Musculoskeletal health in newly diagnosed children with Crohn's disease.

We evaluated the impact of Crohn's disease on muscle and bone strength, mass, density, and geometry in children with newly diagnosed CD and found profound muscle and bone deficits; nevertheless, the prevalence of vertebral fractures at this time point was low. INTRODUCTION: Crohn's disease (CD) is an inflammatory condition of the gastrointestinal tract that can affect the musculoskeletal system. The objective of this study was to determine the prevalence of vertebral fractures and the impact of CD on muscle and bone mass, strength, density, and geometry in children with newly diagnosed CD. METHODS: Seventy-three children (26 girls) aged 7.0 to 17.7 years were examined within 35 days following CD diagnosis by lateral spine radiograph for vertebral fractures and by jumping mechanography for muscle strength. Bone and muscle mass, density, and geometry were assessed by dual-energy x-ray absorptiometry and peripheral quantitative computed tomography (pQCT). RESULTS: Disease activity was moderate to severe in 66 (90%) patients. Mean height (Z-score -0.3, standard deviation (SD) 1.1, p = 0.02), weight (Z-score -0.8, SD 1.3, p < 0.01), body mass index (Z-score -1.0, SD 1.3, p < 0.01), lumbar spine areal bone mineral density (BMD; Z-score -1.1, SD 1.0, p < 0.01), total body bone mineral content (Z-score -1.5, SD 1.0, p < 0.01), and total body lean mass (Z-score -2.5, SD 1.1, p < 0.01) were all low for age and gender. pQCT showed reduced trabecular volumetric BMD at the tibial metaphysis, expansion of the bone marrow cavity and thin cortices at the diaphysis, and low calf muscle cross-sectional area. Jumping mechanography demonstrated low muscle power. Only one patient had a vertebral fracture. CONCLUSIONS: Children with newly diagnosed CD have profound muscle and bone deficits; nevertheless, the prevalence of vertebral fractures at this time point was low.

The time to and determinants of first fractures in boys with Duchenne muscular dystrophy.

Boys with vertebral fractures (VF) identified through routine spine radiographs had milder, less symptomatic, and fewer VF compared to those diagnosed with VF following consultation for back pain. Spontaneous (i.e., medication-unassisted) reshaping of fractured vertebral bodies was absent. Long bone fractures were present even before Duchenne muscular dystrophy (DMD) diagnosis in some boys. INTRODUCTION: The objective of the study was to determine the time to and characteristics of first fractures in Duchenne muscular dystrophy. METHODS: This study was a retrospective longitudinal study of 30 boys with DMD <18 years. Boys were classified into four groups according to their first fracture: those with VF identified on routine lateral spine radiographs, those with VF diagnosed following consultation for back pain, those with long bone fractures, and those without fractures. RESULTS: Compared to boys diagnosed with VF as their initial fracture following consultation for back pain, those with VF surveillance radiographs had shorter durations of glucocorticoid (GC) therapy at the time of VF diagnosis (median 1.6 versus 5.3 years, p < 0.01), higher areal (mean ± standard deviation -1.4 ± 0.7 versus -3.1 ± 0.8, p = 0.01), and volumetric (-0.3 ± 0.5 versus -2.6 ± 0.8, p < 0.01) lumbar spine bone mineral density Z-scores, as well as fewer VF (median 1.4 versus 5.2 per person, p < 0.01) and a lower median spinal deformity index (median 1.5 versus 9.5, p < 0.01). Vertebral body reshaping following VF was not observed. Ten boys sustained a long bone fracture as their first fracture at a mean age of 8.9 ± 4.0 years; four of these boys later sustained a total of 27 incident VF. CONCLUSIONS: Routine lateral spine radiographs led to detection of VF in their earlier stages, vertebral body reshaping following VF was absent, and VF were frequent after the first long bone fracture. These results support the inclusion of a lateral spine radiograph starting at the time of GC initiation as part of routine bone health monitoring in DMD.

The use of intravenous bisphosphonate therapy to treat vertebral fractures due to osteoporosis among boys with Duchenne muscular dystrophy.

UNLABELLED: The impact of intravenous bisphosphonate treatment to treat painful vertebral fractures in boys with DMD has not been documented. In this retrospective observational study of seven boys, 2 years of intravenous bisphosphonate therapy was associated with back pain improvement and stabilization or increases in the height ratios of fractured vertebrae. INTRODUCTION: Boys with Duchenne muscular dystrophy (DMD) are at risk for vertebral fractures. We studied the impact of intravenous bisphosphonate therapy for the treatment of painful vertebral fractures in DMD. METHODS: This was a retrospective observational study in seven boys with DMD (median 11.6 years, range 8.5 to 14.3) treated with intravenous pamidronate (9 mg/kg/year) or zoledronic acid (0.1 mg/kg/year) for painful vertebral fractures. RESULTS: At baseline, 27 vertebral fractures were evident in the seven boys. After 2 years of bisphosphonate therapy, 17 of the fractures had an increase in the most severely affected vertebral height ratio, 10 vertebrae stabilized, and none showed a decrease in height ratio. Back pain resolved completely (N = 3) or improved (N = 4). The median change in lumbar spine volumetric bone mineral density Z-score was 0.5 standard deviations (interquartile range, -0.3 to 1.7). Two boys had three incident vertebral fractures in previously normal vertebral bodies that developed over the observation period. There was a decline in the trabecular bone formation rate on trans-iliac bone biopsy but no evidence of osteomalacia. First-dose side effects included fever and malaise (N = 4), hypocalcemia (N = 2), and vomiting (N = 1); there were no side effects with subsequent infusions. CONCLUSIONS: Intravenous bisphosphonate therapy was associated with improvements in back pain and stabilization to improvement in vertebral height ratios of previously fractured vertebral bodies. At the same time, such therapy does not appear to completely prevent the development of new vertebral fractures in this context.

Anatomical distribution of vertebral fractures: comparison of pediatric and adult spines.

SUMMARY: We compared the distribution of vertebral fractures in adults and children and found that fractures occurred in different locations in the two age groups. This likely relates to the different shape of the immature spine. INTRODUCTION: We hypothesized that the anatomical distribution of vertebral fractures (VF) would be different in children compared to adults. METHODS: We compared the distribution of VF defined using the Genant semi-quantitative method (GSQ method) in adults (N = 221; 545 fractures) and in children early in the course of glucocorticoid therapy (N = 44; 94 fractures). RESULTS: The average age in the adult cohort was 62.9 years (standard deviation (SD), 13.4 years), 26% was male, the mean lumbar spine Z-score was -1.0 (SD, 1.5), and the corresponding T-score was -2.4 (SD, 1.4). The pediatric cohort median age was 7.7 years (range, 2.1-16.6 years), the mean lumbar spine Z-score was -1.7 (SD, 1.5), 52% was male, and disease categories were acute lymphoblastic leukemia (66%), rheumatological conditions (21%), and nephrotic syndrome (14%). The VF distribution was biphasic in both populations, but the peaks differed in location. In adults, the peaks were at T7/T8 and at T12/L1. In children, the focus was higher in the thoracic spine, at T6/T7, and lower in the lumbar spine, at L1/L2. When children were assessed in two age-defined sub-groups, a biphasic VF distribution was seen in both, but the upward shift of the thoracic focus to T6 was observed only in the older group, with the highest rates of fracture present between ages 7 and 10 years. CONCLUSIONS: These results suggest that the anatomical distribution of VF differs between children and adults, perhaps relating to the different shape of the immature spine, notably the changing ratio of kyphosis to lordosis.

Spinal cord injuries without radiographic abnormality at two pediatric trauma centers in Ontario.

BACKGROUND: Spinal cord injury without radiographic abnormality (SCIWORA) represents a traumatic myelopathy, either transient or permanent, that is not associated with visible vertebral fractures or ligamentous abnormalities on plain radiographs or CT. MRI has become essential in the diagnosis and evaluation of trauma patients and in predicting the long-term neurological outcome. METHODS: The medical charts of 578 children with vertebral trauma at the Children's Hospital of Eastern Ontario and the Hospital for Sick Children were retrospectively reviewed. RESULTS: Forty-five patients were identified as having traumatic myelopathy. Three of these patients had SCIWORA. Two sustained thoracic spinal cord injuries as a result of motor vehicle accidents and permanent neurological deficits. The third was involved in a sports-related injury and sustained a cervical spine injury that improved in 48 h. CONCLUSIONS: SCIWORA is uncommon. The serious neurological sequelae that can result from a missed diagnosis merit more attention in identifying a spinal lesion in children with traumatic myelopathy. MRI has played a valuable role in this respect and may be even more predictive of outcome than the presenting neurological findings. The SCIWORA acronym can be modified to SCIWONA (spinal cord injury without neuroimaging abnormality) in order to highlight the importance of MRI in the prognosis.

Iliac bone histomorphometry in children with newly diagnosed inflammatory bowel disease.

UNLABELLED: Children with inflammatory bowel disease (IBD) manifest low bone mass; the cause remains unclear. We performed transilial bone biopsies in 20 IBD children at diagnosis and found a mild cortical bone deficit and slow bone turnover. It is possible that low mechanical stimulation due to inadequate muscle mass contributes to the bone deficit. INTRODUCTION: Children with newly diagnosed IBD can have low bone mineral density and disturbed bone metabolism, but the tissue level characteristics of the bone involvement in pediatric IBD have not been elucidated. METHODS: In the present study, we evaluated the skeletal status, including static histomorphometry on transiliac bone samples, in 20 patients (age range 8.4 to 17.7 years, 12 boys) with newly diagnosed IBD and compared results to published normative data. RESULTS: Despite normal height (mean Z-score 0.04, SD 1.2), areal bone mineral density at the lumbar spine was moderately low (mean age- and sex-specific Z-score -0.8, SD 1.1). Total body bone mineral content and lean mass were low for age and sex as well (mean Z-scores -1.2, SD 0.9 and -2.0, SD 0.9, respectively). Biochemical bone markers indicated low bone formation and resorption activity. Bone histomorphometry revealed a slightly low cortical width (mean 23%, SD 25%, below the result expected for age) but a normal amount of trabecular bone. The percentage of trabecular bone surface covered by osteoid or osteoclasts was low, suggesting that both bone formation and bone resorption were suppressed. CONCLUSIONS: Our results indicate that young patients manifest a mild cortical bone deficit at the iliac crest and slow trabecular bone turnover even at diagnosis, in the setting of IBD.

Brainstem compression: a predictor of postoperative cerebellar mutism.

PURPOSE: Cerebellar mutism is a common complication of posterior fossa tumor resection. We observed marked, preoperative brainstem compression on MR imaging, among patients who developed postoperative mutism. This study was designed to investigate if an association was indeed present. MATERIALS AND METHODS: Patients (18 months-18 years) undergoing resection of a midline, posterior fossa tumor were retrospectively reviewed. Demographic data, tumor pathology, mutism onset and duration, and postoperative complications were obtained from hospital records. Pre- and postoperative MR images were studied to assess tumor size and the severity of pons compression (an estimate of the mechanical and distortional forces imparted by the tumor). RESULTS: Patients with mutism showed greater preoperative pons compression and a greater increase in postoperative pons diameter. CONCLUSION: We predict that brainstem compression may represent white-matter injury from (1) surgical manipulation and traction, and (2) axonal damage caused by the release of the tumor's compressive force and ensuing axon distortion and dysfunction. The results provide support that mutism may be largely caused by white-matter damage disrupted axon integrity and function.

Radioisotope shuntograms at the Children's Hospital of Eastern Ontario.

INTRODUCTION: Nuclear medicine shuntograms using the radiotracer technetium-99m diethylenetriaminepentaacetic acid have been used for many years as an additional method to assess shunt patency and performance. METHODS: The medical records of all children who had shuntograms performed at the Children's Hospital of Eastern Ontario between January 13, 2000, and January 10, 2003, were retrospectively reviewed. There was a total of 68 procedures in 56 patients with an average age of 9 years 3 months. During the same period there were 123 shunt revisions. RESULTS: Forty-two shuntograms were reported as normal. Of these, ten were identified to be false negative. Two children with fractured shunts had shuntograms performed in order to assess for cerebrospinal fluid flow patency; the shuntograms were identified to be normal, confirming shunt dependence, and the shunt replaced. Twenty-six shuntograms were reported as abnormal in 24 patients; 17 went on to have surgery and the shunt malfunction was confirmed. Seven patients did not require surgery: five were declared shunt independent, two patients clinically improved after severe constipation was treated. CONCLUSIONS: Approximately one fourth of all shuntograms reported as normal are not (false-negative rate=25%). Review of five other major studies between 1980 and 2003 have reported false-negative rates between 2 and 36%, which may be explained by variations in shuntogram protocols. A standardized method is proposed.

Resolution of severe, adolescent-onset hypophosphatemic rickets following resection of an FGF-23-producing tumour of the distal ulna.

Oncogenic hypophosphatemic osteomalacia (OHO) is an uncommon hypophosphatemic syndrome characterized by bone pain, proximal muscle weakness and rickets. It has been postulated that OHO results from overproduction of a humoral phosphaturic factor by an occult tumour. Recently, some OHO tumours have been shown to elaborate fibroblast growth factor-23 (FGF-23), which causes renal phosphate wasting when administered to mice. The purpose of this study was to undertake detailed investigations to confirm the diagnosis of OHO in a pediatric patient and to document the biochemical, radiographic and bone histological phenotype before and after tumour removal. We describe an 11-year-old, previously healthy girl with significant pain and functional disability associated with hypophosphatemic rickets. Circulating 1,25-(OH)(2) vitamin D was very low (14 pM; N: 40-140) while the FGF-23 serum level was markedly elevated [359.5 reference units (RU)/ml, N: 33-105]. An iliac bone biopsy revealed severe osteomalacia, but periosteocytic lesions, as are typical for X-linked hypophosphatemic rickets, were not seen. Sequence analyses of the PHEX and FGF23 genes were normal. A radiographic skeletal survey revealed a small exostosis of the left, distal ulnar metaphysis. A tumour was subsequently removed from this site and the pathology was consistent with benign, fibro-osseous tissue. Serum FGF-23 was normal when measured at 7 h post-operatively, while serum phosphate reached the low-normal range at 16 days following surgery. An iliac bone biopsy taken 5 months after the operation showed improvement, but not yet resolution, of the osteomalacia. Biochemical parameters of bone and mineral metabolism suggested that complete resolution of the osteomalacia was not achieved until 12 months following surgery. One year after tumour removal, the patient was pain-free and had resumed a normal level of activity. The rapid normalization of FGF-23 levels following removal of a benign tumour and the subsequent improvement in the biochemical and histological parameters of bone and mineral metabolism suggest that FGF-23 played a key role in this girl's disease.

Cerebral vascular events associated with ulcerative colitis in children.

Although peripheral vascular thrombic events are recognized as a serious extra-intestinal complication of inflammatory bowel disease, the occurrence of cerebral vascular events in association with acute exacerbations of this group of diseases is rare. In this article, relevant literature is reviewed and three children, 5, 12, and 13 years of age, who presented with clinical and magnetic resonance imaging evidence of an acute cerebrovascular event in association with an acute exacerbation of their inflammatory bowel disease are described. Except for the presence of anemia, hematologic and coagulation studies were unremarkable, and a search for evidence of a systemic vasculitis proved negative.

Temporal lobe focal cortical dysplasia: MRI imaging using FLAIR shows lesions consistent with neoplasia.

Focal cortical dysplasia (FCD), a form of neuronal migration disorder, is a malformative lesion of the neocortex that occurs during development of the brain. It can cause partial and generalized epilepsy. Seizures occur at an early age and are often resistant to medication. Surgical resection has been found to be beneficial in these patients. Dual pathology, in the form of mesial temporal sclerosis, has been associated with FCD. At the Children's Hospital of Eastern Ontario, four patients with temporal lobe FCD have recently, been identified. This paper discusses how these children presented and how they were managed, with particular emphasis on their MRI findings and differential diagnoses. In three of the four patients neuroimaging studies showed lesions consistent with a neoplastic process because of the large volume and mass effect. Radiologically, FCD may mimic the MRI appearance of tumors, such as dysembryoplastic neuroepithelial tumors, primitive neuroectodermal tumors, gangliogliomas, oligodendrogliomas, and astrocytomas. These lesions are best visualized on fluid-attenuated inversion recovery (FLAIR) imaging, a technique that has recently become applicable in the clinical setting, as we help demonstrate in this series. With better MRI capability, milder forms of FCD and microdysplasia may be distinguished.

Primary ciliary dyskinesia associated with a novel microtubule defect in a child with Down's syndrome.

We present a child with Down's syndrome, bilateral lower lobe bronchiectasis, sinusitis, and severe ear disease who was found to have a novel ciliary defect, with a frequent, partial absence of the walls of the A subunits of some peripheral doublets. The defect caused the A subunits to be "U-shaped" rather than "O-shaped." A nuclear nasal mucociliary transport study confirmed that this defect was associated with abnormal mucociliary transport. The ciliary defect was not observed in a biopsy performed in a second patient who had Down's syndrome.

Bone marrow metastasis in astrocytic gliomata.

With the increasing survival time of many pediatric patients with malignancies, unexpected symptoms or signs require diligent search for rare complications or second cancers related to the disease or treatment. We recently encountered a patient with extensive glioblastoma multiforme who developed pancytopenia six months after completion of treatment with craniospinal radiation and chemotherapy with etoposide and cyclophosphamide. Bone marrow aspirate and biopsy confirmed bone marrow metastasis from the brain tumor. He showed good partial remission with chemotherapy with carmustine and cis-platinum as demonstrated by serial bone marrow aspirate for cytology and cytogenetics and enjoyed good quality of life for eight months. 14 other patients with astrocytic glioma, two of whom are children, are reported in the literature to have diffuse bone marrow metastasis. Therefore, in patients with malignant astrocytic tumor, bone marrow metastasis, though not common, should be considered when bone pain or cytopenias occur, especially when prolonged.

Prevalence of hypertension in children with primary vesicoureteral reflux.

This study was undertaken to determine the prevalence of hypertension in children with primary, uncomplicated vesicoureteral reflux (VUR) and to evaluate the relationship between blood pressure (BP), grade and duration of reflux, and renal scarring. Subjects were identified retrospectively during a 17-year period; of 146 subjects who agreed to participate, 129 (88.4%) were female. Mean age at diagnosis was 5.0 years (range, 1 month to 16 years), and at follow-up was 14.4 years (range, 5 months to 21 years). Mean duration of follow-up was 9.6 years. Renal scarring was detected in 34.3% of patients by intravenous pyelogram, ultrasonography, or both. The BP at diagnosis was linearly related to the grade of reflux, but values were not higher than expected norms for age. At follow-up, mean systolic and diastolic BP were at the 41.6 percentile and the 18.7 percentile, respectively. No patient's BP was above the 55th percentile. After a mean follow-up period of 10 years, we conclude that primary, uncomplicated VUR, regardless of the number of documented urinary tract infections, duration and severity of reflux, modality of therapy, presence of renal scarring, and duration of follow-up, is not associated with the development of hypertension. Hypertension does not appear to be a complication of VUR and urinary tract infection unless there is preexisting dysplasia.

Antenatal and postnatal findings in intra-abdominal pulmonary sequestration.

A hyperechoic mass in the right upper quadrant of the abdomen was demonstrated in a fetus by antenatal ultrasonography (US) at 20 and 33 weeks' gestation. Postnatal US, myelography and computed tomography were performed preoperatively; the findings were judged consistent with neuroblastoma. Surgical excision and pathological examination revealed bronchopulmonary sequestration.

Evaluation of renal scars by technetium-labeled dimercaptosuccinic acid scan, intravenous urography, and ultrasonography: a comparative study.

The objective of our prospective study was to compare the sensitivity and specificity of ultrasonography, intravenous pyelography, and dimercaptosuccinic acid scan in detecting scarred kidneys. Twenty-seven consecutive subjects with recurrent urinary tract infections, vesicoureteral reflux, scarred kidneys, or a combination of these problems had all three imaging procedures performed. With the total number of scars serving as the gold standard, the sensitivity (94%) and specificity (100%) in identifying renal scars in children were highest for the DMSA scan. Intraobserver (95%) and interobserver (90%) reliability were also high for the DMSA scan. However, the clinical interpretation of the increased sensitivity of the DMSA scan is unknown. Changes on the scan not identified by intravenous urography may not represent true scars. Research into the long-term significance of these scars is indicated.