25.3 months (interquartile range: 14.5-38mo, range 0.7-114.7mo) and 57.7% were male. Independent associations for both AIS and PVI on multivariable analysis were chorioamnionitis, illicit drug exposure, diabetes, gestational age, and maternal age. Variables associated with AIS alone were low Apgar score and prolonged rupture of membranes. Variables associated with PVI alone were small for gestational age and primigravida., Interpretation: Controlled analysis of disease-specific unilateral CP may offer unique perspectives on its pathophysiology. Acute intrapartum factors are mainly associated with AIS, while in utero factors are associated with PVI., (© 2021 Mac Keith Press.)

Background: Hemiparetic cerebral palsy impacts millions of people worldwide. Assessment of bilateral motor function in real life remains a major challenge. We evaluated quantification of upper extremity movement in hemiparetic children using bilateral actigraphy. We hypothesized that movement asymmetry correlates with standard motor outcome measures., Methods: Hemiparetic and control participants wore bilateral wrist Actiwatch2 (Philips) for 48 h with movement counts recorded in 15-s intervals. The primary outcome was a novel statistic of movement asymmetry, the Actigraphic Movement Asymmetry Index (AMAI). Relationships between AMAI and standard motor outcomes (Assisting Hand Assessment, Melbourne Assessment, and Box and Block Test [BB]) were explored with Pearson or Spearman correlation., Results: 30 stroke (mean 11 years 2 months (3 years 10 months); 13 female, 17 male) and 23 control (mean 11 years 1 month (4 years 5 months); 8 female, 15 male) were enrolled. Stroke participants demonstrated higher asymmetry. Correlations between AMAI and standard tests were moderate and strongest during sleep (BB: r = 0.68, p < 0.01)., Conclusions: Standard tests may not reflect the extent of movement asymmetry during daily life in hemiparetic children. Bilateral actigraphy may be a valuable complementary tool for measuring arm movement, potentially enabling improved evaluation of therapies with a focus on child participation., (© 2021. The Author(s).)

Background and Purpose: Perinatal stroke is the leading cause of hemiparetic cerebral palsy resulting in lifelong disability for millions of people worldwide. Options for motor rehabilitation are limited, especially for the most severely affected children. Brain computer interfaces (BCIs) sample brain activity to allow users to control external devices. Functional electrical stimulation enhances motor recovery after stroke, and BCI-activated functional electrical stimulation was recently shown to improve upper extremity function in adult stroke. We aimed to determine the ability of children with perinatal stroke to operate a simple BCI., Methods: Twenty-one children with magnetic resonance imaging–confirmed perinatal stroke (57% male, mean [SD] 13.5 [2.6] years, range 9–18) were compared with 24 typically developing controls (71% male, mean age [SD] 13.7 [3.7] years, range 6–18). Participants trained on a simple EEG-based BCI over 2 sessions (10 trials each) utilizing 2 different mental imagery strategies: (1) motor imagery (imagine opening and closing of hands) and (2) goal oriented (imagine effector object moving toward target) to complete 2 tasks: (1) drive a remote controlled car to a target and (2) move a computer cursor to a target. Primary outcome was Cohen Kappa with a score >0.40 suggesting BCI competence., Results: BCI performance was comparable between stroke and control participants. Mean scores were 0.39 (0.18) for stroke versus 0.42 (0.18) for controls (t[42]=0.478, P=0.94). No difference in performance between venous (M=0.45, SD=0.29) and arterial (M=0.34, SD=0.22) stroke (t[82]=1.89, P=0.090) was observed. No effect of task or strategy was observed in the stroke participants. Over 90% of stroke participants demonstrated competency on at least one of the 4 task-strategy combinations., Conclusions: Children with perinatal stroke can achieve proficiency in basic tasks using simple BCI systems. Future directions include exploration of BCI-functional electrical stimulation systems for rehabilitation for children with hemiparesis and other forms of cerebral palsy.

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.

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., (© 2020 Mac Keith Press.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

Background: Congenital malformations are more common in children who are born prematurely, and prematurity is the leading risk factor for cerebral palsy. The primary objective of this study was to describe the profile of congenital malformations in a Canadian cohort of children with cerebral palsy. The secondary objectives were to compare the profiles of children with cerebral palsy with and without a congenital malformation and explore the possible role of prematurity., Methods: This retrospective cohort study utilized data from the Canadian Cerebral Palsy Registry, a population based registry of children with a confirmed diagnosis of cerebral palsy. Differences between groups were compared using Pearson's chi-square and Student t test as appropriate. Odds ratios and 95% confidence intervals were calculated RESULTS: Congenital malformations were present in 23% participants. In term-born children, brain malformations were the most common, whereas heart and gastrointestinal malformations were more common in children born prematurely. Children with a malformation had higher odds of being born at term (odds ratio 1.57, 95% confidence interval 1.20 to 2.04); having hypotonic, ataxic, or dyskinetic cerebral palsy (odds ratio 1.92, 95% confidence interval 1.35 to 2.72; being nonambulatory (odds ratio 1.70, 95% confidence interval 1.29 to 2.25); and having cerebral palsy-associated comorbidities., Conclusions: One in four children with cerebral palsy have an associated congenital malformation. Their profile of term birth, higher Apgar scores, and lower frequency of perinatal seizures suggests a distinct causal pathway., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: While motor deficits are the hallmark of hemiparetic cerebral palsy, children may also experience impairments in visuospatial attention that interfere with participation in complex activities, including sports or driving. In this study, we used a robotic object hitting task to assess bilateral sensorimotor control and visuospatial skills in children with hemiparesis due to perinatal arterial ischemic stroke (AIS) or periventricular venous infarct (PVI). We hypothesized that performance would be impaired bilaterally and be related to motor behavior and clinical assessment of visuospatial attention., Methods: Forty-nine children with perinatal stroke and hemiparetic cerebral palsy and 155 typically developing (TD) children participated in the study. Participants performed a bilateral object hitting task using the KINARM Exoskeleton Robot, in which they used virtual paddles at their fingertips to hit balls that fell from the top of the screen with increasing speed and frequency over 2.3 min. We quantified performance across 13 parameters including number of balls hit with each hand, movement speed and area, biases between hands, and spatial biases. We determined normative ranges of performance accounting for age by fitting 95% prediction bands to the TD children. We compared parameters between TD, AIS, and PVI groups using ANCOVAs accounting for age effects. Lastly, we performed regression analysis between robotic and clinical measures., Results: The majority of children with perinatal stroke hit fewer balls with their affected arm compared to their typically developing peers. We also found deficits with the ipsilesional ("unaffected") arm. Children with AIS had greater impairments than PVI. Despite hitting fewer balls, we only identified 18% of children as impaired in hand speed or movement area. Performance on the Behavioral Inattention Test accounted for 21-32% of the variance in number of balls hit with the unaffected hand., Conclusions: Children with perinatal stroke-induced hemiparetic cerebral palsy may have complex bilateral deficits reflecting a combination of impairments in motor skill and visuospatial attention. Clinical assessments and interventions should address the interplay between motor and visuospatial skills.

Objectives: To describe current physician referral practices with respect to age at referral to medical specialists for initial diagnosis of cerebral palsy (CP) and rehabilitation specialists for intervention and to identify factors associated with delayed referral., Study Design: National environmental scan of 455 children diagnosed with CP who were born in Canada between 2008 and 2011, selected from 4 sites within the Canadian CP Registry (Edmonton, Calgary, Toronto, and Montreal). Two sources of information were used-children's medical charts and the population-based registry, which provided corresponding data for each child. Primary outcomes extracted from the charts were age at referral for diagnostic assessment, age at diagnosis, age at referral for rehabilitation services, and age at initial rehabilitation intervention. Twelve variables were explored as potential predictors. Descriptive statistics, bivariate analyses, and multiple linear regressions were conducted., Results: Median age (in months) at referral for diagnostic assessment was 8 (mean: 12.7 ± 14.3), diagnosis 16 (mean: 18.9 ± 12.8), referral for rehabilitation services 10 (mean: 13.4 ± 13.5), and rehabilitation initiation 12 (mean: 15.9 ± 12.9). Lower maternal education, mild severity of motor dysfunction, type of CP, early discharge after birth, and region of residence explained between 20% and 32% of the variance in age at referral for assessment, diagnosis, referral for rehabilitation, and rehabilitation initiation., Conclusions: Findings suggest wide variability exists in the age at which young children with CP are referred to specialists for diagnosis and intervention. User-friendly tools are therefore needed to enhance early detection and referral strategies by primary care practitioners, to ensure early interventions to optimize developmental outcomes and enhance opportunities for neural repair at a younger age., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aim: To establish international expert recommendations on clinical features to prompt referral for diagnostic assessment of cerebral palsy (CP)., Method: An online Delphi survey was conducted with international experts in early identification and intervention for children with CP, to validate the results obtained in two previous consensus groups with Canadian content experts and knowledge users. We sent two rounds of questionnaires by e-mail. Participants rated their agreement using a 4-point Likert scale, along with optional open-ended questions for additional feedback. Additionally, a panel of experts and knowledge-users reviewed the results of each round and determined the content of subsequent surveys., Results: Overall, there was high-level of agreement on: (1) six clinical features that should prompt referral for diagnosis; (2) two 'warning sign' features that warrant monitoring rather than immediate referral for diagnosis; and (3) five referral recommendations to other healthcare professionals to occur simultaneously with referral for diagnosis., Interpretation: There was high agreement among international experts, suggesting that the features and referral recommendations proposed for primary care physicians for early detection of CP were broadly generalizable. These results will inform the content of educational tools to improve the early detection of CP in the primary care context., What This Paper Adds: International experts provide strong agreement on clinical features to detect cerebral palsy. Consensus on clinical 'warning signs' to monitor over time. Referral recommendations from primary care to specialized health services are identified., (© 2019 Mac Keith Press.)

Aim: We aimed to determine if the mirror movements that often result in children with unilateral cerebral palsy (CP) after perinatal stroke represent a clinical biomarker of developmental plasticity., Method: This was a prospective, controlled cohort study. Mirror movements in children with unilateral CP from a population-based cohort were compared to those of typically developing controls. The population with stroke was assessed further via electromyography (EMG), motor function, and corticospinal organization investigations. Mirror movements were quantified (0-5) bidirectionally. EMG mirror movements were quantified during voluntary contraction. Motor function was quantified by validated measures including the Assisting Hand Assessment (AHA). Corticospinal organization was categorized as ipsilateral or contralateral using transcranial magnetic stimulation (TMS). The relationships between mirror movements, function, and corticospinal organization were assessed (t-tests, Pearson rank correlation coefficients)., Results: Ninety-two participants were scored (55 males, 37 females, mean [SD] 12y [5y 6mo], range 4-17y), 63 with complete motor outcomes and 39 with TMS data. EMG ratios correlated with clinical mirror movements (r=0.562, p=0.008). Mild mirror activity in controls declined with age (r=-0.459, p<0.001). Mirroring was stronger with tasks performed by the affected hand (p<0.001). Mirror movements correlated with AHA scores (r=-0.255, p=0.04) and poor motor outcome (p<0.001). Unaffected hand mirror activity was higher in children with ipsilateral corticospinal tract arrangements (p<0.001)., Interpretation: Clinical mirror movements correlate with disability and corticospinal organization in children with unilateral CP with perinatal stroke. This simple bedside biomarker could facilitate patient selection for personalized rehabilitation., What This Paper Adds: Mirror movements are a clinical indicator of corticospinal organization in children with unilateral cerebral palsy with perinatal stroke. Mirroring is strongest in children with ipsilateral corticospinal tract reorganization. The concept of a 'directionality factor' to mirror movements highlights additional, clinically relevant functional correlations., (© 2019 Mac Keith Press.)

Objective: This study looks at what profile can be expected in children with cerebral palsy spectrum disorder (CP) and a normal MRI., Methods: The data were excerpted from the Canadian Cerebral Palsy Registry database. Only patients who had undergone MRI were included in the analysis. Neuroimaging classification was ascertained by university-based pediatric neuroradiologists and split into 2 categories: normal and abnormal MRIs. Six factors were then compared between those 2 groups: prematurity, perinatal adversity, presence of more than 1 comorbidity, CP subtype, bimanual dexterity (Manual Ability Classification System [MACS]), and gross motor function (Gross Motor Function Classification System [GMFCS])., Results: Participants with no perinatal adversity were 5.518 times more likely to have a normal MRI ( p < 0.0001, 95% confidence interval [CI] 4.153-7.330). Furthermore, participants with dyskinetic, ataxic/hypotonic, and spastic diplegic forms of CP were 2.045 times more likely to have a normal MRI than those with hemiplegia, triplegia, and quadriplegia ( p < 0.0001, 95% CI 1.506-2.778). No significant difference was found in prematurity, GMFCS levels, MACS levels, and the number of comorbidities., Conclusions: Normal MRIs were associated with lack of perinatal adversity as well as with the dyskinetic, ataxic/hypotonic, and spastic diplegic CP subtypes. As MRI normality is not strongly associated with the severity of CP, continuous follow-up in children with normal imaging appears warranted. Further advanced imaging modalities, as well as strong consideration for metabolic and genetic testing, may provide additional insights into causal pathways in this population., (© 2019 American Academy of Neurology.)

Aim: To identify characteristics of young children with cerebral palsy (CP), and intrinsic and extrinsic factors, that may be associated with parental perceptions regarding family-centred health care services., Method: We conducted a cross-sectional study, drawing our sample from the Canadian Cerebral Palsy Registry (CCPR). Parents rated the extent of family-centred care provided by their child's health care teams using the 56-item Measures of Process of Care (MPOC) questionnaire. Environmental and CP phenotypic variables were extracted from the CCPR for group comparisons. Low and high MPOC-56 raters were also compared., Results: Valid responses were obtained from 282 families (90%). All MPOC-56 subscales were highly rated (median ≥6.0), indicating satisfaction with health care services, with the exception of the Providing General Information subscale (median 4.8, interquartile range 3.2-6.0). Parents from Nova Scotia rated all subscales significantly higher than parents from other regions. CP subtype and severity were not significantly associated with MPOC-56 subscale scores. Higher socio-economic status was associated with lower MPOC-56 subscale scores. Higher paternal educational attainment and household income were significantly associated with lower scores on the Providing General Information and Providing Specific Information about the Child subscales respectively., Interpretation: Participants affirmed the provision of family-centred services from Canadian pediatric rehabilitation centres. Sociodemographic factors were associated with parental perceptions of family-centred services., What This Paper Adds: Sociodemographic factors were associated with parental perceptions of family-centred care. Factors intrinsic to the child's cerebral palsy were not associated with parental perceptions., (© 2018 Mac Keith Press.)

Background: Perinatal stroke causes most hemiparetic cerebral palsy and leads to lifelong disability. Understanding developmental neuroplasticity following early stroke is increasingly translated into novel therapies. Diaschisis refers to alterations brain structures remote from, but connected to, stroke lesions. Ipsilesional thalamic diaschisis has been described following adult stroke but has not been investigated in perinatal stroke. We hypothesized that thalamic diaschisis occurs in perinatal stroke and its degree would be inversely correlated with clinical motor function., Methods: Population-based, controlled cohort study. Participants were children (<19 years) with unilateral perinatal stroke (arterial ischemic stroke [AIS] or periventricular venous infarction [PVI]), anatomical magnetic resonance imaging (MRI) >6 months of age, symptomatic hemiparetic cerebral palsy, and no additional neurologic disorders. Typically developing controls had comparable age and gender proportions. T1-weighted anatomical scans were parcellated into 99 regions of interest followed by generation of regional volumes. The primary outcome was thalamic volume expressed as ipsilesional (ILTV), contralesional (CLTV) and thalamic ratio (CLTV/ILTV). Standardized clinical motor assessments were correlated with thalamic volume metrics., Results: Fifty-nine participants (12.9 years old ±4.0 years, 46% female) included 20 AIS, 11 PVI, and 28 controls. ILTV was reduced in both AIS and PVI compared to controls (p < .001, p = .029, respectively). Ipsilesional thalamic diaschisis was not associated with clinical motor function. However, CLTV was significantly larger in AIS compared to both controls and PVI (p = .005, p < .001, respectively). CLTV was inversely correlated with all four clinical motor assessments (all p < .003)., Conclusion: Bilateral thalamic volume changes occur after perinatal stroke. Ipsilesional volume loss is not associated with clinical motor function. Contralesional volume is inversely correlated with clinical motor function, suggesting the thalamus is involved in the known developmental plasticity that occurs in the contralesional hemisphere after early unilateral injury., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Advanced maternal age is associated with higher frequencies of antenatal and perinatal conditions, as well as a higher risk of cerebral palsy in offspring. We explore the association between maternal age and specific cerebral palsy risk factors., Methods: Data were extracted from the Canadian Cerebral Palsy Registry. Maternal age was categorized as ≥35 years of age and less than 20 years of age at the time of birth. Chi-square and multivariate logistic regressions were performed to calculate odds ratios and their 95% confidence intervals., Results: The final sample consisted of 1391 children with cerebral palsy, with 19% of children having mothers aged 35 or older and 4% of children having mothers below the age of 20. Univariate analyses showed that mothers aged 35 or older were more likely to have gestational diabetes (odds ratio 1.9, 95% confidence interval 1.3 to 2.8), to have a history of miscarriage (odds ratio 1.8, 95% confidence interval 1.3 to 2.4), to have undergone fertility treatments (odds ratio 2.4, 95% confidence interval 1.5 to 3.9), and to have delivered by Caesarean section (odds ratio 1.6, 95% confidence interval 1.2 to 2.2). These findings were supported by multivariate analyses. Children with mothers below the age of 20 were more likely to have a congenital malformation (odds ratio 2.4, 95% confidence interval 1.4 to 4.2), which is also supported by multivariate analysis., Conclusions: The risk factor profiles of children with cerebral palsy vary by maternal age. Future studies are warranted to further our understanding of the compound causal pathways leading to cerebral palsy and the observed greater prevalence of cerebral palsy with increasing maternal age., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The goal of this study was to explore the association between neonatal infection and outcomes in children with cerebral palsy., Methods: We conducted a retrospective cohort study using the Canadian CP Registry. Neonatal infection was defined as meeting one of the following criteria: (1) septicemia, (2) septic shock, or (3) administration of antibiotics for ≥10 days. Phenotypic profiles of children with cerebral palsy with and without an antecedent neonatal infection were compared. Subgroup analysis was performed, stratified by gestational age (term versus preterm)., Results: Of the 1229 registry participants, 505 (41.1%) were preterm, and 192 (15.6%) met the criteria for neonatal infection with 29% of preterm children having a neonatal infection compared with 6.5% in term-born children. Children with prior neonatal infection were more likely to have a white matter injury (odds ratio 2.2, 95% confidence interval 1.5 to 3.2), spastic diplegic neurological subtype (odds ratio 1.6, 95% confidence interval 1.1 to 2.3), and sensorineural auditory impairment (odds ratio 2.1, 95% confidence interval 1.4 to 3.3). Among preterm children, neonatal infection was not associated with a difference in phenotypic profile. Term-born children with neonatal infection were more likely to have spastic triplegia or quadriplegia (odds ratio 2.4, 95% confidence interval 1.3 to 4.3), concomitant white matter and cortical injury (odds ratio 4.1, 95% confidence interval 1.6 to 10.3), and more severe gross motor ability (Gross Motor Function Classification System IV to V) (odds ratio 2.6, 95% confidence interval 1.4 to 4.8) compared with preterm children., Conclusions: Findings suggest a role of systemic infection on the developing brain in term-born infants, and the possibility to develop targeted therapeutic and preventive strategies to reduce cerebral palsy morbidity., (Copyright © 2017. Published by Elsevier Inc.)

Perinatal stroke is the leading cause of hemiparetic cerebral palsy (CP), resulting in life-long disability. In this study, we examined the relationship between robotic upper extremity motor impairment and corticospinal tract (CST) diffusion properties. Thirty-three children with unilateral perinatal ischemic stroke (17 arterial, 16 venous) and hemiparesis were recruited from a population-based research cohort. Bilateral CSTs were defined using diffusion tensor imaging (DTI) and four diffusion metrics were quantified: fractional anisotropy (FA), mean (MD), radial (RD), and axial (AD) diffusivities. Participants completed a visually guided reaching task using the KINARM robot to define 10 movement parameters including movement time and maximum speed. Twenty-six typically developing children underwent the same evaluations. Partial correlations assessed the relationship between robotic reaching and CST diffusion parameters. All diffusion properties of the lesioned CST differed from controls in the arterial group, whereas only FA was reduced in the venous group. Non-lesioned CST diffusion measures were similar between stroke groups and controls. Both stroke groups demonstrated impaired reaching performance. Multiple reaching parameters of the affected limb correlated with lesioned CST diffusion properties. Lower FA and higher MD were associated with greater movement time. Few correlations were observed between non-lesioned CST diffusion and unaffected limb function though FA was associated with reaction time (R = -0.39, p < .01). Diffusion properties of the lesioned CST are altered after perinatal stroke, the degree of which correlates with specific elements of visually guided reaching performance, suggesting specific relevance of CST structural connectivity to clinical motor function in hemiparetic children., (© 2017 Wiley Periodicals, Inc.)

Perinatal stroke injures developing motor systems, resulting in hemiparetic cerebral palsy. Diffusion tensor imaging can explore structural connectivity. We used diffusion tensor imaging to assess corticospinal tract diffusion in hemiparetic children with perinatal stroke. Twenty-eight children (6-18 years) with unilateral stroke underwent diffusion tensor imaging. Four corticospinal tract assessments included full tract, partial tract, minitract and region of interest. Diffusion characteristics (fractional anisotropy, mean, axial, and radial diffusivity) were calculated. Ratios (lesioned/nonlesioned) were compared across segments and to validated long-term motor outcomes (Pediatric Stroke Outcome Measure, Assisting Hand Assessment, Melbourne Assessment). Fractional anisotropy and radial diffusivity ratios decreased as tract size decreased, while mean diffusivity showed consistent symmetry. Poor motor outcomes were associated with lower fractional anisotropy in all segments and radial diffusivity correlated with both Assisting Hand Assessment and Melbourne Assessment. Diffusion imaging of segmented corticospinal tracts is feasible in hemiparetic children with perinatal stroke. Correlations with disability support clinical relevance and utility in model development for personalized rehabilitation.

Perinatal stroke causes hemiparetic cerebral palsy and lifelong motor disability. Bilateral motor cortices are key hubs within the motor network and their neurophysiology determines clinical function. Establishing biomarkers of motor cortex function is imperative for developing and evaluating restorative interventional strategies. Proton magnetic resonance spectroscopy (MRS) quantifies metabolite concentrations indicative of underlying neuronal health and metabolism in vivo. We used functional magnetic resonance imaging (MRI)-guided MRS to investigate motor cortex metabolism in children with perinatal stroke. Children aged 6-18 years with MRI-confirmed perinatal stroke and hemiparetic cerebral palsy were recruited from a population-based cohort. Metabolite concentrations were assessed using a PRESS sequence (3T, TE = 30 ms, voxel = 4 cc). Voxel location was guided by functional MRI activations during finger tapping tasks. Spectra were analysed using LCModel. Metabolites were quantified, cerebral spinal fluid corrected and compared between groups (ANCOVA) controlling for age. Associations with clinical motor performance (Assisting Hand, Melbourne, Box-and-Blocks) were assessed. Fifty-two participants were studied (19 arterial, 14 venous, 19 control). Stroke participants demonstrated differences between lesioned and nonlesioned motor cortex N-acetyl-aspartate [NAA mean concentration = 10.8 ± 1.9 vs. 12.0 ± 1.2, P < 0.01], creatine [Cre 8.0 ± 0.9 vs. 7.4 ± 0.9, P < 0.05] and myo-Inositol [Ins 6.5 ± 0.84 vs. 5.8 ± 1.1, P < 0.01]. Lesioned motor cortex NAA and creatine were strongly correlated with motor performance in children with arterial but not venous strokes. Interrogation of motor cortex by fMRI-guided MRS is feasible in children with perinatal stroke. Metabolite differences between hemispheres, stroke types and correlations with motor performance support functional relevance. MRS may be valuable in understanding the neurophysiology of developmental neuroplasticity in cerebral palsy. Hum Brain Mapp 38:1574-1587, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: While sensory dysfunction is common in children with hemiparetic cerebral palsy (CP) secondary to perinatal stroke, it is an understudied contributor to disability with limited objective measurement tools. Robotic technology offers the potential to objectively measure complex sensorimotor function but has been understudied in perinatal stroke. The present study aimed to quantify kinesthetic deficits in hemiparetic children with perinatal stroke and determine their association with clinical function., Methods: Case-control study. Participants were 6-19 years of age. Stroke participants had MRI confirmed unilateral perinatal arterial ischemic stroke or periventricular venous infarction, and symptomatic hemiparetic cerebral palsy. Participants completed a robotic assessment of upper extremity kinesthesia using a robotic exoskeleton (KINARM). Four kinesthetic parameters (response latency, initial direction error, peak speed ratio, and path length ratio) and their variabilities were measured with and without vision. Robotic outcomes were compared across stroke groups and controls and to clinical measures of sensorimotor function., Results: Forty-three stroke participants (23 arterial, 20 venous, median age 12 years, 42% female) were compared to 106 healthy controls. Stroke cases displayed significantly impaired kinesthesia that remained when vision was restored. Kinesthesia was more impaired in arterial versus venous lesions and correlated with clinical measures., Conclusions: Robotic assessment of kinesthesia is feasible in children with perinatal stroke. Kinesthetic impairment is common and associated with stroke type. Failure to correct with vision suggests sensory network dysfunction.

The objective of this paper is to (1) identify from the literature a potential critical period for the maturation of the corticospinal tract (CST) and (2) report pilot data on an intensive, activity-based therapy applied during this period, in children with lesions to the CST. The best estimate of the CST critical period for the legs is when the child is younger than 2 years of age. Previous interventions for walking in children with CST damage were mainly applied after this age. Our preliminary results with training children younger than 2 years showed improvements in walking that exceeded all previous reports. Further, we refined techniques for measuring motor and sensory pathways to and from the legs, so that changes can be measured at this young age. Previous activity-based therapies may have been applied too late in development. A randomized controlled trial is now underway to determine if intensive leg therapy improves the outcome of children with early stroke., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The permanent nature of motor deficits is a consistent cornerstone of cerebral palsy definitions. Such pessimism is disheartening to children, families, and researchers alike and may no longer be appropriate for it ignores the fantastic plastic potential of the developing brain. Perinatal stroke is presented as the ideal human model of developmental neuroplasticity following distinct, well-defined, focal perinatal brain injury. Elegant animal models are merging with human applied technology methods, including noninvasive brain stimulation for increasingly sophisticated models of plastic motor development following perinatal stroke. In this article, how potential central therapeutic targets are identified and potentially modulated to enhance motor function within these models is discussed. Also, future directions and emerging clinical trials are reviewed., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Perinatal stroke is presented as the ideal human model of developmental neuroplasticity. The precise timing, mechanisms, and locations of specific perinatal stroke diseases provide common examples of well defined, focal, perinatal brain injuries. Motor disability (hemiparetic cerebral palsy) constitutes the primary adverse outcome and the focus of models explaining how motor systems develop in health and after early injury. Combining basic science animal work with human applied technology (functional magnetic resonance imaging, diffusion tensor imaging, and transcranial magnetic stimulation), a model of plastic motor development after perinatal stroke is presented. Potential central therapeutic targets are revealed. The means to measure and modulate these targets, including evidence-based rehabilitation therapies and noninvasive brain stimulation, are suggested. Implications for clinical trials and future directions are discussed., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Congenital hemiplegia is the most common form of cerebral palsy in children born at term, and stroke is the number one cause. Neonatal ischemic stroke includes perinatal arterial ischemic stroke, presumed pre- or perinatal stroke, and cerebral sinovenous thrombosis, all of which have emerged as important contributors to cerebral palsy. Of increasing interest is how the overlapping list of associations and risks for stroke and cerebral palsy relate to each other. Stroke-induced injury is focal, and the preservation of normal areas of brain may afford unique opportunities for plastic adaptation. The implications of this essential difference are stressed in a discussion of how the epidemiology, pathophysiology, diagnosis, and therapeutic advancements in perinatal stroke relate to the outcome of cerebral palsy.

Background: Perinatal stroke (PS) causes most hemiparetic cerebral palsy (CP) and results in lifelong disability. Children with severe hemiparesis have limited rehabilitation options. Brain computer interface- activated functional electrical stimulation (BCI-FES) of target muscles may enhance upper extremity function in hemiparetic adults. We conducted a pilot clinical trial to assess the safety and feasibility of BCI-FES in children with hemiparetic CP. Methods: Thirteen participants (mean age = 12.2 years, 31% female) were recruited from a population-based cohort. Inclusion criteria were: (1) MRIconfirmed PS, (2) disabling hemiparetic CP, (3) age 6–18 years, (4) informed consent/assent. Those with neurological comorbidities or unstable epilepsy were excluded. Participants attended two BCI sessions: training and rehabilitation. They wore an EEG-BCI headset and two forearm extensor stimulation electrodes. Participants’ imagination of wrist extension was classified on EEG, after which muscle stimulation and visual feedback were provided when the correct visualization was detected. Results: No serious adverse events or dropouts occurred. The most common complaints were mild headache, headset discomfort and muscle fatigue. Children ranked the experience as comparable to a long car ride and none reported as unpleasant. Sessions lasted a mean of 87 min with 33 min of stimulation delivered. Mean classification accuracies were (M = 78.78%, SD = 9.97) for training and (M = 73.48, SD = 12.41) for rehabilitation. Mean Cohen’s Kappa across rehabilitation trials was M = 0.43, SD = 0.29, range = 0.019–1.00, suggesting BCI competency. Conclusion: Brain computer interface-FES was well -tolerated and feasible in children with hemiparesis. This paves the way for clinical trials to optimize approaches and test efficacy. [ABSTRACT FROM AUTHOR]

Introduction: Perinatal stroke (PS) is a focal vascular brain injury and the leading cause of hemiparetic cerebral palsy. Motor impairments last a lifetime but treatments are limited. Transcranial direct-current stimulation (tDCS) may enhance motor learning in adults but tDCS effects on motor learning are less studied in children. Imaging-based simulations of tDCS-induced electric fields (EF) suggest differences in the developing brain compared to adults but have not been applied to common pediatric disease states. We created estimates of tDCS-induced EF strength using five tDCS montages targeting the motor system in children with PS [arterial ischemic stroke (AIS) or periventricular infarction (PVI)] and typically developing controls (TDC) aged 6-19 years to explore associates between simulation values and underlying anatomy. Methods: Simulations were performed using SimNIBS https://simnibs.github.io/simnibs/build/html/index.html using T1, T2, and diffusion-weighted images. After tissue segmentation and tetrahedral mesh generation, tDCS-induced EF was estimated based on the finite element model (FEM). Five 1mA tDCS montages targeting motor function in the paretic (non-dominant) hand were simulated. Estimates of peak EF strength, EF angle, field focality, and mean EF in motor cortex (M1) were extracted for each montage and compared between groups. Results: Simulations for eighty-three children were successfully completed (21 AIS, 30 PVI, 32 TDC). Conventional tDCS montages utilizing anodes over lesioned cortex had higher peak EF strength values for the AIS group compared to TDC. These montages showed lower mean EF strength within target M1 regions suggesting that peaks were not necessarily localized to motor network-related targets. EF angle was lower for TDC compared to PS groups for a subset of montages. Montages using anodes over lesioned cortex were more sensitive to variations in underlying anatomy (lesion and tissue volumes) than those using cathodes over non-lesioned cortex. Discussion: Individualized patient-centered tDCS EF simulations are prudent for clinical trial planning and may provide insight into the efficacy of tDCS interventions in children with PS. [ABSTRACT FROM AUTHOR]