Motor Function In Young Children Research Articles

Safety and feasibility of autologous cord blood infusion for improving motor function in young children with cerebral palsy in Japan: A single-center study

IntroductionCerebral palsy (CP) is the most prevalent motor disorder of childhood. It typically results from in utero or perinatal brain injury. Recently, it has been reported that autologous cord blood (ACB) infusion for children with CP improved gross motor function and brain connectivity, but unfortunately, it has never been tried in Japan. We conducted a pilot study of the infusing of ACB, which was delivered from private bank, in the children with CP to assess the safety and feasibility to the procedure as well as any effect in improving neurological function. MethodsAfter demonstrating the induction of tissue regeneration in animal model studies conducted a single-arm pilot study of intravenous ACB infusion in 6 young Japanese children with CP (ages 1–6 years). Primary outcomes were safety assessed by vital signs, clinical symptoms, and blood and urinary examinations at baseline and 1 weeks, 1, 2 and 3 years after treatment. In addition, motor function evaluations, neurodevelopmental examinations, magnetic resonance imaging, and electroencephalography (EEG) were performed at the same time. ResultsInfusion was generally well-tolerated, although one patient experienced microhematuria 1 year after treatment and another one patient experienced febrile convulsion once 9 months after treatment. These events were transient, no relapse was seen during observation study. All patients improved a median of 6.8 points on the 1-year Gross Motor Functional Measure-66 (GMFM-66) scores, greater than predicted by age and severity. Furthermore, the 2-year and 3-year GMFM-66 scores were also greater than expected (median 6.2 points and 5.5 points, respectively). Overall scales and language-social scales of the developmental quotient (DQ) improved in 3 of 6 patients, who had greater changes in their GMFM-66 scores than the other cases after treatment. There were no significant correlations among the GMFM-66 scores, DQ, and infusion cell counts. ConclusionACB infusion was safe and feasible for clinical use in patients with CP. However, much more clinical study with larger numbers of patients and in-depth studies of treatment mechanism of CP are needed.

Umbilical cord blood and cord tissue mesenchymal stromal cells in children with cerebral palsy

Background & Aim: Umbilical cord blood (CB) and mesenchymal stromal cells (MSC) have shown safety in children with cerebral palsy (CP). While early phase clinical trials suggest potential functional benefit, small sample sizes, heterogeneous populations, and variable cell doses have impaired accurate assessment of motor gains following treatment. Aim: Describe change in gross motor function in young children with CP after treatment with high-dose allogeneic unrelated donor CB or allogeneic, third party human cord tissue-derived MSC (hCT-MSC) 12 months post treatment. Methods, Results & Conclusion: We conducted a phase 2 randomized trial of 90 children ages 2-4 years with hypertonic CP due to hypoxic ischemic encephalopathy, periventricular leukomalacia, or in utero stroke/bleed. Randomization, stratified by etiology and severity (Gross Motor Function Classification System (GMFCS) level), was to: (a) 10×107 total nucleated cells (TNC)/kg allogeneic CB at baseline, (b) three doses of 2×106 cells/kg hCT-MSC given at baseline, 3, and 6 months, or (c) Natural History in which 10×107 TNC/kg allogeneic CB was given at one year. Infusions were intravenous and premedicated with diphenhydramine and methylprednisolone without immunosuppression. Primary outcome was change in motor function one-year post enrollment, measured by the Gross Motor Function Measure-66 (GMFM-66). Ninety children (median 3.5 years) were randomized and completed baseline and 6-month evaluations. Due to the COVID pandemic, only 68 completed 12-month assessments. The only adverse events (AEs) related to the cell products were 8 transient infusion reactions (3 CB, 5 hCT-MSC). An additional 95 non-severe AEs and 33 severe AEs were unrelated to the products. At 6 months, there was no statistical difference in change in GMFM-66 scores between Natural History (n=31) and either treatment group (CB n=31, hCTMSC n=28). At 12 months, after adjustment for baseline GMFCS level, GMFM-66 score, and etiology of CP, the mean GMFM-66 score of the hCT- MSC group (n=23) was 1.4 points higher than Natural History (n=25;95% CI: -1.1, 4.0;p=0.27) and the CB group (n=20) was 3.3 points higher than Natural History (95% CI: 0.59, 5.93;p=0.02). High dose allogeneic CB, but not hCT-MSC, infusion is associated with gross motor improvement in young children with CP, consistent with the dose effect in a prior study of autologous CB. A phase 3 randomized placebo-controlled study should be performed to confirm the CB observation.

The relationship between the Family Empowerment Scale and Gross Motor Function Measure-66 in Young Children with cerebral palsy.

Cerebral palsy (CP) is the most common cause of motor disability in children. A concept to consider in order to meet the needs of children with CP and their families is family empowerment. Family empowerment can be defined as the process by which families acquire the skills, knowledge and resources to allow them to gain control and improve the quality of their lives. The relationship between gross motor function and family empowerment may be important because children with CP vary so widely in their ability to perform motor skills, which may affect their family's levels of empowerment. The purpose of this research was to investigate the relationship between the Family Empowerment Scale (FES) and Gross Motor Function Measure-66 (GMFM-66) in children with CP who were under 3 years of age. Forty-one children with a mean age of 23.8 months participated in this study. The FES was completed by the participants' parents or regular caregivers and includes a total score and subscales of empowerment in the family, in service situations and in community/political environments. The GMFM-66 was administered by a physical therapist and consists of a total score of gross motor function (GMFM-66) and subscores for Dimension B (sitting), Dimension C (crawling and kneeling), Dimension D (standing) and Dimension E (walking, running and jumping). Statistically significant positive correlations were found between the FES total and GMFM (total score and Dimensions B-E) with coefficients varying from 0.43-0.62. Significant relationships were also found between most subscales of the FES and the GMFM-66. This study provides evidence of a relationship between family empowerment and gross motor function in young children with CP and suggests that caregivers of children with higher gross motor function report higher levels of self-efficacy.

REGISTRIES AND CARE OF NEUROMUSCULAR DISORDERS: P.285Validation of the Brazilian Portuguese version of the motor function measure - short form (MFM-20) for neuromuscular diseases in children from two to seven years old

Neuromuscular disorders (NMD) include a large number of conditions involving muscle weakness. There is a lack of tools to assess motor function in young children with NMD. The Motor Function Measure (MFM-32), validated in Brazil as MFM-P, monitors the severity and progression of motor function in patients with NMD, from six to sixty years old. As this version was not validated in children under six years of age, the authors of the original version, from Pediatric Reeducation Service L'Escale (France), developed the Motor Function Measure - Short Form (MFM-20), designed for children from two to seven years old. The aim of this study was to test the reliability and validity of MFM-20 in Brazilian Portuguese. The translation of MFM-20 was performed by the same researchers that translated MFM-32 in Brazil. After a pretest in a sample of five subjects, the translated version was applied with twenty-six children with NMD. To verify the inter-rater reliability, the Wilcoxon Test compared the scores given within one-week interval and the Student's Test compared the scores given by two physical therapists at the first day. To verify the converging construct validity between MFM-20 and Hammersmith Motor Functional Scale (HMFH), Barthel's Index (BI) and Vignos and Brooke Scale (VBS), as well as the discriminating construct validity between MFM-20 and the Medical Research Council Scale (muscular strength), Pearson correlation tests were applied. Twenty six patients with mean age 4.6 ± 1.5 years old were included in this study, with the following clinical diagnosis: Duchenne muscular dystrophy (n=9), congenital muscular dystrophy (n=5), congenital myopathy (n=6) and type 2 spinal muscular atrophy (n= 6). The reliability analysis demonstrated good reproducibility for intra-rater on the first day (35.8±8.8) and after one week (37.0±9.0); p= 0,050, and good inter-rater reproducibility (examiner 1: 35.8±8.8 and examiner 2: 35.1±9.2). The converging validity analysis demonstrated good correlation between MFM-20 and HMFS, VBS and BI, with correlation coefficients: 0.907, -0.918 and 0.797, respectively. The discriminating validity analysis demostrated positive correlation between MFM-20 and Medical Research Council, with a correlation coefficient 0.873. The Brazilian Portuguese version of MFM-20 showed validity, representing advances for patients in Brazilian's centers.

Concurrent Validity of Two Standardized Measures of Gross Motor Function in Young Children with Autism Spectrum Disorder

ABSTRACTAims: This study provides information on how two standardized measures based on different theoretical frameworks can be used in collecting information on motor development and performance in 4- and 5-year-olds with autism spectrum disorder (ASD). The purpose of the study was to determine the concurrent validity of the Miller Function and Participation Scales (M-FUN) with the Peabody Developmental Motor Scales, Second Edition (PDMS-2) in young children with ASD. Methods: The gross motor sections of the PDMS-2 and the M-FUN were administered to 22 children with ASD between the ages of 48 and 71 months. Concurrent validity between overall motor scores and agreement in identification of motor delay were assessed. Results: A very strong correlation (Pearson's r =.851) was found between the M-FUN scale scores and the PDMS-2 gross motor quotients (GMQs). Strong agreement in identification of children with average motor skills and delayed motor skills at 1.5 standard deviations below the mean was also found. Conclusions: This study supports the concurrent validity of the M-FUN with the PDMS-2 for young children with ASD. While both tests provide information regarding motor delay, the M-FUN may provide additional information regarding the neurological profile of the child.

Effect of Autologous Cord Blood Infusion on Motor Function and Brain Connectivity in Young Children with Cerebral Palsy: A Randomized, Placebo-Controlled Trial.

Cerebral palsy (CP) is a condition affecting young children that causes lifelong disabilities. Umbilical cord blood cells improve motor function in experimental systems via paracrine signaling. After demonstrating safety, we conducted a phase II trial of autologous cord blood (ACB) infusion in children with CP to test whether ACB could improve function (ClinicalTrials.gov, NCT01147653; IND 14360). In this double‐blind, placebo‐controlled, crossover study of a single intravenous infusion of 1–5 × 107 total nucleated cells per kilogram of ACB, children ages 1 to 6 years with CP were randomly assigned to receive ACB or placebo at baseline, followed by the alternate infusion 1 year later. Motor function and magnetic resonance imaging brain connectivity studies were performed at baseline, 1, and 2 years post‐treatment. The primary endpoint was change in motor function 1 year after baseline infusion. Additional analyses were performed at 2 years. Sixty‐three children (median age 2.1 years) were randomized to treatment (n = 32) or placebo (n = 31) at baseline. Although there was no difference in mean change in Gross Motor Function Measure‐66 (GMFM‐66) scores at 1 year between placebo and treated groups, a dosing effect was identified. In an analysis 1 year post‐ACB treatment, those who received doses ≥2 × 107/kg demonstrated significantly greater increases in GMFM‐66 scores above those predicted by age and severity, as well as in Peabody Developmental Motor Scales‐2 Gross Motor Quotient scores and normalized brain connectivity. Results of this study suggest that appropriately dosed ACB infusion improves brain connectivity and gross motor function in young children with CP. Stem Cells Translational Medicine 2017;6:2071–2078

P.120 - Segmental body composition in young children with SMA type 2: Correlation with motor function abilities

The aim of the present study was to investigate the correlation between fat mass (FM) and fat-free mass (FFM), measured by total and segmental body dual energy x-ray absorptiometry (DEXA), and the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Upper limb module (ULM). 40 children with SMA type 2 (mean age 4.07 ± 1.90 years) were included in the study. Total FFM and FM were not correlated with HFMSE scores. However, when we investigated the correlation of segmental FFM and FM with motor function scores, we found that lower limbs FFM was significantly correlated with HFMSE scores (r = 0.375; p = 0.017), while no correlations were found between upper limbs FFM and HFMSE (r = 0.050; p = 0.756) or ULM (r = 0,154; p = 0,392). When we divided the whole cohort into Low-Functioning (HFMSE < 12) and High-Functioning (HFMSE > 12) children, we found that the Low-Functioning group had lower upper and lower limbs FFM, and higher upper and lower limbs FM, compared to the High-Functioning group. To our knowledge this is the first study investigating the correlation between total and segmental body composition and motor function in young children with SMA 2. The present study demonstrated that segmental lean mass at the lower limbs was correlated with global motor function abilities, as assessed by the HFMSE, and that segmental lean and fat mass was significantly different when children were stratified by level of functional abilities. These data further highlight the validity of HFMSE as an outcome measure in SMA, and may be helpful in monitoring the effects of therapeutic strategies.

Autologous Cord Blood Infusion for the Treatment of Brain Injury in Children with Cerebral Palsy

Background: Cerebral palsy (CP) results from in utero or perinatal injury to the developing brain, often through stroke, hypoxic insult, or hemorrhage. Current treatments are supportive, focusing on managing sequelae with physical therapies, medications, and surgery. However, there are no therapies to address the underlying brain injury. Umbilical cord blood (CB) has been shown to prevent neurologic damage in children with leukodystrophiesand to improve motor function in animal models of brain injury and CP. Previously, we demonstrated safety of intravenous autologous CB infusion in young children with brain injuries. The Cerebral Palsy-Autologous Cord Blood (CP-AC) study was designed to assess the efficacy of a single intravenous infusion of autologous CB in young children with spastic CP.Methods: The CP-AC study is a prospective, randomized, double blind, placebo controlled crossover study of a single intravenous infusion of autologous CB in children ages 1-6 years with spastic CP. The Gross Motor Classification System (GMFCS) was utilized to classify the level of motor function at study entry and follow-up. Children were eligible if they were (1) GMFCS level 2-4 or (2) GMFCS level 1 with hemiplegia if they used their affected hand as an assist only. Children with known genetic conditions, intractable seizures, or severe microcephaly were ineligible. Autologous CB units had to have a documented pre-cyropreservation total cell dose of ≥1x107/kg, negative sterility culture, negative maternal infectious disease screening, and confirmed identity through HLA typing of the subject and a segment attached to the CB unit. Subjects were evaluated at baseline, one year, and two years with functional evaluations (Gross Motor Function Measure-66 (GMGM-66), Peabody Developmental Motor Scales-2, Assisting Hand Assessment, Bayley Scales of Infant Development) and brain MRI. They were randomized to the order in which they received CB and placebo infusions (given one year apart). The primary endpoint was change in GMFM-66 score at one year after the initial infusion (CB or placebo). Cryopreserved CB units were shipped to and stored at Duke until the day of treatment when they were thawed and washed in dextran 40 +5% human serum albumin (DA). Infusions, dosed at 1-5x107/kg based on the pre-cryopreservation total nucleated cell count (TNCC) and diluted in 1.25mL/kg of DA, were administered intravenously over 5-10 minutes in the outpatient setting after premedication with oral acetaminophen, IV Benadryl, and IV Solumedrol. Subjects received IV fluids and were monitored for 2-4 hours post-infusion.Results: Sixty-three children were enrolled with a median age of 2 years (range 1- 6) at baseline. Median TNCC of CB infusion was 2x107/kg (range 0.4-5) with a median CD34 dose of 0.5x105/kg (range 0.05-4). Despite negative pre-cryopreservation cultures, one CB unit grew β-hemolytic strepfrom a sample of the thawed CB unit. There were no clinical infections in this or any other study patient. One subject had transient infusion reactions consisting of hives +/- low-grade fever after each infusion; an additional dose of Benadryl was administered after the first reaction. Preliminary analysis of the 63 patients at one year showed no statistically significant overall difference in GMFM-66 change scores between placebo and treated groups (6.9 vs. 7.5, p =0.72). However, treated subjects who received pre-cryopreservation cell doses of >2.5x107/kg demonstrated statistically significant improvement in GMFM-66 change scores compared to subjects who received lower cell doses (p <0.01). A similar result was observed comparing subjects who received above (or below) the median infused cell dose of 1.98x107/kg (p =0.05) (Figure 1). The infused cell dose was not related to type of CP (p =0.32) or severity (p=0.46).Conclusions: When adequately dosed, cord blood may improve motor function in young children with spastic CP. We observed improvement at pre-cryopreservation cell doses (>2.5x107/kg) that correspond with the minimum cell dose used for hematopoietic reconstitution in patients undergoing allogeneic CB transplantation. In order to extend this therapy to children who do not have adequate autologous CB units available, safety and efficacy of allogeneic CB products should be investigated. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Food and fluid texture consumption in a population-based cohort of preschool children with cerebral palsy: relationship to dietary intake.

To determine the texture constitution of children's diets and its relationship to oropharyngeal dysphagia (OPD), dietary intake, and gross motor function in young children with cerebral palsy (CP). A cross-sectional, population-based cohort study comprising 99 young children with CP (65 males, 35 females) aged 18 to 36months (mean age 27mo; Gross Motor Function Classification System [GMFCS] level I, n=45; II, n=13; III, n=14; IV, n=10; V, n=17). CP subtypes were classified as spastic unilateral (n=35), spastic bilateral (n=49), dyskinetic (n=5), and other (n=10), in accordance with the criteria of the Surveillance of Cerebral Palsy in Europe. Habitual dietary intake of food textures, energy, and water were determined from parent-completed 3-day weighed food records. Parent-reported feeding ability of food textures was reported on the Pediatric Evaluation of Disability Inventory and a feeding questionnaire. OPD was classified based on clinical feeding assessment using the Dysphagia Disorders Survey (rated by a certified assessor, KAB) and a subjective Swallowing Safety Recommendation (classified by a paediatric speech pathologist, KAB). Food/fluid textures were modified for 39% of children. Children with poorer gross motor function tended to receive a greater proportion of energy from fluids (GMFCS levels IV-V: β=0.9, p=0.002) in their diets and fewer chewable foods (level III: β=-0.7, p=0.03; levels IV-V: β=-1.8, p<0.001) compared to level I to II participants. Fluids represented a texture for which children frequently had OPD and the texture most frequently identified as unsafe (or recommended for instrumental assessment). These findings indicate that swallowing safety, feeding efficiency, and energy/water intake should be considered when providing feeding recommendations for children with CP.

Effects of Home-Based Locomotor Treadmill Training on Gross Motor Function in Young Children With Cerebral Palsy: A Quasi-Randomized Controlled Trial

ObjectiveTo examine the effects of an intensive home-based program of treadmill training on motor skills related to walking in preambulatory children with cerebral palsy (CP). DesignQuasi-randomized controlled trial. SettingHomes of the participants. ParticipantsChildren with CP (N=12) with Gross Motor Function Classification System levels I and II were assigned to the intervention group (n=6; mean age ± SD, 21.76±6.50mo) and control group (n=6; 21.25±6.07mo). All children were tested preintervention, postintervention, at a 1-month follow-up, and at a 4-month follow-up. InterventionsAll children received their weekly scheduled physical therapy sessions at their homes. In addition, children in the intervention group walked on a portable treadmill in their homes 6 times per week, twice daily for 10- to 20-minute sessions, for 6 weeks. The intervention was carried out by the children's parents with weekly supervision by a physical therapist. Main Outcome MeasuresGross Motor Function Measure-66 Dimensions D/E, Peabody Developmental Motor Scales-2 (PDMS-2), Pediatric Evaluation of Disability Inventory (PEDI), timed 10-m walk test (10MWT), and Functional Mobility Scale (FMS). The Friedman test and Mann-Whitney U test were conducted for within-group and between-group differences, respectively. ResultsThere was a significant between-group treatment effect for the PDMS-2 at posttest (P=.01) and 1-month postintervention follow-up (P=.09), as well as for the PEDI at posttest (P=.01), the 1-month postintervention follow-up (P=.009), and the 4-month postintervention follow-up (P=.04). The FMS was significant at the posttest (P=.04). ConclusionsHome-based treadmill training accelerates the attainment of walking skills and decreases the amount of support used for walking in young children with CP.

Motor Function Measure: Validation of a Short Form for Young Children With Neuromuscular Diseases

ObjectiveTo validate a useful version of the Motor Function Measure (MFM) in children with neuromuscular diseases aged <7 years old. DesignTwo prospective cohort studies that documented the MFM completion of children aged between 2 and 7 years old. SettingFrench-speaking rehabilitation departments from France, Belgium, and Switzerland. ParticipantsHealthy children (n=194) and children with a neuromuscular disease (n=88). InterventionsPatients were rated by the MFM either once or twice by trained medical professionals, with a delay between the 2 MFMs ranging between 8 and 30 days. Main Outcome MeasureIntra- and interrater reliability of the MFM. ResultsThe subtests making up the MFM-32, a scale monitoring severity and progression of motor function in patients with a neuromuscular disease in 3 functional domains, were carried out in healthy children aged 2 to 7 years. Twenty items of the MFM-32 were successfully completed by these children and were used to constitute the MFM-20. Principal component analysis of the MFM-20 confirmed the 3 functional domains. Inter- and intrarater reliability of the 3 subscores and total score were high (intraclass correlation coefficient >.90), and discriminant validity was good. ConclusionsThe MFM-20 can be used as an outcome measure for assessment of motor function in young children with neuromuscular disease.

Myofascial Structural Integration: A Promising Complementary Therapy for Young Children With Spastic Cerebral Palsy

Increasing evidence suggests that structural changes within muscle and surrounding tissues are associated with creating and/or increasing muscle stiffness and resistance to stretch in spastic cerebral palsy. The goal of this preliminary study was to determine whether myofascial structural integration, a specific, complementary, deep-tissue manipulation technique designed to reorganize muscle and surrounding soft tissue, would improve motor function in young children with spastic cerebral palsy. In a randomized crossover design, the authors assessed motor function using established measurement techniques at baseline and after the treatment and control conditions in 8 children with spastic cerebral palsy, aged 2 to 7 years. The average change for the group after therapy was greater than the change after the control condition. Results showed that there were major improvements in 6 children after the therapy; 3 of the children also showed improvements after the control phase. Myofascial structural integration holds promise as a novel complementary treatment for spastic cerebral palsy.