Exploring an objective measure of overactivity in children with rare genetic syndromes.

BACKGROUND: Overactivity is prevalent in several rare genetic neurodevelopmental syndromes, including Smith-Magenis syndrome, Angelman syndrome, and tuberous sclerosis complex, although has been predominantly assessed using questionnaire techniques. Threats to the precision and validity of questionnaire data may undermine existing insights into this behaviour. Previous research indicates objective measures, namely actigraphy, can effectively differentiate non-overactive children from those with attention-deficit hyperactivity disorder. This study is the first to examine the sensitivity of actigraphy to overactivity across rare genetic syndromes associated with intellectual disability, through comparisons with typically-developing peers and questionnaire overactivity estimates. METHODS: A secondary analysis of actigraphy data and overactivity estimates from The Activity Questionnaire (TAQ) was conducted for children aged 4-15 years with Smith-Magenis syndrome (N=20), Angelman syndrome (N=26), tuberous sclerosis complex (N=16), and typically-developing children (N=61). Actigraphy data were summarized using the M10 non-parametric circadian rhythm variable, and 24-hour activity profiles were modelled via functional linear modelling. Associations between actigraphy data and TAQ overactivity estimates were explored. Differences in actigraphy-defined activity were also examined between syndrome and typically-developing groups, and between children with high and low TAQ overactivity scores within syndromes. RESULTS: M10 and TAQ overactivity scores were strongly positively correlated for children with Angelman syndrome and Smith-Magenis syndrome. M10 did not substantially differ between the syndrome and typically-developing groups. Higher early morning activity and lower evening activity was observed across all syndrome groups relative to typically-developing peers. High and low TAQ group comparisons revealed syndrome-specific profiles of overactivity, persisting throughout the day in Angelman syndrome, occurring during the early morning and early afternoon in Smith-Magenis syndrome, and manifesting briefly in the evening in tuberous sclerosis complex. DISCUSSION: These findings provide some support for the sensitivity of actigraphy to overactivity in children with rare genetic syndromes, and offer syndrome-specific temporal descriptions of overactivity. The findings advance existing descriptions of overactivity, provided by questionnaire techniques, in children with rare genetic syndromes and have implications for the measurement of overactivity. Future studies should examine the impact of syndrome-related characteristics on actigraphy-defined activity and overactivity estimates from actigraphy and questionnaire techniques.

Concordance of objective and subjective measures of sleep in children with neurodevelopmental conditions: A systematic review and meta-analysis.

The purpose of this systematic review and meta-analysis is to delineate the concordance of objective and subjective measures of sleep in children with neurodevelopmental conditions (NDCs). A systematic literature search identified 31 studies that compare objective and subjective estimates of sleep parameters in autism, ADHD or rare genetic syndromes associated with intellectual disability. The meta-analyses revealed smaller mean differences and larger correlations indicative of greater concordance for parameters associated with sleep scheduling compared to parameters associated with sleep duration and night awakenings. Relative to objective measures, subjective measures produced: 1) greater estimates of total sleep time, sleep efficiency and time in bed; and 2) lower estimates of wake after sleep onset and number of night awakenings. Subgroup analyses also revealed differences in concordance between measurement comparison types (e.g., stronger correlations between actigraphy and sleep diaries, compared to actigraphy and questionnaires) and NDC diagnostic groups. The results predominantly replicate concordance trends observed in typically-developing samples, although some NDC-specific patterns of concordance were identified. This indicates that objective and subjective sleep measures retain broadly similar properties across populations, although researchers and clinicians should be cautious of the impact of NDC-related characteristics on sleep parameter estimates. These findings should inform sleep assessment design and the interpretation of sleep parameter estimates in NDCs, increasing the rigour of sleep parameter description across research and clinical settings.

Mapping health services for adults with cerebral palsy in Ireland: a pilot study.

Background: Cerebral palsy (CP) is a common cause of physical disability in childhood. The majority of children with CP survive to adulthood. Once discharged from children's services, adults with CP find it challenging to navigate health services. The aim of this study was to pilot and refine a methodology to map services for adults with CP in Ireland. Methods: We used a multi-informant mapping methodology consisting of: 1. Defining health services; 2. Identifying informants; 3. Designing a survey; 4. Collecting data; 5. Data checking and analysis. We collected data on services from service users and service providers using an online survey. We verified data against information available online and by asking organisations to provide details about the service. Results: Fifteen service users and nine service providers completed the online survey. Data on 265 unique services at 32 organisations were provided. The most commonly provided services were physiotherapy (12%) and occupational therapy (11%). We confirmed the name of 89 services (34%) against online information. We received further details from eight organisations about 27 services. Specifically, we received details about the organisation name for 27 of the 265 services (10%), service name for 25 services (9%), service type for 25 services (9%), a website for 19 services (7%), and data on eligibility criteria and types of supports provided for between 25 or 26 services (9% or 10%). Conclusion: This pilot study highlighted the complexity of mapping services for adults with CP in Ireland. We recommend that an alternative methodology should be used to map services for adults with CP in Ireland.

A prospective assessment of gait kinematics and related clinical examination measures in cerebral palsy crouch gait.

Background While prospectively assessed crouch gait in cerebral palsy (CP) does not necessarily progress, prospective changes in clinical examination measures have not been reported. This study prospectively examined the association between selected clinical examination variables and change in crouch gait in a cohort with bilateral CP. Methods Inclusion criteria were a diagnosis of ambulant bilateral CP, knee flexion at mid-stance >19 0 and a minimum of two-years between gait analyses. The change in kinematic variables was assessed using Statistical Parameter Mapping (SPM) and changes in clinical measures using appropriate paired tests. Linear regression examined the association between progression of crouch and clinical examination variables. Results There was no mean change in crouch in 27 participants over 3.29 years. However, there was significant variability within this group. Clinical hamstring tightness (60.00 0 to 70.48 0, p<0.01) and external knee rotation during stance (SPM analysis, p<0.001) increased but there was no association between changes in clinical examination variables and changes in crouch (p-values 0.06 - 0.89).    Conclusions This prospective study found no association between the changes in clinical examination variables and changes in crouch highlighting the likely multi-factorial aetiology of this gait pattern and the need for larger prospective studies. The variability crouch gait progression among the 27 participants highlights the pitfall of group mean values in such a heterogeneous population.

The prevalence and profile of autism in individuals born preterm: a systematic review and meta-analysis.

INTRODUCTION: Preterm birth (<37 weeks) adversely affects development in behavioural, cognitive and mental health domains. Heightened rates of autism are identified in preterm populations, indicating that prematurity may confer an increased likelihood of adverse neurodevelopmental outcomes. The present meta-analysis aims to synthesise existing literature and calculate pooled prevalence estimates for rates of autism characteristics in preterm populations. METHODS: Search terms were generated from inspection of relevant high-impact papers and a recent meta-analysis. Five databases were searched from database creation until December 2020 with PRISMA guidelines followed throughout. RESULTS: 10,900 papers were retrieved, with 52 papers included in the final analyses, further classified by assessment method (screening tools N=30, diagnostic assessment N=29). Pooled prevalence estimates for autism in preterm samples was 20% when using screening tools and 6% when using diagnostic assessments. The odds of an autism diagnosis were 3.3 times higher in individuals born preterm than in the general population. CONCLUSIONS: The pooled prevalence estimate of autism characteristics in individuals born preterm is considerably higher than in the general population. Findings highlight the clinical need to provide further monitoring and support for individuals born preterm.

The association between gait analysis measures associated with crouch gait, functional health status and daily activity levels in cerebral palsy.

PURPOSE: The aim of this study was to examine the relationship between gait analysis measures associated with crouch gait, functional health status and daily activity in ambulant cerebral palsy (CP). METHODS: Three-dimensional gait analysis was carried out on 35 ambulant participants with bilateral CP crouch gait (knee flexion at mid-stance (KFMS) ⩾ 190). KFMS, knee-flexion at initial contact, gait speed and step-lengths were extracted for analysis. Steps/day and sedentary time/day were assessed using an ActivPAL accelerometer. Functional health status was assessed using the five relevant domains of the Pediatric Outcomes Data Collection Instrument (PODCI) questionnaire. Associations between variables were assessed with correlation coefficients and multivariable linear regression. RESULTS: There were no significant correlations between KFMS and PODCI domains (ρ=-0.008-0.110) or daily activity (ρ=-0.297-0.237) variables. In contrast, multivariable analysis found that step-length was independently associated with the Sports and Physical Function (p= 0.030), Transfers and Basic Mobility (p= 0.041) and Global Function (< 0.001) domains of the PODCI assessment. Gait speed was independently associated with mean steps/day (p< 0.001). CONCLUSIONS: Step length and gait speed are more strongly associated with functional health status and daily activity than knee flexion during stance in children and adolescents with CP crouch gait.

Unmet healthcare needs in adults with childhood-onset neurodisabilities: a protocol for a systematic review.

Background Many adults with childhood-onset neurodisabilities, such as those with intellectual disability or cerebral palsy, report difficulties accessing the healthcare that they require when they are no longer eligible for paediatric services. Compared to the general population, this population is at greater risk of developing many ageing-related diseases and has higher rates of preventable deaths and premature mortality. Addressing unmet healthcare needs is essential to ensuring equitable access in a quality healthcare system. The aim of this systematic review is to synthesise the current available evidence related to unmet healthcare needs in adults with a range of childhood-onset neurodisabilities. Methods A systematic review of quantitative research studies of adults with a range of diagnoses that fall under the neurodisability umbrella and outcomes related to unmet healthcare needs will be undertaken. The Conducting Systematic Reviews and Meta-Analyses of Observational Studies (COSMOS-E) guidelines will be adhered to. Searches of key databases will be undertaken, and a two-phase screening process carried out by pairs of independent reviewers to select studies that meet the inclusion criteria. Data will be extracted using a purposefully designed form. Risk of bias will be assessed using the Joanna Briggs Institute Critical Appraisal Tools. If it is possible to pool prevalence data, a meta-analysis will be undertaken. Where pooling of data is not possible, a structured synthesis approach will be used, and results will be presented in tables and summarised narratively. Conclusions In recent years, there has been increased emphasis placed on promoting positive ageing and improving the healthcare experiences throughout the lifespan for people with neurodisabilities. Findings of this systematic review can inform decision-making related to healthcare for this vulnerable population and has the potential to contribute to reducing preventable deaths and premature mortality and promoting positive and healthy ageing for this group.

A prospective assessment of the progression of flexed-knee gait over repeated gait analyses in the absence of surgical intervention in bilateral cerebral palsy.

BACKGROUND: Flexed-knee gait is a common pattern associated with cerebral palsy (CP). It leads to excessive forces on the knee and is thought to contribute to pain and deformity. While studies have shown improvements in mid-stance knee flexion following surgery there remains a lack of prospective data on the progression of flexed-knee gait in the absence of surgery. RESEARCH QUESTION: Does knee flexion progress over repeated assessments in the absence of surgery in a prospectively assessed cohort with CP? METHODS: Inclusion criteria were a diagnosis of bilateral CP, knee flexion at mid-stance >19° and no surgery within one year of the first gait analysis. Gait analysis was carried out at six-month intervals (minimum of three and maximum of six assessments). The progression of knee flexion over repeated analyses was assessed. The association between changes in knee flexion between assessments and gender, age, GMFCS level, change in ankle dorsiflexion, change in height and change in weight was examined. RESULTS: Forty-eight participants met the initial inclusion criteria and 32 (GMFCS I = 11, II = 17, III = 4) completed the minimum three assessments. Of the 32 included participants, 21 participants (66%) demonstrated decreased knee flexion at mid-stance (mean decrease 6.6° ± 3.4°; range 2.0°-13.0°) and 11 participants (34%) demonstrated increased knee flexion at mid-stance (mean increase 10.4° ± 7.1°; range 2.0°-20.0°) at one-year follow-up. Eighteen (56%) then demonstrated an overall decrease (mean 7.4° ± 5.1°) in knee flexion between the first and last assessment with last follow-up at 1-2 years (n = 3), 2-3 years (n = 3) and 3-4 years (n = 12). The majority of participants (78%) demonstrated episodes of both increasing and decreasing Knee flexion between individual assessments and further analysis found that age was associated with this inter-assessment variability in knee flexion. SIGNIFICANCE: Flexed-knee gait is not always progressive in bilateral CP and demonstrated variability associated with age.

The short-term effects of selective dorsal rhizotomy on gait compared to matched cerebral palsy control groups.

OBJECTIVES: To examine the short-term effects of selective dorsal rhizotomy (SDR) ± soft-tissue surgery on gait in cerebral palsy (CP) compared to matched controls with no surgical intervention. METHODS: Participants had gait analysis before and one year after SDR. Non SDR participants were retrospectively matched for age and all significant gait parameters. The SDR group was further subdivided into those who had concomitant orthopaedic surgery and those who had SDR only. RESULTS: The SDR group consisted of 29 participants (mean age 5.8 years at baseline, 7.7 years at follow-up). Of these, 13 had concomitant orthopaedic surgery. The non SDR group consisted of 18 participants (mean age at baseline 6.1 years, 8.1 years at follow-up). SDR ± soft-tissue surgery significantly improved step-lengths, knee flexion at initial contact and mid-stance, ankle dorsiflexion, foot progression and timing of peak knee flexion. None of these improvements in gait were seen without surgical intervention. While more improvements were seen in those who had SDR and orthopaedic surgery, SDR only resulted in improved step-lengths, knee extension, foot progression and timing of peak knee flexion. CONCLUSIONS: SDR ± soft-tissue surgery results in short-term improvements in gait which are not seen without surgical intervention. While those who had SDR and soft-tissue surgery demonstrated more changes in gait, many improvements were attributable to SDR only.

Deep phenotyping of 14 new patients with IQSEC2 variants, including monozygotic twins of discordant phenotype.

Whole-exome sequencing has established IQSEC2 as a neurodevelopmental disability gene. The IQSEC2 variant phenotype includes developmental delay, intellectual disability, epilepsy, hypotonia, autism, developmental regression, microcephaly and stereotypies but is yet to be fully described. Presented here are 14 new patients with IQSEC2 variants. In addition to the established features, we observed: gait ataxia in 7 of 9 (77.8%), drooling in 9 of 14 (64.2%), early feeding difficulties in 7 of 14 (50%), structural brain abnormalities in 6 of 13 (46.2%), brachycephaly in 5 of 14 (35.7%), and scoliosis and paroxysms of laughter each in 4 of 14 (28.6%). We suggest that these are features of the IQSEC2-related disorder. Gastrostomy requirement, plagiocephaly, strabismus and cortical blindness, each seen in 2 of 14 (14.3%), may also be associated. Shared facial features were noted in 8 of 14 patients, and shared hair patterning was identified in 5 of 14 patients. This study further delineates the IQSEC2 phenotypic spectrum and supports the notion of an emerging IQSEC2 syndrome. We draw parallels between the IQSEC2-related disorder and the Angelman-/Rett-/Pitt-Hopkins syndrome group of conditions and recommend the addition of IQSEC2 to epilepsy and developmental delay gene panels. We observed discordant phenotypes in monozygotic twins and apparent gonadal mosaicism, which has implications for recurrence risk counselling in the IQSEC2-related disorder.

Idiopathic toe walking-A follow-up survey of gait analysis assessment.

BACKGROUND: Toe-walking is a normal variant in children up to 3 years of age but beyond this a diagnosis of idiopathic toe-walking (ITW) must be considered. ITW is an umbrella term that covers all cases of toe-walking without any diagnosed underlying medical condition and before assigning these diagnosis potential differential diagnoses such as cerebral palsy, peripheral neuropathy, spinal dysraphism and myopathy must be ruled out. Gait laboratory assessment (GLA) is thought to be useful in the evaluation of ITW, and kinematic, kinetic and electromyography features associated with ITW have been described. However, the longer term robustness of a diagnosis based on GLA has not been investigated. The primary aim of this study was to examine if a diagnosis of ITW based on GLA features persisted. METHODS: All patients referred to a national gait laboratory service over a ten year period with queried ITW were sent a postal survey to establish if a diagnosis of ITW which had been offered following GLA persisted over time. The gait and clinical parameters differentiating those reported as typical ITW and not-typical-ITW following GLA were examined in the survey respondents. RESULTS: Of 102 referrals to the laboratory with queried ITW, a response rate of 40.2% (n = 41) was achieved. Of the respondents, 78% (n = 32) were found to be typical of ITW following GLA and this diagnosis persisted in the entire group at an average of 7 years post GLA. The other nine subjects were reported as not typical of ITW following GLA and 44.4% (n = 4) received a subsequent differential diagnosis. The clinical examination and gait analysis features differentiating these groups were consistent with previous literature. CONCLUSION: GLA appears to be a useful objective tool in the assessment of ITW and a diagnosis based on described features persists in the long-term.

The natural history of crouch gait in bilateral cerebral palsy: A systematic review.

AIM: To systematically review the natural history of crouch gait in bilateral cerebral palsy (CP) in the absence of surgical intervention and to review any relationship between clinical variables and progression of knee crouch. METHODS: Relevant literature was identified by searching article databases (PubMed, CINAHL, EMBASE, and Web of Science). Included studies reported on participants with bilateral CP who had 3-dimensional gait analysis on at least two occasions with no surgical interventions between analyses. RESULTS: Five papers (4 retrospective cohort studies; 1 case report) comprised the final selection. Studies varied in follow-up times and participant numbers. Increased knee flexion over time was reported in the four retrospective studies with two distinct patterns of increasing knee flexion evident. Only the case-study reported improved knee extension between assessments. Four studies demonstrated increased hamstring tightness over time with the biggest increases related to longer follow-up time rather than increase in crouch. CONCLUSION AND IMPLICATIONS: The existing literature suggests that the natural history of crouch gait is towards increasing knee flexion over time. Future prospective studies of bigger groups are needed to examine the relationship between increasing crouch and clinical variables.

Novel PLS3 variants in X-linked osteoporosis: Exploring bone material properties.

BACKGROUND: Idiopathic Juvenile Osteoporosis (IJO) refers to significantly lower than expected bone mass manifesting in childhood with no identifiable aetiology. IJO classically presents in early pubertal period with multiple fractures including metaphyseal and vertebral crush fractures, and low bone-mass. METHODS: Here we describe two patients and provide information on their clinical phenotype, genotype and bone material analysis in one of the patients. RESULTS: Patient 1: 40-year old adult male diagnosed with IJO in childhood who re-presented with a hip fracture as an adult. Genetic analysis identified a pathogenic PLS3 hemizygous variant, c.1765del in exon 16. Patient 2: 15-year old boy with multiple vertebral fractures and bone biopsy findings suggestive of IJO who also has a diagnosis of autism spectrum disorder. Genetic analysis identified a maternally inherited PLS3 pathogenic c.1295T>A variant in exon 12. Analyses of the transiliac bone sample revealed severe reduction of trabecular volume and bone turnover indices and elevated bone matrix mineralisation. DISCUSSION: We propose that genetic testing for PLS3 should be undertaken in patients presenting with a current or previous history of IJO as this has implications for genetic counselling and cascade screening. The extensive evaluation of the transiliac biopsy sample of Patient 2 revealed a novel bone phenotype. CONCLUSION: This report includes a review of IJO and genetic causes of osteoporosis, and suggests that existing cases of IJO should be screened for PLS3. Through analysis of bone material properties in Patient 2, we can conclude that PLS3 does have a role in bone mineralisation.

Water-filled training tubes increase core muscle activation and somatosensory control of balance during squat.

This study examined trunk muscle activation, balance and proprioception while squatting with a water-filled training tube (WT) and a traditional barbell (BB), with either closed (CE) or open eyes (OE). Eighteen male elite Gaelic footballers performed an isometric squat under the following conditions: BB-OE, BB-CE, WT-OE and WT-CE. The activity of rectus abdominis (RA), external oblique (EO) and multifidus (MF) was measured using electromyography, along with sway of the centre of pressure (CoP) using a force platform. Only the EO and the MF muscles exhibited an increased activity with WT (p < 0.01). In the medio-lateral direction both the velocity and range of the CoP increased significantly with WT (p < 0.01). Interestingly, the range of the CoP for the WT-CE condition was significantly lower than WT-OE (p < 0.05, d = 0.44), whilst the velocity of the CoP was marginally reduced (d = 0.29). WT elicited a greater level core muscle activation and created a greater challenge to postural stability when compared to a BB. It appears that WT does not benefit from vision but emphasises the somatosensory control of balance. The use of WT may be beneficial in those sports requiring development of somatosensory/proprioceptive contribution to balance control.

Recurrent internal hip rotation gait in cerebral palsy: Case reports of two patients.

Internal hip rotation in cerebral palsy (CP) is typically treated with a femoral derotation osteotomy. This has been shown to be largely a successful procedure but recurrence rates up to 41% have been reported. Reported risk factors include younger age, reduced hip joint impulse and ankle plantar-flexion.  We report on two patients with bilateral CP demonstrating recurrent unilateral internal hip rotation despite surgical intervention(s).  Both demonstrate a number of the reported risk factors for recurrence.  In addition, this case report specifically compared gait kinematic patterns pre and post recurrence. On comparing both patient's hip rotation and ankle dorsi/plantarflexion kinematics they are seen to be almost identical both pre-operatively and post-operatively. Both patients appear to revert to approximately 30 o of internal hip rotation which has been shown to maximise hip abductor function. Therefore, surgical derotation in isolation is unlikely to be successful in this group and we suggest that this hip and ankle pattern may help predict recurrence in unilateral internal hip rotation.

Pathological Movements of the Pelvis and Trunk During Gait in Children With Cerebral Palsy: A Cross-Sectional Study With 3-Dimensional Kinematics and Lower Lumbar Spinal Loading.

Background: Increased loading at the lumbar spine, particularly in the coronal plane, has been reported in children with cerebral palsy (CP). As pelvic and trunk movements associated with Trendelenburg and Duchenne type gait are most significant in the coronal plane, the potential exists for lower lumbar spinal loading to be negatively affected in children with CP and these types of movement patterns. Objective: The objective of this study was to assess trunk and pelvic kinematics and lower lumbar spinal loading patterns in children with CP and Trendelenburg and Duchenne type gait. Design: This was a cross-sectional study. Methods: Three-dimensional kinematic (lower limb and thorax) and L5-S1 kinetic data were recorded. Children were divided according to clinical presentation of Trendelenburg or Duchenne type gait. Several discrete kinematic and kinetic parameters were assessed between groups. Results: Three distinct pelvic and trunk movement patterns were identified for children with CP: Trendelenburg, Duchenne, and complex Trendelenburg-Duchenne. Peak L5-S1 lateral bending moments were increased by 62% in children with CP and Duchenne type gait. Children with CP and complex Trendelenburg-Duchenne gait demonstrated the largest deviations from normal, with increased peak ipsilateral and contralateral directed moments of 69% and 54%, respectively, compared with children with typical development. Limitations: A test-retest reliability analysis or measure of minimal detectable change was not conducted as part of this study. Results suggest that measures of minimal detectable change may be high for some of the reported variables. In addition, the inverse dynamic approach determines only the net intersegmental reactive forces that reflect the effect of external loads. Previous studies have shown that spinal loads may be larger than the net intersegmental force. Conclusions: Trendelenburg and Duchenne type movements were not always distinct, and a third type of movement, a combination of the two, was the most common in this study. Clinicians should be aware that children with CP and the Duchenne type or the complex Trendelenburg-Duchenne type of gait pattern experience abnormal loading that may have significant implications for the lower spine in the long term.

Run kinematics with and without a jogging stroller.

BACKGROUND: Jogging strollers have become increasingly popular as they allow a parent the freedom to run without having to leave their children. Few studies have examined the effects of running with a stroller and no study to date has examined the effects on joint kinematics. The aim of this study was to compare lower limb and trunk kinematics while running with and without a jogging stroller. METHODS: Participants (N=15) ran on a 16-metre indoor runway, with and without a stroller, at their self-selected comfortable training speed. Three-dimensional trunk and lower limb kinematics were assessed using the CODA cx1 active marker system. FINDINGS: The jogging stroller led to reduced movement of the trunk in both the transverse [mean difference -11.4°, 95% confidence interval (CI) (-14.8°, -8.2°), p<0.001] and coronal [-2.9°, 95% CI (-0.8°, -4.9°), p=0.009] planes most likely due to fixing of the upper limbs. There was also a 6.7° [95% CI (-9°, -4.6°), p<0.001] increase in forward trunk lean, 2.8° [95% CI (-4.2°, -1.7°), p<0.001] increase in anterior pelvic tilt and a 3° [95% CI (-4.4°, -1.5°), p=0.001] decrease in hip extension. There were no significant changes in knee or ankle kinematics and no changes in stride length, cadence or stance time. INTERPRETATION: Our data suggest that jogging strollers lead to minor changes in trunk, pelvis and hip kinematics with no significant changes at the knee and ankle. Due to the changes in kinematics we suggest that flexibility work for the spine, pelvis and hips may be recommended.