Incidence and sequence of scoliosis and windswept hip deformity: which comes first in 4148 children with cerebral palsy? A longitudinal cohort study.

BACKGROUND: The aim was to analyse whether scoliosis or windswept hip deformity (WSH) occurs first for children with cerebral palsy (CP). METHODS: This longitudinal cohort study using data from 1994 - 2020 (26 years) involved 41,600 measurements of 4148 children (2419 [58.3%] boys) with CP born 1990 - 2018 and registered into the Swedish CP follow-up program. Children were followed from a mean age of 2.8 [SD 1.4] years, until they developed either scoliosis or WSH or were removed at surgery. RESULTS: WSH developed first in 16.6% of the children (mean age 8.1 [SD 5.0] years), and scoliosis in 8.1% (mean age 8.1 [SD 4.9] years). The incidence of WSH was higher than scoliosis across all levels I-V of the Gross Motor Function Classification System (GMFCS), both sexes, and for those with dyskinetic (20.0%) or spastic (17.0%) CP. The incidence of scoliosis was highest (19.8%) and developed earliest in children with GMFCS level V (mean age 5.5 [SD 3.5] years), and in children with dyskinetic (17.9%) CP (mean age 7.0 [SD 4.7] years). CONCLUSIONS: WSH presents earlier than scoliosis in most children with CP. Children with higher GMFCS level or dyskinetic CP are more likely to develop these deformities at a younger age.

Probability of independent walking and wheeled mobility in individuals with cerebral palsy.

AIM: To estimate the probability of independent walking and wheeled mobility in individuals with cerebral palsy (CP) at home and in the community in relation to age and gross motor function. METHOD: This was a longitudinal cohort study using data reported into the combined Swedish CP follow-up programme and national quality registry from October 2000 to October 2022. Walking, walking with aids, wheeled mobility, and assisted mobility defined independent or assisted mobility at home and in the community, based on the Functional Mobility Scale with additional data on wheelchair performance, were assessed. RESULTS: There were 52 858 examinations reported for 6647 individuals with CP (age range 0-32 years, follow-up period 0-22 years). Most children and adults in Gross Motor Function Classification System (GMFCS) levels I or II walked without assistive devices. The probability of dependence on others for mobility in the community was high for both children and adults in GMFCS levels III to V. INTERPRETATION: Although independent mobility is vital for participation and social inclusion, many children and adults with CP are dependent on others for mobility. We recommend clinicians, together with families and individuals with CP, explore how to increase access to independent mobility from an early age and continuously throughout the life course. WHAT THIS PAPER ADDS: • There is a high probability of independent walking in Gross Motor Function Classification System (GMFCS) levels I to II. • Mobility options vary most at home and in the community in GMFCS level III. • Being dependent on others for mobility is likely in GMFCS levels III to V.

Microglia produce the amyloidogenic ABri peptide in familial British dementia.

Mutations in ITM2B cause familial British, Danish, Chinese and Korean dementias. In familial British dementia (FBD) a mutation in the stop codon of the ITM2B gene (also known as BRI2 ) causes a C-terminal cleavage fragment of the ITM2B/BRI2 protein to be extended by 11 amino acids. This fragment, termed amyloid-Bri (ABri), is highly insoluble and forms extracellular plaques in the brain. ABri plaques are accompanied by tau pathology, neuronal cell death and progressive dementia, with striking parallels to the aetiology and pathogenesis of Alzheimer's disease. The molecular mechanisms underpinning FBD are ill-defined. Using patient-derived induced pluripotent stem cells, we show that expression of ITM2B/BRI2 is 34-fold higher in microglia than neurons, and 15-fold higher in microglia compared with astrocytes. This cell-specific enrichment is supported by expression data from both mouse and human brain tissue. ITM2B/BRI2 protein levels are higher in iPSC-microglia compared with neurons and astrocytes. Consequently, the ABri peptide was detected in patient iPSC-derived microglial lysates and conditioned media but was undetectable in patient-derived neurons and control microglia. Pathological examination of post-mortem tissue support ABri expression in microglia that are in proximity to pre-amyloid deposits. Finally, gene co-expression analysis supports a role for ITM2B/BRI2 in disease-associated microglial responses. These data demonstrate that microglia are the major contributors to the production of amyloid forming peptides in FBD, potentially acting as instigators of neurodegeneration. Additionally, these data also suggest ITM2B/BRI2 may be part of a microglial response to disease, motivating further investigations of its role in microglial activation. This has implications for our understanding of the role of microglia and the innate immune response in the pathogenesis of FBD and other neurodegenerative dementias including Alzheimer's disease.

Is there evidence for a relationship between cognitive impairment and fatigue after acquired brain injury: a systematic review and meta-analysis.

PURPOSE: Fatigue is a major symptom of ABI. Greater fatigue is associated with cognitive impairment. Our aim was to systematically review, describe and analyse the literature on the extent of this relationship. METHODS: Five databases were searched from inception. Studies were included where: participants had a defined clinical diagnosis of ABI which included TBI, stroke or subarachnoid haemorrhage; a fatigue measure was included; at least one objective cognitive measure was used. Three reviewers individually identified studies and determined quality using the Quality Assessment Tool for Observational Cohort and Cross-sectional Studies. RESULTS: Sixteen of the 412 identified studies, investigating the relationship between cognitive dysfunction and fatigue, comprising a total of 1,745 participants, were included. Quality ranged from fair to good. Meta-analysis found fatigue was significantly associated with an overall pattern of cognitive slowing on tasks of sustained attention. A narrative synthesis found weak associations with fatigue and information processing, attention, memory and executive function. CONCLUSION: Analysis found sustained attentional performance had stronger associations with fatigue after ABI. Whereas, weak associations were found between fatigue and information processing, attention and to some extent memory and executive function. More focused research on specific cognitive domains is needed to understand the mechanisms of fatigue.

Cognitive dysfunction is associated with higher fatigue levels after stroke, traumatic brain injury or subarachnoid haemorrhage.Management of cognitive dysfunction may improve fatigue and participation in meaningful activities after stroke, traumatic brain injury or subarachnoid haemorrhage.Intervention strategies that reduce cognitive load during everyday activities (e.g., grading the burden on attentional resources), may potentially be effective in managing post-ABI fatigue.Agreement on core measures could facilitate integration of findings into clinical practice.

Postural asymmetries, pain, and ability to change position of children with cerebral palsy in sitting and supine: a cross-sectional study.

PURPOSE: To examine any associations between postural asymmetries, postural ability, and pain for children with cerebral palsy in sitting and supine positions. METHODS: A cross-sectional study of 2,735 children with cerebral palsy, 0-18 years old, reported into the Swedish CPUP registry. Postural asymmetries, postural ability, the gross motor function classification system levels I-V, sex, age and report of pain were used to determine any relationship between these variables. RESULTS: Over half the children had postural asymmetries in sitting (n = 1,646; 60.2%) or supine (n = 1,467; 53.6%). These increased with age and as motor function decreased. Children were twice as likely to have pain if they had an asymmetric posture (OR 2.1-2.7), regardless of age, sex and motor function. Children unable to maintain or change position independently were at higher risk for postural asymmetries in both supine (OR 2.6-7.8) and sitting positions (OR 1.5-4.2). CONCLUSIONS: An association was found between having an asymmetric posture and ability to change position in sitting and/or lying; and with pain. The results indicate the need to assess posture and provide interventions to address asymmetric posture and pain.Implications for rehabilitationPostural asymmetries are present in children with cerebral palsy at all levels of gross motor function.Postural asymmetries increase with age and are associated with pain.Assessment of posture should be included in surveillance programs to enable early detection and treatment.

Relationship between scoliosis, windswept hips and contractures with pain and asymmetries in sitting and supine in 2450 children with cerebral palsy.

PURPOSE: This cross-sectional study of 2450 children with cerebral palsy aimed to analyse the prevalence and association of scoliosis, windswept hips, hip and knee contractures. METHODS: Logistic regression was used to estimate associations with pain, postural asymmetries, and ability to change position for children at Gross Motor Function Classification System (GMFCS) levels I-V, aged 0-18 years. RESULTS: Most children with a deformity or contracture had postural asymmetries in both sitting and supine positions; 10.5% had scoliosis, 8.7% windswept hips, 6.6% hip flexion and 19.2% knee contractures. Severe postural asymmetries increased the likelihood for scoliosis 9 times, for windswept hips 6 to 9 times, and for hip and knee flexion contractures 7 and 12 times respectively, adjusted for age, sex and GMFCS level. Hip flexion contractures and windswept hips increased the likelihood for pain by 1.5-1.6 times. CONCLUSION: The likelihood of having scoliosis, windswept hips and flexion contractures in the hips and knees increased if the child had postural asymmetries, and for increased age and higher GMFCS levels. Efforts should focus on preventing postural asymmetries from occurring or progressing, and on increasing the child's ability to change position. Reducing postural asymmetries may also reduce the likelihood of pain.Implications for RehabilitationThe risk of having scoliosis, windswept hip deformity and flexion contractures in the hips and knees increased if the child had postural asymmetries in sitting or lying.Efforts should focus on preventing or reducing postural asymmetries, and on increasing the child's ability to change position.Reducing postural asymmetries may also reduce the risk of pain.

Familial Alzheimer's Disease Mutations in PSEN1 Lead to Premature Human Stem Cell Neurogenesis.

Mutations in presenilin 1 (PSEN1) or presenilin 2 (PSEN2), the catalytic subunit of γ-secretase, cause familial Alzheimer's disease (fAD). We hypothesized that mutations in PSEN1 reduce Notch signaling and alter neurogenesis. Expression data from developmental and adult neurogenesis show relative enrichment of Notch and γ-secretase expression in stem cells, whereas expression of APP and ß-secretase is enriched in neurons. We observe premature neurogenesis in fAD iPSCs harboring PSEN1 mutations using two orthogonal systems: cortical differentiation in 2D and cerebral organoid generation in 3D. This is partly driven by reduced Notch signaling. We extend these studies to adult hippocampal neurogenesis in mutation-confirmed postmortem tissue. fAD cases show mutation-specific effects and a trend toward reduced abundance of newborn neurons, supporting a premature aging phenotype. Altogether, these results support altered neurogenesis as a result of fAD mutations and suggest that neural stem cell biology is affected in aging and disease.

Modelling frontotemporal dementia using patient-derived induced pluripotent stem cells.

Frontotemporal dementia (FTD) describes a group of clinically heterogeneous conditions that frequently affect people under the age of 65 (Le Ber et al., 2013). There are multiple genetic causes of FTD, including coding or splice-site mutations in MAPT, GRN mutations that lead to haploinsufficiency of progranulin protein, and a hexanucleotide GGGGCC repeat expansion in C9ORF72. Pathologically, FTD is characterised by abnormal protein accumulations in neurons and glia. These aggregates can be composed of the microtubule-associated protein tau (observed in FTD with MAPT mutations), the DNA/RNA-binding protein TDP-43 (seen in FTD with mutations in GRN or C9ORF72 repeat expansions) or dipeptide proteins generated by repeat associated non-ATG translation of the C9ORF72 repeat expansion. There are currently no disease-modifying therapies for FTD and the availability of in vitro models that recapitulate pathologies in a disease-relevant cell type would accelerate the development of novel therapeutics. It is now possible to generate patient-specific stem cells through the reprogramming of somatic cells from a patient with a genotype/phenotype of interest into induced pluripotent stem cells (iPSCs). iPSCs can subsequently be differentiated into a plethora of cell types including neurons, astrocytes and microglia. Using this approach has allowed researchers to generate in vitro models of genetic FTD in human cell types that are largely inaccessible during life. In this review we explore the recent progress in the use of iPSCs to model FTD, and consider the merits, limitations and future prospects of this approach.

Wake-Promoting and EEG Spectral Effects of Modafinil After Acute or Chronic Administration in the R6/2 Mouse Model of Huntington's Disease.

Huntington's disease (HD) is characterised by progressive symptoms including cognitive deficits and sleep/wake disturbances reflected in an abnormal electroencephalography (EEG). Modafinil, a wake-promoting and cognitive-enhancing drug, has been considered as a treatment for HD. We used HD (R6/2) mice to investigate the potential for using modafinil to treat sleep-wake disturbance in HD. R6/2 mice show sleep-wake and EEG changes similar to those seen in HD patients, with increased rapid eye movement sleep (REMS), decreased wakefulness/increased non-REMS (NREMS), and pathological changes in EEG spectra, particularly an increase in gamma power. We recorded EEG from R6/2 and wild-type mice treated with modafinil acutely (with single doses between 25 and 100 mg/kg; at 12 and 16 weeks of age), or chronically (64 mg/kg modafinil/day from 6 to 15 weeks). Acutely, modafinil increased wakefulness in R6/2 mice and restored NREMS to wild-type levels at 12 weeks. It also suppressed the pathologically increased REMS. This was accompanied by decreased delta power, increased peak frequency of theta, and increased gamma power. At 16 weeks, acute modafinil also restored wakefulness and NREMS to wild-type levels. However, whilst REMS decreased, it did not return to normal levels. By contrast, in the chronic treatment group, modafinil-induced wakefulness was maintained at 15 weeks (after 9 weeks of treatment). Interestingly, chronic modafinil also caused widespread suppression of power across the EEG spectra, including a reduction in gamma that increases pathologically in R6/2 mice. The complex EEG effects of modafinil in R6/2 mice should provide a baseline for further studies to investigate the translatability of these result to clinical practice.

Developmental coordination disorders and sensory processing and integration: Incidence, associations and co-morbidities.

INTRODUCTION: Children with developmental coordination disorder or sensory processing and integration difficulties face challenges to participation in daily living. To date there has been no exploration of the co-occurrence of developmental coordination disorders and sensory processing and integration difficulties. METHOD: Records of children meeting Diagnostic and Statistical Manual - V criteria for developmental coordination disorder (n = 93) age 5 to 12 years were examined. Data on motor skills (Movement Assessment Battery for Children - 2) and sensory processing and integration (Sensory Processing Measure) were interrogated. RESULTS: Of the total sample, 88% exhibited some or definite differences in sensory processing and integration. No apparent relationship was observed between motor coordination and sensory processing and integration. The full sample showed high rates of some difficulties in social participation, hearing, body awareness, balance and motion, and planning and ideation. Further, children with co-morbid autistic spectrum disorder showed high rates of difficulties with touch and vision. CONCLUSION: Most, but not all, children with developmental coordination disorder presented with some difficulties in sensory processing and integration that impacted on their participation in everyday activities. Sensory processing and integration difficulties differed significantly between those with and without co-morbid autistic spectrum disorder.

Physical risk factors influencing wheeled mobility in children with cerebral palsy: a cross-sectional study.

BACKGROUND: There is a lack of understanding of the factors that influence independent mobility and participation in meaningful activities. The purpose of this study was to analyse physical factors influencing independent use of manual and power wheelchairs in a total population of children with cerebral palsy (CP). METHODS: A cross-sectional study based on the most recent examination of all children with CP, born 2002-2013, reported into the Swedish cerebral palsy registry (CPUP), from January 2012 to June 2014. There were 2328 children (58 % boys, 42 % girls), aged 0-11 years, at all levels of gross motor function and hand function. Hazard ratios adjusted for age and sex were used to calculate the risk for not being able to self-propel based on Gross Motor Function Classification System (GMFCS) levels, upper extremity range of motion and hand function including Manual Ability Classification System (MACS), House functional classification system, Thumb-in-palm deformity, Zancolli (spasticity of wrist/finger flexors) and bimanual ability. RESULTS: In total 858 children used wheelchairs outdoors (692 manual, 20 power, 146 both). Only 10 % of the 838 children self-propelled manual wheelchairs, while 90 % were pushed. In contrast 75 % of the 166 children who used power mobility outdoors were independent. Poor hand function was the greatest risk factor for being unable to self-propel a manual wheelchair, while classification as GMFCS V or MACS IV-V were the greatest risk factors for not being able to use a power wheelchair independently. CONCLUSIONS: The majority of children with CP, aged 0-11 years did not self-propel manual wheelchairs regardless of age, gross motor function, range of motion or manual abilities. Power mobility should be considered at earlier ages to promote independent mobility for all children with CP who require a wheelchair especially outdoors.

Secondary health conditions experienced by people with spinal cord injury within community living: implications for a National Disability Insurance Scheme.

BACKGROUND: Australia's National Disability Insurance Scheme (NDIS) provides supports for individuals, delivered through a personalised participant planning process, to influence choice and goal attainment. AIM: This study aimed to use both quantitative and qualitative methods to examine the impact of secondary health conditions on the experiences of people with spinal cord injury (SCI) who have returned to community living, in the context of Australia's National Disability Strategy and recently launched NDIS. Exploration of lived experience of health conditions following SCI utilising this mixed methods approach may offer important insights for effective planning within an NDIS. METHODS: A cross-sectional survey using the Spinal Cord Injury Secondary Conditions Scale (SCISCS), demographic questionnaire and in-depth interview was undertaken with 33 people with SCI living in the community. Demographic and SCISCS data were reported using descriptive statistics. Interviews were audio-taped, transcribed and analysed thematically. RESULTS: Participants were on average 58.5 years of age and 20 years post-injury. Five key themes emerged relating to (i) spasm and pain; (ii) sexual dysfunction; (iii) pressure areas; (iv) fatigue; and (v) the impact of secondary health conditions on life role participation and choice of supports and equipment. CONCLUSION: Secondary health conditions can significantly impact occupational participation following SCI. Appropriate intervention, including customised equipment and direct support, if delivered as part of an effective NDIS, may prevent or reduce the severity of these conditions and offer the potential to influence health and participation outcomes of people who have returned to community living.

Establishing best practice in seating assessment for children with physical disabilities using qualitative methodologies.

PURPOSE: To identify best practice in children's seating assessment in the UK and Ireland. METHOD: The researchers observed six children's seating assessments performed by four therapists at three regional centres, to capture routine seating assessment practice. Observed assessment components were recorded on an 83-item checklist derived from existing published literature, and supported by video-recording. A Delphi technique obtained opinions on best practice seating assessment from seven expert therapists using three rounds of questionnaires. Themes were rated by respondents on 'importance', 'desirability' and 'feasibility'. Consensus of 70% was sought on all rated sub-themes. OBSERVATION: two assessment items (problem identification and prescription) were observed on every occasion. All other items occurred zero to five times. Standardised assessment methods were not observed. Delphi: themes identified were 'assessment process', 'assessment approach' and 'broader issues'. Consensus was reached on importance and desirability of 'assessment process' and 'assessment approach' sub-themes. CONCLUSIONS: Variation in seating assessment practice occurred between regions, yet there was agreement on theoretical best practice components. This may reflect the complexity of seating assessment in reality. The need for, and benefits of, a consistent approach was clearly identified. Future research should be directed toward developing a best practice assessment tool, which links assessment findings to appropriate seating solutions.

Occupational therapy students' attitudes towards inclusion education in Australia, United Kingdom, United States and Taiwan.

This international, cross-cultural study investigated the attitudes of occupational therapy students from Australia, United Kingdom, United States and Taiwan towards inclusive education for students with disabilities. The possible impact of professional education on students' attitudes was also explored. A total of 485 students from 11 entry-level occupational therapy education programmes from Australia, the United Kingdom, the United States and Taiwan participated in the study. Among them, 264 were freshmen (first-year students) and 221 were seniors (final-year students). Data collected from a custom-designed questionnaire were analysed both quantitatively and qualitatively. In general, the occupational therapy students reported having positive attitudes towards inclusion. Considerable differences, however, existed among the student groups from the four countries. Professional education appeared to have a significant impact on students' attitudes towards inclusion from first year to senior year. Although students were in favour of inclusion, they also cautioned that their support for inclusive practices depended on various factors such as adequate preparation, support and assistance to students with disabilities. Limitations of the study included the small, convenience sample and different degree structures of the participating programmes. Future research studies need to compare occupational therapy students' attitudes with students from other health care professions. A longitudinal study on the impact of the professional education programme on students' attitudes towards inclusive education is warranted.

Occupational therapy students' attitudes towards individuals with disabilities: a comparison between Australia, Taiwan, the United Kingdom, and the United States.

INTRODUCTION: Students who are enrolled in professional education programs such as occupational therapy may have inherent attitudes towards the future clients they work with. These attitudes may be influenced by the level of their professional education as well as cultural values of their country of origin. PURPOSE: The purpose of the study was to examine occupational therapy students' attitudes towards individuals with disabilities from an international, cross-cultural perspective and to investigate the possible impact of professional education on students' attitudes. METHOD: 485 occupational therapy students from 11 university programs (3 from Australia, 3 from the United Kingdom, 3 from the United States, and 2 from Taiwan) completed the Interactions with Disabled Person's (IDP) scale. RESULTS: Significant differences were found between occupational therapy students from Australia, Taiwan, the United States, and the United Kingdom on the following IDP variables: overall attitude towards individuals with disabilities, 'discomfort', 'sympathy', 'uncertainty', 'coping', 'fear', and 'vulnerability'. Significant differences between first year students as a total group and final year students as a total group were found on their overall attitudes towards individuals with disabilities, 'discomfort', and 'uncertainty'. CONCLUSION/IMPLICATIONS: The attitudes towards individuals with disabilities among first year and final year occupational therapy students varies between countries and the students' year level also impacts on their attitudes towards individuals with a disability.

Effectiveness of training on the community skills of children with intellectual disabilities.

BACKGROUND: Children with intellectual disabilities often have difficulties in daily tasks, requiring training to increase functional independence. This study measured the effectiveness of community skills training in a telephone task and a shopping task, and examined if community-based training was more effective than classroom-based training. MATERIAL AND METHODS: A randomized control trial with 40 children aged 9-11 years was completed. Intervention groups attended an eight-week training programme; the control group received no treatment. One intervention group practised skills in local shops. All participants were assessed before and after treatment in a shopping task and telephone task, using task analysis methodology. RESULTS: Data showed a highly statistically significant difference between intervention and control groups in the shopping task (p=0.007); however, there was no significant difference between classroom and classroom supplemented by community-based learning in the shopping task. There was no significant difference between the intervention and control groups in the telephone task. CONCLUSION: Results suggested that skills training was effective in one of the skill areas with this client group. Further research is required to determine if community-based training is more effective than classroom-based learning.

Seat inclinations affect the function of children with cerebral palsy: a review of the effect of different seat inclines.

PURPOSE: An evaluation of the current research evaluating the impact of seat inclinations upon postural control, muscle activity and upper extremity function in children with cerebral palsy. METHOD: A literature review searching 13 electronic databases was undertaken. Inclusion criteria were applied to abstracts found; full text research articles were retrieved and a critical review of the eligible articles completed. RESULTS: Ten studies were reviewed which investigated the effect of seat inclinations. Improved postural control and a reduction in pathological movements were achieved in anterior tilt; reduced postural sway was evident for children with spastic cerebral palsy sitting on anterior incline, and increased sway for those with hypotonia; extensor thrust was evoked when in posterior incline; and there was evidence of improved arm and hand function whilst seated in the functional sitting position as opposed a posterior seat incline. CONCLUSIONS: (i) The current literature is inconclusive, however there are indications that neutral and anterior seat inclines do positively affect function for children with cerebral palsy; (ii) Individual assessment of seating ability and need is advocated for these children rather than the adoption of a universal seat incline.