Performance on the iSTEP and 10 m-ISWT in boys with haemophilia.

INTRODUCTION: Boys with haemophilia (BwH) have improved health outcomes. Measures of physical function in haemophilia are not challenging or sensitive enough to reflect physical limitations or guide rehabilitation. To identify meaningful tests, we aimed to: evaluate the performance of BwH on two physical performance measures: iSTEP and 10 m-ISWT; identify factors which predict performance and compare BwH to their unaffected peers. METHODS: BwH completed both iSTEP and 10 m-ISWT. Disease severity, age, BMI, HJHS, lower limb muscle torque, time spent in moderate to vigorous physical activity, sedentary time, were included as factors to predict performance. Results were compared to unaffected peers. RESULTS: 43 boys median age 10 (10 mild/moderate, 26 severe, 7 inhibitors) were recruited. BwH were less likely to complete the iSTEP and performed less well on the 10 m-ISWT than age matched peers. Ceiling effects were apparent for iSTEP, but not the 10 m-ISWT test. Age was the only significant predictor for performance in the iSTEP, with older boys being more likely to achieve a higher level or complete the test. Greater age, lower BMI, milder disease severity and more time spent in MVPA all predicted better performance on the 10 m-ISWT, with BMI and habitual physical activity a potential rehabilitation focus for underperforming individuals. HJHS and muscle strength did not predict performance on either test. CONCLUSION: Despite the space need to conduct the 10 m-ISWT, it appears to be a superior performance measure than the iSTEP in BwH and provides clinically meaningful information, which can be interpreted using age-specific normative reference equations.

Radical resection of lumbosacral lipomas in children: the Great Ormond Street Hospital experience.

PURPOSE: In 2009, Pang described a radical resection technique for congenital lumbosacral lipomas, with lower long-term symptomatic re-tethering rates compared with partial resections and conservative management, and low surgical morbidity. We adopted this technique in 2011, and aim to describe our first results. METHODS: In this monocentric retrospective audit, we included dorsal, transitional, chaotic, and caudal-type lumbosacral lipomas. Exclusion criteria were previously operated lipomas, pure filar lipomas, and concomitant major congenital anatomical urogenital/gastrointestinal abnormalities. Neuro-uro-orthopaedic status at presentation and at three months, one year and last postoperative follow-up, intraoperative electrophysiology, and extent of resection were collected. RESULTS: From January 2011 to September 2019, 91 patients were operated (median age 2y2m; 63 transitional; 14 caudal; 8 dorsal; 6 chaotic). Preoperatively, 67% were symptomatic. Preoperative and one-year postoperative rates of impaired ambulation (44% to 43%), hypoesthesia (8% to 5%), urodynamic/uroradiological abnormalities (49% to 37%), and foot/ankle deformities (8% to 5%) were comparable, whilst pain improved (25% to 5%) but catheterisation rates increased (21% to 36%). 23/92 (25%) suffered wound-related complications. 2/91 (2%) developed symptomatic re-tethering requiring second surgery. Mean cord/sac ratio was 0.47. 43% had > 20 mm3 residual fat, which improved with increasing surgical experience. CONCLUSION: Radical lipoma resection, guided by intraoperative neuromonitoring, with reconstruction of the neural placode and expansion duraplasty is technically feasible and results in low rates of late deterioration and re-tethering. Lipoma-type and pre-operative status are important outcome predictors. Operative risks are not insignificant. Future studies need to determine appropriate selection criteria for surgery.

Clinical status, biochemical profile and management of a single cohort of patients with arginase deficiency.

Arginase deficiency is a rare autosomal recessive urea cycle disorder (UCD) caused by mutations in the ARG1 gene encoding arginase that catalyses the hydrolysis of arginine to ornithine and urea. Patients have hyperargininaemia and progressive neurological impairment but generally suffer fewer metabolic decompensations compared to other UCDs. The objective is to describe the clinical features, biochemical profile, neuroradiological findings and experience of managing children with arginase deficiency. Twenty-year retrospective review of patient medical records at a single metabolic centre was performed. Six patients from three unrelated families were identified. Mean age at first symptom was 3.3 (1.5-9.0) years, while mean age at diagnosis was 8.8 (0.16-15.92) years. Four patients developed spastic diplegia and two of six with spastic quadriplegia with classical features including hyperreflexia, clonus and toe walking. This resulted in gait abnormalities that have been monitored using the GAITRite system and required Achilles tendon release in five children. Generalised tonic-clonic seizures and/or absences were present in three of six children and were controlled with anticonvulsants. All patients had moderate learning difficulties. Neuroimaging showed cerebral/cerebellar atrophy in four patients and basal ganglia abnormalities in two. Arginine levels were universally elevated throughout follow-up despite protein restriction, essential amino acid supplementation and ammonia scavengers, and neurological outcome was generally poor. Two patients died following severe metabolic decompensation in adolescence. Children with arginase deficiency continue to present a management challenge of what appears to be an inexorable course of neurocognitive impairment. Further insight into disease mechanisms may provide insight into novel treatment strategies.

Age-related gait standards for healthy children and young people: the GOS-ICH paediatric gait centiles.

OBJECTIVE: To develop paediatric gait standards in healthy children and young people. METHODS: This observational study aims to address the lack of population standards for gait measurements in children. Analysing gait in children affected by neurological or musculoskeletal conditions is an important component of paediatric assessment but is often confounded by developmental changes. The standards presented here do not require clinician expertise to interpret and offer an alternative to developmental tables of normalised gait data. Healthy children aged 1-19 years were recruited from community settings in London and Hertfordshire, UK. The GAITRite walkway was used to record measurements for each child for velocity, cadence, step length, base of support and stance, single and double support (as percentage of gait cycle). We fitted generalised linear additive models for location, scale and shape (gamlss). RESULTS: We constructed percentile charts for seven gait variables measured on 624 (321 males) contemporary healthy children using a gamlss package in R. A clinical application of gait standards was explored. CONCLUSION: Age-related, gender-specific standards for seven gait variables were developed and are presented here. They have a familiar format and can be used clinically to aid diagnoses and to monitor change over time for both medical therapy and natural history of the condition. The clinical example demonstrates the potential of the Great Ormond Street Institute of Child Health Paediatric Gait Centiles to enable meaningful interpretation of change in an individual's performance and describes characteristic features of gait from a specific population throughout childhood.

Immunotherapy-responsive childhood neurodegeneration with systemic and central nervous system inflammation.

Subacute neuroregression in association with raised neopterin and overexpression of interferon stimulated genes (ISGs) could indicate a type 1 interferonopathy. Here we describe a novel immunotherapy-responsive, clinico-immunological and imaging phenotype with evidence of innate immune activation. Three children (patient 1: 22-month-old boy; patient 2: 5-year-old girl; patient 3: 4-year-old girl) presented with asymmetric bilateral mixed dystonia and spasticity, regression in language (expressive more than receptive) and bulbar symptoms with no evidence of seizures. Symptoms evolved over several weeks to months. Brain MRI changes mimicked cerebral atrophy, initially asymmetric. CSF revealed raised neopterins. Blood RNA assay showed abnormal overexpression of ISGs and transient raised alanine aminotransferase (ALT). Importantly, all three children were treated with intravenous methylprednisolone and immunoglobulin with significant and sustained improvement in their motor and language function, and normalisation of imaging. Immune-mediated encephalitis can masquerade as subacute neuroregression.

Median life span of a cohort of National Institute for Health and Care Excellence clinical guidelines was about 60 months.

OBJECTIVES: To describe the length of time National Institute for Health and Care Excellence (NICE) clinical guidelines have remained valid. STUDY DESIGN AND SETTING: The present study is a survival analysis of a cohort of published NICE clinical guidelines. The National Health Service in England and Wales uses NICE clinical practice guidelines as a reference for treatment and care of individuals. They need to be updated as new evidence arises, to remain credible and relevant, and are currently assessed 3 years after publication. RESULTS: Survival analysis suggested that about 86% of guidelines are still up-to-date 3 years after their publication. The median life span was 60 months (95% confidence interval: 51, 69). CONCLUSION: These findings are similar to those in other studies of the life span of guidelines. Efficient mechanisms must be in place to detect the minority of guidelines that become outdated quickly.

Use of the auditory clap task in physiotherapy developmental assessment.

This study assessed the test-retest reliability of the auditory clapping task in normal children. This task forms part of the physiotherapy neurodevelopmental assessment for children over five years of age, and is an auditory sequential short term memory (STM) test which is not language biased. Trends associated with age, gender and type of rhythm were also examined in five, seven and nine year old children. Results suggest that this is a reliable test, with significant increase in STM performance demonstrated with increasing age. Girls performed significantly better than boys, and significantly longer rhythmic than non-rhythmic sequences were recalled.