Protocol for combined N-of-1 trials to assess cerebellar neurostimulation for movement disorders in children and young adults with dyskinetic cerebral palsy.

BACKGROUND: Movement and tone disorders in children and young adults with cerebral palsy are a great source of disability. Deep brain stimulation (DBS) of basal ganglia targets has a major role in the treatment of isolated dystonias, but its efficacy in dyskinetic cerebral palsy (DCP) is lower, due to structural basal ganglia and thalamic damage and lack of improvement of comorbid choreoathetosis and spasticity. The cerebellum is an attractive target for DBS in DCP since it is frequently spared from hypoxic ischemic damage, it has a significant role in dystonia network models, and small studies have shown promise of dentate stimulation in improving CP-related movement and tone disorders. METHODS: Ten children and young adults with DCP and disabling movement disorders with or without spasticity will undergo bilateral DBS in the dorsal dentate nucleus, with the most distal contact ending in the superior cerebellar peduncle. We will implant Medtronic Percept, a bidirectional neurostimulator that can sense and store brain activity and deliver DBS therapy. The efficacy of cerebellar DBS in improving quality of life and motor outcomes will be tested by a series of N-of-1 clinical trials. Each N-of-1 trial will consist of three blocks, each consisting of one month of effective stimulation and one month of sham stimulation in a random order with weekly motor and quality of life scales as primary and secondary outcomes. In addition, we will characterize abnormal patterns of cerebellar oscillatory activity measured by local field potentials from the intracranial electrodes related to clinical assessments and wearable monitors. Pre- and 12-month postoperative volumetric structural and functional MRI and diffusion tensor imaging will be used to identify candidate imaging markers of baseline disease severity and response to DBS. DISCUSSION: Our goal is to test a cerebellar neuromodulation therapy that produces meaningful changes in function and well-being for people with CP, obtain a mechanistic understanding of the underlying brain network disorder, and identify physiological and imaging-based predictors of outcomes useful in planning further studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT06122675, first registered November 7, 2023.

Mapping the Current Research on Mindfulness Interventions for Individuals with Cerebral Palsy: A Scoping Review.

Cerebral palsy (CP) is a chronic neurological disorder that can cause motor and cognitive disabilities. Mindfulness is a form of meditation that has gained attention as a potential therapeutic intervention for improving the health and well-being of patients with CP. Four databases were searched until January 2023. A scoping review was conducted to explore the role of mindfulness in the management of CP by reviewing the available scientific literature. Studies that examined the effects of mindfulness on motor function, communication, and quality of life in patients with CP were analyzed. The gray literature and reference lists of included articles were not identified. The results were presented in numerical and thematic forms. From an initial pool of 30 registered studies, only 3 met the inclusion criteria. These selected studies reported positive effects of mindfulness interventions on communication abilities and stress management in patients with CP. The available evidence suggests that mindfulness may have beneficial effects on motor function, communication, and quality of life in patients with CP. The findings of this review highlight the potential of mindfulness as a complementary therapy for improving the health and well-being of patients with CP.

Potential optimized route for mesenchymal stem cell transplantation in a rat model of cerebral palsy.

Cerebral palsy (CP) is a movement and posture disorder that affects over 50 million people worldwide. Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation has emerged as an attractive therapeutic strategy for CP. The administration route appears to be crucial for hUC-MSC to provide adequate neuroprotection. Wistar rats were given hypoxia-ischemia to make the CP model on postnatal day 5. On postnatal day 21, DiR-labeled hUC-MSC were transplanted into the CP rats by intravenous, intrathecal, and lateral ventricle for cell tracking. Uninfused CP rats served as the negative control. The motor behavioral and pathological alteration was analyzed 11, 25, and 39 days after transplantation to assess motor function, immune inflammation, neurotrophy, and endogenous repair. In vivo imaging tracking techniques revealed that intravenous infusion resulted in fewer transplanted cells in the target brain than intrathecal and lateral ventricle infusion (p＜0.05). Three different routes of hUC-MSC infusion improved the motor function of CP rats (p＜0.05). At 11 days post-infusion, intrathecal infusion outperformed intravenous with a significant neurotrophic and oligodendrocyte maturation effect (p＜0.05). Intrathecal infusion equaled lateral ventricle infusion after 25 days. At 39 days post-infusion, lateral ventricle infusion exceeded intravenous and intrathecal infusion with a significant immunosuppressive effect (p＜0.05). Considering the improved effect and less trauma shown early in the intrathecal infusion, repeated intrathecal administration may ultimately lead to the greatest benefit.

Transition from child to adult services for young people with cerebral palsy in Ireland: Influencing factors at multiple ecological levels.

AIM: To explore the factors that influence the process of transitioning from child to adult services in Ireland among young people with cerebral palsy, their parents, and service providers. METHOD: This study followed a qualitative descriptive approach. Semi-structured interviews were conducted with 54 participants, including young people with cerebral palsy aged 16 to 22 years (n = 13), their parents (n = 14), and service providers (n = 27). Data were analysed using the Framework Method. Findings were categorized using an ecological model across four levels: individual, microsystem, mesosystem, and exosystem. RESULTS: Limited awareness, preparation, and access to information hindered successful transition. Microsystem factors such as family knowledge, readiness, resilience, and health professional expertise influenced transition experience. Mesosystem factors encompassed provider-family interaction, interprofessional partnerships, and interagency collaboration between child and adult services. Exosystem factors included inadequate availability and distribution of adult services, limited referral options, coordination challenges, absence of transition policies, staffing issues, and funding allocation challenges. INTERPRETATION: Transition is influenced by diverse factors at multiple ecological levels, including interactions within families, between health professionals, and larger systemic factors. Given the complexity of transition, a comprehensive multi-level response is required, taking into account the interactions among individuals, services, and systems.

Individualized orthotic alignment and footwear for balance and mobility in children with bilateral spastic cerebral palsy: A randomized trial.

AIM: To examine whether designed-to-be-rigid ankle-foot orthoses and footwear combinations with individualized alignment and footwear designs (AFO-FC/IAFD) would be more effective than designed-to-be-rigid AFO with non-individualized alignment and footwear designs (AFO-FC/NAFD) in children with cerebral palsy (CP). METHOD: Nineteen children with bilateral spastic CP were randomized to AFO-FC/NAFD (n = 10) or AFO-FC/IAFD (n = 9) groups. Fifteen were male, average age 6 years 11 months (range 4 years 2 months-9 years 11 months), classified in Gross Motor Function Classification System levels II (n = 15) and III (n = 4). The Pediatric Balance Scale (PBS), Gait Outcomes Assessment List (GOAL), Patient-Reported Outcomes Measurement Information System (PROMIS), and Orthotic and Prosthetic Users' Survey (OPUS) measures of satisfaction were collected at baseline and after 3 months' wear. RESULTS: Compared with the AFO-FC/NAFD group, those with AFO-FC/IAFD demonstrated greater change in PBS total scores (mean 12.8 [standard deviation 10.5] vs 3.5 [5.8]; p = 0.03) and GOAL total scores (3.5 [5.8] vs -0.44 [5.5]; p = 0.03). There were no significant changes in OPUS or PROMIS scores. INTERPRETATION: After 3 months, individualized orthosis alignment and footwear designs had a greater positive effect on balance and parent-reported mobility than a non-individualized approach. No effect was documented for the PROMIS and OPUS. Results may inform orthotic management for ambulatory children with bilateral spastic CP. WHAT THIS PAPER ADDS: Balance and parent-reported mobility increased more over time for the ankle-foot orthoses and footwear combinations with individualized alignment and footwear designs (AFO-FC/IAFD) group. Changes in balance over time suggest a therapeutic effect of the AFO-FC/IAFD approach.

Safety and efficacy of non-invasive brain stimulation for the upper extremities in children with cerebral palsy: A systematic review.

AIM: To evaluate available evidence examining safety and efficacy of non-invasive brain stimulation (NIBS) on upper extremity outcomes in children with cerebral palsy (CP). METHOD: We electronically searched 12 sources up to May 2023 using JBI and Cochrane guidelines. Two reviewers selected articles with predetermined eligibility criteria, conducted data extraction, and assessed risk of bias using the Cochrane Risk of Bias criteria. RESULTS: Nineteen studies were included: eight using repetitive transcranial magnetic stimulation (rTMS) and 11 using transcranial direct current stimulation (tDCS). Moderate certainty evidence supports the safety of rTMS and tDCS for children with CP. Very low to moderate certainty evidence suggests that rTMS and tDCS result in little to no difference in upper extremity outcomes. INTERPRETATION: Evidence indicates that NIBS is a safe and feasible intervention to target upper extremity outcomes in children with CP, although it also indicates little to no significant impact on upper extremity outcomes. These findings are discussed in relation to the heterogeneous participants' characteristics and stimulation parameters. Larger studies of high methodological quality are required to inform future research and protocols for NIBS.

The cost of respiratory hospitalizations in children with cerebral palsy.

AIM: To establish the burden of respiratory illness in cerebral palsy (CP) on the Western Australian health care system by quantifying the costs of respiratory hospitalizations in children with CP, compared with non-respiratory hospitalizations. METHOD: A 2-year (2014-2015) retrospective study using linked hospital data (excluding emergency department visits), in a population of children with CP in Western Australia aged 18 years and under (median age at hospitalization 7 years; interquartile range 5-12 years). RESULTS: In 671 individuals (57% male) there were 726 emergency hospitalizations, and 1631 elective hospitalizations. Although there were more elective hospitalizations, emergency hospitalizations were associated with longer stays in hospital, and more days in an intensive care unit, resulting in a higher total cost of emergency hospitalizations than elective hospitalizations (total costs: emergency AU$7 748 718 vs elective AU$6 738 187). 'Respiratory' was the leading cause of emergency hospitalizations, contributing to 36% of all emergency admission costs. For a group of high-cost inpatient users (top 5% of individuals with the highest total inpatient costs) the most common reason for hospitalization was 'respiratory'. Where non-respiratory admissions were complicated by an additional respiratory diagnosis, length of stay was greater. INTERPRETATION: Respiratory hospitalizations in CP are a significant driver of health care costs. In the paediatric group, they are a burden for a subgroup of children with CP. WHAT THIS PAPER ADDS: Respiratory illness is the most costly area for unplanned, emergency hospitalizations for children and young people with cerebral palsy. The top 5% of individuals with the highest total inpatient costs account for a disproportionate amount of health care costs.

Functional electrical stimulation during walking in children with unilateral spastic cerebral palsy: A randomized cross-over trial.

AIM: To study if functional electrical stimulation (FES) of the peroneal nerve, which activates dorsiflexion, can improve body functions, activities, and participation and could be an effective alternative treatment in individuals with unilateral spastic cerebral palsy (CP). METHOD: A randomized cross-over trial was performed in 25 children with unilateral spastic CP (classified in Gross Motor Function Classification System levels I and II) aged 4 to 18 years (median age at inclusion 9 years 8 months, interquartile range = 7 years-13 years 8 months), 15 patients were male. The study consisted of two 12-week blocks of treatment, that is, conventional treatment (ankle foot orthosis [AFO] or adapted shoes) and FES, separated by a 6-week washout period. Outcome measures included the Goal Attainment Scale (GAS), the Cerebral Palsy Quality of Life questionnaire, and a three-dimensional gait analysis. RESULTS: Eighteen patients completed the trial. The proportion of GAS goals achieved was not significantly higher in the FES versus the conventional treatment phase (goal 1 p = 0.065; goal 2 p = 1.00). When walking while stimulated with FES, ankle dorsiflexion during mid-swing decreased over time (p = 0.006, average decrease of 4.8° with FES), with a preserved increased ankle range of motion compared to conventional treatment (p < 0.001, mean range of motion with FES +10.1° compared to AFO). No changes were found in the standard physical examination or regarding satisfaction with orthoses and feelings about the ability to dress yourself. In four patients, FES therapy failed; in 12 patients FES therapy continued after the trial. INTERPRETATION: FES is not significantly worse than AFO; however, patient selection is critical, and a testing period and thorough follow-up are needed.

Therapeutic effects of repetitive transcranial magnetic stimulation in patients with cerebral palsy: a systematic review and network meta-analysis.

The purpose of this study was to systematically evaluate the efficacy of repetitive transcranial magnetic stimulation in children with cerebral palsy and to compare the differences in efficacy of different treatment parameters. Computer searches of PubMed, Embase, Cochrane Library, Scopus, Web of Science, China Knowledge Network, Wanfang Data Knowledge Service Platform, Vipshop and China Biomedical Literature Database were conducted to collect randomized controlled trials (RCTs) of TMS to improve function in children with cerebral palsy. The search period was from the establishment of the database to April 2023. Two researchers independently screened the literature and extracted data information, and the risk of bias was assessed for the included studies using the Cochrane Systematic Evaluation Manual 5.1.0. Statistical analysis was performed using RevMan 5.4 and Stata software. A total of 18 studies containing 1675 patients with cerebral palsy were included, and r-TMS did not differ significantly from other treatments in improving language function [MD = 2.80, 95% CI (-1.51, 7.11), Z = 1.27, P = 0.20] after treatment. The results of the reticulated meta-analysis showed the best probability ranking of the effect of three different frequencies of r-TMS on motor function scores in children with cerebral palsy: combined LF-rTMS + HF-rTMS (49.8%) > LF-rTMS (45.6%) > HF-rTMS (4.6%) > conventional rehabilitation (0%). Publication bias showed no significant asymmetry in the inverted funnel plot, but the possibility of publication bias could not be excluded. The results of this study showed that r-TMS was not statistically significant in improving language function in children with cerebral palsy compared to conventional treatment. r-TMS was almost unanimously significantly effective in motor function in children with cerebral palsy according to current literature data, and the combined high- and low-frequency transcranial magnetic therapy was better than low-frequency transcranial magnetic therapy.

Hip displacements and correctable scoliosis were prevalent in children with cerebral palsy registered in a Danish follow-up programme from 2010 to 2020.

AIM: We need a better understanding of non-surgical interventions for hip dislocations and scoliosis. This study estimated the cumulative incidence of problems among children with cerebral palsy and described the type and frequency of therapist-led interventions. METHODS: The study comprised 1482 children (58% male) aged 0-15 years, with a mean age of 3.6 years, who were registered in the Danish Cerebral Palsy Follow-up Programme from 2010 to 2020. We used the Kaplan-Meier estimator to examine the cumulative incidence of hip displacement, hip dislocation, correctable scoliosis and non-correctable scoliosis. The type and frequency of therapist-led interventions are reported descriptively. RESULTS: The cumulative incidence of hip displacement and hip dislocation were 15.8% and 3.5%, respectively, and 39.0% and 13.9% for correctable and non-correctable scoliosis. The most frequently reported type of therapist-led intervention was a joint range of motion exercise. We found that 60.5% with hip displacements and 43.8% with correctable scoliosis used a standing aid. A further 5.4% used a spinal orthosis to prevent deformity and 8.1% for stabilisation. CONCLUSION: Hip displacement and correctable scoliosis were prevalent in children with cerebral palsy, whereas the occurrence of hip dislocations and non-correctable scoliosis was low. The use of assistive aids was low.

Is more always better? Effectiveness of constraint-induced movement therapy in children with high-risk or unilateral cerebral palsy (0-6 years): Systematic review and meta-analysis.

BACKGROUND: While constraint-induced movement therapy is strongly recommended as an intervention for infants with unilateral cerebral palsy, the optimal dosage remains undefined. This systematic review aims to identify the most effective level of intensity of constraint-induced movement therapy to enhance manual function in infants at high risk of asymmetric brain lesions or unilateral cerebral palsy diagnosis. METHODS: This systematic review with meta-analysis encompassed a comprehensive search across four electronic databases to identify articles that met the following criteria: randomised controlled trials, children aged 0-6 with at high risk or with unilateral cerebral palsy, and treatment involving constraint-induced movement therapy for upper limb function. Studies with similar outcomes were pooled by calculating the standardised mean difference score for each subgroup, and subgroups were stratified every 30 h of total intervention dosage (30-60, 61-90, >90 h). Risk of bias was assessed with Cochrane Collaboration's tool. RESULTS: Seventeen studies were included. Meta-analyses revealed significant differences among subgroups. The 30-60 h subgroup showed a weak effect for spontaneous use of the affected upper limb during bimanual performance, grasp function, and parents' perception of how often children use their affected upper limb. Additionally, this subgroup demonstrated a moderate effect for the parents' perception of how effectively children use their affected upper limb. CONCLUSIONS: Using a dosage ranging from 30 to 60 h when applying a constraint-induced movement therapy protocol holds promise as the most age-appropriate and cost-effectiveness approach for improving upper limb functional outcomes and parent's perception.

Virtual Reality and Active Video Game Integration within an Intensive Bimanual Therapy Program for Children with Hemiplegia.

AIMS: To describe the nature of custom and non-custom virtual reality and active video game (VR/AVG) implementation within a Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) intervention program for children with hemiplegia. METHODS: Six children aged 8-11 years participated in a 10-day HABIT-ILE intervention (65 h; 6.5 planned VR/AVG hours). VR/AVG implementation details were recorded daily and summarized with descriptive statistics; active motor engagement was quantified as minutes of active game participation. Post-intervention interviews with interventionists were analyzed with qualitative content analysis. RESULTS: On average, participants received 79% of the planned VR/AVG dosage (314/400 planned minutes, range 214-400 min), of which the per-session active motor engagement average was 68% (27 min, SD 12 min). Participation involved equivalent amounts of custom (49%) and non-custom (51%) VR/AVG system use. Material and verbal adaptations facilitated alignment with HABIT-ILE principles. Interventionists identified type of task (gross versus fine motor), children's perceived motivation, and VR/AVG attributes as factors influencing active motor engagement and alignment with HABIT-ILE principles. CONCLUSIONS: Describing individual and technological challenges of VR/AVG integration within HABIT-ILE can advance knowledge about VR/AVG use in intensive interventions and identify directions for subsequent research.

Effect of constraint-induced movement therapy in reducing severity of mirror movements in children with unilateral spastic cerebral palsy.

To determine the effec t of constraint-induced movement therapy (CIMT ) in improving hand function and reduction in severity of mirror movements in children with unilateral spastic cerebral palsy who have mirror movement disorder. Spastic hemiplegic CP children of either gender, aged 6 to 16 years, with mirror movements of grade 1 and 2 who were able to make a gross grip, were included in this single arm feasibility study. CIMT was provided as an intervention to these children for six hours per day for 15 consecutive week days. Woods and Teuber criteria was applied for the assessment of mirror m oveme nt s. Pre - and po stinte rventi on assess ment results showed that there was improvemen t in the unimanual and bimanual hand func tion in CP-affected children (p<0.05) and reduction in the severity of mirror movements ( p<0 .05). Constra intinduced movement therapy improved hand function and reduced the severity of mirror movements in children with unilateral spastic cerebral palsy.

Sports Activities in Children with Cerebral Palsy: A Narrative Review.

Physical exercise is known to have beneficial effects on psychosocial well-being and cognitive performance. Children with cerebral palsy (CP) showed lower levels of physical activity (PA) than healthy children; this fact, in addition to the basic clinical condition, increased the sedentary habit with a psychological impact and motor impairment of these children. Furthermore, children and adolescents with CP are less committed to sports activities than typically developing children of the same age. The aim of the present narrative review was to increase the amount of knowledge regarding the effectiveness and importance of specific and individualized sports in children with CP. A comprehensive search of MED-LINE and EMBASE databases was performed, including specific search terms such as "cerebral palsy" combined with "sport", "physical activity", and the names of different sports. No publication date limits were set. We included studies with an age range of 0-18 years. The main results pointed out that most of the sports improved motor function, quality of life, and coordination in children and adolescents with CP. Physicians, therapists, and parents should become aware of the benefits of sports activities for this population of patients. Specific sports activities could be included as a usual indication in clinical practice in addition to rehabilitation treatment.

Deep brain stimulation effect in genetic dyskinetic cerebral palsy: The case of ADCY5- related disease.

BACKGROUND: Cerebral Palsy (CP) represents a frequent cause of disability in childhood. Early in life, genetic disorders may present with motor dysfunction and diagnosed as CP. Establishing the primary, genetic etiology allows more accurate prognosis, genetic counselling, and planning for symptomatic interventions in homogeneous etiological groups. Deep brain stimulation (DBS) is recommended in refractory movement disorders, including isolated pediatric dystonias. For dystonia evolving in more complex associations in genetic CP, the effect of DBS is still understudied and currently only sporadically described. OBJECTIVES: To report the effect of DBS applied to the globus pallidus pars interna (GPi) in children with complex movement disorders caused by pathogenic ADCY5 variants, diagnosed as dyskinetic CP previous to genetic diagnostic. METHODS: We conducted a retrospective study on evolution of treatment with DBS in ADCY5-related disease. A standardized proforma including the different type of movement disorders and associated neurological signs was completed at each follow-up time, based on video recordings, as well as functional assessments used in children with CP. RESULTS: Four children (mean of age, 13 ± 2.9 years) received GPi-DBS. The same de novo pathogenic missense variant (c.1252C > T, p.R418W) was identified in three out of four and a splice site variant (c.2088 + 2G > T) in one subject. Developmental delay and overlapping features including axial hypotonia, chorea, dystonic attacks, myoclonus, and cranial dyskinesia were present. The median age at DBS was 9 years and follow-up with DBS, 2.6 years. We identified a pattern of clinical response with early suppression of dystonic attacks, followed by improvement of myoclonus and facial dyskinesia. Effect on chorea was delayed and more limited. Two patients gained notable functional benefit related to sitting, standing, gait, use of upper limbs and speech. CONCLUSION: ADCY5-related disease may benefit from GPi-DBS. The most significant clinical response relates to the early and sustained benefit on dystonic attacks and a variable but still positive response on the other hyperkinetic features. Genetic etiology of CP will contribute to further elucidate genotype-phenotype correlations and to refine DBS indication as network-related symptomatic interventions.

Interventions with an Impact on Cognitive Functions in Cerebral Palsy: a Systematic Review.

This systematic review aimed at investigating those interventions that impact on cognitive functioning in children and adults with cerebral palsy (CP). A systematic database search was conducted and twenty-eight studies suitable for inclusion were identified, of which only nine were randomized controlled trials (RCTs). Among all the studies included, ten were multi-modal (cognitive and physical tasks), eleven physical, five cognitive, and two alternative and augmentative communication interventions. The evidence suggests that multi-modal and physical interventions improve general cognitive functioning. Multi-modal and cognitive interventions have an impact on visual perception. Both interventions, together with physical interventions have an effect on a specific executive function domain (inhibitory control), and only cognitive interventions improved other executive function domains such as working memory. However, no RCT assessed the effects of all executive function domains. Few studies have looked at interventions to improve memory and language, and there is a scarcity of long-term research. Future RCTs must be of higher quality and better account for age and sex differences, as well as the clinical heterogeneity of CP. To date, there is evidence that multi-modal, cognitive or physical interventions have an impact on general cognitive functioning, visual perception and executive functions in children with CP, which may support their cognitive development.The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42020152616.

Long-Term Follow-Up of Pediatric Patients with Dyskinetic Cerebral Palsy and Deep Brain Stimulation.

BACKGROUND: Deep brain stimulation (DBS) has been increasingly used in the management of dyskinetic cerebral palsy (DCP). Data on long-term effects and the safety profile are rare. OBJECTIVES: We assessed the efficacy and safety of pallidal DBS in pediatric patients with DCP. METHODS: The STIM-CP trial was a prospective, single-arm, multicenter study in which patients from the parental trial agreed to be followed-up for up to 36 months. Assessments included motor and non-motor domains. RESULTS: Of the 16 patients included initially, 14 (mean inclusion age 14 years) were assessed. There was a significant change in the (blinded) ratings of the total Dyskinesia Impairment Scale at 36 months. Twelve serious adverse events (possibly) related to treatment were documented. CONCLUSION: DBS significantly improved dyskinesia, but other outcome parameters did not change significantly. Investigations of larger homogeneous cohorts are needed to further ascertain the impact of DBS and guide treatment decisions in DCP. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Umbilical Cord Blood Cell Clearance Post-Infusion in Immune-Competent Children with Cerebral Palsy.

Umbilical cord blood cells have therapeutic potential for neurological disorders, through a paracrine mechanism of action. A greater understanding of the safety and immunological effects of allogeneic donor cord blood cells in the context of a healthy recipient immune system, such as in cerebral palsy, is needed. This study aimed to determine how quickly donor cord blood cells were cleared from the circulation in children with cerebral palsy who received a single intravenous infusion of 12/12 human leucocyte antigen (HLA)-matched sibling cord blood cells. Twelve participants with cerebral palsy aged 2-12 years received cord blood cell infusions as part of a phase I trial of umbilical blood infusion for cerebral palsy. Digital droplet PCR analysis of DNA copy number variants specific to donor and recipient was used to assess donor DNA clearance at five timepoints post-infusion, a surrogate measure of cell clearance. Donor cells were cleared by 3 months post-infusion in 11/12 participants. When detected, donor DNA was at a fraction of 0.01-0.31% of total DNA with no signs of graft-versus-host disease in any participant. The donor DNA clearance times provided by this study have important implications for understanding the safety of allogeneic cord blood cell infusion for cerebral palsy and translational tissue engineering or regenerative medicine research in other disorders.

The assessment and management of voiding dysfunction in adults living with cerebral palsy.

PURPOSE: Improvements in life expectancy have resulted in an increasing number of adults with cerebral palsy, of which over a third will have neurogenic lower urinary tract dysfunction (NLUTD). This review explores urinary dysfunction in adults with cerebral palsy. METHODS: Relevant literature on NLUTD in adults with cerebral palsy was identified using an unrestricted search of PubMed. RESULTS: Urinary incontinence is the most common complaint, often accompanied by frequency and urgency. Special consideration should be given to women and in those with worse motor or cognitive dysfunction as they have been shown to have more severe urologic symptoms. NLUTD can have significant morbidity and impact quality of life. Hospital admission, urinary tract infections, and hydronephrosis are common urologic complications, with poor urinary function associated with decreased quality of life (QOL). Neurogenic detrusor overactivity is the most common urodynamic abnormality, with elevated detrusor leak point pressure and reduced bladder capacity. Detrusor sphincter dyssynergy is present in some patients and maybe secondary to generalized spasticity or incomplete upper motor neuron injury. Elevated bladder capacity is also present in a portion of patients, and becomes particularly relevant in adults as a result of increased spasticity of the urinary sphincter. Conservative management like functional toileting strategies, medications, and incontinence aids are successful in most patients. Medical management with anticholinergics is well described, and frequently the only intervention required, particularly in children. Intermittent clean catheterization has mixed results with this population, as its efficacy is limited by pelvic spasticity and patient factors. Surgical intervention, while often successful, should be restricted to select patients, as it is associated with significant morbidity in this population. CONCLUSION: Management of NLUTD in adults with CP involves conservative management, medications, and in rare cases surgical intervention.

Electrical Stimulation for Children with Cerebral Palsy: A Meta-analysis for Randomized Controlled Trials.

BACKGROUND: Different types of electrical stimulation (ES) showed diverse effects on children with cerebral palsy (CP). Previous studies reported inconsistent results for effects of ES on children with CP. The present study aimed to conduct a meta-analysis to summarize these diverse results. METHODS: We searched for studies exploring effects of ES on children with CP in databases (PubMed and Web of Science) from their inception until December 2022. Standard mean differences (SMDs) and 95% confidence intervals (CIs) were computed using STATA 12.0 software. RESULTS: The meta-analysis included 19 randomized controlled trials (including 265 CP patients in test group and 263 CP patients in corresponding control group). The study showed an increased improvement in gross motor function, walking speed, step length, and daily living activities in ES group compared with corresponding control group with random effects models (gross motor function: SMD = 2.04, 95% CI = 1.43-2.65; walking speed: SMD = 3.71, 95% CI = 1.49-5.92; step length: SMD = 1.89, 95% CI = 0.65-3.13; daily living activities: SMD = 5.18, 95% CI = 3.04-7.31), whereas the study showed no significant difference in change of muscle strength between ES group and the corresponding control group with a random effects model (SMD = 0.42, 95% CI = -0.12 to 0.97). CONCLUSION: The study demonstrated that ES might be used as therapy to improve gross motor function, gait, and daily living activities in children with CP.