Acute psychosocial stress modulates neural and behavioral substrates of cognitive control.

Acute psychosocial stress affects learning, memory, and attention, but the evidence for the influence of stress on the neural processes supporting cognitive control remains mixed. We investigated how acute psychosocial stress influences performance and neural processing during the Go/NoGo task-an established cognitive control task. The experimental group underwent the Trier Social Stress Test (TSST) acute stress induction, whereas the control group completed personality questionnaires. Then, participants completed a functional magnetic resonance imaging (fMRI) Go/NoGo task, with self-report, blood pressure and salivary cortisol measurements of induced stress taken intermittently throughout the experimental session. The TSST was successful in eliciting a stress response, as indicated by significant Stress > Control between-group differences in subjective stress ratings and systolic blood pressure. We did not identify significant differences in cortisol levels, however. The stress induction also impacted subsequent Go/NoGo task performance, with participants who underwent the TSST making fewer commission errors on trials requiring the most inhibitory control (NoGo Green) relative to the control group, suggesting increased vigilance. Univariate analysis of fMRI task-evoked brain activity revealed no differences between stress and control groups for any region. However, using multivariate pattern analysis, stress and control groups were reliably differentiated by activation patterns contrasting the most demanding NoGo trials (i.e., NoGo Green trials) versus baseline in the medial intraparietal area (mIPA, affiliated with the dorsal attention network) and subregions of the cerebellum (affiliated with the default mode network). These results align with prior reports linking the mIPA and the cerebellum to visuomotor coordination, a function central to cognitive control processes underlying goal-directed behavior. This suggests that stressor-induced hypervigilance may produce a facilitative effect on response inhibition which is represented neurally by the activation patterns of cognitive control regions.

Development of GO Move: A Website for Children With Unilateral Cerebral Palsy.

It is unknown if an online tool is wanted by therapists and parents of individuals with unilateral cerebral palsy (UCP) to support implementation of goal-directed home programs, and if wanted, the recommended features for the tool. The objective was to explore the experiences of therapists and parents who have implemented home programs, seek guidance on translating a paper-based home program toolbox into a mobile website, and develop the website. Qualitative descriptive methodology guided data collection using semi-structured interviews and thematic analysis, validated with field notes and member checking. A team science, iterative approach was used to integrate the themes into the development of the mobile website. Five primary themes including recommendations for the functionality, features, content, and naming of the mobile website were identified. Parents and therapists value home programs. Participants provided recommendations regarding content and features, and the GO Move mobile website was developed based on the recommendations.

Development of Go Move: A Website for Children With Unilateral Cerebral PalsyTherapists and parents of children with unilateral cerebral palsy were interviewed to understand their experience of home programs and gain input for creating a mobile website with information on goal setting and implementing home programs. The interviews provided valuable information about the functionality, features, content, and naming of the website. GO Move, a mobile website aimed to provide information on goal setting, activity selection, and tracking of exercises and activities in the home environment for children with unilateral cerebral palsy, was developed based on the information from the interviews.

RAB1A haploinsufficiency phenocopies the 2p14-p15 microdeletion and is associated with impaired neuronal differentiation.

Hereditary spastic parapareses (HSPs) are clinically heterogeneous motor neuron diseases with variable age of onset and severity. Although variants in dozens of genes are implicated in HSPs, much of the genetic basis for pediatric-onset HSP remains unexplained. Here, we re-analyzed clinical exome-sequencing data from siblings with HSP of unknown genetic etiology and identified an inherited nonsense mutation (c.523C>T [p.Arg175Ter]) in the highly conserved RAB1A. The mutation is predicted to produce a truncated protein with an intact RAB GTPase domain but without two C-terminal cysteine residues required for proper subcellular protein localization. Additional RAB1A mutations, including two frameshift mutations and a mosaic missense mutation (c.83T>C [p.Leu28Pro]), were identified in three individuals with similar neurodevelopmental presentations. In rescue experiments, production of the full-length, but not the truncated, RAB1a rescued Golgi structure and cell proliferation in Rab1-depleted cells. In contrast, the missense-variant RAB1a disrupted Golgi structure despite intact Rab1 expression, suggesting a dominant-negative function of the mosaic missense mutation. Knock-down of RAB1A in cultured human embryonic stem cell-derived neurons resulted in impaired neuronal arborization. Finally, RAB1A is located within the 2p14-p15 microdeletion syndrome locus. The similar clinical presentations of individuals with RAB1A loss-of-function mutations and the 2p14-p15 microdeletion syndrome implicate loss of RAB1A in the pathogenesis of neurodevelopmental manifestations of this microdeletion syndrome. Our study identifies a RAB1A-related neurocognitive disorder with speech and motor delay, demonstrates an essential role for RAB1a in neuronal differentiation, and implicates RAB1A in the etiology of the neurodevelopmental sequelae associated with the 2p14-p15 microdeletion syndrome.

Characterizing the mechanisms of social connection.

Understanding how individuals form and maintain strong social networks has emerged as a significant public health priority as a result of the increased focus on the epidemic of loneliness and the myriad protective benefits conferred by social connection. In this review, we highlight the psychological and neural mechanisms that enable us to connect with others, which in turn help buffer against the consequences of stress and isolation. Central to this process is the experience of rewards derived from positive social interactions, which encourage the sharing of perspectives and preferences that unite individuals. Sharing affective states with others helps us to align our understanding of the world with another's, thereby continuing to reinforce bonds and strengthen relationships. These psychological processes depend on neural systems supporting reward and social cognitive function. Lastly, we also consider limitations associated with pursuing healthy social connections and outline potential avenues of future research.

Testing the efficacy of real-time fMRI neurofeedback for training people who smoke daily to upregulate neural responses to nondrug rewards.

Although the use of nondrug rewards (e.g., money) to facilitate smoking cessation is widespread, recent research has found that such rewards may be least effective when people who smoke cigarettes are tempted to do so. Specifically, among people who smoke, the neural response to nondrug rewards appears blunted when access to cigarettes is anticipated, and this blunting is linked to a decrease in willingness to refrain from smoking to earn a monetary incentive. Accordingly, methods to enhance the value of nondrug rewards may be theoretically and clinically important. The current proof-of-concept study tested if real-time fMRI neurofeedback training augments the ability to upregulate responses in reward-related brain areas relative to a no-feedback control condition in people who smoke. Adults (n = 44, age range = 20-44) who reported smoking >5 cigarettes per day completed the study. Those in the intervention group (n = 22, 5 females) were trained to upregulate brain responses using feedback of ongoing striatal activity (i.e., a dynamic "thermometer" that reflected ongoing changes of fMRI signal intensity in the striatum) in a single neurofeedback session with three training runs. The control group (n = 22, 5 females) underwent a nearly identical procedure but received no neurofeedback. Those who received neurofeedback training demonstrated significantly greater increases in striatal BOLD activation while attempting to think about something rewarding compared to controls, but this effect was present only during the first training run. Future neurofeedback research with those who smoke should explore how to make neurofeedback training more effective for the self-regulation of reward-related brain activities.

Social feedback promotes positive social sharing, trust, and closeness.

Positive social sharing is an interpersonal emotion regulation strategy that enhances positive affect and social belonging, particularly when met with positive social feedback. Despite the ubiquity of positive social sharing both in person and online, what drives this behavior is not well understood. We hypothesized that positive social feedback serves as a reward that reinforces sharing behavior and strengthens social bonds. Participants made trial-by-trial choices about whether to share social media photos with peers who returned positive ("likes") or negative ("dislikes") feedback. Unbeknownst to participants, peer conditions were manipulated to yield varying amounts of positive and negative feedback. Social bonding was subsequently measured using a trust game and subjective closeness ratings. Participants shared more with peers who provided greater rates of positive feedback. This effect generalized to trust decisions and subjective feelings of closeness and varied individually as a function of interpersonal emotion regulation in daily life. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Goal Attainment after Treatment with Abobotulinumtoxina and a Tailored Home Therapy Programme in Children with Upper Limb Spasticity: Descriptive, Exploratory Analysis of a Large Randomized, Controlled Study

OBJECTIVE: This exploratory analysis of a large, randomized, double-blind study (NCT02106351) describes the effect of treatment with abobotulinumtoxinA followed by a tailored home exercises therapy programme in enabling children with upper limb spasticity due to cerebral palsy to achieve their functional goals using goal attainment scaling (GAS). METHODS: Children with cerebral palsy and spasticity in ≥ 1 upper limb received up to 4 injection cycles of abobotulinumtoxinA (2 U/kg (cycle 1 only), 8U/kg and 16U/kg) into the elbow and wrist flexors and other upper limb muscles selected to support individual treatment goals. Children followed a home exercises therapy programme, which included stretches and exercises specifically chosen to facilitate goal achievement and engagement in activities. RESULTS: For cycle 1, most children had active function goals set as their primary goal (69.7% vs 19.2% passive function goals). GAS T- scores and goal responder rates at week 16 indicated that most types of primary goal were achieved at least as expected during cycle 1 (all groups). Primary goal GAS T-scores were generally maintained for the first 3 abobotulinumtoxinA treatment cycles. CONCLUSION: Most children with upper limb spasticity treated with repeat cycles of abobotulinumtoxinA supported by an individualized home exercises therapy programme achieved their functional goals.

Control preference persists with age.

The opportunity to exert control in one's environment is desirable, and individuals are willing to seek out control, even at a financial cost. Additionally, control-related activation of reward regions in the brain and the positive affect associated with the opportunity to exert control suggest that control is rewarding. The present study explores whether there are age-related differences in the preference for control. Older and younger adults chose whether to maintain control and play a guessing game themselves or to cede this control to the computer. Maintaining and ceding control were associated with different amounts of monetary reward that could be banked upon a successful guess. This required participants to weigh the value associated with control compared to monetary rewards. We found that older adults preferred control and traded monetary reward for control, similar to younger adults. The results suggest that the preference for exerting control may be preserved across age. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Delineation of a novel neurodevelopmental syndrome associated with PAX5 haploinsufficiency.

PAX5 is a transcription factor associated with abnormal posterior midbrain and cerebellum development in mice. PAX5 is highly loss-of-function intolerant and missense constrained, and has been identified as a candidate gene for autism spectrum disorder (ASD). We describe 16 individuals from 12 families who carry deletions involving PAX5 and surrounding genes, de novo frameshift variants that are likely to trigger nonsense-mediated mRNA decay, a rare stop-gain variant, or missense variants that affect conserved amino acid residues. Four of these individuals were published previously but without detailed clinical descriptions. All these individuals have been diagnosed with one or more neurodevelopmental phenotypes including delayed developmental milestones (DD), intellectual disability (ID), and/or ASD. Seizures were documented in four individuals. No recurrent patterns of brain magnetic resonance imaging (MRI) findings, structural birth defects, or dysmorphic features were observed. Our findings suggest that PAX5 haploinsufficiency causes a neurodevelopmental disorder whose cardinal features include DD, variable ID, and/or ASD.

The Observational Gait Scale Can Help Determine the GMFCS Level in Children With Cerebral Palsy.

PURPOSE: To evaluate the association between the Observational Gait Scale (OGS) and the Gross Motor Function Classification System (GMFCS) in walking children with cerebral palsy (CP). METHODS: The charts of 512 children with CP GMFCS levels I to IV were reviewed for the OGS score and GMFCS level at their initial visit. RESULTS: The OGS score decreased with increasing GMFCS levels. The average OGS for GMFCS level I was 13.1 (2.8), level II was 11.3 (2.7), level III was 7.7 (2.7), and level IV was 6.1 (2.0). A significant negative relationship was seen between the OGS and the GMFCS. In particular, each GMFCS level was different across all levels in a pairwise comparison. In addition, multivariate modeling analysis confirmed that the association between the OGS and the GMFCS was still valid, after adjusting for age and gender. CONCLUSIONS: The OGS is a quick tool to rate gait and help confirm a child's GMFCS level.

Retrospective analysis of a clinical exome sequencing cohort reveals the mutational spectrum and identifies candidate disease-associated loci for BAFopathies.

PURPOSE: BRG1/BRM-associated factor (BAF) complex is a chromatin remodeling complex that plays a critical role in gene regulation. Defects in the genes encoding BAF subunits lead to BAFopathies, a group of neurodevelopmental disorders with extensive locus and phenotypic heterogeneity. METHODS: We retrospectively analyzed data from 16,243 patients referred for clinical exome sequencing (ES) with a focus on the BAF complex. We applied a genotype-first approach, combining predicted genic constraints to propose candidate BAFopathy genes. RESULTS: We identified 127 patients carrying pathogenic variants, likely pathogenic variants, or de novo variants of unknown clinical significance in 11 known BAFopathy genes. Those include 34 patients molecularly diagnosed using ES reanalysis with new gene-disease evidence (n = 21) or variant reclassifications in known BAFopathy genes (n = 13). We also identified de novo or predicted loss-of-function variants in 4 candidate BAFopathy genes, including ACTL6A, BICRA (implicated in Coffin-Siris syndrome during this study), PBRM1, and SMARCC1. CONCLUSION: We report the mutational spectrum of BAFopathies in an ES cohort. A genotype-driven and pathway-based reanalysis of ES data identified new evidence for candidate genes involved in BAFopathies. Further mechanistic and phenotypic characterization of additional patients are warranted to confirm their roles in human disease and to delineate their associated phenotypic spectrums.

Finding positive meaning in memories of negative events adaptively updates memory.

Finding positive meaning in past negative memories is associated with enhanced mental health. Yet it remains unclear whether it leads to updates in the memory representation itself. Since memory can be labile after retrieval, this leaves the potential for modification whenever its reactivated. Across four experiments, we show that positively reinterpreting negative memories adaptively updates them, leading to the re-emergence of positivity at future retrieval. Focusing on the positive aspects after negative recall leads to enhanced positive emotion and changes in memory content during recollection one week later, remaining even after two months. Consistent with a reactivation-induced reconsolidation account, memory updating occurs only after a reminder and twenty four hours, but not a one hour delay. Multi-session fMRI showed adaptive updates are reflected in greater hippocampal and ventral striatal pattern dissimilarity across retrievals. This research highlights the mechanisms by which updating of maladaptive memories occurs through a positive emotion-focused strategy.

Muscle Selection and Dosing in a Phase 3, Pivotal Study of AbobotulinumtoxinA Injection in Upper Limb Muscles in Children With Cerebral Palsy.

Background: Guidelines recommend botulinum toxin-A in pediatric upper limb spasticity as part of routine practice. Appropriate dosing is a prerequisite for treatment success and it is important that injectors have an understanding on how to tailor dosing within a safe and effective range. We report upper limb dosing data from a phase 3 study of abobotulinumtoxinA injections in children with cerebral palsy. Methods: This was a double-blind, repeat-treatment study (NCT02106351). In Cycle 1, children were randomized to abobotulinumtoxinA at 2 U/kg control dose or clinically relevant 8 U/kg or 16 U/kg doses. Doses were divided between the primary target muscle group (PTMG, wrist or elbow flexors) and additional muscles tailored to clinical presentation. During Cycles 2-4, children received doses of 8 U/kg or 16 U/kg and investigators could change the PTMG and other muscles to be injected. Injection of muscles in the other upper limb and lower limbs was also permitted in cycles 2-4, with the total body dose not to exceed 30 U/kg or 1,000 U (whichever was lower) in the case of upper and lower limb treatment. Results: 212 children were randomized, of which 210 received ≥1 abobotulinumtoxinA injection. Per protocol, the elbow and wrist flexors were the most commonly injected upper limb muscles. Across all 4 cycles, the brachialis was injected in 89.5% of children (dose range 0.8-6 U/kg), the brachioradialis in 83.8% (0.4-3 U/kg), the flexor carpi ulnaris in 82.4% (0.5-3 U/kg) and the flexor carpi radialis in 79.5% (0.5-4 U/kg). Other frequently injected upper limb muscles were the pronator teres(70.0%, 0.3-3 U/kg). adductor pollicis (54.3%, 0.3-1 U/kg), pronator quadratus (44.8%, 0.1-2 U/kg), flexor digitorum superficialis (39.0%, 0.5-4 U/kg), flexor digitorum profundus (28.6%, 0.5-2 U), flexor pollicis brevis/opponens pollicis (27.6%, 0.3-1 U/kg) and biceps (27.1%, 0.5-6 U/kg). AbobotulinumtoxinA was well-tolerated at these doses; muscular weakness was reported in 4.3% of children in the 8 U/kg group and 5.7% in the 16 U/kg group. Conclusions: These data provide information on the pattern of injected muscles and dose ranges used in this study, which were well-tolerated. Per protocol, most children received injections into the elbow and wrist flexors. However, there was a wide variety of other upper limb muscles injected as physicians tailored injection patterns to clinical need.

Neural response to monetary loss among youth with disruptive behavior disorders and callous-unemotional traits in the ABCD study.

Etiological models highlight reduced punishment sensitivity as a core risk factor for disruptive behavior disorders (DBD) and callous-unemotional (CU) traits. The current study examined neural sensitivity to the anticipation and receipt of loss, one key aspect of punishment sensitivity, among youth with DBD, comparing those with and without CU traits. Data were obtained from the Adolescent Brain and Cognitive Development (ABCD)SM Study (N = 11,874; Mage = 9.51; 48% female). Loss-related fMRI activity during the monetary incentive delay task was examined across 16 empirically-derived a priori brain regions (e.g., striatum, amygdala, insula, anterior cingulate cortex, medial prefrontal cortex) and compared across the following groups: (1) typically developing (n = 693); (2) DBD (n = 995), subdivided into those (3) with CU traits (DBD + CU, n = 198), and (4) without CU traits (DBD-only, n = 276). Latent variable modeling was also employed to examine network-level activity. There were no significant between-group differences in brain activity to loss anticipation or receipt. Null findings were confirmed with and without covariates, using alternative grouping approaches, and in dimensional models. Network-level analyses also demonstrated comparable activity across groups during loss anticipation and receipt. Findings suggest that differences in punishment sensitivity among youth with DBD are unrelated to loss anticipation or receipt. More precise characterizations of other aspects punishment sensitivity are needed to understand risk for DBD and CU traits.

Germline mutation in POLR2A: a heterogeneous, multi-systemic developmental disorder characterized by transcriptional dysregulation.

De novo germline variation in POLR2A was recently reported to associate with a neurodevelopmental disorder. We report twelve individuals harboring putatively pathogenic de novo or inherited variants in POLR2A, detail their phenotypes, and map all known variants to the domain structure of POLR2A and crystal structure of RNA polymerase II. Affected individuals were ascertained from a local data lake, pediatric genetics clinic, and an online community of families of affected individuals. These include six affected by de novo missense variants (including one previously reported individual), four clinical laboratory samples affected by missense variation with unknown inheritance-with yeast functional assays further supporting altered function-one affected by a de novo in-frame deletion, and one affected by a C-terminal frameshift variant inherited from a largely asymptomatic mother. Recurrently observed phenotypes include ataxia, joint hypermobility, short stature, skin abnormalities, congenital cardiac abnormalities, immune system abnormalities, hip dysplasia, and short Achilles tendons. We report a significantly higher occurrence of epilepsy (8/12, 66.7%) than previously reported (3/15, 20%) (p value = 0.014196; chi-square test) and a lower occurrence of hypotonia (8/12, 66.7%) than previously reported (14/15, 93.3%) (p value = 0.076309). POLR2A-related developmental disorders likely represent a spectrum of related, multi-systemic developmental disorders, driven by distinct mechanisms, converging at a single locus.

Neural responses to negative events and subsequent persistence behavior differ in individuals recovering from opioid use disorder compared to controls.

Background: Negative emotion is associated with substance craving and use in individuals recovering from substance use disorders, including prescription opioid use disorder (POUD). Decisions to abandon or persist towards a goal after negative emotion-eliciting events, and neural responses that shape such decisions, may be important in maintaining recovery from POUD.Objectives: We examined differences in neural responses to negative events and subsequent persistence decisions in individuals recovering from POUD without a history of a substance use disorder. Methods: 20 individuals with POUD (POUD group: 4 females, abstinent 2-3 weeks after admission to an inpatient treatment facility post-detoxification, no other substance use disorder), and 20 individuals with no substance use history (control group: 6 females) completed a persistence-after-setbacks task during functional magnetic resonance imaging. Participants advanced along a path toward a reward; after encountering each negative event (i.e., progress-erasing setback), participants made decisions to persist or abandon the path. Persistence decision rates were compared between groups and blood-oxygen-level-dependent signal to negative events was analyzed within a striatum region of interest (ROI) as well as whole-brain.Results: The POUD group persisted less (t(38) = 2.293, p = .028, d = .725) and showed lower striatum (left ventral putamen) signal to negative events compared to the control group (p < .05, corrected for striatum ROI).Conclusions: In POUD, neural and behavioral responses to negative events differ from controls. These differences are a target for research to address whether POUD treatment increases persistence and striatum responses to negative events and improves recovery outcomes.

The Protective Effects of Perceived Control During Repeated Exposure to Aversive Stimuli.

The ability to perceive and exercise control is a major contributor to our mental and physical wellbeing. When faced with uncontrollable aversive stimuli, organisms develop heightened anxiety and become unwilling to exert effort to avoid the stimuli. In contrast, when faced with controllable aversive stimuli, organisms demonstrate behavioral vigor via avoidance attempts toward trying to seek and exercise control over the environment. As such, controllability confers protective effects against reduced avoidance motivation trigged by aversive environments. These observations beg the question of whether controllability can be potent enough to reverse passivity following repeated exposure to uncontrollable aversive stimuli and how this protective effect is encoded neurally. Human participants performed a Control in Aversive Domain (CAD) task where they were first subjected to a series of repeated uncontrollable aversive stimuli (i.e., aversive tones) across several contexts that were followed by a series of controllable aversive stimuli in a novel context. Faced with persistent uncontrollability, participants significantly reduced their avoidance attempts over time and biased toward giving up. However, the subsequent presence of controllability rescued participants' avoidance behavior. Strikingly, participants who responded more strongly to the protective effects of control also had greater ventromedial prefrontal cortical (vmPFC) activation-a region previously observed to be associated with encoding the subjective value of control. Taken together, these findings highlighted the protective effect conferred by perceived control against passivity and offered insights into the potential role of the vmPFC in controllable environments, with implications for understanding the beneficial influence of perceived control on adaptive behavior.

The influence of contextual factors on the subjective value of control.

The propensity to perceive and exert control in our environment contributes to both our adaptive behavior and general well-being. Prior studies have shown that humans have an inherent behavioral bias toward control-conferring environments and that this bias translates into greater subjective affect and is protective of our well-being. As such, it is vital to understand contextual factors that can alter our preference for control. In our previous work, we demonstrated that the behavioral bias toward control can be captured experimentally as the subjective value of control using a novel Value of Control task. We adapted this task in two experiments to study whether one's subjective value of control is (a) tied to overestimation of success probability or outcome magnitude (Experiment 1) and (b) affected by the contextual valence of a decision (e.g., gain, loss; Experiment 2). Using a within-subjects design (Experiment 1), we found that participants showed similar behavioral bias toward control regardless of whether probability or magnitude was manipulated, suggesting that the perception of control can increase both how much a reward is subjectively worth and the probability estimation for obtaining the given reward. Using a between-subjects design (Experiment 2), we showed that when the outcome was framed as a potential loss, participants significantly lowered their subjective value of control, suggesting that outcome valence plays a role in shaping how much perceived control influences our behavior. Collectively, these findings offer further insight into the malleability of an individual's perception of control and drive to perform control-seeking behaviors. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Constraint Induced Movement Therapy Camp for Children with Hemiplegic Cerebral Palsy Augmented by Use of an Exoskeleton to Play Games in Virtual Reality.

AIM: To determine the acceptability and effects of a pediatric constraint induced movement therapy (P-CIMT) camp for children with hemiplegic cerebral palsy (hCP) augmented by use of an exoskeleton to play games in virtual reality (VR). METHOD: 31 children with hCP attended a P-CIMT camp 6 hours per day for 10 days over 2 successive weeks (60 hours) that included 30 minutes of unilateral training with the Hocoma Armeo®Spring Pediatric that combines the assistance of an exoskeleton and VR games. The primary outcome measure was the Assisting Hand Assessment (AHA); secondary outcome measures were the Melbourne Assessment of Uni-lateral Hand Function (MUUL), and the Canadian Occupational Performance Measure (COPM). Assessments were completed at pre-intervention, post-intervention, and 6 months following intervention. RESULTS: Participants demonstrated clinically and statistically significant improvement in bimanual performance (AHA) (p < .001) and COPM Performance (p < .001) and Satisfaction with performance (p < .001). Improvement in unilateral performance (MUUL) was statistically (p < .001) but not clinically significant. CONCLUSIONS: A P-CIMT camp augmented by the Hocoma Armeo®Spring Pediatric was feasible and accepted by participants. Bimanual hand function and occupational performance improved immediately following intervention, and the treatment effects persisted 6 months following intervention.

Efficacy and safety of abobotulinumtoxinA for upper limb spasticity in children with cerebral palsy: a randomized repeat-treatment study.

AIM: To assess the efficacy and safety of repeat abobotulinumtoxinA injections in reducing upper limb spasticity in children with cerebral palsy (CP). METHOD: This was a double-blind, repeat-cycle study (NCT02106351) in children with CP (2-17y). Children were randomized to receive 2U/kg (control), 8U/kg, or 16U/kg abobotulinumtoxinA injections into the target muscle group (wrist or elbow flexors) and additional muscles alongside occupational therapy via a home-exercise therapy program (HETP; minimum five 15min sessions/wk). Children received 8U/kg or 16U/kg plus HETP in cycles 2 to 4. RESULTS: During cycle 1, 210 children (126 males, 84 females; mean age [SD] 9y [4y 5mo], range 2-17y; n=70/group) had at least one upper limb abobotulinumtoxinA injection and 209 complied with the HETP. At week 6 of cycle 1, children in the 8U/kg or 16U/kg groups had significantly lower Modified Ashworth scale scores versus the 2U/kg group (primary outcome: treatment differences of -0.4 [p=0.012] and -0.7 [p<0.001] respectively). All groups improved on Physician Global Assessment and children in all groups achieved their treatment goals at least as expected. Therapeutic benefits were sustained during cycles 2 to 4; muscular weakness was the only treatment-related adverse event reported in at least one child/group (4.3% and 5.7% vs 1.4% respectively). INTERPRETATION: Treatment with 8U/kg or 16U/kg abobotulinumtoxinA significantly reduced upper limb spasticity versus the 2U/kg control dose. Therapeutic benefits of abobotulinumtoxinA plus HETP were sustained with repeat treatment cycles. WHAT THIS PAPER ADDS: AbobotulinumtoxinA injections significantly reduced upper limb spasticity in children with cerebral palsy. Children treated with abobotulinumtoxinA and targeted home exercises showed global improvement and goal attainment. Benefits were sustained over 1 year with repeat cycles of abobotulinumtoxinA and home exercises. AbobotulinumtoxinA injections into the upper limb were well tolerated over 1 year.