Physical Examination Tool for Swollen and Tender Lower Limb Joints in Juvenile Idiopathic Arthritis: A Pilot Diagnostic Accuracy Study.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children, with lower limb involvement highly prevalent. Recent evidence has highlighted the lack of specific lower limb physical examination (PE) tools for clinicians assisting the paediatric rheumatology team in identifying lower extremity disease in patients with JIA. Early clinical detection may lead to more prompt and targeted interventions to reduce lower limb problems in children with JIA. The aim of this pilot study is to provide preliminary data on the diagnostic accuracy of a lower limb PE tool in JIA. METHODS: Children with JIA requiring magnetic resonance imaging (MRI) on their lower limb joints per their usual care were eligible. Lower limb joint counts were conducted clinically by a podiatrist and paediatric rheumatologist using the proposed twenty joint per side, PE tool. The PE were compared to MRI assessments completed by two independent paediatric radiologists. Data were analysed using agreement (observed, positive and negative) and Cohen's kappa with 95% CIs. RESULTS: Fifteen participants were recruited into the study in which 600 lower limb joints were clinically examined. Statistical analysis showed excellent inter-rater reliability between podiatrist and paediatric rheumatologist for both joint swelling and tenderness. Results of the intra-rater reliability of the podiatrist using the PE tool indicated excellent percentage agreements (98.5-100%) and substantial kappa coefficients (0.93-1). The inter-rater reliability between radiological assessments contrasted the PE results, showing low agreement and poor reliability. Comparisons between PE and MRI resulted in poor kappa coefficients and low agreement percentages. The most agreeable joint between MRI and PE was the ankle joint, while the worst performing joint was the sub-talar joint. CONCLUSION: Results indicate potential clinical reliability; however, the validity and diagnostic accuracy of the proposed PE tool remains unclear due to low kappa coefficients and inconsistent agreements between PE and MRI results. Further research will be required before the tool may be used in a clinical setting.

High Bone Mineral Density Osteogenesis Imperfecta in a Family with a Novel Pathogenic Variant in COL1A2.

Osteogenesis imperfecta (OI) is a heterogenous group of heritable bone dysplasias characterized by bone fragility, typically low bone mass, joint laxity, easy bruising, and variable short stature. Classical OI is caused by autosomal dominant pathogenic variants in COL1A1 or COL1A2 that result in either reduced production of normal type 1 collagen or structurally abnormal collagen molecules. Pathogenic variants in these genes generally result in low bone mass. Here, we report a family that had 2 affected individuals who presented with minimal trauma fractures and were found to have elevated bone mineral density (BMD) and a previously unreported variant in COL1A2 c.3356C>T p.(Ala1119Val). We report the change in BMD using dual-energy X-ray and peripheral quantitative computed tomography over a 2.3-year period in the proband. This case report highlights the importance of BMD studies and genetic testing in the diagnostic process for brittle bone disorders.

18F-FDG PET/CT compared to conventional imaging modalities in pediatric primary bone tumors.

BACKGROUND: F-Fluoro-2-deoxy-D: -glucose (FDG) positron emission tomography (PET) is useful in adults with primary bone tumors. Limited published data exist in children. OBJECTIVE: To compare hybrid FDG positron emission tomography/computed tomography (PET/CT) with conventional imaging (CI) modalities in detecting malignant lesions, predicting response to chemotherapy and diagnosing physeal involvement in pediatric primary bone tumors. MATERIALS AND METHODS: Retrospective analysis of PET/CT and CI reports with histopathology or follow-up > 6 months as reference standard. Response parameters and physeal involvement at diagnosis were compared to histopathology. RESULTS: A total of 314 lesions were detected in 86 scans. Excluding lung lesions, PET/CT had higher sensitivity and specificity than CI (83%, 98% and 78%, 97%, respectively). In lung lesions, PET/CT had higher specificity than CI (96% compared to 87%) but lower sensitivity (80% compared to 93%). Higher initial SUV(max) and greater SUV(max) reduction on PET/CT after chemotherapy predicted a good response. Change in tumor size on MRI did not predict response. Both PET/CT and MRI were very sensitive but of low specificity in predicting physeal tumor involvement. CONCLUSION: PET/CT appears more accurate than CI in detecting malignant lesions in childhood primary bone tumors, excluding lung lesions. It seems better than MRI at predicting tumor response to chemotherapy.

The effect of hip position upon the location of the sciatic nerve: an MRI Study.

BACKGROUND: Allowance for the positional changes of the sciatic nerve is important when considering the safest position of the leg to perform hip operations, specifically the ischial osteotomy during a pelvic triple or periacetabular osteotomy. As for its proximity to the osteotomy site the sciatic nerve can be injured during these operations with the consequence of severe functional impairment. This is the first in-vivo study that demonstrates the effect of hip position upon the location of the sciatic nerve. METHODS: We determined how altering the position of the hip moves the nerve toward or away from the infracotyloid groove, the desired starting point of the ischial osteotomy site just inferior to the acetabulum when performing a pelvic triple or periacetabular osteotomy. Magnetic resonance imaging scans of the left hip in 3 different positions (neutral/supine, 30 to 45 degrees flexion, 30 to 45 degrees flexion/abduction/external rotation) were performed in 11 healthy children (5 boys and 6 girls, age 7 to 17 y) without prior hip surgery. The distance between the sciatic nerve and the infracotyloid groove was measured on the magnetic resonance images. Distance ratios based on the neutral position were calculated for flexion and flexion/abduction/external rotation for each of the participants. RESULTS: The sciatic nerve moves toward the ischium osteotomy site in hip flexion without abduction (mean flexion: neutral ratio 0.79, P<0.01). However the nerve moves away from the osteotomy site when the hip is 30 to 45 degrees flexed, abducted, and externally rotated (mean flexion/abduction/external rotation: neutral ratio 1.34), meaning the distance from nerve to infracotyloid groove increases significantly (P<0.01). The mean distances were 14.8 mm (11 to 20 mm) in neutral, 11.8 mm (9 to 16 mm) in flexion, and 20.0 mm (9 to 30 mm) in flexion/abduction/external rotation. CONCLUSIONS: The likely safest position of the hip/leg to perform the ischium osteotomy as part of a pelvic triple or periacetabular osteotomy is in flexion, abduction, and external rotation. In this position the osteotomy can be performed via a medial or anterior approach with the nerve the furthest away from the osteotomy site. LEVEL OF EVIDENCE: Level II.

18F-FDG PET/CT in paediatric lymphoma: comparison with conventional imaging.

PURPOSE: In children with Hodgkin's disease and non-Hodgkin's lymphoma, the ability of (18)F-fluoro-2-deoxy-D-glucose PET/CT and conventional imaging (CI) to detect malignant lesions and predict poor lesion response to therapy was assessed and compared. METHODS: A retrospective review of findings reported on PET/CT and CI was performed using a lesion-based analysis of 16 lymph node and 8 extra-nodal regions. Lesions were defined by histopathological findings or follow-up > 6 months. RESULTS: The study included 209 PET/CT scans with a valid CI comparator. A total of 5,014 regions (3,342 lymph node, 1,672 extra-nodal) were analysed. PET/CT performed significantly better than CI in the detection of malignant lesions with sensitivity and specificity of 95.9 and 99.7% compared to 70.1 and 99.0%, respectively. For predicting poor lesion response to therapy, PET/CT had fewer false-positive lesions than CI. The specificity for predicting poor lesion response to treatment for PET/CT was 99.2% compared to 96.9% for CI. PET/CT was the correct modality in 86% of lesions with discordant findings. CONCLUSION: PET/CT is more accurate than CI in detecting malignant lesions in childhood lymphoma and in predicting poor lesion response to treatment. In lesions with discordant findings, PET/CT results are more likely to be correct.

Durability of hand-sewn valves in the right ventricular outlet.

OBJECTIVE: The objective was to compare the medium- and long-term outcomes for pericardial monocusp valves, polytetrafluoroethylene (Gore-Tex, WL Gore and Associates Inc, Flagstaff, Ariz) 0.1-mm monocusp valves, and bileaflet 0.l-mm polytetrafluoroethylene valves and their efficiency in the right ventricular outlet. METHODS: We reviewed all hand-sewn right ventricular outlet valves created by the author (Graham R. Nunn) in the setting of repaired tetralogy of Fallot or equivalent right ventricular outlet pathology when the native pulmonary valve could not be preserved. The valves were assessed by serial transthoracic echocardiography and more recently by magnetic resonance imaging angiography for late valve function. The bileaflet polytetrafluoroethylene valves were constructed in a standardized fashion from a semicircle of 0.1-mm polytetrafluoroethylene (the radius of which equaled the length of the outflow tract incision) that gave a lengthened free edge to the leaflets, central fixation of the free edge posteriorly just proximal to the branch pulmonary arteries, and generous augmentation of the outflow tract with polytetrafluoroethylene patch-plasty. The bileaflet configuration shortens the closing time against the posterior wall, and the leaflets are forced to maintain their configuration without prolapse into the right ventricular outlet. The valve can be generously oversized in young children to try to avoid the need for replacement. RESULTS: A total of 54 patients met the selection criteria--22 patients received fresh autologous pericardial monocusps, 7 patients received polytetrafluoroethylene (0.1-mm) monocusps, and 25 patients received bileaflet polytetrafluoroethylene (0.1-mm) outlet valves. The pericardial valves have the longest follow-up, and all valves developed free pulmonary incompetence. Polytetrafluoroethylene monocusps had reliable competence early after surgery but progressed to pulmonary incompetence. The bileaflet polytetrafluoroethylene (0.1-mm) valves have remained competent with regurgitant fractions of only 5% to 30% (magnetic resonance imaging angiography), and this has remained stable with time. The maximum follow-up for these valves is 5 years. No stenosis or peripheral emboli have been recognized, and no valves have been replaced to date. CONCLUSION: Hand-sewn bileaflet polytetrafluoroethylene valves in the right ventricular outlet can reliably provide competence and maintain function in the medium term. Their shape and size allow placement in young children with a reasonable expectation that they will remain competent with growth of the native annulus and not require replacement. Their durability is superior to the pericardial and polytetrafluoroethylene monocusp valves in this series.

Evaluation of the extracardiac conduit modification of the Fontan operation for thrombus formation using magnetic resonance imaging.

BACKGROUND: The prevalence of thrombosis after the Fontan procedure depends upon the surgical technique used and the method of detection employed. Current investigations for thrombosis lack sensitivity and specificity or, in the paediatric population, require a general anaesthetic. We undertook a study to examine the feasibility of using magnetic resonance imaging (MRI) to detect thrombosis within the conduit, cardiac chambers and pulmonary arteries after the extracardiac conduit modification of the Fontan procedure. METHODS: Of the 50 children who had undergone this procedure at our institution between 1997 and 2002, 26 were eligible for, and 13 underwent, MRI study. The mean age was 10.2 years (range 8.2-16.8 years, median 9.5 years) and the average time from operation was 63 months (range 29-79 months, median 68 months). The mean age at Fontan operation was 4.9 years (range 2.1-10.5 years). Ten were on low dose aspirin, two were on warfarin and one was not anti-coagulated. In all cases, satisfactory imaging of the venous pathways and pulmonary arteries was obtained and there were no thrombi detected. CONCLUSIONS: We conclude that MRI is a potentially useful tool for the detection of thrombus in patients who have undergone the Fontan operation.

EEC syndrome, Arg227Gln TP63 mutation and micturition difficulties: Is there a genotype-phenotype correlation?

We report on two unrelated families with EEC syndrome (ectrodactyly, ectodermal dysplasia, cleft lip/palate), each with an Arg227Gln TP63 gene mutation, where the phenotype overlapped extensively with the allelic disorder, limb-mammary syndrome (LMS). Features common to both families were an ectodermal dysplasia principally affecting tooth, breast and nipple development, dacryostenosis and severe micturition difficulties. Additional findings included post-axial digital hypoplasia, cleft uvula, anal stenosis, hypoplasia of the perineal body and biopsy-proven interstitial cystitis. No individual had cleft lip. Split hand-split foot malformation (SHFM) occurred in one child-born after the molecular diagnosis was established. Unlike previous reports, the urinary symptoms were refractory to treatment with oral Fibrase and persisted into adulthood. Of the six cases/families now reported with EEC syndrome and Arg227Gln TP63 mutation, four have manifested this distinct urological abnormality, indicative of a genotype-phenotype correlation.

Axenfeld-Rieger malformation and distinctive facial features: Clues to a recognizable 6p25 microdeletion syndrome.

Deletion of distal 6p is associated with a distinctive clinical phenotype including Axenfeld-Rieger malformation, hearing loss, congenital heart disease, dental anomalies, developmental delay, and a characteristic facial appearance. We report the case of a child where recognition of the specific ocular and facial phenotype, led to identification of a 6p microdeletion arising from a de novo 6:18 translocation. Detailed analysis confirmed deletion of the FOXC1 forkhead gene cluster at 6p25. CNS anomalies included hydrocephalus and hypoplasia of the cerebellum, brainstem, and corpus callosum with mild to moderate developmental delay. Unlike previous reports, hearing was normal.

Anterior spinal cord infarction owing to possible fibrocartilaginous embolism.

Anterior spinal artery syndrome is characterised by acute flaccid quadriparesis or paraparesis, disturbance of pain and temperature sensation, and loss of sphincter control. Fibrocartilaginous embolism is a rarely recognised, but important cause of spinal cord infarction. Fibrocartilaginous embolisation usually occurs after minor trauma without major bony lesions, typically with an intervening symptom-free interval and progressive 'stroke-in-evolution' course. There is evidence that the embolus originates from the intervertebral disc, but the mechanism whereby disc fragments enter the spinal vessels is not well understood. We describe the evolution of MRI findings in a case of anterior spinal artery territory infarction thought to be secondary to fibrocartilaginous embolism.

Segregation of a novel FBN1 gene mutation, G1796E, with kyphoscoliosis and radiographic evidence of vertebral dysplasia in three generations.

Skeletal and spinal radiographic findings are described in five individuals of a three-generation kindred with kyphoscoliosis. The affected individuals have a novel FBN1 gene mutation, G1796E. To our knowledge, this is the first report of a family with an FBN1 gene mutation cosegregating with an unusual autosomal dominant progressive kyphoscoliosis of variable severity, together with radiological abnormalities of the spine, and some skeletal but no ocular or cardiac manifestations of Marfan syndrome. This previously undescribed phenotype represents yet another in the widening spectrum of fibrillinopathies caused by an FBN1 gene mutation.