Executive Function Assessment in 2-Year-Olds Born Preterm.

OBJECTIVE: Our objective was to investigate the executive function and its relationship with gestational age, sex, maternal education, and neurodevelopmental outcome at 2 years corrected age in children born preterm. METHOD: Executive function was assessed by means of the Multisearch Multilocation Task (MSML), Reversed Categorization Task (RevCat), and Snack Delay Task (SDT). Infant and maternal characteristics were gathered from the child's record. The developmental outcome was measured by the Bayley Scales and a multidisciplinary risk evaluation for autism. RESULTS: The executive function battery was completed by 97 children. The majority were able to successfully complete the MSML and SDT but failed RevCat. The lower the gestational age and the maternal education, the lower the executive function scores. Better cognition and motor function, as well as low autism risk, were associated with better executive function scores. Executive function was not related to sex. INTERPRETATION: This cohort study provides evidence that it is feasible to assess executive function in 2-year-olds born preterm. Executive function is related to gestational age and maternal education and is positively correlated with behavioral outcome. Therefore, executive functions can be a valuable target for early intervention, resulting in improvements in neurodevelopmental outcomes in children born preterm.

Wheelchair skills training improves power mobility and participation in young people with cerebral palsy.

AIM: To explore the effect of a 4-week structured power wheelchair skills training programme (WSTP) intervention on mobility skills and participation in children and young people (CYP) with cerebral palsy (CP). METHOD: This was a one-group, repeated-measures study; baseline, intervention, and retention phases, each lasting 4 weeks, were used. Twelve participants (three females, nine males) with a mean age of 15 years 11 months (SD = 3 years 6 months) classified in Gross Motor Function Classification System levels IV and V participated in the study. To be included in the study, individuals had to be aged 6 to 21 years and currently using a power wheelchair. Participants received 12 WSTP training sessions of 45 minutes, 3 times per week. Power mobility skills were assessed using the Wheelchair Skills Test (WST) before baseline, before the intervention, after the intervention, and at the follow-up; mobility-related participation was assessed with the Canadian Occupational Performance Measure (COPM). Generalized mixed models with Bonferroni correction were used to assess the differences between the assessment points (p < 0.05). RESULTS: Statistical analysis showed a 10.4% (12.5) increase in WST total scores (p < 0.001) after the intervention compared to before the intervention, and a 1-point (0.9) increase in the COPM performance subdomain (p = 0.002). INTERPRETATION: Power mobility skills and mobility-related participation improved after a 4-week WSTP intervention in CYP with CP. Thus, task-based power mobility skills training based on the WSTP, and in line with individualized needs and capabilities, taking place in a natural environment, should be recommended. Power mobility skills training needs to be structured and individualized; the training interventions must consider the individual, the task, and the environment.

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.

Longitudinal trajectory of medial gastrocnemius muscle growth in the first years of life.

AIM: To define the longitudinal trajectory of gastrocnemius muscle growth in 6- to 36-month-old children with and without spastic cerebral palsy (SCP) and to compare trajectories by levels of gross motor function (Gross Motor Function Classification System, GMFCS) and presumed brain-lesion timing. METHOD: Twenty typically developing children and 24 children with SCP (GMFCS levels I-II/III-IV = 15/9), were included (28/16 females/males; mean age at first scan 15.4 months [standard deviation 4.93, range 6.24-23.8]). Three-dimensional freehand ultrasound was used to repeatedly assess muscle volume, length, and cross-sectional area (CSA), resulting in 138 assessments (mean interval 7.9 months). Brain lesion timing was evaluated with magnetic resonance imaging classification. Linear mixed-effects models defined growth rates, adjusted for GMFCS levels and presumed brain-lesion timing. RESULTS: At age 12 months, children with SCP showed smaller morphological muscle size than typically developing children (5.8 mL vs 9.8 mL, p < 0.001), while subsequently no differences in muscle growth were found between children with and without SCP (muscle volume: 0.65 mL/month vs 0.74 mL/month). However, muscle volume and CSA growth rates were lower in children classified in GMFCS levels III and IV than typically developing children and those classified in GMFCS levels I and II, with differences ranging from -56% to -70% (p < 0.001). INTERPRETATION: Muscle growth is already hampered during infancy in SCP. Muscle size growth further reduces with decreasing functional levels, independently from the brain lesion. Early monitoring of muscle growth combined with early intervention is needed.

Transferability of an executive function intervention in children with cerebral palsy: A randomized controlled trial.

AIM: To evaluate the transfer effects of a home-based computerized executive function intervention on non-targeted cognitive functions (visual perception and memory), quality of life (QoL), and participation in children with cerebral palsy (CP), and to determine whether any improvements were maintained 9 months after the intervention. METHOD: Sixty children with CP (aged 8-12 years) were randomly allocated to the intervention (15 females/15 males, mean age 10 years 4 months [SD = 1 years 8 months], age range 8-12 years) or waitlist (control) (15 females/15 males, mean age 10 years [SD = 1 years 9 months], age range 8-12 years) group. The intervention group underwent a home-based executive function intervention programme for 30 minutes per day, 5 days a week, for 12 weeks. All participants were assessed before the intervention, immediately after and 9 months after the intervention was completed. RESULTS: After the intervention was completed, performance in immediate verbal memory, verbal learning, and visual perception (object and picture recognition) was significantly better in the intervention group than in the waitlist (control) group. No improvements were found in visual memory, visuospatial perception, QoL, or participation after the intervention. Scores at the follow-up showed that any beneficial effects were not maintained 9 months after the intervention was completed. INTERPRETATION: A home-based computerized executive function intervention produced transfer effects on memory and visual perception immediately after the intervention in children with CP, although any beneficial effects were not sustained at the 9-month follow-up.

Hospital-based surveillance of children with cerebral palsy in Suriname: The Suriname cerebral palsy register.

AIM: To describe the aetiological risk factors, clinical characteristics, access to rehabilitation, and educational status of children with cerebral palsy (CP) in Suriname. METHOD: Hospital-based surveillance of children with CP aged younger than 18 years was conducted at the Academic Hospital Paramaribo, Suriname (known as the Suriname CP Register [SUR-CPR]). Data were collected on sociodemographic characteristics, aetiological risk factors, clinical characteristics, rehabilitation, and educational status. Registry data on aetiological risk factors were compared with available national prevalence rates in Suriname. Descriptive statistics were reported. RESULTS: Between August 2018 and March 2020, 82 children with CP (mean [SD] age 5 years 10 months [3 years 10 months]) attending the Academic Hospital Paramaribo were registered in the SUR-CPR. The mean (SD) age at diagnosis was 5 years 5 months (4 years 1 month). Spastic CP was predominant in 90.8% of children and 58.8% were classified in Gross Motor Function Classification System levels III to V. Overall, 43.9% had preterm birth compared with 13.9% reported nationally (p < 0.001) and 61.6% had birth-related complications compared with 15% reported nationally (p < 0.001). Additionally, 39.1% had birth asphyxia and 23.2% had early feeding difficulties. Sixty-two percent were admitted to the neonatal intensive care unit, 54.0% of whom required ventilation. Most children (82.5%) had CP acquired pre- or perinatally and 17.5% had CP acquired postneonatally. Seventeen percent had never received any rehabilitation services, and 31.9% of the school-aged children were not enrolled in any education system. INTERPRETATION: The high burden of known aetiological risk factors, delayed diagnosis, and severe functional impairment among children with CP registered at the Academic Hospital Paramaribo is concerning. Public health interventions targeting early diagnosis and early intervention could improve the functional outcome of children with CP in Suriname. WHAT THIS PAPER ADDS: Almost half of the children with cerebral palsy (CP) had preterm birth, low birthweight, and signs of birth asphyxia. Most of the children were diagnosed after 5 years of age. Overall, 52.5% of children had severe forms of CP of whom only 36.6% received any assistive devices.

Deep Brain Stimulation for GNAO1-Associated Dystonia: A Systematic Review and Meta-Analysis.

OBJECTIVES: Guanine nucleotide-binding protein alpha-activating activity polypeptide O (GNAO1) syndrome, a rare congenital monogenetic disorder, is characterized by a neurodevelopmental syndrome and the presence of dystonia. Dystonia can be very pronounced and even lead to a life-threatening status dystonicus. In a small number of pharmaco-refractory cases, deep brain stimulation (DBS) has been attempted to reduce dystonia. In this study, we summarize the current literature on outcome, safety, and outcome predictors of DBS for GNAO1-associated dystonia. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis on individual patient data. We included 18 studies describing 28 unique patients. RESULTS: The mean age of onset of symptoms was 2.4 years (SD 3.8); 16 of 28 patients were male, and dystonia was nearly always generalized (20/22 patients). Symptoms were present before DBS for a median duration of 19.5 months, although highly variable, occurring between 3 and 168 months. The exact phenotype, genotype, and radiologic abnormalities varied and seemed to be of little importance in terms of DBS outcome. All studies described an improvement in dystonia. Our meta-analysis focused on pallidal DBS and found an absolute and relative improvement in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) of 32.5 points (37.9%; motor part; p = 0.001) and 5.8 points (21.5%; disability part; p = 0.043) at last follow-up compared with preoperative state; 80% of patients were considered responders (BFMDRS-M reduction by ≥25%). Although worsening over time does occur, an improvement was still observed in patients after >10 years. All reported cases of status dystonicus resolved after DBS surgery. Skin erosion and infection were observed in 18% of patients. CONCLUSION: Pallidal DBS can be efficacious and safe in GNAO1-associated dystonia.

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.

The Impact of Intraventricular Hemorrhage and Periventricular Leukomalacia on Mortality and Neurodevelopmental Outcome in Very Preterm and Very Low Birthweight Infants: A Prospective Population-based Cohort Study.

OBJECTIVE: To survey the incidence of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) by gestational age and to report the impact on mortality and neurodevelopmental outcome in very preterm/very low birthweight infants. STUDY DESIGN: This was a population-based cohort study of 1927 very preterm/very low birthweight infants born in 2014-2016 and admitted to Flemish neonatal intensive care units. Infants underwent standard follow-up assessment until 2 years corrected age with the Bayley Scales of Infant and Toddler Development and neurological assessments. RESULTS: No brain lesion was present in 31% of infants born at <26 weeks of gestation and 75.8% in infants born at 29-32 weeks of gestation. The prevalence of low-grade IVH/PVL (grades I and II) was 16.8% and 12.7%, respectively. Low-grade IVH/PVL was not related significantly to an increased likelihood of mortality, motor delay, or cognitive delay, except for PVL grade II, which was associated with a 4-fold increase in developing cerebral palsy (OR, 4.1; 95% CI, 1.2-14.6). High-grade lesions (III-IV) were present in 22.0% of the infants born at <26 weeks of gestational and 3.1% at 29-32 weeks of gestation, and the odds of death were ≥14.0 (IVH: OR, 14.0; 95% CI, 9.0-21.9; PVL: OR, 14.1; 95% CI, 6.6-29.9). PVL grades III-IV showed an increased odds of 17.2 for motor delay and 12.3 for cerebral palsy, but were not found to be associated significantly with cognitive delay (OR, 2.9; 95% CI, 0.5-17.5; P = .24). CONCLUSIONS: Both the prevalence and severity of IVH/PVL decreased significantly with advancing gestational age. More than 75% of all infants with low grades of IVH/PVL showed normal motor and cognitive outcome at 2 years corrected age. High-grade PVL/IVH has become less common and is associated with adverse outcomes.

Effectiveness of wheeled mobility skill interventions in children and young people with cerebral palsy: A systematic review.

AIM: To systematically review the effectiveness of wheeled mobility interventions in children and young people with cerebral palsy (CP). METHOD: A systematic literature search was performed in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, EBSCO, PEDro, and Web of Science using database-specific concepts such as 'child' and 'wheelchair'. Studies focusing on wheeled mobility skill interventions with participants aged 6 to 21 years with CP were included. RESULTS: Twenty studies with 203 participants were included. The impact of wheeled mobility skill interventions was assessed on mobility skills (n = 18), activity and participation (n = 10), and quality of life (n = 3). No studies reported effects on stress, fatigue, and motivational aspects. Interventions included power wheelchair skill training (n = 12), computer-based training (n = 5), smart wheelchair training (n = 2), and manual wheelchair training (n = 1), showing positive wheeled mobility intervention effects. Study quality based on the Methodological Index for Non-Randomized Studies scale was 9 out of 16 and 14 out of 24 for non-comparative and comparative studies respectively. Risk of bias was serious-to-critical on the Risk of Bias in Non-Randomized Studies of Interventions. INTERPRETATION: Wheeled mobility interventions showed promising beneficial effects on wheeled mobility, activity and participation, and quality of life for children and young people with CP. Future studies with structured and standardized training programmes and assessment tools are warranted to further accelerate the wheeled mobility skill acquisition process in this population. WHAT THIS PAPER ADDS: Wheeled mobility interventions improve wheeled mobility skills in individuals with cerebral palsy. The mobility skill acquisition process benefits from structured and standardized training. Knowledge of the intervention effects on participation and quality of life is limited. Most studies had moderate quality of evidence because of methodological limitations.

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.

Muscle synergy structure and gait patterns in children with spastic cerebral palsy.

AIM: To determine if muscle synergy structure (activations and weights) differs between gait patterns in children with spastic cerebral palsy (CP). METHOD: In this cross-sectional study, we classified 188 children with unilateral (n=82) or bilateral (n=106) spastic CP (mean age: 9y 5mo, SD: 4y 3mo, range: 3y 9mo-17y 7mo; 75 females; Gross Motor Function Classification System [GMFCS] level I: 106, GMFCS level II: 55, GMFCS level III: 27) into a minor deviations (n=34), drop foot (n=16), genu recurvatum (n=26), apparent equinus (n=53), crouch (n=39), and jump gait pattern (n=20). Surface electromyography recordings from eight lower limb muscles of the most affected side were used to calculate synergies with weighted non-negative matrix factorization. We compared synergy activations and weights between the patterns. RESULTS: Synergy structure was similar between gait patterns, although weights differed in the more impaired children (crouch and jump gait) when compared to the other patterns. Variability in synergy structure between participants was high. INTERPRETATION: The similarity in synergy structure between gait patterns suggests a generic motor control strategy to compensate for the brain lesion. However, the differences in weights and high variability between participants indicate that this generic motor control strategy might be individualized and dependent on impairment level.

Spontaneous Swallowing Frequency, Dysphagia, and Drooling in Children With Cerebral Palsy.

OBJECTIVE: To evaluate relationships between spontaneous swallowing frequency, dysphagia, and drooling in children with cerebral palsy. Spontaneous swallowing frequency was predicted to be inversely related to both dysphagia and drooling among children with cerebral palsy. A secondary objective compared patterns among spontaneous swallowing frequency, drooling, and age in healthy children vs children presenting with cerebral palsy. DESIGN: Cross sectional study. SETTING: Children with cerebral palsy were tested at a Cerebral Palsy Reference Center in a university hospital. Healthy children were tested in their home setting. PARTICIPANTS: Twenty children with cerebral palsy were recruited from the local registry for cerebral palsy children and purposive sampling among parents. A group of 30 healthy children was recruited by purposive sampling among family, friends, and the local community. Children below 1 year of age up to 5 years of age were included in the healthy group. This age range was targeted to maximize the potential for drooling in this group. MAIN OUTCOME MEASURES: Both groups provided data on spontaneous swallowing frequency (swallows per minute, or SPM), dysphagia, and drooling. Motor impairment was documented in the children with cerebral palsy. RESULTS: SPM was significantly lower in children with cerebral palsy. Among children with cerebral palsy, SPM correlated significantly with dysphagia severity and trended toward a significant correlation with drooling at rest. In this subgroup, SPM was not correlated with age or degree of motor impairment. Dysphagia was significantly correlated with drooling at rest and both dysphagia and drooling at rest were correlated with degree of motor impairment. The 2 groups did not differ in the degree of drooling at rest. Among healthy children, age but not SPM demonstrated a significant inverse correlation with drooling quotient at rest. CONCLUSIONS: Spontaneous swallowing frequency is related to dysphagia and drooling in children with cerebral palsy. The pattern of relationships among spontaneous swallowing frequency and drooling is different between children with cerebral palsy and younger healthy children.

Outcomes of Monoamniotic Twin Pregnancies from the First Trimester Onward.

INTRODUCTION: Monochorionic monoamniotic (MCMA) twins are rare, and information is lacking on pregnancy outcomes from the first trimester onward. This study compares the pregnancy and neonatal outcomes between MCMA and monochorionic diamniotic (MCDA) twin pregnancies from the first trimester onward. We also report on the outcomes of MCMA twin pregnancies continuing after 28 weeks and on the neurodevelopmental outcomes of MCMA twins. METHODS: A retrospective single-center cohort study of MCMA and MCDA twin pregnancies followed from the first trimester with a fortnightly ultrasound scan. We excluded pregnancies with a major anomaly diagnosed on the first-trimester ultrasound scan. MCMA twin pregnancies were offered inpatient monitoring from 28 weeks onward, and an elective cesarean section was advised between 32 and 33 weeks. MCDA pregnancies were managed as inpatients only if medically indicated, and an elective birth between 36 and 37 weeks was recommended. RESULTS: We analyzed the outcomes of 52 MCMA and 671 MCDA twin pregnancies. In MCMA twins, the fetal and neonatal survival rate was 81/104 (78%) versus 1,192/1,342 (89%) in MCDA twins (p = 0.016). Double intrauterine demise (IUD) was more common in MA than in DA pairs (13% vs. 3%) (p = 0.002). No IUD occurred in the 40 MCMA pregnancies that continued after 28 weeks, but five women (13%) required an urgent cesarean section for fetal distress. Thirty-eight of 52 eligible infants (73%) underwent a neurodevelopmental assessment. Thirty-three (87%) had cognitive and motor development scores within normal limits. Four infants had mild cognitive or motor impairment, and one infant was diagnosed with spastic diplegia. CONCLUSION: MCMA twins are associated with decreased survival rates compared to MCDA due to increased rates of double IUD. After 28 weeks, about one in eight women required an urgent delivery for fetal distress. Most infants had normal neurodevelopmental outcomes.

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.

Daily parenting of children with cerebral palsy: The role of daily child behavior, parents' daily psychological needs, and mindful parenting.

The purpose of this study was to advance the current understanding of the daily dynamics that are involved in raising a child with Cerebral Palsy (CP). Specifically, we examined the role of mindful parenting and of day-to-day variation in parents' psychological needs and child behavior in explaining day-to-day variation in parents' autonomy-supportive, psychologically controlling, and responsive parenting behavior. Parents (N = 58) of children with CP (Mage = 12.68 years) participated in a 7-day diary study. Multilevel analyses indicated that parents' autonomy-supportive, psychologically controlling, and responsive behaviors fluctuate considerably between days. Further, daily fluctuations in both child behavior and parents' own psychological needs were found to be associated with this daily variability in parenting. In addition, interindividual differences in mindful parenting were associated positively with parents' responsiveness and negatively with psychologically controlling parenting across the week. These findings point towards the changeability of parenting behavior among parents of a child with CP and suggest that interventions targeting parenting behavior in the context of CP will be most effective when taking into account both the parents' and the child's functioning.

The clinical relevance of intragenic NRXN1 deletions.

BACKGROUND: Intragenic NRXN1 deletions are susceptibility variants for neurodevelopmental disorders; however, their clinical interpretation is often unclear. Therefore, a literature study and an analysis of 43 previously unpublished deletions are provided. METHODS: The literature cohort covered 629 heterozygous NRXN1 deletions: 148 in controls, 341 in probands and 140 in carrier relatives, and was used for clinical hypothesis testing. Exact breakpoint determination was performed for 43 in-house deletions. RESULTS: The prevalence of exonic NRXN1 deletions in controls was ~1/3000 as compared with ~1/800 in patients with neurodevelopmental/neuropsychiatric disorders. The differential distribution of deletions across the gene between controls and probands allowed to distinguish distinct areas within the gene. Exon 6-24 deletions appeared only twice in over 100000 control individuals, had an estimated penetrance for neurodevelopmental disorders of 32.43%, a de novo rate of 50% and segregated mainly with intellectual disability (ID) and schizophrenia. In contrast, exon 1-5 deletions appeared in 20 control individuals, had an estimated penetrance of 12.59%, a de novo rate of 32.5% and were reported with a broad range of neurodevelopmental phenotypes. Exact breakpoint determination revealed six recurrent intron 5 deletions. CONCLUSION: Exon 6-24 deletions have a high penetrance and are mainly associated with ID and schizophrenia. In contrast, the actual contribution of exon 1-5 deletions to a neurodevelopmental/neuropsychiatric disorder in an individual patient and family remains very difficult to assess. To enhance the clinical interpretation, this study provides practical considerations for counselling and an interactive table for comparing a deletion of interest with the available literature data.

Complication rate after scoliosis surgery in children with cerebral palsy.

Scoliosis is an important problem in children with cerebral palsy (CP). However, the choice for a spinal fusion has to be weighed against the risks of major surgery in this vulnerable population. Paediatricians are frequently consulted preoperatively to assess the (respiratory) risk involved, but data on this question specific for CP are rare. Therefore, we investigated the complication rate after scoliosis surgery in children with CP, compared to idiopathic scoliosis (IS), and we searched for risk factors for the most common complications. In a retrospective monocenter study we analyzed the medical records from all children with CP and IS undergoing scoliosis surgery from 2010 until 2014. Duration of hospitalization and postoperative complications were compared within a 6-month follow-up. Univariate and multivariate logistic regression models were used to identify risk factors. The study included 44 patients with CP (mean age 15y0mo) and 78 patients with IS (mean age 14y6mo). Children with CP experience a higher rate of complications : respiratory and cardiovascular, as well as wound infections and decubitus ulcers (p<0.05). Postoperative pneumonia was the most frequent complication in both patient groups (43% and 18% in CP and IS respectively), with epilepsy being a significant risk factor (OR 3.85, p= 0.037) in children with CP. Intensive care unit and total hospital stay were longer in the CP group (p<0.001). These results may add information on perioperative care and surgical decision making.

FAHN/SPG35: a narrow phenotypic spectrum across disease classifications.

The endoplasmic reticulum enzyme fatty acid 2-hydroxylase (FA2H) plays a major role in the formation of 2-hydroxy glycosphingolipids, main components of myelin. FA2H deficiency in mice leads to severe central demyelination and axon loss. In humans it has been associated with phenotypes from the neurodegeneration with brain iron accumulation (fatty acid hydroxylase-associated neurodegeneration, FAHN), hereditary spastic paraplegia (HSP type SPG35) and leukodystrophy (leukodystrophy with spasticity and dystonia) spectrum. We performed an in-depth clinical and retrospective neurophysiological and imaging study in a cohort of 19 cases with biallelic FA2H mutations. FAHN/SPG35 manifests with early childhood onset predominantly lower limb spastic tetraparesis and truncal instability, dysarthria, dysphagia, cerebellar ataxia, and cognitive deficits, often accompanied by exotropia and movement disorders. The disease is rapidly progressive with loss of ambulation after a median of 7 years after disease onset and demonstrates little interindividual variability. The hair of FAHN/SPG35 patients shows a bristle-like appearance; scanning electron microscopy of patient hair shafts reveals deformities (longitudinal grooves) as well as plaque-like adhesions to the hair, likely caused by an abnormal sebum composition also described in a mouse model of FA2H deficiency. Characteristic imaging features of FAHN/SPG35 can be summarized by the 'WHAT' acronym: white matter changes, hypointensity of the globus pallidus, ponto-cerebellar atrophy, and thin corpus callosum. At least three of four imaging features are present in 85% of FA2H mutation carriers. Here, we report the first systematic, large cohort study in FAHN/SPG35 and determine the phenotypic spectrum, define the disease course and identify clinical and imaging biomarkers.

Tone Reduction and Physical Therapy: Strengthening Partners in Treatment of Children with Spastic Cerebral Palsy.

The aim of this paper is to provide a clinically applicable overview of different tone reducing modalities and how these can interact with or augment concurrent physical therapy (PT). Botulinum toxin (BoNT), oral tone-regulating medication, intrathecal baclofen (ITB), and selective dorsal rhizotomy are discussed within a physiotherapeutic context and in view of current scientific evidence. We propose clinical reasoning strategies to identify treatment goals as well as the appropriate and corresponding treatment interventions. Instrumented measurement of spasticity, standardized clinical assessment, and 3D clinical motion analysis are scientifically sound tools to help select the appropriate treatment and, when needed, to selectively target or spare individual muscles. In addition, particular attention is given to strength training as a necessary tool to tackle muscle weakness associated with specific modalities of tone reduction. More research is needed to methodologically assess the long-term effectiveness of such individualized tone treatment, optimize parameters such as medication dosage, and gain more insight into the kind of PT techniques that are essential in conjunction with tone reduction.