Abusive Head Trauma Animal Models: Focus on Biomarkers.

Abusive head trauma (AHT) is a serious traumatic brain injury and the leading cause of death in children younger than 2 years. The development of experimental animal models to simulate clinical AHT cases is challenging. Several animal models have been designed to mimic the pathophysiological and behavioral changes in pediatric AHT, ranging from lissencephalic rodents to gyrencephalic piglets, lambs, and non-human primates. These models can provide helpful information for AHT, but many studies utilizing them lack consistent and rigorous characterization of brain changes and have low reproducibility of the inflicted trauma. Clinical translatability of animal models is also limited due to significant structural differences between developing infant human brains and the brains of animals, and an insufficient ability to mimic the effects of long-term degenerative diseases and to model how secondary injuries impact the development of the brain in children. Nevertheless, animal models can provide clues on biochemical effectors that mediate secondary brain injury after AHT including neuroinflammation, excitotoxicity, reactive oxygen toxicity, axonal damage, and neuronal death. They also allow for investigation of the interdependency of injured neurons and analysis of the cell types involved in neuronal degeneration and malfunction. This review first focuses on the clinical challenges in diagnosing AHT and describes various biomarkers in clinical AHT cases. Then typical preclinical biomarkers such as microglia and astrocytes, reactive oxygen species, and activated N-methyl-D-aspartate receptors in AHT are described, and the value and limitations of animal models in preclinical drug discovery for AHT are discussed.

Advanced Neuroimaging Approaches to Pediatric Brain Tumors.

Central nervous system tumors are the most common pediatric solid tumors; they are also the most lethal. Unlike adults, childhood brain tumors are mostly primary in origin and differ in type, location and molecular signature. Tumor characteristics (incidence, location, and type) vary with age. Children present with a variety of symptoms, making early accurate diagnosis challenging. Neuroimaging is key in the initial diagnosis and monitoring of pediatric brain tumors. Conventional anatomic imaging approaches (computed tomography (CT) and magnetic resonance imaging (MRI)) are useful for tumor detection but have limited utility differentiating tumor types and grades. Advanced MRI techniques (diffusion-weighed imaging, diffusion tensor imaging, functional MRI, arterial spin labeling perfusion imaging, MR spectroscopy, and MR elastography) provide additional and improved structural and functional information. Combined with positron emission tomography (PET) and single-photon emission CT (SPECT), advanced techniques provide functional information on tumor metabolism and physiology through the use of radiotracer probes. Radiomics and radiogenomics offer promising insight into the prediction of tumor subtype, post-treatment response to treatment, and prognostication. In this paper, a brief review of pediatric brain cancers, by type, is provided with a comprehensive description of advanced imaging techniques including clinical applications that are currently utilized for the assessment and evaluation of pediatric brain tumors.

Newly Diagnosed Children with Cancer Have Lower 25-Vitamin D Levels than Their Cancer-Free Peers: A Comparison across Age, Race, and Sex.

Children with cancer have a greater risk for vitamin D concerns because of compromised health before diagnosis, the disease itself, and treatments for the cancer. This IRB-approved retrospective, matched case−control study of children with and without cancer included three race categories: black, other, and Caucasian. This is the first study to directly compare serum 25-hydroxy vitamin D (25(OH)D) levels and status in newly diagnosed pediatric cancer patients with age-, sex-, and race-matched cancer-free children from the same geographic region of the US, all of whom are free from other conditions that negatively impact 25(OH)D levels. Univariable and multivariable ordinal logistic regressions were performed. In the 544 children (mean age of 8.5 years, 53% female), there were 136 newly diagnosed children with cancer and 408 matched non-cancer controls. Serum 25(OH)D levels at cancer diagnosis were lower (22.4 ng/mL) than in controls (30.1 ng/mL; p < 0.0001). Differences persisted across race (p < 0.001) and age (p < 0.001), but not sex. Older children exhibited lower 25(OH)D levels. Only 18.4% of the children with cancer had sufficient levels. Black children with cancer had the greatest rate of deficiency (39%). Race differences were evident: children of color (other and black) displayed higher levels of insufficiency; black children were most deficient.

Radiosynthesis of 1-(2-[18F]Fluoroethyl)-L-Tryptophan using a One-pot, Two-step Protocol.

The kynurenine pathway (KP) is a primary route for tryptophan metabolism. Evidence strongly suggests that metabolites of the KP play a vital role in tumor proliferation, epilepsy, neurodegenerative diseases, and psychiatric illnesses due to their immune-modulatory, neuro-modulatory, and neurotoxic effects. The most extensively used positron emission tomography (PET) agent for mapping tryptophan metabolism, α-[11C]methyl-L-tryptophan ([11C]AMT), has a short half-life of 20 min with laborious radiosynthesis procedures. An onsite cyclotron is required to radiosynthesize [11C]AMT. Only a limited number of centers produce [11C]AMT for preclinical studies and clinical investigations. Hence, the development of an alternative imaging agent that has a longer half-life, favorable in vivo kinetics, and is easy to automate is urgently needed. The utility and value of 1-(2-[18F]fluoroethyl)-L-tryptophan, a fluorine-18-labeled tryptophan analog, has been reported in preclinical applications in cell line-derived xenografts, patient-derived xenografts, and transgenic tumor models. This paper presents a protocol for the radiosynthesis of 1-(2-[18F]fluoroethyl)-L-tryptophan using a one-pot, two-step strategy. Using this protocol, the radiotracer can be produced in a 20 ± 5% (decay corrected at the end of synthesis, n > 20) radiochemical yield, with both radiochemical purity and enantiomeric excess of over 95%. The protocol features a small precursor amount with no more than 0.5 mL of reaction solvent in each step, low loading of potentially toxic 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane (K222), and an environmentally benign and injectable mobile phase for purification. The protocol can be easily configured to produce 1-(2-[18F]fluoroethyl)-L-tryptophan for clinical investigation in a commercially available module.

Tracheal narrowing in children and adults with mucopolysaccharidosis type IVA: evaluation with computed tomography angiography.

BACKGROUND: Mucopolysaccharidosis type IVA (MPS IVA) is characterized by progressive skeletal dysplasia and respiratory issues with difficult airway management during anesthesia. OBJECTIVE: To characterize tracheal abnormalities in children and adults with MPS IVA including interplay of the trachea, vasculature, bones and thyroid at the thoracic inlet. MATERIALS AND METHODS: Computed tomography (CT) angiograms of the chest were analyzed for trachea shape, narrowing and deviation at the thoracic inlet, course of vasculature, bone alignment and thyroid location. The tracheal cross-sectional area was measured at the cervical, thoracic inlet and intrathoracic levels. RESULTS: Thirty-seven patients (mean age: 18.1 years) were included. The mean tracheal cross-sectional area narrowing at the thoracic inlet was 63.9% (range: -2.1-96%), with a trend for increased tracheal narrowing in older children. The trachea was commonly deviated rightward posterior (22/37, 59%). T- or W-shaped tracheas had two times greater tracheal narrowing than D- or U-shaped tracheas (P<0.05). The brachiocephalic artery was tortuous in 35/37 (95%) with direct impingement on the trachea in 24/37 (65%). No correlation was observed between bony thoracic inlet diameter and tracheal narrowing. The thyroid was located in the thoracic inlet in 28/37 (76%) cases, significantly associated with tracheal narrowing (P=0.016). CONCLUSION: Narrowing, deviation and abnormal shape of the trachea at the thoracic inlet are common in children and adults with MPS IVA, with a trend toward increased narrowing with advancing age in children. A W- or T-shaped trachea is associated with focal tracheal narrowing. Crowding of the thoracic inlet, due to vascular tortuosity and thyroid position, appears to play a major role.

A Comparison of Lumbar Spine and Lateral Distal Femur Bone Density in Girls With Rett Syndrome.

INTRODUCTION/BACKGROUND: Patients with Rett syndrome (RS) are at risk for low bone mineral density (BMD) and femoral fractures. In patients with RS, assessment with lateral distal femur (LDF) dual-energy X-ray absorptiometry (DXA) is recommended and clinically relevant. This study is the first to assess LDF BMD in girls with RS, and to compare LDF BMD results with lumbar spine BMD results in RS. Method Eleven girls (mean age 8.4 yr) with molecularly diagnosed RS and clinical DXA scan(s) were identified; medical charts were retrospectively reviewed. Baseline and serial lumbar spine and LDF BMD Z-scores were evaluated based on patients' ambulation status, presence of epilepsy, and mutation type. Results At the time of first scan, 8 of 11 patients had normal lumbar spine BMD and low LDF BMD Z-scores. Two patients had fracture history. Fully ambulatory (3) patients had higher lumbar spine and LDF BMD than partially (5) and nonambulatory (3) patients. Patients with epilepsy had lower average BMD at all sites. No difference was seen in lumbar spine or LDF BMD in patients with high-risk BMD mutations. Seven patients had serial DXA scans with an average observation of 5.1 yr (range 3.1 yr to 6.2 yr). Lumbar spine BMD over time was variable, while LDF bone mass accrual occurred at a lower rate than typically developing girls. Conclusion Females with RS exhibited lower BMD Z-scores at the LDF than at the lumbar spine. LDF and lumbar spine results were discordant. Ambulatory status and the presence of epilepsy were related to BMD. LDF BMD accrual deviated from normal as patients aged.

The Utility of DXA Assessment at the Forearm, Proximal Femur, and Lateral Distal Femur, and Vertebral Fracture Assessment in the Pediatric Population: 2019 ISCD Official Position.

Dual-energy X-ray absorptiometry (DXA) is widely used in the evaluation of bone fragility in children. Previous recommendations emphasized total body less head and lumbar spine DXA scans for clinical bone health assessment. However, these scan sites may not be possible or optimal for all groups of children with conditions that threaten bone health. The utility of DXA scans of the proximal femur, forearm, and radius were evaluated for adequacy of reference data, precision, ability of predict fracture, and applicability to all, or select groups of children. In addition, the strengths and limitations of vertebral fracture assessment by DXA were evaluated. The new Pediatric Positions provide guidelines on the use of these additional measures in the assessment of skeletal health in children.

Adult Tourniquet for Use in School-Age Emergencies.

BACKGROUND: Gunshot injuries are a leading cause of morbidity and mortality in the pediatric population. The Pediatric Trauma Society supports the use of tourniquets for exsanguinating hemorrhage in severe extremity trauma. The Combat Application Tourniquet (CAT) used with success in adults has not been prospectively tested in children. Our objective with this study was to determine if the CAT is successful in arresting extremity arterial blood flow in school-aged children. METHODS: Sixty school-aged volunteers (ages 6-16 years) recruited by age cohort had the CAT applied to an upper arm and thigh while peripheral pulse was monitored by Doppler. The number of windlass turns (maximum allowed: 3 [1080°]) required to arrest arterial pulse was recorded. Success was analyzed by BMI percentile for age and extremity circumference. RESULTS: The CAT was successful in occluding arterial blood flow as detected by Doppler pulse in all 60 (100%) of the upper extremities tested. In the lower extremity, 56 (93%) had successful occlusion. The 3-turn maximum allowed by the protocol was not adequate in some obese, older subjects (BMI >30). In both the upper and lower extremity, the number of turns required to occlude blood flow gradually increased with an increase in arm and thigh circumference. CONCLUSIONS: Prospective testing of a cohort of school-aged children 6 to 16 years revealed the CAT tourniquet to be suitable for use in both the upper and lower extremity.

Computerized Tomography Analysis of Young Children for Prevention of Aspiration Injuries.

OBJECTIVE: The Small Parts Test Fixture (SPTF) (16 CFR 1501) was developed from cadavers of young children and foreign body (FB) data. Recent FB studies reveal that the SPTF misses outliers. Computerized tomography (CT) provides detailed dimensional data for young children. Our null hypothesis is that the SPTF (31.75 mm) is smaller than relevant portions of the aerodigestive tract. METHODS: A 3-year retrospective review (2011-2014) of head/neck CT data for infants and children (N = 106) aged 6 months to 6 years was completed. Six measurements (mm) were recorded: 1) maxillary incisors to posterior edge of hard palate (MI/HP); 2) posterior edge of hard palate to first cervical (C1) vertebra (HP/C1); 3) soft palate to posterior pharyngeal wall; and 4) interpalatine tonsillar distance; 5, 6) larynx diameter, and width. Two ratios were calculated: 1) ratio of lengths (hard palate to soft palate), and 2) laryngeal dimensional ratio. RESULTS: A linear trend of increasing dimensions with increased age was noted. The length measured MI/HP best correlates with known data of potential FBs causing injury or death. This MI/HP length can range from 33.8 to 45.8 mm for all children younger than 3 years of age and exceeds the SPTF diameter (31.75 mm). There were no statistical anatomical differences by gender in any of the age groups. CONCLUSION: Computed tomography measurements appear larger than SPTF values developed from cadavers. These CT data support enlargement of the SPTF to enhance safety for choking hazards in children. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:1468-1476, 2019.

Maturation of pelvic ossification centers on computed tomography in normal children.

BACKGROUND: The pelvis is composed of three paired primary ossification centers: the pubis, the ischium and the ilium. During maturation, multiple secondary ossification centers can be seen in the synchondroses between these bones and in the pelvic apophyses. The fragmented appearance of these centers can be confused with pathology. OBJECTIVE: To examine development of pelvic ossification centers by CT and determine normal appearance throughout childhood. MATERIALS AND METHODS: Three pediatric radiologists reviewed 325 pelvic CT scans in children and young adults 5-18 years old and graded 6 pelvic ossification centers to evaluate maturational changes in critical structures. RESULTS: Rate and progression of ossification and age at complete fusion vary with gender at the different ossification centers in the growing pelvis. CONCLUSION: Knowledge of the normal CT appearance of ossification centers throughout childhood is important to differentiate the normal appearance from pathology.

Molecular genetics and metabolism, special edition: Diagnosis, diagnosis and prognosis of Mucopolysaccharidosis IVA.

Mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome) is an autosomal recessive disorder caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to the accumulation of specific glycosaminoglycans (GAGs), chondroitin-6-sulfate (C6S) and keratan sulfate (KS), which are mainly synthesized in the cartilage. Therefore, the substrates are stored primarily in the cartilage and its extracellular matrix (ECM), leading to a direct impact on bone development and successive systemic skeletal spondylepiphyseal dysplasia. The skeletal-related symptoms for MPS IVA include short stature with short neck and trunk, odontoid hypoplasia, spinal cord compression, tracheal obstruction, obstructive airway, pectus carinatum, restrictive lung, kyphoscoliosis, platyspondyly, coxa valga, genu valgum, waddling gait, and laxity of joints. The degree of imbalance of growth in bone and other organs and tissues largely contributes to unique skeletal dysplasia and clinical severity. Diagnosis of MPS IVA needs clinical, radiographic, and laboratory testing to make a complete conclusion. To diagnose MPS IVA, total urinary GAG analysis which has been used is problematic since the values overlap with those in age-matched controls. Currently, urinary and blood KS and C6S, the enzyme activity of GALNS, and GALNS molecular analysis are used for diagnosis and prognosis of clinical phenotype in MPS IVA. MPS IVA can be diagnosed with unique characters although this disorder relates closely to other disorders in some characteristics. In this review article, we comprehensively describe clinical, radiographic, biochemical, and molecular diagnosis and clinical assessment tests for MPS IVA. We also compare MPS IVA to other closely related disorders to differentiate MPS IVA. Overall, imbalance of growth in MPS IVA patients underlies unique skeletal manifestations leading to a critical indicator for diagnosis.

Bone mineral density in mucopolysaccharidosis IVB.

To date, the only published reports of bone mineral density (BMD) in MPS IV involve patients with MPS IVA; no reports exist describing BMD for MPS IVB. In this prospective study of BMD in three patients with MPS IVB, BMD was acquired by dual-energy X-ray absorptiometry (DXA) at whole body (WB), lumbar spine (LS), and lateral distal femur (LDF). Functional abilities, ambulatory status, medical history, and height z-score were evaluated. Three patients with MPS IVB (two females), aged 17.7, 31.4 and 31.7 years, were evaluated. Every patient was ambulatory and one sustained two fractures caused by trauma. Whole body and hip DXA scans were technically invalid in every patient due to the presence of prosthetic hip hardware. Lumbar spine was valid in only 1 patient due skeletal abnormalities, and was normal (Z-score of - 0.8). The LDF was valid in every patient and was low at all three regions of interest: average LDF z-scores were - 3.1 (range, - 2.9 to - 3.6), - 2.3 (range, - 2.0 to - 2.5), and - 2.1 (range, - 2.0 to - 2.3) for region 1-region 3, respectively. Patients with MPS IVB have low BMD of the lower extremities even with full-time ambulation. Routine body sites to measure by DXA were problematic; hip and WB were invalid due to artifact, and LS had limited utility. The LDF was the only body site consistently available on all patients. Patients did not experience low-energy fractures despite low BMD.

Activity of daily living for Morquio A syndrome.

The aim of this study was to evaluate the activity of daily living (ADL) and surgical interventions in patients with mucopolysaccharidosis IVA (MPS IVA). The factor(s) that affect ADL are age, clinical phenotypes, surgical interventions, therapeutic effect, and body mass index. The ADL questionnaire comprises three domains: "Movement," "Movement with cognition," and "Cognition." Each domain has four subcategories rated on a 5-point scale based on the level of assistance. The questionnaire was collected from 145 healthy controls and 82 patients with MPS IVA. The patient cohort consisted of 63 severe and 17 attenuated phenotypes (2 were undefined); 4 patients treated with hematopoietic stem cell transplantation (HSCT), 33 patients treated with enzyme replacement therapy (ERT) for more than a year, and 45 untreated patients. MPS IVA patients show a decline in ADL scores after 10years of age. Patients with a severe phenotype have a lower ADL score than healthy control subjects, and lower scores than patients with an attenuated phenotype in domains of "Movement" and "Movement with cognition." Patients, who underwent HSCT and were followed up for over 10years, had higher ADL scores and fewer surgical interventions than untreated patients. ADL scores for ERT patients (2.5years follow-up on average) were similar with the-age-matched controls below 10years of age, but declined in older patients. Surgical frequency was higher for severe phenotypic patients than attenuated ones. Surgical frequency for patients treated with ERT was not decreased compared to untreated patients. In conclusion, we have shown the utility of the proposed ADL questionnaire and frequency of surgical interventions in patients with MPS IVA to evaluate the clinical severity and therapeutic efficacy compared with age-matched controls.

Pamidronate Treatment to Prevent Reoccurring Fractures in Children With Cerebral Palsy.

BACKGROUND: Some children with cerebral palsy (CP) have frequent fractures due to low bone mineral density and receive treatment with pamidronate, an intravenous bisphosphonate. Our review evaluates the outcome of pamidronate treatment in these children. METHODS: A retrospective chart review was performed, and 32 patients (14 girls and 18 boys) with CP Gross Motor Function Classification System level III (2 patients), IV (3 patients), and V (27 patients) treated with 5 courses of pamidronate for low mineral density were identified. Patients with a minimum of 2 years of follow-up were included in the study. Data collection was a review of the demographics and pretreatment, peritreatment, and posttreatment fracture history. RESULTS: The mean age at treatment was 11.6 years (range, 2.9 to 19.6 y). There were 102 fractures (mean duration 2.5 y) pretreatment and 28 fractures posttreatment. With an average follow-up of 6.4 years, posttreatment rate of fracture decreased to 0.10 fractures per year from the pretreatment rate of 2.4 fractures per year (P<0.001). The femur was the most common bone fractured both pretreatment (54%) and posttreatment (61%); the major site was the distal third of the femur. There were 11 fractures during the course of pamidronate treatment at a rate of 0.33 fractures per year. Only 11 patients (34%) sustained fracture posttreatment. No correlation with fracture pattern or occurrence was found with patient age, number of pretreatment fractures, or sex. Most fractures were caused by low-energy injuries, and most were managed nonoperatively. CONCLUSIONS: In patients with CP and disuse osteoporosis, the most common fracture sustained involved the distal femur via low-velocity injury, and most fractures were treated nonoperatively. Although the fracture pattern and the treatment remained unchanged, reoccurring fractures in these children can be effectively treated medically to interrupt the fracturing tendency.

Bone mineral density in MPS IV A (Morquio syndrome type A).

Mucopolysaccharidosis IV A (MPS IV A), Morquio A, is caused by deficiency in lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS), which is responsible for the catabolism of the glycosaminoglycans (GAGs) keratan sulfate (KS) and chondroitin 6-sulfate (C6S). Accumulation of GAGs results in disrupted cartilage formation and skeletal dysplasia. In this prospective cross-sectional study, bone mineral density (BMD) of the whole body (WB), lumbar spine (LS), and lateral distal femur (LDF) was acquired by dual-energy X-ray absorptiometry (DXA) on patients with MPS IV A. Functional abilities, medical history, Tanner score, and laboratory results were reviewed. Age and sex-matched norms were used to calculate Z-scores. Participants included 18 patients (13 females; 16 were unrelated) with a mean age of 21.4years (3.3 to 40.8years). While every patient was able to bear weight, 9 were full-time ambulators. Whole-body DXA could be obtained on only 6 patients (5 full-time ambulators) because of respiratory compromise caused by the position, presence of hardware, or positioning difficulties. Mean WB Z-score was -2.0 (range-0.3 to -4.1). Technical issues invalidating LS DXA in 8 patients included kyphosis at the thoracolumbar junction resulting in overlap of vertebrae in the posterior-anterior view. Mean LS BMD Z-score in full-time ambulators was -3.4 (range-1.6 to -5.0) and in the non-/partial ambulator was -4.0 (-3.7 to -4.2). Lateral distal femur BMD was acquired on every patient, and average Z-scores were -2 or less at all sites; full-time ambulators exhibited higher BMD. In conclusion, the LDF proved to be the most feasible site to measure in patients with MPS IV A. The higher LDF values in ambulators suggest this should be a consideration in promoting bone health for this group.

Longitudinal assessment of bone growth and development in a facility-based population of young adults with cerebral palsy.

AIM: Osteoporosis is a significant clinical problem in persons with moderate to severe cerebral palsy (CP), causing fractures with minimal trauma. Over the past decade, most studies examining osteoporosis and CP have been cross-sectional in nature, focused exclusively on children and adolescents and only involving one evaluation of bone mineral density (BMD). The purpose of this study was to assess BMD in a group including adults with CP, and changes in each individual's BMD over a 5- to 6-year period. METHOD: The study group included 40 residents of a long-term care facility aged 6 to 26 years at the time of their initial evaluation. Twenty-one patients (52.5%) were male, 35 (88%) were white, and 38 (95%) were in Gross Motor Function Classification System level V. BMD was assessed by dual-energy X-ray absorptiometry on the right and left distal femurs for three distinct regions of interest. RESULTS: Five residents had a fracture that occurred during the study period; this represented a fracture rate of 2.1% per year in the study group. Longitudinally, annualized change in the median BMD was 0.7% to 1.0% per year in the different regions of the distal femur, but ranged widely among the study group, with both increases and decreases in BMD. Increase in BMD over time was negatively correlated with age and positively correlated with change in weight. INTERPRETATION: Changes in BMD over time in profoundly involved persons with CP can range widely, which is important to recognize when evaluating potential interventions to improve BMD. Age and changes in body weight appear the most relevant factors.

Adaptation of the lateral distal femur DXA scan technique to adults with disabilities.

The technique that best addresses the challenges of assessing bone mineral density in children with neuromuscular impairments is a dual-energy X-ray absorptiometry (DXA) scan of the lateral distal femur. The purpose of this study was to adapt this technique to adults with neuromuscular impairments and to assess the reproducibility of these measurements. Thirty-one adults with cerebral palsy had both distal femurs scanned twice, with the subject removed and then repositioned between each scan (62 distal femurs, 124 scans). Each scan was independently analyzed twice by 3 different technologists of varying experience with DXA (744 analyses). Precision of duplicate analyses of the same scan was good (range: 0.4%-2.3%) and depended on both the specific region of interest and the experience of the technologist. Precision was reduced when comparing duplicate scans, ranging from 7% in the metaphyseal (cancellous) region to 2.5% in the diaphyseal (cortical) region. The least significant change was determined as recommended by the International Society for Clinical Densitometry for each technologist and each region of interest. Obtaining reliable, reproducible, and clinically relevant assessments of bone mineral density in adults with neuromuscular impairments can be challenging. The technique of obtaining DXA scans of the lateral distal femur can be successfully applied to this population but requires a commitment to developing the necessary expertise.

Magnetic resonance evaluation of the knee in children and adolescents with achondroplasia.

BACKGROUND: Achondroplasia is the most common form of skeletal dysplasia. Although the radiographic features are well described, MRI features of the knee in achondroplasia have not been reported. OBJECTIVE: To describe common MRI characteristics of the knee joint in symptomatic children and adolescents with achondroplasia. MATERIALS AND METHODS: We retrospectively evaluated 10 knee MRI examinations in 8 children and young adults (age range 11-20 years, mean 16.3 years) with achondroplasia. We measured modified Insall-Salvati index, knee flexion angle, anterior cruciate ligament (ACL)-Blumensaat line angle, ACL-tibial angle, posterior cruciate ligament (PCL) angle, intercondylar notch width index, and intercondylar notch depth index. We compared our findings with an age- and gender-matched control group of 20 children (age range 15-18 years; mean 16 years) with normal knee MRIs. RESULTS: All 10 knees in the achondroplasia group had discoid lateral meniscus; 8 meniscal tears were identified. Patella baja was present in half of the study cases. Greater knee flexion and increased ACL-Blumensaat line and PCL angles were seen in all achondroplasia knees. ACL-tibial angle was similar in the study and in the control group. Children with achondroplasia had deeper A-shape femoral notches that extended more anteriorly than those seen in the control group. MRI findings were confirmed in all seven knees with arthroscopic correlation. CONCLUSION: Discoid lateral meniscus, often with tear, is a consistent feature in knee MRIs of symptomatic children and adolescents with achondroplasia. Other findings include patella baja, knee flexion, deep A-shape intercondylar notch, increased ACL-Blumensaat line angle and taut PCL.

Assessment of bone health in children with disabilities.

Evaluating the bone health of children with disabilities is challenging and requires consideration of many factors in clinical decision-making. Feeding problems and growth deficits, immobility/inability to bear weight, effect of medications, and the nature of his or her disease can all directly affect a child's overall picture of bone health. Familiarity with the tools available to assess bone health is important for practitioners. The most commonly used method to assess bone density, dual energy x-ray absorptiometry, can be performed effectively when one appreciates the techniques that make scanning patients with disabilities possible. There are specific techniques that are especially useful for measuring bone density in children with disabilities; standard body sites are not always obtainable. Consideration of clinical condition and treatment must be considered when interpreting dual energy x-ray absorptiometry scans. Serial measurements have been shown to be effective in monitoring change in bone content and in providing information on which to base decisions regarding medical treatment.

Dual-energy X-ray absorptiometry interpretation and reporting in children and adolescents: the revised 2013 ISCD Pediatric Official Positions.

The International Society for Clinical Densitometry Official Revised Positions on reporting of densitometry results in children represent current expert recommendations to assist health care providers determine which skeletal sites should be measured, which, if any, adjustments should be made, reference databases to be used, and the elements to include in a dual-energy X-ray absorptiometry report. The recommended scanning sites remain the total body less head and the posterior-anterior spine. Other sites such as the proximal femur, lateral distal femur, lateral vertebral assessment, and forearm are discussed but are only recommended for specific pediatric populations. Different methods of interpreting bone density scans in children with short stature or growth delay are presented. The use of bone mineral apparent density and height-adjusted Z-scores are recommended as suitable size adjustment techniques. The validity of appropriate reference databases and technical considerations to consider when upgrading software and hardware remain unchanged. Updated reference data sets for all contemporary bone densitometers are listed. The inclusion of relevant demographic and health information, technical details of the scan, Z-scores, and the wording "low bone mass or bone density" for Z-scores less than or equal to -2.0 standard deviation are still recommended for clinical practice. The rationale and evidence for the development of the Official Positions are provided. Changes in the grading of quality of evidence, strength of recommendation, and worldwide applicability represent a change in current evidence and/or differences in opinion of the expert panelists used to validate the position statements for the 2013 Position Development Conference.