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Approximately 5%-10% of elementary school children show delayed development of fine motor skills. To address these problems, detection is required. Current assessment tools are time-consuming, require a trained supervisor, and are not motivating for children. Sensor-augmented toys and machine learning have been presented as possible solutions to address this problem. This study examines whether sensor-augmented toys can be used to assess children's fine motor skills. The objectives were to (1) predict the outcome of the fine motor skill part of the Movement Assessment Battery for Children Second Edition (fine MABC-2) and (2) study the influence of the classification model, game, type of data, and level of difficulty of the game on the prediction. Children in elementary school (n=95, age 7.8 [SD 0.7] years) performed the fine MABC-2 and played 2 games with a sensor-augmented toy called \"Futuro Cube.\" The game \"roadrunner\" focused on speed while the game \"maze\" focused on precision. Each game had several levels of difficulty. While playing, both sensor and game data were collected. Four supervised machine learning classifiers were trained with these data to predict the fine MABC-2 outcome: k-nearest neighbor (KNN), logistic regression (LR), decision tree (DT), and support vector machine (SVM). First, we compared the performances of the games and classifiers. Subsequently, we compared the levels of difficulty and types of data for the classifier and game that performed best on accuracy and F1 score. For all statistical tests, we used α=.05. The highest achieved mean accuracy (0.76) was achieved with the DT classifier that was trained on both sensor and game data obtained from playing the easiest and the hardest level of the roadrunner game. Significant differences in performance were found in the accuracy scores between data obtained from the roadrunner and maze games (DT, P=.03; KNN, P=.01; LR, P=.02; SVM, P=.04). No significant differences in performance were found in the accuracy scores between the best performing classifier and the other 3 classifiers for both the roadrunner game (DT vs KNN, P=.42; DT vs LR, P=.35; DT vs SVM, P=.08) and the maze game (DT vs KNN, P=.15; DT vs LR, P=.62; DT vs SVM, P=.26). The accuracy of only the best performing level of difficulty (combination of the easiest and hardest level) achieved with the DT classifier trained with sensor and game data obtained from the roadrunner game was significantly better than the combination of the easiest and middle level (P=.046). The results of our study show that sensor-augmented toys can efficiently predict the fine MABC-2 scores for children in elementary school. Selecting the game type (focusing on speed or precision) and data type (sensor or game data) is more important for determining the performance than selecting the machine learning classifier or level of difficulty.

Virtual reality is nowadays used to facilitate motor recovery in stroke patients. Most virtual reality studies have involved chronic stroke patients; however, brain plasticity remains good in acute and subacute patients. Most virtual reality systems are only applicable to the proximal upper limbs （arms） because of the limitations of their capture systems. Nevertheless, the functional recovery of an affected hand is most difficult in the case of hemiparesis rehabilitation after a stroke. The recently developed Leap Motion controller can track the fine movements of both hands and fingers. Therefore, the present study explored the effects of a Leap Motion-based virtual reality system on subacute stroke. Twenty-six subacute stroke patients were assigned to an experimental group that received virtual reality training along with conventional occupational rehabilitation, and a control group that only received conventional rehabilitation. The Wolf motor func- tion test （WMFT） was used to assess the motor function of the affected upper limb; functional magnetic resonance imaging was used to measure the cortical activation. After four weeks of treatment, the motor functions of the affected upper limbs were significantly improved in all the patients, with the improvement in the experimental group being significantly better than in the control group. The action perfor- mance time in the WMFT significantly decreased in the experimental group. Furthermore, the activation intensity and the laterality index of the contralateral primary sensorimotor cortex increased in both the experimental and control groups. These results confirmed that Leap Motion-based virtual reality training was a promising and feasible supplementary rehabilitation intervention, could facilitate the recovery of motor functions in subacute stroke patients. The study has been registered in the Chinese Clinical Trial Registry （registration number： ChiCTR-OCH- 12002238）.

Objective: Studies have shown that docosahexaenoic acid (DHA) has a beneficial effect in the treatment of spinal cord injury. A meta-analysis was used to study the effect of DHA on the neurological recovery in the rat spinal cord injury model, and the relationship between the recovery of motor function after spinal cord injury and the time and method of administration and the dose of DHA. Data source: Published studies on the effect of DHA on spinal cord injury animal models from seven databases were searched from their inception to January 2019, including PubMed, MEDLINE, EMBASE, the China National Knowledge Infrastructure, Wanfang, VIP, and SinoMed databases. The search terms included \"spinal cord injury\" \"docosahexaenoic acid\", and \"rats\". Data selection: Studies that evaluated the influence of DHA in rat models of spinal cord injury for locomotor functional recovery were included. The intervention group included any form of DHA treatment and the control group included treatment with normal saline, vehicle solution or no treatment. The Systematic Review Centre for Laboratory animal Experimentation's risk of bias assessment tool was used for the quality assessment of the included studies. Literature inclusion, quality evaluation and data extraction were performed by two researchers. Meta-analysis was then conducted on all studies that met the inclusion criteria. Statistical analysis was performed on the data using RevMan 5.1.2. software. Outcome measures: The primary outcome measure was the score on the Basso, Beattie, and Bresnahan scale. Secondary outcome measures were the sloping plate test, balance beam test, stair test and grid exploration test. Results: A total of 12 related studies were included, 3 of which were of higher quality and the remaining 9 were of lower quality. The highest mean Basso, Beattie, and Bresnahan scale score occurred at 42 days after DHA treatment in spinal cord injury rats. At 21 days after treatment, the mean difference in Basso, Beattie, Bresnahan scores between the DHA group and the control group was the most significant (pooled MD = 4.14; 95% CI = 3.58-4.70; P < 0.00001). In the subgroup analysis, improvement in the Basso, Beattie, and Bresnahan scale score was more significant in rats administered DHA intravenously (pooled MD = 2.74; 95% CI = 1.41-4.07; P < 0.0001) and subcutaneously (pooled MD = 2.99; 95% CI = 2.29-3.69; P < 0.00001) than in the groups administered DHA orally (pooled MD = 3.04; 95% CI = -1.01 to 7.09; P = 0.14). Intravenous injection of DHA at 250 nmol/kg (pooled MD = 2.94; 95% CI = 2.47-3.41; P < 0.00001] and 1000 nmol/kg [pooled MD = 3.60; 95% CI = 2.66-4.54; P < 0.00001) significantly improved the Basso, Beattie, and Bresnahan scale score in rats and promoted the recovery of motor function. Conclusion: DHA can promote motor functional recovery after spinal cord injury in rats. The administration of DHA by intravenous or subcutaneous injection is more effective than oral administration of DHA. Intravenous injection of DHA at doses of 250 nmol/kg or 1000 nmol/kg is beneficial. Because of the small number and the low quality of the included studies, more high-quality research is needed in future to substantiate the results.

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.

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 (r s = −0.733; p < 0.001), TUG (r s = −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.

Background: Cerebral Palsy (CP) is a neurological disorder of movement and posture. Recent studies have shown that Virtual Reality (VR) is a useful and low-cost tool used in treating children and adolescents with cerebral palsy. Nevertheless, there is no substantial evidence supporting that VR therapy can help CP patients, not only as the primary treatment, but as a supplement. Objectives: The present systematic review aimed to investigate the effectiveness of VR intervention programs on the functional capacity of children and adolescents with CP, according to the International Classification of Functioning, Disability and Health (ICF). Methods: A systematic online search was conducted in PubMed, Scopus, and PEDro databases, as well as in the Google Scholar search engine, from inception till September 2022. The methodological quality of included studies was rated with the PEDro scale. Results: Twenty-two randomized-controlled trials were eligible for inclusion. The results indicated that there was a significant improvement after the implementation, of interventional VR programs, in balance and visual perception, while the results were controversial for muscle strength, coordination, gross motor function, gait, upper limb function, independence in activities of Daily Life Activities and participation. Conclusion: Significant balance and visual perception improvements may result from VR programs applied in children and adolescents with CP. Important factors that may influence the results are the functional level of the participants, the sample size, the context in which the therapeutic intervention is carried out (rehabilitation center, home), and the conventional treatments that the VR intervention programs are compared against.

Local inflammation plays a pivotal role in the process of secondary damage after spinal cord injury. We recently reported that acute intravenous application of extracellular vesicles (EVs) secreted by human umbilical cord mesenchymal stromal cells dampen the induction of inflammatory processes following traumatic spinal cord injury. However, systemic application of EVs is associated with delayed delivery to the site of injury and the necessity for high doses to reach therapeutic levels locally. To resolve these two constraints, we injected EVs directly at the lesion site acutely after spinal cord injury. We report here that intralesional application of EVs resulted in a more robust improvement of motor recovery, assessed with the BBB score and sub-score, as compared to the intravenous delivery. Moreover, intralesional application was more potent in reducing inflammation and scarring after spinal cord injury than intravenous administration. Hence, development of EV-based therapy for spinal cord injury should aim at an early application of vesicles close to the lesion.

In an aged society, the deterioration of physical and cognitive functions is prevalent. To motivate the rehabilitation of older persons, an initiative known as “shopping rehabilitation” incorporates shopping as an element of a nudge. The purpose of this study was to clarify motor function changes and cognitive functions of participants during shopping rehabilitation, through a semi-experimental study. We measured changes in the Kihon Checklist score before and after rehabilitation interventions. A paired t-test was used to analyze changes in the overall score of the basic checklist before and after the rehabilitation intervention. In December 2020, 59 participants answered the Kihon Checklist after their shopping rehabilitation intervention. During the 6-month intervention period, the number of participants with a checklist score of 8 or higher was significantly reduced after the intervention (p = 0.050). In the sub-analysis, the score improved significantly for the group with families (p = 0.050). Improvement was observed in the group living alone, but the difference was not significant (p = 0.428). The shopping rehabilitation intervention improved the Kihon Checklist score. Continuous observations and research are necessary to measure the long-term effects of shopping rehabilitation and the mechanisms that foster their maintenance and effects.

Despite extensive neuroimaging research of primary sensory cortices involved in auditory and visual functions, subcortical structures within these domains, such as the inferior and superior colliculi, the medial and lateral geniculate nuclei and the superior olivary complex, are currently understudied with magnetic resonance imaging (MRI) in living humans. This is because a precise localization of these nuclei is hampered by the limited contrast and sensitivity of conventional neuroimaging methods for deep brain nuclei. In this work, we used 7 Tesla multi-modal (T -weighted and diffusion fractional anisotropy) 1.1 mm isotropic resolution MRI to achieve high sensitivity and contrast for single-subject brainstem and thalamic nuclei delineation. After precise coregistration to stereotactic space, we generated an human probabilistic atlas of auditory (medial geniculate nucleus, inferior colliculus, and superior olivary complex) and visual (lateral geniculate nucleus and superior colliculus) subcortical nuclei. We foresee the use of this atlas as a tool to precisely identify the location and shape of auditory/visual deep nuclei in research as well as clinical human studies.

Background: Pingchan granule (PCG) is a traditional Chinese medicine for treating Parkinson’s disease (PD). Objective: This study aimed at evaluating the efficacy and safety of PCG for motor and non-motor symptoms of PD. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 292 participants with mild-to-moderate PD were included and followed for 36 weeks (24 week treatment, 12-week follow-up after intervention), randomly assigned at a 1:1 ratio to receive PCG or placebo. The primary outcomes included the severity of motor symptoms assessed by the Unified Parkinson’s disease Rating Scale (UPDRS) part 3 (UPDRS-III) score and the rate of disease progression assessed by the total UPDRS score. Secondary outcomes included non-motor symptoms assessed using the Scale for Outcomes in Parkinson’s Disease-Autonomic (SCOPA-AUT), Parkinson’s disease Sleep Scale (PDSS), 24-item Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), UPDRS part 2 (UPDRS-II), and 39-item Parkinson’s Disease Questionnaire (PDQ-39) scores. Assessments were done at baseline (T0), 12 weeks (T1), 24 weeks (T2), and 36 weeks (T3). Results: Generalized estimating equation analyses revealed that the PCG group had significantly better improvement in UPDRS-III score at T1, T2, and T3 [time-by-group interaction, T1: β, −0.92 (95% CI, −1.59–−0.25; p = 0.01); T2: β, −2.08 (95% CI, −2.90–−1.27; p < 0.001); T3: β, −4.54 (95% CI, −5.37–−3.71; p < 0.001))]. The PCG group showed a greater decrease (rate of disease change) in the total UPDRS score between T0 and T2 [−2.23 (95% CI, −2.72–−1.73; p < 0.001) points per week vs . −0.21 (95% CI, −0.80–0.39; p = 0.50) points per week in the placebo group, p < 0.001]. Ameliorations of SCOPA-AUT, PDSS, HAM-D, HAM-A, UPDRS-II, and PDQ-39 scores were also observed. Conclusion: PCG had a long-lasting and extensive symptomatic efficacy for both motor and non-motor symptoms of PD with good tolerance. Trial registration: Chinese Clinical Trial Register, ChiCTR-INR-17011949.