A new methodological approach to characterize selective motor control in children with cerebral palsy.

Introduction: Despite being a primary impairment in individuals with cerebral palsy (CP), selective motor control (SMC) is not routinely measured. Personalized treatment approaches in CP will be unattainable without the ability to precisely characterize the types and degrees of impairments in motor control. The objective of this study is to report the development and feasibility of a new methodological approach measuring muscle activation patterns during single-joint tasks to characterize obligatory muscle co-activation patterns that may underly impaired SMC. Methods: Muscle activation patterns were recorded during sub-maximal voluntary isometric contraction (sub-MVIC) tasks at the hip, knee, and ankle with an interactive feedback game to standardize effort across participants. We calculated indices of co-activation, synergistic movement, mirror movement, and overflow (indices range 0-2, greater scores equal to greater impairment in SMC) for each isolated joint task in 15 children - 8 with typical development (TD) (mean age 4.7 ± 1.0 SD years) and 7 with CP (mean age 5.8 ± 0.7 SD years). Indices were compared with Mann-Whitney tests. The relationships between the indices and gross motor function (GMFM-66) were examined with Pearson's r. Results: Mean indices were higher in the CP vs. the TD group for each of the six tasks, with mean differences ranging from 0.05 (abduction and plantarflexion) to 0.44 (dorsiflexion). There was great inter-subject variability in the CP group such that significant group differences were detected for knee flexion mirroring (p = 0.029), dorsiflexion coactivation (p = 0.021), and dorsiflexion overflow (p = 0.014). Significant negative linear relations to gross motor function were found in all four indices for knee extension (r = -0.56 to -0.75), three of the indices for ankle dorsiflexion (r = -0.68 to -0.78) and in two of the indices for knee flexion (r = -0.66 to -0.67), and ankle plantarflexion (r = -0.53 to -0.60). Discussion: Indices of coactivation, mirror movement, synergy, and overflow during single-joint lower limb tasks may quantify the type and degree of impairment in SMC. Preliminary concurrent validity between several of the indices of SMC and gross motor function was observed. Our findings established the feasibility of a new methodological approach that quantifies muscle activation patterns using electromyography paired with biofeedback during single-joint movement.

Limited associations between passive range of motion and gross motor function in ambulant/semi-ambulant children and adolescents with cerebral palsy: A cross-sectional study.

BACKGROUND AND AIM: Cerebral palsy (CP) is the most common childhood motor disability, and the Cerebral Palsy Follow-Up Program (CPUP) in Nordic countries uses a traffic light system for passive range of motion (ROM) assessment to aid interpretation and guide decisions regarding interventions. However, the arbitrary chosen ROM threshold values and their potential clinical impact are uncertain. We investigated whether lower extremity ROM values were positively associated with gross motor function and whether gross motor function scores differ between the CPUP ROM thresholds. METHODS: This was a cross-sectional analysis of CPUP data for 841 ambulatory children and adolescents with CP, at a mean (SD) age of 9 (3). Regression analyses were employed to explore the relationship between gross motor capacity and performance (using the Gross Motor Function Measure (GMFM-66) and the Functional Mobility Scale (FMS) 5/50/500 m, respectively) and lower extremity ROM, measured with a goniometer. ROM was assessed both as continuous and categorical variables. RESULTS: We found that two out of ten continuous ROM measures were positively associated with gross motor function. Limited differences in gross motor function between the ROM thresholds were seen for seven out of ten ROM measures. The CPUP traffic light thresholds primarily differentiated gross motor function between the red and green categories, predominantly for the subgroup of participants with bilateral spastic CP. CONCLUSION: Limited associations between passive ROM and gross motor function in children and adolescents with CP were observed, indicating that there is more to consider than ROM when identifying whether interventions are needed.

Effects of routine physical therapy with and without kinesio taping in improving gross motor function in sitting and standing in spastic diplegic cerebral palsy children.

OBJECTIVE: To determine the effectiveness of Kinesio taping along with routine physical therapy on improving gross motor function in sitting and standing among spastic diplegic Cerebral Palsy children. DESIGN: Randomized controlled trial. SETTINGS: University Teaching Hospital University of Lahore, Lahore. PARTICIPANTS: 53 participants with diagnosed spastic diplegic cerebral palsy were randomly allocated in control and experimental groups. INTERVENTION: 26 Participants were treated by kinesio taping which was applied in a criss-cross manner along with routine physical therapy program while the control group (n = 27) received NDT exercise program that comprises of stretching, functional reaching, weight-bearing exercises and walking. OUTCOME MEASURE: Gross motor function was assessed using 2 components of Gross Motor Function Classification System (GMFCS-88), i.e., sitting as well as standing at the base line and after every 3rd week for 12 weeks follow up. RESULTS: In study and control group the mean score of gross motor function for sitting at baseline was 33.96 ± 3.11 and 31.50 ± 3.32 respectively. After intervention, it changed to 47.70 ± 5.46 and 43.46 ± 1.81 respectively. Mean score for Gross Motor Function calculated at base line in study and control group for standing was 27.37 ± 1.14 and 26 ± 3.01 respectively. At the end of intervention, the score improved to 36.55 ± 4.27 and 33.69 ± 2.46 respectively. CONCLUSION: In comparison to control group, significant increase in gross motor function of intervention group was seen after the 12 weeks of intervention. In this way, over back muscles the application of kinesio tape in a Criss-Cross manner may be helpful. Also it can be used as an additional approach along with routine physical therapy to improve standing and sitting in spastic diplegic children.

Efficacy of a Soft Robotic Exoskeleton to Improve Lower Limb Motor Function in Children with Spastic Cerebral Palsy: A Single-Blinded Randomized Controlled Trial.

PURPOSE: Soft robotic exoskeletons (SREs) are portable, lightweight assistive technology with therapeutic potential for improving lower limb motor function in children with cerebral palsy. To understand the effects of long-term SRE-assisted walking training on children with spastic cerebral palsy (SCP), we designed a study aiming to elucidate the effects of SRE-assisted walking training on lower limb motor function in this population. METHODS: In this randomized, single-blinded (outcome assessor) controlled trial, forty children diagnosed with SCP were randomized into the routine rehabilitation (RR) group (N = 20) and the SRE group (N = 20) for comparison. The RR group received routine rehabilitation training, and the SRE group received routine rehabilitation training combined with SRE-assisted overground walking training. Assessments (without SRE) were conducted pre- and post-intervention (8 weeks after the intervention). The primary outcome measures included the 10 m walk test (10MWT) and the 6 min walk test (6MWT). Secondary outcome measures comprised the gross motor function measure-88, pediatric balance scale modified Ashworth scale, and physiological cost index. RESULTS: Both groups showed significant improvements (p < 0.01) across all outcome measures after the 8-week intervention. Between-group comparisons using ANCOVA revealed that the SRE group demonstrated greater improvement in walking speed from the 10MWT (+6.78 m/min, 95% CI [5.74-7.83]; p < 0.001) and walking distance during the 6MWT (+34.42 m, 95% CI [28.84-39.99]; p < 0.001). The SRE group showed greater improvement in all secondary outcome measures (p < 0.001). CONCLUSIONS: The study findings suggested that the integration of SRE-assisted overground walking training with routine rehabilitation more effectively enhances lower limb motor function in children with SCP compared to routine rehabilitation alone.

Agreement of synchronous remote and in-person application of the Alberta Infant Motor Scale: Cohort study.

INTRODUCTION: Using standardized scales to assess motor development via telemedicine can increase access for low-income populations. Our aim was to verify the agreement and feasibility between remotely and synchronously applying the Alberta Infant Motor Scale (AIMS) and the in-person format. METHODS: This was a concordance study, with 77 typical infants aged 4-18 months (mean = 13 months). The AIMS was applied remote via video calls and face-to-face. We applied a questionnaire to caregivers to verify feasibility. RESULTS: There was a high level of agreement between the remote and in-person assessments, with intraclass correlation coefficients above 0.98 and low standard error measure values (<1 item for each posture, <2 items for the total raw score, and =5% for the normative score). The smallest detectable change was between 1.67 and 2.45 for each posture, 3 for the total raw score, and 6% for the normative score. The Bland-Altman analysis showed low bias with the mean difference close to zero (<0.80) and low error with little dispersion of the difference points around the mean. Caregivers' perspectives on the synchronous remote assessment were positive, with good quality, clear information during the assessment, and comfort with the method. DISCUSSION: The synchronous remote application of the AIMS may be an alternative for families without access to in-person services that assess motor development.

Relationship Between Postural Asymmetry, Balance, and Pain in Children With Spastic Cerebral Palsy.

BACKGROUND: Primary symptoms of cerebral palsy (CP), such as spasm and weakness, can lead to secondary musculoskeletal problems. Exploring the interplay and impact of secondary symptoms is essential in CP management. METHODS: A total of 56 children (32 males and 24 females) aged eight to 12 years in level I to III of Gross Motor Function Classification System (GMFCS) completed The Pediatric Balance Scale and Wong-Baker Faces Scale and the Posture and Postural Ability Scale. Relationships between the three groups were examined using the Kruskal-Wallis test, Tukey test, gamma coefficient, De Somers D, phi coefficient, Cramér V, and one-way analysis of variance. RESULTS: There was a significant correlation between balance and postural asymmetry (P < 0.001), and no significant difference in balance was there between the severe and moderate asymmetry groups (P = 0.759) and between the mild asymmetry and no asymmetry groups (P = 0.374). Furthermore, there was a significant relationship between postural asymmetry and each of the variables of pain (P < 0.001) and gross motor function (P = 0.002). Although a meaningful correlation was identified between balance and gross motor function (P < 0.001), the relationship between postural asymmetry and balance in GMFCS levels was not found (P = 0.052, P = 0.052, P = 0.233). Conversely, no significant relationship was detected between pain and gross motor function (P = 0.072). SIGNIFICANCE: Postural asymmetry negatively impacts balance and correlates with pain intensity. Addressing postural problems can contribute to pain management and improved balance.

Cerebral Palsy and Motor Impairment After Extreme Prematurity: Prediction of Diagnoses at Ages 2 and 10 Years.

OBJECTIVE: To identify perinatal factors in children born extremely preterm (EP) that were associated with motor impairment (MI) at 2 and 10 years of age and develop a predictive algorithm to estimate the risk of MI during childhood. STUDY DESIGN: Participants of the Extremely Low Gestational Age Newborns Study (ELGANS) were classified as: no MI, MI only at 2 years, MI only at 10 years, and MI at both 2 and 10 years, based on a standardized neurological examination at 2 and the Gross Motor Function Classification System (GMFCS) at 10 years of age. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to develop the final predictive model. RESULTS: Of the 849 study participants, 64 (7.5%) had a diagnosis of MI at both 2 and 10 years and 63 (7.4%) had a diagnosis of MI at 1 visit but not the other. Of 22 total risk factors queried, 4 variables most reliably and accurately predicted MI: gestational age, weight z-score growth trajectory during neonatal intensive care unit (NICU) stay, ventriculomegaly, and cerebral echolucency on head ultrasound. By selecting probability thresholds of 3.5% and 7.0% at ages 2 and 10, respectively, likelihood of developing MI can be predicted with a sensitivity and specificity of 71.2%/72.1% at age 2 and 70.7%/70.7% at age 10. CONCLUSION: In our cohort, the diagnosis of MI at 2 years did not always predict a diagnosis of MI at 10 years. Specific risk factors are predictive of MI and can estimate an individual infant's risk at NICU discharge of MI at age 10 years.

Intrathecal baclofen efficacy for managing motor function and spasticity severity in patients with cerebral palsy: a systematic review and meta-analysis.

BACKGROUND: Spasticity can significantly affect a patient's quality of life, caregiver satisfaction, and the financial burden on the healthcare system. Baclofen is one of only a few options for treating spasticity. The purpose of this study is to investigate the impact of intrathecal baclofen (ITB) therapy on severe40.23 spasticity and motor function in patients with cerebral palsy. METHODS: We conducted a systematic review in PubMed, Scopus, Ovid, and the Cochrane Library in accordance with the PRISMA guidelines. We included studies based on eligibility criteria that included desired participants (cerebral palsy patients with spasticity), interventions (intrathecal baclofen), and outcomes (the Ashworth scales and the Gross Motor Function Measure [GMFM]). The within-group Cohen's d standardized mean differences (SMD) were analyzed using the random effect model. RESULTS: We screened 768 papers and included 19 in the severity of spasticity section and 6 in the motor function section. The pre-intervention average spasticity score (SD) was 3.2 (0.78), and the post-intervention average score (SD) was 1.9 (0.72), showing a 40.25% reduction. The SMD for spasticity reduction was - 1.7000 (95% CI [-2.1546; -1.2454], p-value < 0.0001), involving 343 patients with a weighted average age of 15.78 years and a weighted average baclofen dose of 289 µg/day. The SMD for the MAS and Ashworth Scale subgroups were - 1.7845 (95% CI [-2.8704; -0.6986]) and - 1.4837 (95% CI [-1.8585; -1.1088]), respectively. We found no relationship between the participants' mean age, baclofen dose, measurement time, and the results. The pre-intervention average GMFM (SD) was 40.03 (26.01), and the post-intervention average score (SD) was 43.88 (26.18), showing a 9.62% increase. The SMD for motor function using GMFM was 0.1503 (95% CI [0.0784; 0.2223], p-value = 0.0030), involving 117 patients with a weighted average age of 13.63 and a weighted average baclofen dose of 203 µg/day. In 501 ITB implantations, 203 medical complications were reported, including six new-onset seizures (2.96% of medical complications), seven increased seizure frequency (3.45%), 33 infections (16.26%), eight meningitis (3.94%), and 16 cerebrospinal fluid leaks (7.88%). Delivery system complications, including 75 catheter and pump complications, were also reported. CONCLUSION: Despite the risk of complications, ITB has a significant impact on the reduction of spasticity. A small but statistically significant improvement in motor function was also noted in a group of patients.

Effectiveness of simple and basic home-based exercise programs including pediatric massage executed by caregivers at their homes in the management of children with spastic cerebral palsy: A randomized controlled trial.

PURPOSE: This study aimed to assess the effectiveness of simple and basic home-based exercise programs (HEPs), including pediatric massage (PM), executed by caregivers at their homes in the management of children with spastic cerebral palsy (CP). METHODS: Sixty-eight children with spastic CP (diplegia) aged 4-12 years were randomly assigned to PM and HEP groups for a randomized controlled trial continuing from November 01, 2021 to June 2022. Parents provided home-based exercises to both groups, five times a week for 12 weeks. However, the PM group was additionally provided with PM. Modified Ashworth Scale (MAS), Gross Motor Function Measure (GMFM-88) and Gross Motor Function Classification System (GMFCS) were used for evaluation of spasticity and gross motor activity at baseline as well as after six and 12 weeks of intervention. Comparative analysis of data was carried out with SPSS-20. RESULTS: Mean age in HEP and PM groups was 6.65±2.12 and 7.09±2.22 years respectively. Data revealed homogeneity of both groups at the beginning of study. The PM group showed a statistically significant decrease in MAS scores after six and 12 weeks of intervention (p < 0.05) when compared with the HEP group, but similar changes did not happen in GMFM scores and GMFCS levels. However, comparative analysis revealed statistically significant change in GMFM scores and GMFCS levels (p < 0.05) when compared from baseline to 12 weeks of intervention in both groups. CONCLUSION: PM along with HEPs can be used effectively to reduce spasticity and to improve gross motor ability if performed for a period of at least six and 12 weeks respectively. In conjunction with HEPs, PM has better outcomes in the management of tone and movement disorders of spastic CP than HEPs alone.

Using the gross motor function measure evolution ratio to compare different dosage of hyperbaric treatment with conventional therapies in children with cerebral palsy - could it end the controversy?

The Gross Motor Function Measure is used in most studies measuring gross motor function in children with cerebral palsy. In many studies, including those evaluating the effect of hyperbaric treatment, the Gross Motor Function Measure variations were potentially misinterpreted because of the lack of control groups. The Gross Motor Function Measure Evolution Ratio (GMFMER) uses historical data from the Gross Motor Function Classification System curves and allows to re-analyze previous published studies which used the Gross Motor Function Measure by considering the natural expected evolution of the Gross Motor Function Measure. As the GMFMER is defined by the ratio between the recorded Gross Motor Function Measure score increase and the expected increase attributed to natural evolution during the duration of the study (natural evolution yields a GMFMER of 1), it becomes easy to assess and compare the efficacy of different treatments. Objective: The objective of this study is to revisit studies done with different dosage of hyperbaric treatment and to compare the GMFMER measured in these studies with those assessing the effects of various recommended treatments in children with cerebral palsy. Methods: PubMed Searches were conducted to included studies that used the Gross Motor Function Measure to evaluate the effect of physical therapy, selective dorsal rhizotomy, botulinum toxin injection, hippotherapy, stem cell, or hyperbaric treatment. The GMFMER were computed for each group of the included studies. Results: Forty-four studies were included, counting 4 studies evaluating the effects of various dosage of hyperbaric treatment in children with cerebral palsy. Since some studies had several arms, the GMFMER has been computed for 69 groups. The average GMFMER for the groups receiving less than 2 h/week of physical therapy was 2.5 ± 1.8 whereas in context of very intensive physical therapy it increased to 10.3 ± 6.1. The GMFMER of stem cell, selective dorsal rhizotomy, hippotherapy, and botulinum toxin treatment was, 6.0 ± 5.9, 6.5 ± 2.0, 13.3 ± 0.6, and 5.0 ± 2.9, respectively. The GMFMER of the groups of children receiving hyperbaric treatment were 28.1 ± 13.0 for hyperbaric oxygen therapy and 29.8 ± 6.8 for hyperbaric air. Conclusion: The analysis of the included studies with the GMFMER showed that hyperbaric treatment can result in progress of gross motor function more than other recognized treatments in children with cerebral palsy.

Psychostimulant Medications for Physical Function and Spasticity in Children With Cerebral Palsy: Protocol for a Randomized Controlled Trial.

BACKGROUND: Cerebral palsy (CP) is a prevalent nonprogressive disorder that leads to impaired movement (ie, spasticity), posture, and balance, which affects functions such as walking and upper extremity tasks. Current medical treatments show efficacy in improving motor performance but have considerable side effects. Emerging off-label use of central nervous system (CNS) medications for improving motor performance has shown promising results in children with CP and other populations. OBJECTIVE: The aim of this study is to describe a protocol for a pilot randomized controlled trial (RCT) to examine the safety, tolerability, and efficacy of methylphenidate (MPH) and modafinil on spasticity and motor performance in children with CP. METHODS: This will be a protocol study for a pilot, triple-masked, placebo-controlled RCT (a class I trial following the American Academy of Neurology criteria) with blinded patients, outcome assessors, and intervention delivery team. Eligible children should be diagnosed with CP levels I or II based on the Gross Motor Function Classification System and be aged between 7 and 12 years. Thirty-six children with CP will be randomized into 3 groups to receive (1) MPH (2.5 mg of MPH + 100 mg placebo), (2) modafinil (100 mg modafinil + 2.5 mg placebo), or (3) a placebo (2.5 mg placebo + 100 mg placebo), in addition to physical therapy for 12 weeks. Primary outcomes include the Gross Motor Function Measure-66 and the Modified Ashworth Scale. Secondary outcomes include the Timed Up and Go test, 5 Time Sit to Stand test, Modified Clinical Test for Sensory Interaction of Balance, and 10-Meter Walk Test. RESULTS: The protocol has been accepted by Kuwait University (VDR/EC-225) and the Ministry of Health of Kuwait (2022/2157). The inclusion of participants will start in June 2024. CONCLUSIONS: The combination of CNS stimulant medications and controlling for rehabilitation has not been studied yet. The findings of this study may determine if using CNS stimulant medications is beneficial for the reduction of spasticity and improvement of physical function in children with spastic CP. TRIAL REGISTRATION: ClinicalTrials.gov NCT05675098; https://clinicaltrials.gov/study/NCT05675098. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/53728.

Increased Upper Extremity Muscle Mass in Ambulatory Children with Cerebral Palsy.

AIM: To compare muscle mass in the upper and lower extremities between ambulatory children with cerebral palsy (CP) and typically developing (TD) children. MATERIALS AND METHODS: A total of 21 children aged 2 to 12 years with CP and a Gross Motor Function Classification System (GMFCS) level of I, II, or III were matched with 21 TD children for age, sex, and body mass index. The lean body mass (LBM) of each extremity was calculated from whole-body dual-energy X-ray absorptiometry. RESULTS: The LBM of the upper extremities was greater in children with CP compared to TD children, and the difference was significant in the GMFCS level II group (1340.6 g vs. 1004.2 g, p = 0.027). There was no significant difference in the LBM of the lower extremities between the CP and TD groups (p = 0.190). The ratio of lower extremity LBM to total extremity LBM was lower in children with CP, while the ratio of upper extremity LBM to total extremity LBM was higher in children with CP (73.2% vs. 78.5% [p < 0.001] and 26.7% vs. 21.5% [p < 0.001], respectively). CONCLUSIONS: Ambulatory children with CP, especially in the GMFCS level II group, exhibit greater muscle mass in the upper extremities compared to TD children.

Prevalence of Sensory Processing Deficits in Children with Spastic Cerebral Palsy - An Indian Caregiver's Perspective.

This study aims to analyze the prevalence and patterns of sensory processing deficits (SPD) in Indian children with spastic cerebral palsy (CP) using child sensory profile-2 (CSP-2) caregiver questionnaire. The authors surveyed 230 caregivers of children aged 3 to 14 y with spastic CP, using CSP-2. The difference in prevalence and distribution of SPDs among the CP subtypes and Gross Motor Function Classification System (GMFCS) levels was done. Overall prevalence of "Definite" (>2 SD) SPDs was 83%. Forty-seven percent had definite SPDs in more than one sensory subsection. Prevalence of definite SPDs was similar among the spastic CP subtypes. "Conduct" domain had more affection among hemiplegics and quadriplegics. "Avoiding" pattern was observed more in quadriplegics and "Seeking" pattern was observed less in diplegics. Severe GMFCS levels had more definite sensory processing deficits. SPDs are highly prevalent in children with spastic CP with unique patterns of affection among the spastic CP subtypes.

Efectividad de la Terapia Acuática en la Función Motora Gruesa en Población Infantojuvenil con Parálisis Cerebral. Una Revisión Narrativa / Effectiveness of Aquatic Therapy on Gross Motor Function in Children and Young People with Cerebral Palsy. A Narrative Review

Introducción. La parálisis cerebral (PC) es una de las principales causas de discapacidad en la población infantil, afectando diversas áreas del desarrollo como la función motora gruesa; equilibrio y marcha. Hay evidencia de los beneficios de la terapia acuática y de cómo puede complementar la rehabilitación. Objetivo. Describir la efectividad de las intervenciones acuáticas en personas con PC, determinar mejoras en la función motora gruesa uso de métodos, protocolos y dosificación. Métodos. Se analizaron 9 estudios aleatorizados controlados desde el 2012 a la fecha, seleccionados por un experto y cuyos sujetos tenían PC espástica, Gross Motor Function Classification System (GMFCS) I a IV, entre los 2 y 20 años. Post intervención acuática se reportan mejoras significativas en el promedio de los ítems medidos por Gross motor function measure (GMFM). De los métodos que contribuyeron a mejoras se encuentra Halliwick y ejercicios acuáticos sin un programa específico. Resultados. Se obtuvieron mejoras de 35 a 100 minutos, y de 12 a 30 sesiones en total. No se logra concluir el tipo de terapia más efectiva, ya que las medidas de resultado y las características de los sujetos eran diversas. Conclusión. Una dosificación mínima de 2 veces por semana, 35 minutos de intervención en un total de 16 sesiones (9,3 horas en total) pareciera mejorar la función motora gruesa, cuyos resultados son transferibles a las actividades en tierra inmediatamente, sin embargo, no se obtiene información si se mantienen a mediano o largo plazo.

Background. Cerebral palsy (CP) is one of the main causes of disability in the child population, affecting various areas of development such as gross motor function; balance and gait. There is evidence of the benefits of aquatic therapy and how it can complement rehabilitation. Objective. to describe the effectiveness of aquatic interventions in people with CP, to determine improvements in gross motor function using methods, protocols, and dosage. Methods. Nine randomized controlled studies were analyzed from 2012 to date, selected by an expert and whose subjects had spastic CP, Gross Motor Function Classification System (GMFCS) I to IV, between 2 and 20 years of age. Results. After the aquatic intervention, significant improvements were reported in the average of the Gross motor function measure (GMFM) items measured. Of the methods that contributed to improvements, there is Halliwick and aquatic exercises without a specific program. Results. Improvements were obtained from 35 to 100 minutes, and from 12 to 30 sessions in total. It is not possible to conclude the most effective type of therapy, since the outcome measures and the characteristics of the subjects were diverse. Conclusion. A minimum dosage of 2 times per week, 35 minutes of intervention in a total of 16 sessions (9.3 hours in total) seems to improve gross motor function, the results of which are immediately transferable to activities on land, however, it is not obtains information if they are maintained in the medium or long term.

Psychometric Evaluation of the Persian Version of the Functional Mobility Scale: Assessing Validity and Reliability.

AIM: This study aimed to assess the content, concurrent validity, test-retest, and intra-rater reliability of the Persian version of the Functional Mobility Scale (FMS) for evaluating functional mobility in children and adolescents with cerebral palsy (CP). METHODS: Following international standards for measurement translation, we developed a Persian version of the FMS. A total of 160 participants took part in this study. Concurrent validity was assessed using Spearman's coefficient to correlate with the Gross Motor Function Classification System (GMFCS). Test-retest (n = 30) and intra-rater (n = 30) reliability of the FMS were also examined by Cohen's weighted kappa coefficient. RESULTS: Concurrent validity ranged from -0.912 to -0.941 for children and -0.912 to -0.936 for adolescents. Test-retest ranged from 0.902 to 1. Intra-rater ranged from 0.933 to 0.987. CONCLUSION: The Persian version of the FMS demonstrates very strong validity and almost perfect reliability for assessing and classifying functional mobility in children and adolescents with CP. These findings suggest that this tool could be a useful addition to clinical practice and research for the Persian-speaking population.

The effect of intrathecal recombinant arylsulfatase A therapy on structural brain magnetic resonance imaging in children with metachromatic leukodystrophy.

This study aimed to evaluate the effect of intrathecal (IT) recombinant human arylsulfatase A (rhASA) on magnetic resonance imaging (MRI)-assessed brain tissue changes in children with metachromatic leukodystrophy (MLD). In total, 510 MRI scans were collected from 12 intravenous (IV) rhASA-treated children with MLD, 24 IT rhASA-treated children with MLD, 32 children with untreated MLD, and 156 normally developing children. Linear mixed models were fitted to analyze the time courses of gray matter (GM) volume and fractional anisotropy (FA) in the posterior limb of the internal capsule. Time courses for demyelination load and FA in the centrum semiovale were visualized using locally estimated scatterplot smoothing regression curves. All assessed imaging parameters demonstrated structural evidence of neurological deterioration in children with MLD. GM volume was significantly lower at follow-up (median duration, 104 weeks) in IV rhASA-treated versus IT rhASA-treated children. GM volume decline over time was steeper in children receiving low-dose (10 or 30 mg) versus high-dose (100 mg) IT rhASA. Similar effects were observed for demyelination. FA in the posterior limb of the internal capsule showed a higher trend over time in IT rhASA-treated versus children with untreated MLD, but FA parameters were not different between children receiving the low doses versus those receiving the high dose. GM volume in IT rhASA-treated children showed a strong positive correlation with 88-item Gross Motor Function Measure score over time. In some children with MLD, IT administration of high-dose rhASA may delay neurological deterioration (assessed using MRI), offering potential therapeutic benefit.

Validation of a modified version of the gross motor function measure in PPPR5D related neurodevelopmental disorder.

BACKGROUND: Protein phosphatase 2 regulatory subunit B' Delta (PPP2R5D)-related neurodevelopmental disorder is a rare genetic condition caused by pathogenic variants in the PPP2R5D gene. Clinical signs include hypotonia, gross motor delay, intellectual disability (ID), epilepsy, speech delays, and abnormal gait among other impairments. As this disorder was recognized within the last decade, there are only 103 people published diagnoses to date. A thorough understanding of the motor manifestations of this disorder has not yet been established. Knowledge of the natural history of PPP2R5D related neurodevelopmental disorder will lead to improved standard of care treatments as well as serve as a baseline foundation for future clinical trials. Appropriate outcome measures are necessary for use in clinical trials to uniformly measure function and monitor potential for change. The aim of this study was to validate the gross motor function measure (GMFM) in children and adults with PPP2R5D-related neurodevelopmental disorder in order to better characterize the disorder. RESULTS: Thirty-eight individuals with PPP2R5D pathogenic variants, median age 8.0 years (range 1-27) were evaluated. Gross motor, upper limb and ambulatory function were assessed using the GMFM-66, six-minute walk test (6MWT), 10-meter walk run (10MWR), timed up and go (TUG), and revised upper limb module (RULM). The pediatric disability inventory computer adapted test (PEDI-CAT) captured caregiver reported assessment. Median GMFM-66 score was 60.6 (SD = 17.3, range 21.1-96.0). There were strong associations between the GMFM-66 and related mobility measures, 10MWR (rs = -0.733; p < 0.001), TUG (rs= -0.747; p = 0.003), 6MWT (r = 0.633; p = 0.006), RULM (r = 0.763; p < 0.001), PEDICAT-mobility (r = 0.855; p < 0.001), and daily activities (r = 0.822; p < 0.001) domains. CONCLUSIONS: The GMFM is a valid measure for characterizing motor function in individuals with PPP2R5D related neurodevelopmental disorder. The GMFM-66 had strong associations with the RULM and timed function tests which characterized gross motor, upper limb and ambulatory function demonstrating concurrent validity. The GMFM-66 was also able to differentiate between functional levels in PPP2R5D related neurodevelopmental disorder demonstrating discriminant validity. Future studies should examine its sensitivity to change over time, ability to identify sub-phenotypes, and suitability as an outcome measure in future clinical trials in individuals with PPP2R5D variants.

The Effects of Family Functioning on Gross Motor Function, Activity, and Participation in Children with Cerebral Palsy.

Objectives: The present study aimed to investigate whether family functioning (FF) could impact gross motor function, activity, and participation in children with cerebral palsy (CP). Materials & Methods: Sixty-seven children with spastic diplegic CP who were admitted to the Special Education and Rehabilitation Clinic were included in the study. The guidelines of the American Academy of Neurology were followed for the diagnosis of spastic diplegia. The type of home where the family lives, the family's average income, the child's age, gender, and number of siblings, and the age and educational level of the child's primary caregiver were recorded. The gross motor function capacity of children with CP was assessed with the Gross Motor Function Classification System (GMFCS). The Pediatric Evaluation of Disability Inventory (PEDI) was used to evaluate activity and participation performance. Results: The children living in detached houses had statistically higher PEDI mobility levels than those living in apartments (p < 0.05). PEDI's social function and self-care levels were higher in 12 to 18-year-old children with two siblings (p < 0.05). The age and educational status of the primary caregiver were found to have an important impact on the PEDI scores. According to the results, social function and self-care levels were higher in children whose primary caregivers were 30 to 65 years old and had high levels of education above high school (p < 0.05 The effects of family income and gender on PEDI scores were statistically non-significant (p˃ 0.05). Variables related to family functioning had no statistically significant effect on GMFCS scores (p˃ 0.05). Conclusion: These factors can enable healthcare providers to collaborate with the families to develop more comprehensive intervention plans emphasizing family strengths and supporting their needs.

Longitudinal assessment of brain lesions in children with cerebral palsy and association with motor functioning.

BACKGROUND: The semi-quantitative scale of structural brain Magnetic Resonance Imaging (sqMRI) is a valid and reliable measure of brain lesion extent in children with cerebral palsy (CP) >3-years. This system scores lesion burden for each major brain region. The sum of the scores gives a global score ranging from 0 to 48. PURPOSE: To investigate how sqMRI scores changed from infancy to school-age, and whether these were associated with lesion load, age at first assessment, and gross motor function and its changes. MATERIALS AND METHODS: Twenty-eight children with CP underwent MRI and motor (Gross Motor Function Measure-66; GMFM-66) assessments when <40-months and again when 8-12-years. We investigated whether (i) toddler/preschool-age sqMRI scores (Time 1) reflected school-age sqMRI scores (Time 2); (ii) temporal changes in sqMRI scores (Time 1-Time 2 difference) were related to the child's age at Time 1 and lesion extent; (iii) early or later sqMRI scores were associated with motor functioning; (iv) sqMRI scores' longitudinal changes were associated with motor changes. RESULTS: Except for the corticosubcortical (grey-matter only) layers, sqMRI scores were significantly higher ('higher lesion load') at Time 1 than at Time 2. Age at Time 1 was not associated with temporal changes in global sqMRI scores. Higher lesion load at Time 2, but not at Time 1, was associated with smaller temporal changes in the global sqMRI score. The sqMRI scores were associated with concurrent, but not future or past motor GMFM-66 scores. Longitudinal changes in sqMRI scores were not associated with longitudinal changes in motor GMFM-66 scores. CONCLUSION: sqMRI scores of brain lesion extent at school-age are lower and a better indication of later-life motor functioning than very early life sqMRI scores. It may be best to interpret MRI white matter lesions with caution in very early life due to possible changes in lesion appearance and the unpredictable role of functional plasticity.

Efficacy and safety of pegzilarginase in arginase 1 deficiency (PEACE): a phase 3, randomized, double-blind, placebo-controlled, multi-centre trial.

Background: Arginase 1 Deficiency (ARG1-D) is a rare debilitating, progressive, inherited, metabolic disease characterized by marked increases in plasma arginine (pArg) and its metabolites, with increased morbidity, substantial reductions in quality of life, and premature mortality. Effective treatments that can lower arginine and improve clinical outcomes is currently lacking. Pegzilarginase is a novel human arginase 1 enzyme therapy. The present trial aimed to demonstrate efficacy of pegzilarginase on pArg and key mobility outcomes. Methods: This Phase 3 randomized, double-blind, placebo-controlled, parallel-group clinical trial (clinicaltrials.govNCT03921541, EudraCT 2018-004837-34), randomized patients with ARG1-D 2:1 to intravenously/subcutaneously once-weekly pegzilarginase or placebo in conjunction with their individualized disease management. It was conducted in 7 countries; United States, United Kingdom, Canada, Austria, France, Germany, Italy. Primary endpoint was change from baseline in pArg after 24 weeks; key secondary endpoints were change from baseline at Week 24 in Gross Motor Function Measure part E (GMFM-E) and 2-min walk test (2MWT). Full Analysis Set was used for the analyses. Findings: From 01 May 2019 to 29 March 2021, 32 patients were enrolled and randomized (pegzilarginase, n = 21; placebo, n = 11). Pegzilarginase lowered geometric mean pArg from 354.0 µmol/L to 86.4 µmol/L at Week 24 vs 464.7 to 426.6 µmol/L for placebo (95% CI: -67.1%, -83.5%; p < 0.0001) and normalized levels in 90.5% of patients (vs 0% with placebo). In addition, clinically relevant functional mobility improvements were demonstrated with pegzilarginase treatment. These effects were sustained long-term through additional 24 weeks of subsequent exposure. Pegzilarginase was well-tolerated, with adverse events being mostly transient and mild/moderate in severity. Interpretation: These results support pegzilarginase as the first potential treatment to normalize pArg in ARG1-D and achieve clinically meaningful improvements in functional mobility. Funding: Aeglea BioTherapeutics.