Changes Induced by Early Hand-Arm Bimanual Intensive Therapy Including Lower Extremities in Young Children With Unilateral Cerebral Palsy: A Randomized Clinical Trial.

Importance: Intensive interventions are provided to young children with unilateral cerebral palsy (UCP), classically focused on the upper extremity despite the frequent impairment of gross motor function. Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) effectively improves manual dexterity and gross motor function in school-aged children. Objective: To verify if HABIT-ILE would improve manual abilities in young children with UCP more than usual motor activity. Design, Setting, and Participants: This prospective randomized clinical trial (November 2018 to December 2021), including 2 parallel groups and a 1:1 allocation, recruitment took place at European university hospitals, cerebral palsy specialized centers, and spontaneous applications at 3 sites: Brussels, Belgium; Brest, France; and Pisa, Italy. Matched (age at inclusion, lesion type, cause of cerebral palsy, and affected side) pairs randomization was performed. Young children were assessed at baseline (T0), 2 weeks after baseline (T1), and 3 months after baseline (T2). Health care professionals and assessors of main outcomes were blinded to group allocation. At least 23 young children (in each group) aged 12 to 59 months with spastic/dyskinetic UCP and able to follow instructions were needed. Exclusion criteria included uncontrolled seizures, scheduled botulinum toxin injections, orthopedic surgery scheduled during the 6 months before or during the study period, severe visual/cognitive impairments, or contraindications to magnetic resonance imaging. Interventions: Two weeks of usual motor activity including usual rehabilitation (control group) vs 2 weeks (50 hours) of HABIT-ILE (HABIT-ILE group). Main Outcomes and Measures: Primary outcome: Assisting Hand Assessment (AHA); secondary outcomes: Gross Motor Function Measure-66 (GMFM-66), Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT), and Canadian Occupational Performance Measure (COPM). Results: Of 50 recruited young children (26 girls [52%], median age; 35.3 months for HABIT-ILE group; median age, 32.8 months for control group), 49 were included in the final analyses. Change in AHA score from T0 to T2 was significantly greater in the HABIT-ILE group (adjusted mean score difference [MD], 5.19; 95% CI, 2.84-7.55; P < .001). Changes in GMFM-66 (MD, 4.72; 95% CI, 2.66-6.78), PEDI-CAT daily activities (MD, 1.40; 95% CI, 0.29-2.51), COPM performance (MD, 3.62; 95% CI, 2.91-4.32), and satisfaction (MD, 3.53; 95% CI, 2.70-4.36) scores were greater in the HABIT ILE group. Conclusions and Relevance: In this clinical trial, early HABIT-ILE was shown to be an effective treatment to improve motor performance in young children with UCP. Moreover, the improvements had an impact on daily life activities of these children. Trial registration: ClinicalTrials.gov Identifier: NCT04020354.

Mirror movements after bimanual intensive therapy in children with unilateral cerebral palsy: A randomized controlled trial.

AIM: To investigate potential changes in mirror movements after Hand and Arm Bimanual Intensive Therapy Including Lower Extremity (HABIT-ILE) training in children with unilateral cerebral palsy (CP). METHOD: Thirty-one children with unilateral CP (mean age 9 years 4 months, SD 4 years 3 months; range 5 years 4 months-17 years 3 months; 14 females, 17 males) were randomized to either a control or treatment group. After allocation, children were assessed three times: before (T1, baseline) and after (T2) a 2-week interval and again at 3 months after T1 (T3) as follow-up. Between T1 and T2, the treatment group received 90 hours of HABIT-ILE training, while the control group continued their customary treatment. Mirror movements were assessed in all children using the Woods and Teuber Scale, as well as the Assisting Hand Assessment, Pediatric Evaluation of Disability Inventory, and Canadian Occupational Performance Measure. RESULTS: Repeated measures analysis of variance indicated a significant decrease in mirror movements in the more-affected (mean difference = 0.97; 95% confidence interval [CI] = 0.51-1.42; p < 0.001) and less-affected (mean difference = 0.71; 95% CI = 0.37-1.0; p < 0.001) hands of children after HABIT-ILE; these improvements were maintained at the 3-month follow-up. Moreover, the mirror movement changes observed at the second assessment (T2) were inversely correlated with changes in the assessment of activities of daily living, especially in the less-affected hand. INTERPRETATION: HABIT-ILE decreased the intensity of mirror movements in a group of children with CP. Furthermore, mirror movement changes were associated with bimanual performance and activities of daily living in these children. WHAT THIS PAPER ADDS: The intensity of mirror movements decreased in both hands after 2 weeks of Hand and Arm Bimanual Intensive Therapy Including Lower Extremity (HABIT-ILE) training. Mirror movement changes were maintained at the 3-month follow-up after HABIT-ILE. Mirror movement changes were associated with improvements in bimanual performance and activities of daily living.

Efficacy of hand-arm bimanual intensive therapy including lower extremities (HABIT-ILE) in young children with bilateral cerebral palsy (GMFCS III-IV) in a low and middle-income country: protocol of a randomised controlled trial.

INTRODUCTION: Cerebral palsy (CP) is highly prevalent in sub-Saharan Africa, where clinically-based studies have shown a considerable over-representation of the severe bilateral subtype. However, children's access to rehabilitation care is limited by many local factors, notably the lacking of rehabilitation services, insufficient knowledge of caregivers and financial constraints. In such a context there is an urgent need for studies of the evidence-based rehabilitation approach. Here, we describe the protocol of a randomised controlled study to investigate the efficacy of Hand-Arm Bimanual Intensive Therapy Including the Lower Extremities (HABIT-ILE) in young children with bilateral CP in Benin Republic, a representative low and middle-income country of western Africa. METHODS AND ANALYSIS: Forty children with bilateral CP aged between 24 and 59 months and with level III-IV in the gross motor function classification will be randomised to either a high intensity conventional therapy or HABIT-ILE therapy. Both therapies will be delivered as a day-camp model over 2 weeks to a total of 50 hours (5 hours per day). The assessor-blinded primary outcomes will include the gross motor function measure and both hands assessment. Secondary outcomes will be the adapted version of the ACTIVLIM-CP questionnaire, the Canadian Occupational Performance Measure, and a perception of CP interview form. Children will be assessed at baseline, after intervention and at 6-week follow-up. A 2 (group)×3 (test sessions) repeated analysis of variance will evaluate changes after the interventions. ETHICS AND DISSEMINATION: This study has been approved by the ethics committee of the rehabilitation department of the National Teaching Hospital Hubert Koutoukou Maga of Cotonou, Benin (approval decision: N°01-2019/MS/CNHU-HKM/CEI/CUMPR). All participants' parents/caregivers will provide their written informed consent. Data will be managed with confidentiality. TRIAL REGISTRATION NUMBER: PACTR201911894444879.

Unusual Presentation of COVID-19 Disease Leading to Respiratory Distress and Coma.

Multiple neurological complications including Guillain-Barré syndrome (GBS) have been associated with COVID-19. We describe a case of GBS related to SARS-CoV-2 infection with an unusual presentation beginning with mobilization problems at home without previous classic respiratory or general manifestations. Asymptomatic infection with COVID-19 can lead to critical situations with respiratory insufficiency because of neurological complications such as GBS. LEARNING POINTS: Asymptomatic infection with COVID-19 can result in critical situations with respiratory insufficiency and need for mechanical ventilation because of neurological complications such as Guillain-Barré syndrome (GBS).All patients presenting with GBS should be tested for SARS-CoV-2.Neurological complications including neuromuscular impairment can be part of respiratory failure secondary to COVID-19 infection.

Brain activation changes following motor training in children with unilateral cerebral palsy: An fMRI study.

BACKGROUND: Intensive motor-learning-based interventions have demonstrated efficacy for improving motor function in children with unilateral spastic cerebral palsy (USCP). Although this improvement has been associated mainly with neuroplastic changes in the primary sensori-motor cortices, this plasticity may also involve a wider fronto-parietal network for motor learning. OBJECTIVE: To determine whether hand-arm bimanual intensive therapy including lower extremities (HABIT-ILE) induces brain activation changes in an extensive network for motor skill learning and whether these changes are related to functional changes observed after HABIT-ILE. METHODS: In total, 25 children with USCP were behaviourally assessed in manual dexterity and everyday activities before and after HABIT-ILE. Functional imagery monitored brain activity while participants manipulated objects using their less-affected, more-affected or both hands. Two random-effects-group analyses performed at the whole-brain level assessed the brain activity network before and after therapy. Three other random-effects-group analyses assessed brain activity changes after therapy. Spearman's correlations were used to evaluate the correlation between behavioural and brain activity changes. RESULTS: The same fronto-parietal network was identified before and after therapy. After the intervention, the more-affected hand manipulation elicited a decrease in activity on the motor cortex of the non-lesional hemisphere and an increase in activity on motor areas of the lesional hemisphere. The less-affected hand manipulation generated a decrease in activity of sensorimotor areas in the non-lesional hemisphere. Both-hands manipulation elicited an increase in activity of both hemispheres. Furthermore, we observed an association between brain activity changes and changes in everyday activity assessments. CONCLUSION: Brain activation changes were observed in a fronto-parietal network underlying motor skill learning with HABIT-ILE in children with USCP. Two different patterns were observed, probably related to different phases of motor skill learning, representing an increased practice-dependent brain recruitment or a brain activation refinement by more efficient means. CLINICALTRIALS.GOV: NCT01700777 &NCT02667613.

Protocol of changes induced by early Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (e-HABIT-ILE) in pre-school children with bilateral cerebral palsy: a multisite randomized controlled trial.

BACKGROUND: Cerebral palsy (CP), which is the leading cause of motor disability during childhood, can produce sensory and cognitive impairments at different degrees. Most recent therapeutic interventions for these patients have solely focused on upper extremities (UE), although more than 60% of these patients present lower extremities (LE) deficits. Recently, a new therapeutic concept, Hand-arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE), has been proposed, involving the constant stimulation of UE and LE. Based on motor skill learning principles, HABIT-ILE is delivered in a day-camp setting, promoting voluntary movements for several hours per day during 10 consecutive week days. Interestingly, the effects of this intervention in a large scale of youngsters are yet to be observed. This is of interest due to the lack of knowledge on functional, neuroplastic and biomechanical changes in infants with bilateral CP. The aim of this randomized controlled study is to assess the effects of HABIT-ILE adapted for pre-school children with bilateral CP regarding functional, neuroplastic and biomechanical factors. METHODS: This international, multicentric study will include 50 pre-school children with CP from 12 to 60 months of age, comparing the effect of 50 h (2 weeks) of HABIT-ILE versus regular motor activity and/or customary rehabilitation. HABIT-ILE presents structured activities and functional tasks with continuous increase in difficulty while the child evolves. Assessments will be performed at 3 period times: baseline, two weeks later and 3 months later. The primary outcome will be the Gross Motor Function Measure 66. Secondary outcomes will include Both Hands Assessment, Melbourne Assessment-2, Semmes-Weinstein Monofilament Test, algometry assessments, executive function tests, ACTIVLIM-CP questionnaire, Pediatric Evaluation of Disability Inventory (computer adaptative test), Young Children's Participation and Environment Measure, Measure of the Process of Care, Canadian Occupational Performance Measure, neuroimaging and kinematics. DISCUSSION: The results of this study should highlight the impact of a motor, intensive, goal-directed therapy (HABIT-ILE) in pre-school children at a functional, neuroplastic and biomechanical level. In addition, this changes could demonstrated the impact of this intervention in the developmental curve of each child, improving functional ability, activity and participation in short-, mid- and long-term. NAME OF THE REGISTRY: Evaluation of Functional, Neuroplastic and Biomechanical Changes Induced by an Intensive, Playful Early-morning Treatment Including Lower Limbs (EARLY-HABIT-ILE) in Preschool Children With Uni and Bilateral Cerebral Palsy (HABIT-ILE). TRIAL REGISTRATION: NCT04017871 REGISTRATION DATE: July 12, 2019.

Motor Skill Training May Restore Impaired Corticospinal Tract Fibers in Children With Cerebral Palsy.

Background. In children with unilateral cerebral palsy (UCP), the fibers of the corticospinal tract (CST) emerging from the lesioned hemisphere are damaged following the initial brain injury. The extent to which the integrity of these fibers is restorable with training is unknown. Objective. To assess changes in CST integrity in children with UCP following Hand-and-Arm-Bimanual-Intensive-Therapy-Including-Lower-Extremity (HABIT-ILE) compared to a control group. Methods. Forty-four children with UCP participated in this study. Integrity of the CSTs was measured using diffusion tensor imaging before and after 2 weeks of HABIT-ILE (treatment group, n = 23) or 2 weeks apart without intensive treatment (control group, n = 18). Fractional anisotropy (FA) and mean diffusivity (MD) were the endpoints for assessing the integrity of CST. Results. As highlighted in our whole tract analysis, the FA of the CST originating from the nonlesioned and lesioned hemispheres increased significantly after therapy in the treatment group compared to the control group (group * test session interaction: P < .001 and P = .049, respectively). A decrease in MD was also observed in the CST emerging from the nonlesioned and lesioned hemispheres (group * time interaction: both P < .001). In addition, changes in manual ability correlated with changes in FA in both CSTs (r = 0.463, P = .024; r = 0.643, P < .001) and changes in MD in CST emerging from nonlesioned hemisphere (r = -0.662, P < .001). Conclusions. HABIT-ILE improves FA/MD in the CST and hand function of children with UCP, suggesting that CST fibers retain a capacity for functional restoration. This finding supports the application of intensive motor skill training in clinical practice for the benefit of numerous patients.

Normative values and discriminative ability across functional levels of ACTIVLIM-CP, a measure of global activity performance for children with cerebral palsy.

Purpose: This study aims to provide normative values of a global activity performance questionnaire (ACTIVLIM-CP) and investigate its ability to discriminate children with cerebral palsy of various functional levels.Methods: Parents of 503 typically developing children aged 2-18 years old (mean age ± standard deviation (SD): 9.56 ± 4.62 years) and 285 children with cerebral palsy aged 2-18 years old (mean age ± SD: 10.08 ± 4.09 years) answered ACTIVLIM-CP. To provide normative values, influence of typically developing children's characteristics on ACTIVLIM-CP measures was investigated with a multiple linear regression. A Kruskal-Wallis test and Dunn's post-hoc tests were performed to investigate age differences in ACTIVLIM-CP measures. Discriminative ability of ACTIVLIM-CP was investigated using a one-way analysis of variance and post-hoc tests between children with cerebral palsy who differed in manual and gross motor functional levels.Results: In typically developing children, age was the strongest predictor, explaining 74% of the variance of ACTIVLIM-CP measures (ß = 0.86, t = 38.21, p < 0.001). ACTIVLIM-CP measure increased with age until 17-18 years old where all children reached the maximal value, although 50% of the children at 12 years old already reached the maximal measure. Normative values were developed for each age bracket. In addition, ACTIVLIM-CP was able to discriminate children with CP's performance measures across most manual ability and gross motor functional levels.Conclusions: Normative values developed in this study with a representative sample of typically developing children allow clinicians to appraise the functional delay of children with cerebral palsy from the normal development of global activity performance. The good discriminative ability of ACTIVLIM-CP support its precision, construct validity, and clinical relevance to describe global activity limitations in children with cerebral palsy with manual ability levels and gross motor function levels II-V.Implications for rehabilitationNormative data of ACTIVLIM-CP developed with a representative sample of typically developing children can be used with children with CP to differentiate the age effect from the disruption caused by cerebral palsy.ACTIVLIM-CP showed the ability to discriminate across children with cerebral palsy having different manual and gross motor function, highlighting its precision, construct validity, and its clinical relevance to describe limitations in children with manual ability levels and gross motor function levels II-V.ACTIVLIM-CP covers a wide age range, is a cost-effective, easy and freely-available assessment of global activity performance in activities of daily living for clinicians.

Reliability and responsiveness of the Jebsen-Taylor Test of Hand Function and the Box and Block Test for children with cerebral palsy.

AIM: To assess the reliability and to evaluate the responsiveness of both the Jebsen-Taylor Test of Hand Function (JTTHF) and the Box and Block Test (BBT) in children with cerebral palsy (CP). METHOD: In this retrospective study, the reliability analyses were conducted with paired t-tests considering a short (mean 14d) and a long (mean 120d) time in between two assessment periods. In addition, an intraclass correlation coefficient (ICC) was used to assess the level of congruency. The responsiveness to therapy was conducted with a paired t-test in the whole sample regarding the age, the manual ability level as classified with the Manual Ability Classification System (MACS), and the topography. RESULTS: Our main results confirmed the tests' reliability in a short time period for the JTTHF in both hands and for the BBT on the less affected hand. These results were consistent with the ICC. The responsiveness was confirmed, except on the less affected hand for the JTTHF, with similar results for age, MACS, and topography approach. INTERPRETATION: This study supports the use of the JTTHF and the BBT to examine changes after short-term interventions for children with CP. These results should be interpreted with association to normative values or with a control group when used over long assessment periods. WHAT THIS PAPER ADDS: The Box and Block Test (BBT) is reliable in a brief period of assessment in children with cerebral palsy (CP). The Jebsen-Taylor Test of Hand Function (JTTHF) is reliable in a brief period of assessment in children with CP. The JTTHF and BBT are responsive to changes in a brief period of intensive therapy in children with CP. The reliability and responsiveness of the JTTHF and BBT are weak over long assessment periods.

CONFIABILIDAD Y SENSIBILIDAD DE LA PRUEBA JEBSEN-TAYLOR TEST OF HAND FUNCTIÓN Y LA PRUEBA BOX AND BLOCK TEST EN NIÑOS CON PARÁLISIS CEREBRAL: OBJETIVO: Evaluar la confiabilidad y la sensibilidad de las pruebas Jebsen-Taylor Test of Hand Function (JTTHF) y Box and Block Test (BBT) en niños con parálisis cerebral (PC). MÉTODO: En este estudio retrospectivo, los análisis de confiabilidad fueron realizados con pruebas t para muestras relacionadas, considerando un tiempo corto (media de 14 días) y largo (media de 120 días) entre dos períodos de evaluación. Además, se utilizó el coeficiente de correlación intraclase (CCI) para evaluar el grado de congruencia. La sensibilidad de la terapia fue evaluada con prueba t en toda la muestra, respecto a la edad, nivel de habilidad manual, según el sistema de clasificación de la habilidad manual (MACS), y la topografía. RESULTADOS: Nuestros principales resultados confirman la confiabilidad a corto plazo para la prueba JTTHF en ambas manos y para la prueba BBT en la mano menos afectada. Estos resultados fueron consistentes, de acuerdo con el CCI. La sensibilidad fue confirmada, excepto en la mano menos afectada para la prueba JTTHF, con resultados similares respecto a la edad, MACS y topografía. INTERPRETACIÓN: Este estudio sustenta el uso de las pruebas JTTFH y BBT para evaluar cambios luego de intervenciones de corto plazo para niños con PC. Estos resultados debieran ser interpretados en asociación a valores de normalidad o con un grupo control cuando sean utilizados para evaluar períodos de intervención de largo plazo.

CONFIABILIDADE E RESPONSIVIDADE DO TESTE DA FUNÇÃO MANUAL DE JEBSEN-TAYLOR E DO TESTE DA CAIXA E BLOCOS PARA CRIANÇAS COM PARALISIA CEREBRAL: OBJETIVO: Avaliar a confiabilidade e a responsividade do Teste da Função Manual de Jebsen-Taylor (TFMJT) e do Teste da Caixa e Blocos (TCB) para crianças com paralisia cerebral (PC). MÉTODO: Neste estudo retrospectivo, análises de confiabilidade foram realizadas com testes t pareados considerando um tempo curto (média 14d) e longo (média 120d) entre dois períodos de avaliação. Adicionalmente, coeficiente de correlacão intraclasse (CCI) foi usado para avaliar o nível de conguência. A responsividade a terapia foi conduzida com um teste t pareado em uma amostra considerando a idade, o nível de habilidade manual classificado pelo Sistema de Classificação da Habilidade Manual (MACS), e a topografia. RESULTADOS: Nossos principais resultados confirmaram a confiabilidade dos testes em um curto período de tempo para o TFMJT em ambas as mãos e para o TCB na mão menos afetada. Estes resultados foram consistentes com o CCI. A responsividade foi confirmada, exceto na mão menos afetada para o TFMJT, com resultados similares para a abordagem por idade, MACS e topografia. INTERPRETAÇÃO: Este estudo apóia o uso do TFMJT e do TCB para examinar mudanças após intervenções de curto prazo em crianças com PC. Estes resultados devem ser interpretados em associação com valores normativos ou um grupo controle quando usados em longos períodos de avaliação.

Interrater Reliability of Activity Questionnaires After an Intensive Motor-Skill Learning Intervention for Children With Cerebral Palsy.

OBJECTIVE: To investigate the reliability of parents-reported activity questionnaires after a motor-skill learning intervention for children with cerebral palsy (CP). We hypothesize that the intervention process might influence parental judgment. DESIGN: Double-blind randomized trial. SETTING: Conventional therapy was delivered in the usual context while intensive intervention was provided at the Catholic University of Louvain. PARTICIPANTS: Children with CP (N=41; age range 5-18y, Gross Motor Function Classification System I-IV) were randomized to a control group (CG) (n=21, 2 dropouts) receiving conventional therapy or an intervention group (IG) (n=20) receiving hand-arm bimanual intensive therapy-including lower extremities (HABIT-ILE). INTERVENTIONS: Conventional therapy (mostly neurodevelopmental) was delivered as ongoing treatment (1-5 times/wk). HABIT-ILE, based on motor-skill learning, was delivered over 2 weeks. All children were assessed at T1 (baseline), T2 (3wk after baseline) and T3 (4mo after baseline). MAIN OUTCOMES MEASURES: ABILHAND-Kids and ACTIVLIM-CP questionnaires rated by parents (perception) and 2 examiners (videotapes). RESULTS: Agreement (level/range) between examiners was systematically almost perfect (P≤.001). At baseline, moderate to almost perfect agreement (level/range) was observed between parents and examiners (P≤.001). At T2 and T3, a similar agreement (level/range) was observed for the CG. For the IG, a similar level of agreement was observed, but the range of agreement varied from poor to almost perfect (P≤.001), with parents estimating higher performance measures compared to examiners after intervention. Higher performance was associated with higher satisfaction scores of the child's functional goals at T3. CONCLUSION: Parents and examiners have a similar perception of the child's performance at baseline and during conventional therapy. Their perceptions are less congruent after a motor-skill learning intervention, probably due to the goal-oriented process of the intervention. Therefore, our results favor the use of blind observations of home-videotaped items after intensive motor-skill learning interventions.

Responsiveness of the ACTIVLIM-CP questionnaire: measuring global activity performance in children with cerebral palsy.

AIM: To investigate the responsiveness of the ACTIVLIM-CP questionnaire after two evidence-based interventions for children with cerebral palsy (CP). METHOD: Seventy-five children with CP either participated in an intensive motor-skill learning intervention (hand-arm bimanual intensive therapy including lower extremities [HABIT-ILE], n=47) or received botulinum neurotoxin-A (BoNT-A) injection(s) into lower extremities combined with conventional physical therapy (n=28). All children were assessed three times: at baseline (T0 ; before HABIT-ILE/the day of BoNT-A injection), at T1 (last day of HABIT-ILE/6wks after BoNT-A injection), and at follow-up (T2 ; 3-4mo after the beginning of intervention). Parents completed ACTIVLIM-CP and three other activity questionnaires. Responsiveness was analysed using group (based on intervention), subgroup (based on gross motor function level), and individual approaches. RESULTS: For the HABIT-ILE group, significant improvements in ACTIVLIM-CP were observed for the T0 -T1 period (p<0.001) but not for the T1 -T2 period. No significant changes were found in the BoNT-A group during assessments (p=0.84). In the subgroup analysis for the HABIT-ILE group (T0 -T1 ), greater changes were demonstrated for children in Gross Motor Function Classification System levels III and IV (p<0.001, effect size=1.36). The individual approach was congruent with the group approach. INTERPRETATION: ACTIVLIM-CP demonstrated high responsiveness after HABIT-ILE, showing that this scale may be used to investigate global activity performance in clinical trials focusing on improving daily life activities. WHAT THIS PAPER ADDS: Good responsiveness of ACTIVLIM-CP questionnaire during intensive motor-skill learning intervention. Higher responsiveness for children in Gross Motor Function Classification System (GMFCS) levels III and IV versus I and II after intensive intervention. ACTIVLIM-CP is useful to identify children improving their performance after botulinum neurotoxin-A injection.

Perinatal Western Diet Consumption Leads to Profound Plasticity and GABAergic Phenotype Changes within Hypothalamus and Reward Pathway from Birth to Sexual Maturity in Rat.

Perinatal maternal consumption of energy dense food increases the risk of obesity in children. This is associated with an overconsumption of palatable food that is consumed for its hedonic property. The underlying mechanism that links perinatal maternal diet and offspring preference for fat is still poorly understood. In this study, we aim at studying the influence of maternal high-fat/high-sugar diet feeding [western diet (WD)] during gestation and lactation on the reward pathways controlling feeding in the rat offspring from birth to sexual maturity. We performed a longitudinal follow-up of WD and Control offspring at three critical time periods (childhood, adolescence, and adulthood) and focus on investigating the influence of perinatal exposure to palatable diet on (i) fat preference, (ii) gene expression profile, and (iii) neuroanatomical/architectural changes of the mesolimbic dopaminergic networks. We showed that WD feeding restricted to the perinatal period has a clear long-lasting influence on the organization of homeostatic and hedonic brain circuits but not on fat preference. We demonstrated a period specific evolution of the preference for fat that we correlated with specific brain molecular signatures. In offspring from WD fed dams, we observed during childhood the existence of fat preference associated with a higher expression of key gene involved in the dopamine (DA) systems; at adolescence, a high-fat preference for both groups, progressively reduced during the 3 days test for the WD group and associated with a reduced expression of key gene involved in the DA systems for the WD group that could suggest a compensatory mechanism to protect them from further high-fat exposure; and finally at adulthood, a preference for fat that was identical to control rats but associated with profound modification in key genes involved in the γ-aminobutyric acid network, serotonin receptors, and polysialic acid-NCAM-dependent remodeling of the hypothalamus. Altogether, these data reveal that maternal WD, restricted to the perinatal period, has no sustained impact on energy homeostasis and fat preference later in life even though a strong remodeling of the hypothalamic homeostatic and reward pathway involved in eating behavior occurred. Further functional experiments would be needed to understand the relevance of these circuits remodeling.

ACTIVLIM-CP a new Rasch-built measure of global activity performance for children with cerebral palsy.

OBJECTIVE: Children with cerebral palsy (CP) often have upper extremity (UE) and lower extremity (LE) impairments. While tools measuring separately UE and LE abilities are currently used, activities in which UE and LE are used in combination - numerous in everyday life - cannot be assessed because no instrument allows capturing global activity performance in children with CP. This study aimed to develop a clinical tool for measuring their global activity performance using the Rasch model. STUDY DESIGN: The caregivers of 226 children with CP (2-18 years old) answered a 154-item experimental questionnaire. Within 4-6 weeks, 129 of them filled in the questionnaire a second time. Responses were analyzed using the Rasch RUMM2020 software. RESULTS: The final 43 item scale presented a high reliability (R=0.98) and reproducibility (R=0.97). The item difficulty hierarchy was consistent over time and did not vary according to age, gender, or clinical form, allowing the follow-up of children from 2 to 18 years old. CONCLUSIONS: ACTIVLIM-CP is a unidimensional scale specifically developed to measure global activity performance in children with CP providing a reliable tool to follow children's evolution and document changes related to neurorehabilitation, especially where a combination of UE and LE is targeted. Its responsiveness is still to be tested.

Intensive upper- and lower-extremity training for children with bilateral cerebral palsy: a quasi-randomized trial.

AIM: An approach that simultaneously engages both the upper and lower extremities, hand-arm bimanual intensive therapy including lower extremity (HABIT-ILE), has recently demonstrated improvements in upper and lower extremities in children with unilateral cerebral palsy (CP). It is not known whether children with bilateral CP would benefit from this approach. The aim of this study was to examine the efficacy of HABIT-ILE in children with bilateral CP. METHOD: A quasi-randomized trial design was used, whereby 20 participants (age 6-15y, Gross Motor Function Classification System levels II-IV, Manual Ability Classification System levels I-III) were assigned to a treatment (HABIT-ILE) or a comparison group in the order in which they were enrolled. Children in the HABIT-ILE group were assessed before and after 84 hours of intervention over 13 days, as well as at 3 months' follow-up. Children in the comparison group were assessed at the same time points. Children in both groups were assessed using the Gross Motor Function Measure (GMFM-66) and ABILHAND-Kids (primary measures), and six secondary measures. RESULTS: A group×test session interaction indicated significant improvements in the HABIT-ILE group as assessed by the GMFM-66, lower-extremity performance (6-Minute Walk Test; Pediatric Balance Scale), functional upper-extremity abilities (ABILHAND-Kids/Pediatric Evaluation of Disability Inventory), and the dexterity of the less affected upper extremity. CONCLUSION: HABIT-ILE is efficacious for improving both upper- and lower-extremity function in children with bilateral CP.

Evaluation of the SureSpot direct-reading instrument for the determination of polymeric MDI aerosols.

Recent studies in our laboratories have focused on the reliability of direct-reading instruments for the determination of airborne isocyanate concentrations. The evaluation of airborne isocyanates is complicated because these substances exist as diisocyanate monomers and polyisocyanate oligomers, both in the vapor and aerosol phases. The studies showed that a number of direct-reading instruments, including the SureSpot test kit, do not allow an accurate determination of isocyanates in the aerosol phase. Using a test chamber, concentrations of various commercial polymeric methylenediphenyl diisocyanates (PMDI) were generated in the aerosol phase to examine the correlation between the SureSpot monitor and two laboratory methods. The results obtained with the SureSpot and laboratory methods correlated poorly. More precisely, the results indicated that the SureSpot direct-reading instrument had a distinctive response to each commercial PMDI and, in addition, it was not accurate for the determination of total PMDI in the aerosol phase. It seemed that the analytical response of the SureSpot is based on a calibration curve only reliable for MDI and not for the determination of PMDIs in the aerosol phase. Further investigation also indicated that the calibration provided by the manufacturer could not be converted into a linear curve over the suggested MDI concentrations range. An appropriate calibration procedure was developed in our laboratories for the SureSpot to accurately determine all commercial PMDIs without great variability.