Visual, perceptual functions, and functional vision in children with unilateral cerebral palsy compared to children with neurotypical development.

AIM: To investigate visual (perceptual) function and functional vision in children with unilateral cerebral palsy (CP) and children with neurotypical development (NTD). METHOD: Fifty children with unilateral CP (mean age 11 years 11 months, SD 2 years 10 months, range 7-15 years; 27 males; 26 left-sided unilateral CP; Manual Ability Classification System [MACS] levels: I, 27; II, 16; III, 7) and 50 age- and sex-matched children with NTD participated in a cross-sectional study. Visual acuity, stereoacuity, and visual-perceptual functions were measured with standardized clinical tests. Functional vision was assessed in children with unilateral CP with the Flemish cerebral visual impairment questionnaire (FCVIQ). Group differences were investigated with Mann-Whitney U tests, Kruskal-Wallis tests, and the relative effect sizes r, η2 respectively. Correlations between visual assessments and the FCVIQ were investigated with Spearman's rank correlations. RESULTS: The total group of children with unilateral CP showed reduced visual acuity compared with children with NTD (p = 0.02, r = 0.23). Only children with left-sided unilateral CP scored lower than those with NTD on stereoacuity (p < 0.01, r = 0.36). Children with right/left-sided unilateral CP scored significantly lower than those with NTD on visual-perceptual functions (p = 0.001-0.02), with large effect sizes on visuomotor integration and visual closure (both r = 0.57). Children with unilateral CP classified in MACS level III showed significantly lower scores on visual-perceptual assessments than children classified in MACS level I. Stereoacuity and visual-perceptual functions negatively correlated with the FCVIQ, with the highest association with visual (dis)interest and anxiety-related behaviours. INTERPRETATION: Multi-level visual profiling is warranted in the clinical intake of children with unilateral CP to detect visual impairments that further compromise their level of functioning.

Exploring structural connectomes in children with unilateral cerebral palsy using graph theory.

We explored structural brain connectomes in children with spastic unilateral cerebral palsy (uCP) and its relation to sensory-motor function using graph theory. In 46 children with uCP (mean age = 10 years 7 months ± 2 years 9 months; Manual Ability Classification System I = 15, II = 16, III = 15) we assessed upper limb somatosensory and motor function. We collected multi-shell diffusion-weighted, T1-weighted and T2-FLAIR MRI and identified the corticospinal tract (CST) wiring pattern using transcranial magnetic stimulation. Structural connectomes were constructed using Virtual Brain Grafting-modified FreeSurfer parcellations and multi-shell multi-tissue constrained spherical deconvolution-based anatomically-constrained tractography. Graph metrics (characteristic path length, global/local efficiency and clustering coefficient) of the whole brain, the ipsilesional/contralesional hemisphere, and the full/ipsilesional/contralesional sensory-motor network were compared between lesion types (periventricular white matter (PWM) = 28, cortical and deep gray matter (CDGM) = 18) and CST-wiring patterns (ipsilateral = 14, bilateral = 14, contralateral = 12, unknown = 6) using ANCOVA with age as covariate. Using elastic-net regularized regression we investigated how graph metrics, lesion volume, lesion type, CST-wiring pattern and age predicted sensory-motor function. In both the whole brain and subnetworks, we observed a hyperconnectivity pattern in children with CDGM-lesions compared with PWM-lesions, with higher clustering coefficient (p = [<.001-.047], η p 2 =[0.09-0.27]), characteristic path length (p = .003, η p 2 =0.19) and local efficiency (p = [.001-.02], η p 2 =[0.11-0.21]), and a lower global efficiency with age (p = [.01-.04], η p 2 =[0.09-0.15]). No differences were found between CST-wiring groups. Overall, good predictions of sensory-motor function were obtained with elastic-net regression (R2  = .40-.87). CST-wiring pattern was the strongest predictor for motor function. For somatosensory function, all independent variables contributed equally to the model. In conclusion, we demonstrated the potential of structural connectomics in understanding disease severity and brain development in children with uCP.

In-depth quantification of bimanual coordination using the Kinarm exoskeleton robot in children with unilateral cerebral palsy.

BACKGROUND: Robots have been proposed as tools to measure bimanual coordination in children with unilateral cerebral palsy (uCP). However, previous research only examined one task and clinical interpretation remains challenging due to the large amount of generated data. This cross-sectional study aims to examine bimanual coordination by using multiple bimanual robotics tasks in children with uCP, and their relation to task execution and unimanual performance. METHODS: The Kinarm exoskeleton robot was used in 50 children with uCP (mean age: 11 years 11 months ± 2 years 10 months, Manual Ability Classification system (MACS-levels: l = 27, ll = 16, lll = 7)) and 50 individually matched typically developing children (TDC). All participants performed three tasks: object-hit (hit falling balls), ball-on-bar (balance a ball on a bar while moving to a target) and circuit task (move a cursor along a circuit by making horizontal and vertical motions with their right and left hand, respectively). Bimanual parameters provided information about bimanual coupling and interlimb differences. Differences between groups and MACS-levels were investigated using ANCOVA with age as covariate (α < 0.05, [Formula: see text]). Correlation analysis (r) linked bimanual coordination to task execution and unimanual parameters. RESULTS: Children with uCP exhibited worse bimanual coordination compared to TDC in all tasks (p ≤ 0.05, [Formula: see text] = 0.05-0.34). The ball-on-bar task displayed high effect size differences between groups in both bimanual coupling and interlimb differences (p < 0.001, [Formula: see text] = 0.18-0.36), while the object-hit task exhibited variations in interlimb differences (p < 0.001, [Formula: see text] = 0.22-0.34) and the circuit task in bimanual coupling (p < 0.001, [Formula: see text] = 0.31). Mainly the performance of the ball-on-bar task (p < 0.05, [Formula: see text] = 0.18-0.51) was modulated by MACS-levels, showing that children with MACS-level lll had worse bimanual coordination compared to children with MACS-level l and/or II. Ball-on-bar outcomes were highly related to task execution (r = - 0.75-0.70), whereas more interlimb differences of the object-hit task were moderately associated with a worse performance of the non-dominant hand (r = - 0.69-(- 0.53)). CONCLUSION: This study gained first insight in important robotic tasks and outcome measures to quantify bimanual coordination deficits in children with uCP. The ball-on-bar task showed the most discriminative ability for both bimanual coupling and interlimb differences, while the object-hit and circuit tasks are unique to interlimb differences and bimanual coupling, respectively.

Tyneside Pegboard Test for unimanual and bimanual dexterity in unilateral cerebral palsy: association with sensorimotor impairment.

AIM: We explored the psychometric properties of the recently developed Tyneside Pegboard Test (TPT) for unimanual and bimanual dexterity in children with unilateral cerebral palsy (CP) and investigated the impact of sensorimotor impairments on manual dexterity. METHOD: In this cross-sectional study, the TPT was assessed in 49 children with unilateral CP (mean age 9y 8mo, SD 1y 11mo, range 6-15y; 30 males, 19 females; 23 with right unilateral CP). All participants additionally underwent a standardized upper limb evaluation at body function and activity level. We investigated: (1) known-group, concurrent, and construct validity and (2) impact of sensorimotor impairments including spasticity, grip force, stereognosis, and mirror movements using analysis of covariance, Spearman's rank correlation (r), and multiple linear regression (R2 ) respectively. RESULTS: TPT outcomes significantly differed according to the Manual Ability Classification System (p<0.001, known-group validity). Relationships were found between the unimanual TPT tasks and the Jebsen-Taylor Hand Function Test (r=0.86-0.88, concurrent validity). Bimanual TPT tasks were negatively correlated with the Assisting Hand Assessment, ABILHAND-Kids, and Children's Hand-use Experience Questionnaire (r=-0.38 to -0.78, construct validity). Stereognosis was the main determinant influencing all tasks (p<0.001, R2 =37-50%). Unimanual dexterity was additionally determined by grip strength (p<0.05, R2 =8-9%) and mirror movements in the more impaired hand (p<0.05, R2 =4-8%). Bimanual dexterity was also explained by mirror movements in the more impaired hand (p<0.01, R2 =10-16%) and spasticity (p=0.04, R2 =5%). INTERPRETATION: The TPT is a valid test to measure unimanual and bimanual dexterity in unilateral CP. The results further emphasize the importance of somatosensory impairments in children with unilateral CP. What this paper adds The Tyneside Pegboard Test is valid for measuring unimanual and bimanual dexterity in unilateral cerebral palsy. Children with poorer manual ability show worse unimanual and bimanual dexterity. Stereognosis is the main predictor of both unimanual and bimanual dexterity. Stronger mirror movements in the more impaired hand result in worse bimanual dexterity.

Assessment of mirror movements in children and adolescents with unilateral cerebral palsy: reliability of the Woods and Teuber scale.

AIM: To investigate the inter- and intrarater reliability of the Woods and Teuber scale to detect mirror movements in children and adolescents with unilateral cerebral palsy (CP). METHOD: A convenience sample of children and adolescents with unilateral CP (n=68; 31 males, 37 females; mean age 12y 2mo, SD 3y 6mo) in Manual Ability Classification levels I to III was recruited from Norway, Australia, and Belgium. Three therapists scored mirror movements according to the Woods and Teuber scale from three video-recorded tasks at two separate time points. A two-way, mixed model regression was used to calculate intraclass correlation coefficients (ICCs) reflecting overall inter- and intrarater reliability. In addition, ICCs for each hand and task were calculated separately. RESULTS: The overall interrater reliability ICC was 0.90 and the corresponding intrarater reliability ICC was 0.92. The ICCs for each hand ranged from 0.86 to 0.92 and for each task from 0.63 to 0.89. INTERPRETATION: The Woods and Teuber scale shows excellent reliability for scoring mirror movements in children and adolescents with unilateral CP. The assessment is easy to administer with no need for specific equipment and scoring can be determined from short video recordings, making it a feasible instrument in research and clinical practice.

Combining constraint-induced movement therapy and action-observation training in children with unilateral cerebral palsy: a randomized controlled trial.

BACKGROUND: Upper limb (UL) deficits in children with unilateral cerebral palsy (uCP) have traditionally been targeted with motor execution treatment models, such as modified Constraint-Induced Movement Therapy (mCIMT). However, new approaches based on a neurophysiological model such as Action-Observation Training (AOT) may provide new opportunities for enhanced motor learning. The aim of this study is to describe a randomised controlled trial (RCT) protocol investigating the effects of an intensive treatment model, combining mCIMT and AOT compared to mCIMT alone on UL function in children with uCP. Additionally, the role of neurological factors as potential biomarkers of treatment response will be analysed. METHODS: An evaluator-blinded RCT will be conducted in 42 children aged between 6 and 12 years. Before randomization, children will be stratified according to their House Functional Classification Scale, age and type of corticospinal tract wiring. A 2-week day-camp will be set up in which children receive intensive mCIMT therapy for 6 hours a day on 9 out of 11 consecutive days (54 h) including AOT or control condition (15 h). During AOT, these children watch video sequences showing goal-directed actions and subsequently execute the observed actions with the more impaired UL. The control group performs the same actions after watching computer games without human motion. The primary outcome measure will be the Assisting Hand Assessment. Secondary outcomes comprise clinical assessments across body function, activity and participation level of the International Classification of Function, Disability and Health. Furthermore, to quantitatively evaluate UL movement patterns, a three-dimensional motion analysis will be conducted. UL function will be assessed at baseline, immediately before and after intervention and at 6 months follow up. Brain imaging comprising structural and functional connectivity measures as well as Transcranial Magnetic Stimulation (TMS) to evaluate corticospinal tract wiring will be acquired before the intervention. DISCUSSION: This paper describes the methodology of an RCT with two main objectives: (1) to evaluate the added value of AOT to mCIMT on UL outcome in children with uCP and (2) to investigate the role of neurological factors as potential biomarkers of treatment response. TRIAL REGISTRATION: NCT03256357 registered on 21st August 2017 (retrospectively registered).

Corticospinal Tract Wiring and Brain Lesion Characteristics in Unilateral Cerebral Palsy: Determinants of Upper Limb Motor and Sensory Function.

Brain lesion characteristics (timing, location, and extent) and the type of corticospinal tract (CST) wiring have been proposed as determinants of upper limb (UL) motor function in unilateral cerebral palsy (uCP), yet an investigation of the relative combined impact of these factors on both motor and sensory functions is still lacking. Here, we first investigated whether structural brain lesion characteristics could predict the underlying CST wiring and we explored the role of CST wiring and brain lesion characteristics to predict UL motor and sensory functions in uCP. Fifty-two participants with uCP (mean age (SD): 11 y and 3 m (3 y and 10 m)) underwent a single-pulse Transcranial Magnetic Stimulation session to determine CST wiring between the motor cortex and the more affected hand (n = 17 contralateral, n = 19 ipsilateral, and n = 16 bilateral) and an MRI to determine lesion timing (n = 34 periventricular (PV) lesion, n = 18 corticosubcortical (CSC) lesion), location, and extent. Lesion location and extent were evaluated with a semiquantitative scale. A standardized protocol included UL motor (grip strength, unimanual capacity, and bimanual performance) and sensory measures. A combination of lesion locations (damage to the PLIC and frontal lobe) significantly contributed to differentiate between the CST wiring groups, reclassifying the participants in their original group with 57% of accuracy. Motor and sensory functions were influenced by each of the investigated neurological factors. However, multiple regression analyses showed that motor function was predicted by the CST wiring (more preserved in individuals with contralateral CST (p < 0.01)), lesion extent, and damage to the basal ganglia and thalamus. Sensory function was predicted by the combination of a large and later lesion and an ipsilateral or bilateral CST wiring, which led to increased sensory deficits (p < 0.05). These novel insights contribute to a better understanding of the underlying pathophysiology of UL function and may be useful to delineate individualized treatment strategies.

Time Course of Upper Limb Function in Children with Unilateral Cerebral Palsy: A Five-Year Follow-Up Study.

Knowledge on long-term evolution of upper limb function in children with unilateral cerebral palsy (CP) is scarce. The objective was to report the five-year evolution in upper limb function and identify factors influencing time trends. Eighty-one children (mean age 9 y and 11 mo, SD 3 y and 3 mo) were assessed at baseline with follow-up after 6 months, 1, and 5 years. Passive range of motion (PROM), tone, muscle, and grip strength were assessed. Activity measurements included Melbourne Assessment, Jebsen-Taylor test, Assisting Hand Assessment (AHA), and ABILHAND-Kids. At 5-year follow-up, PROM (p < 0.001) and AHA scores (p < 0.001) decreased, whereas an improvement was seen for grip strength (p < 0.001), Melbourne Assessment (p = 0.003), Jebsen-Taylor test (p < 0.001), and ABILHAND-Kids (p < 0.001). Age influenced the evolution of AHA scores (p = 0.003), with younger children being stable over time, but from 9 years onward, children experienced a decrease in bimanual performance. Manual Ability Classification System (MACS) levels also affected the evolution of AHA scores (p = 0.02), with stable scores in MACS I and deterioration in MACS II and III. In conclusion, over 5 years, children with unilateral CP develop more limitations in PROM, and although capacity measures improve, the spontaneous use of the impaired limb in bimanual tasks becomes less effective after the age of 9 years.

Do mirror movements relate to hand function and timing of the brain lesion in children with unilateral cerebral palsy?

AIM: This study aimed to systematically map the severity of mirror movements in both hands in a prospective cohort of children with unilateral cerebral palsy, and to explore the relationship with hand function and brain lesion type. METHOD: Seventy-eight children were included (41 males, 37 females; age 9y 4mo, SD 3y 1mo, range 5-15y). Mirror movements were scored during three repetitive tasks following Woods and Teuber criteria. Strength, tone, Melbourne Assessment, Jebsen-Taylor test, and Assisting Hand Assessment were evaluated. Lesions were classified into malformations (n=5), periventricular (n=43), cortico-subcortical (n=22), and postnatally acquired lesions (n=8). RESULTS: Significantly more mirror movements were observed in the non-paretic versus the paretic hand (p≤0.003). Higher mirror movement scores in the non-paretic hand significantly correlated with lower distal strength and lower scores on unimanual and bimanual assessments (r=0.29-0.41). In the paretic hand, significant differences were found between lesion types (p=0.03). INTERPRETATION: The occurrence of mirror movements in the non-paretic hand seems related to hand function while mirror movements in the paretic hand seem more related to the lesion timing, whereby children with earlier lesions present with more mirror movements.

The relation between neuroimaging and visual impairment in children and adolescents with cerebral palsy: A systematic review.

OBJECTIVE: The structure-function relation between magnetic resonance imaging (MRI) and visual impairment (VI) in children with cerebral palsy (CP) has not been fully unravelled. The present systematic review aims to summarize the relation between brain lesions on MRI and VI in children and adolescents with CP. METHODS: PubMed, Embase, Web of Science Core Collection, and Cochrane Database were systematically searched according to the PRISMA checklist. A total of 45 articles met the inclusion criteria. RESULTS: White matter lesions were most frequently associated with VI. Only 25 studies described lesions within specific structures, mainly in the optic radiations. Only four studies reported on the thalamus. 8.4% of children with CP showed no brain abnormalities on MRI. Diffusion-weighted MRI studies showed that decreased structural connectivity in the optic radiations, superior longitudinal fasciculus, posterior limb of the internal capsule, and occipital lobe is associated with more severe VI. CONCLUSIONS: All types of brain lesions lead to visual dysfunctions, arguing for a comprehensive visual assessment in all children with CP. Whereas white matter damage is a well-known contributor, the exact contribution of specific visual structures requires further investigation, to enable early prediction, detection, and intervention.

The relation between visual functions, functional vision, and bimanual function in children with unilateral cerebral palsy.

BACKGROUND: Accurate visual information is needed to guide and perform efficient movements in daily life. AIMS: To investigate the relation between visual functions, functional vision, and bimanual function in children with unilateral cerebral palsy (uCP). METHODS AND PROCEDURES: In 49 children with uCP (7-15 y), we investigated the relation between stereoacuity (Titmus Stereo Fly test), visual perception (Test of Visual Perceptual Skills), visuomotor integration (Beery Buktenica Test of Visual-Motor Integration) and functional vision (Flemish cerebral visual impairment questionnaire) with bimanual dexterity (Tyneside Pegboard Test), bimanual coordination (Kinarm exoskeleton robot, Box opening task), and functional hand use (Children's Hand-use Experience Questionnaire; Assisting Hand Assessment) using correlations (rs) and elastic-net regularized regressions (d). OUTCOMES AND RESULTS: Visual perception correlated with bimanual coordination (rs=0.407-0.436) and functional hand use (rs=0.380-0.533). Stereoacuity (rs=-0.404), visual perception (rs=-0.391 to -0.620), and visuomotor integration (rs=-0.377) correlated with bimanual dexterity. Functional vision correlated with functional hand use (rs=-0.441 to -0.458). Visual perception predicted bimanual dexterity (d=0.001-0.315), bimanual coordination (d=0.004-0.176), and functional hand use (d=0.001-0.345), whereas functional vision mainly predicted functional hand use (d=0.001-0.201). CONCLUSIONS AND IMPLICATIONS: Visual functions and functional vision are related to bimanual function in children with uCP highlighting the importance of performing extensive visual assessment to better understand children's difficulties in performing bimanual tasks. WHAT THIS PAPER ADDS: Previous findings showed that up to 62 % of children with unilateral cerebral palsy (uCP) present with visual impairment, which can further compromise their motor performance. However, the relation between visual and motor function has hardly been investigated in this population. This study makes a significant contribution to the literature by comprehensively investigating the multi-level relation between the heterogenous spectrum of visual abilities and bimanual function in children with uCP. We found that mainly decreased visual perception was related to decreased bimanual dexterity, bimanual coordination, and functional hand use while impairments in functional vision were only related to decreased functional hand use. Additionally, elastic-net regression models showed that visual assessments can predict bimanual function in children with uCP, however, effect sizes were only tiny to small. With our study, we demonstrated a relation between visual functions and bimanual function in children with uCP. These findings suggest the relevance of thoroughly examining visual functions in children with uCP to identify the presence of visual impairments that may further compromise their bimanual function.

Does somatosensory discrimination therapy alter sensorimotor upper limb function differently compared to motor therapy in children and adolescents with unilateral cerebral palsy: study protocol for a randomized controlled trial.

BACKGROUND: Besides motor impairments, up to 90% of the children and adolescents with unilateral cerebral palsy (uCP) present with somatosensory impairments in the upper limb. As somatosensory information is of utmost importance for coordinated movements and motor learning, somatosensory impairments can further compromise the effective use of the impaired upper limb in daily life activities. Yet, intervention approaches specifically designated to target these somatosensory impairments are insufficiently investigated in children and adolescents with uCP. Therefore, the aim of this randomized controlled trial (RCT) is to compare the effectiveness of somatosensory discrimination therapy and dose-matched motor therapy to improve sensorimotor upper limb function in children and adolescents with uCP, who experience somatosensory impairments in the upper limb. We will further explore potential behavioral and neurological predictors of therapy response. METHODS: A parallel group, evaluator-blinded, phase-II, single-center RCT will be conducted for which 50 children and adolescents with uCP, aged 7 to 15 years, will be recruited. Participants will be randomized to receive 3 weekly sessions of 45 minutes of either somatosensory discrimination therapy or upper limb motor therapy for a period of 8 weeks. Stratification will be performed based on age, manual ability, and severity of tactile impairment at baseline. Sensorimotor upper limb function will be evaluated at baseline, immediately after the intervention and after 6 months follow-up. The primary outcome measure will be bimanual performance as measured with the Assisting Hand Assessment. Secondary outcomes include a comprehensive test battery to objectify somatosensory function and measures of bimanual coordination, unimanual motor function, and goal attainment. Brain imaging will be performed at baseline to investigate structural brain lesion characteristics and structural connectivity of the white matter tracts. DISCUSSION: This protocol describes the design of an RCT comparing the effectiveness of somatosensory discrimination therapy and dose-matched motor therapy to improve sensorimotor upper limb function in children and adolescents with uCP. The results of this study may aid in the selection of the most effective upper limb therapy, specifically for children and adolescents with tactile impairments. TRIAL REGISTRATION: ClinicalTrials.gov (NCT06006065). Registered on August 8, 2023.

Effectiveness of the home-based training program Tele-UPCAT (Tele-monitored UPper Limb Children Action Observation Training) in unilateral cerebral palsy: a randomized controlled trial.

BACKGROUND: The effects of unilateral cerebral palsy (UCP) are largely observed in the upper limb (UL), which represents the main focus of rehabilitation for this disorder. Thanks to an increment in home training and progress in technology innovative systems have been created. The Tele-UPCAT (Tele-monitored UPper Limb Children Action Observation Training) platform is dedicated to the delivery at home of a program for UL rehabilitation, based on action observation therapy (AOT). AIM: This study aimed to investigate the immediate effectiveness of Tele-UPCAT for promoting UL skills in children with UCP and to determine if immediate effects were retained in the medium and long term. DESIGN: Tele-UPCAT was conducted on an intention-to-treat basis and was proposed as a randomized, allocation concealed (waitlist controlled) and evaluator-blinded clinical trial with two investigative arms: intensive in-home AOT program and standard care (SC). SETTING: This is a home-based AOT program delivered with a customized ICT platform. POPULATION: Thirty children (mean age 11.61±3.55 years) with confirmed diagnosis of spastic UCP with predominant UL involvement and cognitive level within or at normal limits were enrolled in this study. Orthopedic surgery or an intramuscular botulinum toxin A injection in the UL within 6 months prior to enrolment represented an exclusion criteria. METHODS: Participants were randomized using concealed random allocation. They were assessed according to the study design with the Assisting Hand Assessment (AHA), the Box and Block Test (BBT) and the Melbourne Assessment 2 (MA2). Linear mixed models were used for statistical analysis. RESULTS: A significant difference between the AOT and SC groups was identified immediately after the training on the AHA (6.406 [2.73] P=0.021) with an effect size (ES) of 1.99, and for the BBT of the less affected hand (9.826 [4.535] P=0.032) with an ES of 1.44. These effects were sustained at medium and long term. CONCLUSIONS: This study supports the effectiveness of AOT home training in promoting UL skills in children with UCP, with immediate effects lasting for 6 months. CLINICAL REHABILITATION IMPACT: This should encourage the use of technology for rehabilitative purposes and further applications of the AOT paradigm.

The impact of brain lesion characteristics and the corticospinal tract wiring on mirror movements in unilateral cerebral palsy.

Mirror movements (MM) influence bimanual performance in children with unilateral cerebral palsy (uCP). Whilst MM are related to brain lesion characteristics and the corticospinal tract (CST) wiring pattern, the combined impact of these neurological factors remains unknown. Forty-nine children with uCP (mean age 10y6mo) performed a repetitive squeezing task to quantify similarity (MM-similarity) and strength (MM-intensity) of the MM activity. We used MRI data to evaluate lesion type (periventricular white matter, N = 30; cortico-subcortical, N = 19), extent of ipsilesional damage, presence of bilateral lesions, and damage to basal ganglia, thalamus and corpus callosum. The CST wiring was assessed with Transcranial Magnetic Stimulation (17 CSTcontralateral, 16 CSTipsilateral, 16 CSTbilateral). Data was analyzed with regression analyses. In the more-affected hand, MM-similarity and intensity were higher with CSTbilateral/ipsilateral. In the less-affected hand, MM-similarity was higher in children with (1) CSTcontra with CSC lesions, (2) CSTbilat/ipsi with PVL lesions and (3) CSTbilat/ipsi with unilateralized lesions. MM-intensity was higher with larger damage to the corpus callosum and unilateral lesions. A complex combination of neurological factors influences MM characteristics, and the mechanisms differ between hands.

Reliable and Valid Robotic Assessments of Hand Active and Passive Position Sense in Children With Unilateral Cerebral Palsy.

Impaired hand proprioception can lead to difficulties in performing fine motor tasks, thereby affecting activities of daily living. The majority of children with unilateral cerebral palsy (uCP) experience proprioceptive deficits, but accurately quantifying these deficits is challenging due to the lack of sensitive measurement methods. Robot-assisted assessments provide a promising alternative, however, there is a need for solutions that specifically target children and their needs. We propose two novel robotics-based assessments to sensitively evaluate active and passive position sense of the index finger metacarpophalangeal joint in children. We then investigate test-retest reliability and discriminant validity of these assessments in uCP and typically developing children (TDC), and further use the robotic platform to gain first insights into fundamentals of hand proprioception. Both robotic assessments were performed in two sessions with 1-h break in between. In the passive position sense assessment, participant's finger is passively moved by the robot to a randomly selected position, and she/he needs to indicate the perceived finger position on a tablet screen located directly above the hand, so that the vision of the hand is blocked. Active position sense is assessed by asking participants to accurately move their finger to a target position shown on the tablet screen, without visual feedback of the finger position. Ten children with uCP and 10 age-matched TDC were recruited in this study. Test-retest reliability in both populations was good (intraclass correlation coefficients (ICC) >0.79). Proprioceptive error was larger for children with uCP than TDC (passive: 11.49° ± 5.57° vs. 7.46° ± 4.43°, p = 0.046; active: 10.17° ± 5.62° vs. 5.34° ± 2.03°, p < 0.001), indicating discriminant validity. The active position sense was more accurate than passive, and the scores were not correlated, underlining the need for targeted assessments to comprehensively evaluate proprioception. There was a significant effect of age on passive position sense in TDC but not uCP, possibly linked to disturbed development of proprioceptive acuity in uCP. Overall, the proposed robot-assisted assessments are reliable, valid and a promising alternative to commonly used clinical methods, which could help gain a better understanding of proprioceptive impairments in uCP, facilitating the design of novel therapies.

Early interventions in infants with unilateral cerebral palsy: A systematic review and narrative synthesis.

BACKGROUND: Recent systematic reviews have already provided an overview of the impact of early interventions on developmental outcomes in infants at risk for cerebral palsy. However, none has thus far focused specifically on how early interventions might improve motor outcome in infants diagnosed with unilateral cerebral palsy (uCP). Hence, the aim of this systematic review was to provide an overview of early intervention programs used in infants with uCP to improve motor outcome. METHODS: A systematic literature search was performed in PubMed, Embase, Cochrane Central Register of Controlled trials, CINAHL and Web of Science following the PRISMA-statement guidelines. Risk of bias was assessed using the Cochrane risk-of-bias 2 tool. RESULTS: Three single-blinded randomized controlled trials (RCTs) were identified, including 88 infants with uCP. These RCTs suggest that modified constraint-induced movement therapy (mCIMT) is effective and safe for improving upper limb function in infants with uCP. Bimanual training compared to mCIMT was found to be equally effective in one study. No clinical or neurological predictors of treatment response could be identified yet. CONCLUSION: Although more high-quality RCTs are urgently needed, early interventions seem effective, safe and feasible to apply in infants with uCP for improving upper limb motor function. This underlines the importance of prompt referral to diagnostic-specific centres to start up such early interventions.

Effects of combining constraint-induced movement therapy and action-observation training on upper limb kinematics in children with unilateral cerebral palsy: a randomized controlled trial.

Modified constraint-induced movement therapy (mCIMT) improves upper limb (UL) motor execution in unilateral cerebral palsy (uCP). As these children also show motor planning deficits, action-observation training (AOT) might be of additional value. Here, we investigated the combined value of AOT to mCIMT on UL kinematics in children with uCP in a randomized controlled trial. Thirty-six children with uCP completed an UL kinematic and clinical evaluation after participating in a 9-day mCIMT camp wearing a splint for 6 h/day. The experimental group (mCIMT + AOT, n = 20) received 15 h of AOT, i.e. video-observation and execution of unimanual tasks. The control group (mCIMT + placebo, n = 16) watched biological-motion free videos and executed the same tasks. We examined changes in motor control (movement duration, peak velocity, time-to-peak velocity, and trajectory straightness) and kinematic movement patterns (using Statistical Parametric Mapping) during the execution of three unimanual, relevant tasks before the intervention, after and at 6 months follow-up. Adding AOT to mCIMT mainly affected movement duration during reaching, whereas little benefit is seen on UL movement patterns. mCIMT, with or without AOT, improved peak velocity and trajectory straightness, and proximal movement patterns. Clinical and kinematic improvements are poorly related. Although there seem to be limited benefits of AOT to CIMT on UL kinematics, our results support the inclusion of kinematics to capture changes in motor control and movement patterns of the proximal joints.

Structural Brain Lesions and Gait Pathology in Children With Spastic Cerebral Palsy.

The interaction between brain damage and motor function is not yet fully understood in children with spastic cerebral palsy (CP). Therefore, a semi-quantitative MRI (sqMRI) scale was used to explore whether identified brain lesions related to functional abilities and gait pathology in this population. A retrospective cohort of ambulatory children with spastic CP was selected [N = 104; 52 bilateral (bCP) and 52 unilateral (uCP)]. Extent and location-specific scores were defined according to the sqMRI scale guidelines. The gross motor function classification system (GMFCS), the gait profile score (GPS), GPSs per motion plane, gait variable scores (GVS) and multiple-joint (MJ) gait patterns were related to brain lesion scores. In all groups, the global total brain scores correlated to the GPS (total: r s = 0.404, p ≤ 0.001; bCP: r s = 0.335, p ≤ 0.05; uCP: r s = 0.493, p ≤ 0.001). The global total hemispheric scores correlated to the GMFCS (total: r s = 0.392, p ≤ 0.001; bCP: r s = 0.316, p ≤ 0.05; uCP: r s = 0.331, p ≤ 0.05). The laterality scores of the hemispheres in the total group correlated negatively to the GMFCS level (r s = -0.523, p ≤ 0.001) and the GVS-knee sagittal (r s = -0.311, p ≤ 0.01). Lesion location, for the total group demonstrated positive correlations between parietal lobe involvement and the GPS (r s = 0.321, p ≤ 0.001) and between periventricular layer damage and the GMFCS (r s = 0.348, p ≤ 0.001). Involvement of the anterior part of the corpus callosum (CC) was associated with the GVS-hip sagittal in all groups (total: r pb = 0.495, p ≤ 0.001; bCP: r pb = 0.357, p ≤ 0.05; uCP: r pb = 0.641, p ≤ 0.001). The global total hemispheric and laterality of the hemispheres scores differentiated between the minor and both the extension (p ≤ 0.001 and p ≤ 0.001) and flexion (p = 0.016 and p = 0.013, respectively) MJ patterns in the total group. Maximal periventricular involvement and CC intactness were associated with extension patterns (p ≤ 0.05 and p ≤ 0.001, respectively). Current findings demonstrated relationships between brain structure and motor function as well as pathological gait, in this cohort of children with CP. These results might facilitate the timely identification of gait pathology and, ultimately, guide individualized treatment planning of gait impairments in children with CP.

White matter characteristics of motor, sensory and interhemispheric tracts underlying impaired upper limb function in children with unilateral cerebral palsy.

This study explored the role of lesion timing (periventricular white matter versus cortical and deep grey matter lesions) and type of corticospinal tract (CST) wiring pattern (contralateral, bilateral, ipsilateral) on white matter characteristics of the CST, medial lemniscus, superior thalamic radiations and sensorimotor transcallosal fibers in children with unilateral cerebral palsy (CP), and examined the association with upper limb function. Thirty-four children (mean age 10 years 7 months ± 2 years 3 months) with unilateral CP underwent a comprehensive upper limb evaluation and diffusion weighted imaging (75 directions, b value 2800). Streamline count, fractional anisotropy and mean diffusivity were extracted from the targeted tracts and asymmetry indices were additionally calculated. Transcranial magnetic stimulation was applied to assess the CST wiring pattern. Results showed a more damaged CST in children with cortical and deep grey matter lesions (N = 10) and ipsilateral CST projections (N = 11) compared to children with periventricular white matter lesions (N = 24; p < 0.02) and contralateral CST projections (N = 9; p < 0.025), respectively. Moderate to high correlations were found between diffusion metrics of the targeted tracts and upper limb function (r = 0.45-0.72; p < 0.01). Asymmetry indices of the CST and sensory tracts could best explain bimanual performance (74%, p < 0.0001) and unimanual capacity (50%, p = 0.004). Adding lesion timing and CST wiring pattern did not further improve the model of bimanual performance, while for unimanual capacity lesion timing was additionally retained (58%, p = 0.0002). These results contribute to a better understanding of the underlying neuropathology of upper limb function in children with unilateral CP and point towards a clinical potential of tractography.